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By Christian Hoffmann &
Bernd S. Kamps

Copy-editor: R. Camp

23 September

 

Epidemiology

Hagan LM, McCormick DW, Lee C, et al. Outbreak of SARS-CoV-2 B.1.617.2 (Delta) Variant Infections Among Incarcerated Persons in a Federal Prison — Texas, July–August 2021. MMWR 21 September 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7038e3.htm?s_cid=mm7038e3_w

Bad news from this federal prison in Texas. During an outbreak involving the Delta variant, transmission was incredibly high among vaccinated (70%) and unvaccinated (93%) persons. Although hospitalizations, deaths, and attack rates were higher among unvaccinated than vaccinated persons, the duration of positive serial PCR test results was similar between these two groups, and infectious virus was cultured from both vaccinated and unvaccinated participants. This underscores the importance of implementing and maintaining multiple COVID-19 prevention strategies.

 

Virology

Patchett S, Ly Z, Rut W, et al. An A molecular sensor determines the ubiquitin substrate specificity of SARS-CoV-2 papain-like protease. Cell Rep September 20, 2021. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01208-0

The SARS-CoV-2 papain-like protease (PLpro) is essential for processing viral polyproteins for replication and functions in host immune evasion by cleaving ubiquitin (Ub) and ubiquitin-like protein (Ubl) conjugates. This study gives insight into the ensemble of conformations that the highly conserved active site of PLpro can adopt.

 

Vaccine

Sokal A, Barba-Spaeth G, Fernández I, et al. mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. Immunity September 20, 2021. https://www.cell.com/immunity/fulltext/S1074-7613(21)00396-4

Although naïve individuals had weaker neutralizing serum responses than recovered patients, many of their RBD-specific memory B cells (MBCs) displayed high affinity towards multiple variants of concern (VOCs), including Delta and Beta. These data suggest that an additional challenge in naive vaccinees could recall such affinity-matured MBCs and allow them to respond efficiently to VOCs.

 

Transmission

Hu M, Wang J, Lin H, et al. Risk of SARS-CoV-2 Transmission among Air Passengers in China. Clinical Infectious Diseases September 21, 2021, ciab836, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab836/6373518

This analysis of 175 index cases among 5797 passengers on 177 airplanes came to the conclusion that the overall risk of SARS-CoV-2 transmission during domestic travel on planes is relatively low. However, the attack rates (AR) among travellers varied considerably. The seats immediately adjacent to the index cases had an AR of 9.2%, with a relative risk of 27.8 compared to other seats in the upper limit estimation. The middle seat had the highest AR.

 

Dhanasekaran V, Edwards KM, Xie R, et al. Air travel-related outbreak of multiple SARS-CoV-2 variants. Journal of Travel Medicine, September 21, 2021, taab149, https://academic.oup.com/jtm/advance-article/doi/10.1093/jtm/taab149/6372544?searchresult=1

And the thing is: sometimes it’s not only one single index case. In this report, a large cluster of 59 (!) cases were linked to a single flight with 146 passengers from New Delhi to Hong Kong in April 2021. Transmission of three VOI/VOC lineages occurred from at least seven index cases. Take your seats (or stay home).

SARS-CoV-2 transmission associated with a flight from New Delhi to Hong Kong in April 2021. Colors represent WHO variants and Pango lineage designations

 

 

22 September

 

Virology

Meyer B, Chiaravalli J, Gellenoncourt S, et al. Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential. Nat Commun September 21, 2021, 12, 5553. https://www.nature.com/articles/s41467-021-25796-w

An improved understanding of the exact ways in which proteolytic cleavage is regulated, modulates protein activity, and serves to benefit viral replication will be crucial for targeting cellular substrates of viral proteases as a therapeutic strategy. The authors applied mass spectrometry-based methods for N-terminomics to study proteolysis, enabling the identification of novel cleavage and processing sites within viral proteins. They discover that several of these novel viral cleavage sites show altered cleavage following treatment with the cathepsin/calpain inhibitor calpeptin.

 

Variants

Tao K, Tzou PL, Nouhin J, et al. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat Rev Genet September 19, 2021. https://www.nature.com/articles/s41576-021-00408-x

Brilliant review. And the best Figure of the day (Figure 1, your new bedroom poster)!

 

Clinical

Reif J, Heun-Johnson H, Tysinger B, et al. Measuring the COVID-19 Mortality Burden in the United States. Ann Int Med September 21, 2021. https://www.acpjournals.org/doi/10.7326/M21-2239

In approximately 1 year, the COVID-19 pandemic resulted in half the premature mortality caused by all cancer types combined or all cardiovascular diseases combined. This modeling study estimated that the US COVID-19 pandemic resulted in 9.08 million YLL through 13 March 2021. By comparison, Americans lost an estimated 15.4 million YLL from cancer and an estimated 14.7 million from cardiovascular diseases in 2019.

 

Treatment

Yamin R, Jones AT, Hoffmann HH, et al. Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy. Nature September 21, 2021.  https://www.nature.com/articles/s41586-021-04017-w

The antiviral activity of IgG antibodies is the outcome of Fab-mediated virus neutralization coupled with the capacity of the Fc domain to mediate effector functions through interactions with Fcγ receptors (FcγRs) expressed on effector leukocytes. Here, the authors report the development and evaluation of Fc-optimized anti-SARS-CoV-2 mAbs with superior potency to prevent or treat COVID-19 disease.

 

Dong J, Zost SJ, Greaney AJ, et al. Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail. Nat Microbiol September 21, 2021. https://www.nature.com/articles/s41564-021-00972-2

Two non-competing antibodies, designated COV2-2196 and COV2-2130 (later engineered to be long-acting IgG molecules designated as AZD8895 and AZD1061, respectively), synergistically neutralize SARS-CoV-2 in animal models. This study provides a comprehensive mapping of the effect of RBD mutations on the binding of these two antibodies (both are currently being investigated in Phase III studies), underscoring their use as a rationally designed cocktail, given that they have different escape mutations.

 

Karbiener M, Farcet MR, Schwaiger J, et al. Plasma from post-COVID-19 and COVID-19-Vaccinated Donors Results in Highly Potent SARS-CoV-2 Neutralization by Intravenous Immunoglobulins. The Journal of Infectious Diseases September 20, 2021, jiab482, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab482/6372887

As of September 2020, some immunoglobulin (IG) lots from US plasma have contained neutralizing antibodies against the newly emerged SARS-CoV-2. Since then, antibody positivity and antibody titers have increased sharply.

 

 

21 September

 

Vaccine

Self WH, Tenforde MW, Rhoads JP, et al. Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions — United States, March–August 2021. MMWR Morb Mortal Wkly Rep 17 September 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7038e1.htm?s_cid=mm7038e1_w

Vaccine effectiveness against COVID-19 hospitalization during March 11–August 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%). However, as with all real-world data, residual confounding is possible.

 

Warren CM, Snow TT, Lee AS, et al. Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System. JAMA Netw Open September 17, 2021;4(9):e2125524. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784268?resultClick=1

Immunological testing of 22 patients with suspected vaccine allergy suggests that non–IgE-mediated allergic reactions to polyethylene glycol may be responsible for many cases of allergy to mRNA vaccines.

 

Clinical

Reiterer M, Rajan M, Gómez-Banoy N, et al. Hyperglycemia in Acute COVID-19 is Characterized by Insulin Resistance and Adipose Tissue Infectivity by SARS-CoV-2. Cell Report September 15, 2021. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00428-9

This important study suggests that SARS-CoV-2 may trigger adipose tissue dysfunction to drive insulin resistance and adverse outcomes in acute COVID-19.

 

Hippisley-Cox J, Coupland CA, Mehta N, et al. Risk prediction of covid-19 related death and hospital admission in adults after covid-19 vaccination: national prospective cohort study. BMJ September 19, 2021. https://www.bmj.com/content/374/bmj.n2244

The authors identified a range of important clinical risk factors for severe COVID-19 outcomes in vaccinated people. In this national linked dataset from more than 6.9 million adults, risk ratios were highest for people with Down’s syndrome, kidney transplantation, sickle cell disease, care home residency, chemotherapy, recent bone marrow transplantation or solid organ transplantation ever, HIV/AIDS, dementia, Parkinson’s disease, neurological conditions, and liver cirrhosis.

 

Moon RC, Mackey RH, Cao Z, et al. Is COVID-19 Less Deadly Now? — Trends of In-Hospital Mortality Among Hospitalized COVID-19 Patients in the United States. Clinical Infectious Diseases September 17, 2021, ciab830. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab830/6371824

No. Despite more time and experience in treating COVID-19, there has been no continued decline in mortality among in-patients: after an initial decline from April through June 2020 (from 22.2% to 11.9%), adjusted in-hospital mortality in COVID-19 in-patients peaked twice and was significantly higher than June 2020 for subsequent months except in July and October 2020.

 

 

20 September

 

Vaccine

Falsey AR, Frenck RW, Walsh EE, et al. SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3. NEJM September 15, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2113468?query=featured_home

Preliminary findings from a small pivotal trial, suggesting that a third dose could prolong protection and further increase the breadth of protection.

 

Clinical

Seedat S, Chemaitelly H, Ayoub HH, et al. SARS-CoV-2 infection hospitalization, severity, criticality, and fatality rates in Qatar. Sci Rep September 14, 2021, 11, 18182. https://doi.org/10.1038/s41598-021-97606-8

With Qatar’s young population, overall SARS-CoV-2 severity and fatality were not high with < 4 infections in every 1000 being severe or critical and < 2 in every 10,000 being fatal. However, the authors argue that these rates would have been much higher if Qatar’s population had the demographic structure of Europe or the United States.

 

Iroungou BA, Mangouka LG, Bivigou-Mboumba B, et al. Demographic and Clinical Characteristics Associated With Severity, Clinical Outcomes, and Mortality of COVID-19 Infection in Gabon. JAMA Netw Open September 14, 2021; 4(9):e2124190. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784059?resultClick=1

Same findings from Gabon. Young people, only a few severe infections.

 

Treatment

Ananworanich J, Mogg R, Dunne MW, et al. Randomized study of rivaroxaban vs. placebo on disease progression and symptoms resolution in high-risk adults with mild COVID-19. Clinical Infectious Diseases September 15, 2021, ciab813, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab813/6370549

Large RCT, showing no impact of rivaroxaban on disease progression in high-risk adults with mild COVID-19.

 

Cho H, Gonzales-Wartz KK, Huang D, et al. Bispecific antibodies targeting distinct regions of the spike protein potently neutralize SARS-CoV-2 variants of concern. Science Translational Medicine September 14, 2021. https://www.science.org/doi/10.1126/scitranslmed.abj5413

Hyeseon Cho and colleagues from NIH have isolated a panel of monoclonal antibodies from plasmablasts and memory B cells from COVID-19 convalescent individuals that target distinct regions of the SARS-CoV-2 spike protein. From this antibody panel, the authors have designed bispecific antibodies that potently neutralize a range of SARS-CoV-2 variants of concern, including Delta.

 

Pediatrics

Vono M, Huttner A, Lemeille S, et al. Robust innate responses to SARS-CoV-2 in children resolve faster than in adults without compromising adaptive immunity. Cell Rep September 14, 2021. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)01227-4

This study demonstrates that children mount potent antiviral innate responses, similar in amplitude to those of adults with mild COVID-19, yet significantly different in duration: the transience of innate responses in children may explain their limited symptomatology.

 

Beyond Corona

Pappalardo L, Rossi A, Natilli M, et al. Explaining the difference between men’s and women’s football. PLOS, August 4, 2021. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255407

We almost overlooked this important contribution. Bottom line: Men’s and women’s football have similar play intensity. Whereas women do fewer fouls, there are some technical gaps between men and women. Nicely said: According to the authors, the “results are open to various interpretations”.

 

19 September

 

Variants

Blanquart F, Abad C, Ambroise J, et al. Characterisation of vaccine breakthrough infections of SARS-CoV-2 Delta and Alpha variants and within-host viral load dynamics in the community, France, June to July 2021. Euro Surveill September 15, 2021;26(37). https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.37.2100824

A French study, confirming other reports on Delta: higher viral load, longer duration of infection and, probably most important, similar values among fully vaccinated individuals and those who were not.

 

Luna-Muschi A, Borges IC, de Faria E, et al. Clinical features of COVID-19 by SARS-CoV-2 Gamma variant: a prospective cohort study of vaccinated and unvaccinated healthcare workers. J Infection September 16, 2021. https://www.journalofinfection.com/article/S0163-4453(21)00474-6/fulltext

Some differences in the clinical presentation between Gamma variant (P1 from Brazil) and non-VoC infection with a decreased frequency of hyposmia/anosmia and dysgeusia in Gamma variant cases.

 

Diagnostics

Cubas-Atienzar AI, Kontogianni K, Edwards T, et al. Limit of detection in different matrices of 19 commercially available rapid antigen tests for the detection of SARS-CoV-2. Sci Rep 11, 18313 (2021). https://www.nature.com/articles/s41598-021-97489-9

This comprehensive study evaluated the analytical performance of 19 antigen rapid diagnostic tests that are currently on the market and in use in multiple countries. Check your RDT: the most sensitive tests on dry swabs and direct culture supernatant were Espline, Mologic, Sure-Status and Roche and the least sensitive on all matrices were Biocredit, iChroma, Standard-F and Genedia.

 

Collateral damage

Peña PA, Jena A. Mass Shootings in the US During the COVID-19 Pandemic. JAMA Netw Open September 16, 2021;4(9):e2125388. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784187?resultClick=1

Beautifully put. After arguing that “mass shootings are rare events with causes that are not well understood”, the authors analyzed 2985 (!) mass shootings in the US, involving 3185 people killed and 12,547 injured. Bottom line: mass shootings are on the increase, possibly indicating that mass murderers may also be stressed these days (well, has anyone suggested gun laws?)

Twenty-eight-day moving mean. Mass shootings are defined as shootings in which 4 or more people were killed or injured, not counting the perpetrator.

 

Pediatrics

Strutner J, Ramchandar N, Dubey S, et al. Comparison of RT-PCR Cycle Threshold Values from Respiratory Specimens in Symptomatic and Asymptomatic Children with SARS-CoV-2 Infection. Clinical Infectious Diseases September 15, 2021, ciab403, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab403/6370557

In this retrospective review of 728 children who tested positive by RT-PCR for SARS CoV-2, the mean Ct was significantly lower in symptomatic children and was lowest in children under 5, indicating that symptomatic children and younger children may have a higher viral load in the nasopharynx.

 

 

18 September

 

Today we’ll have a Vaccines special. A lot of data on the long-term efficacy of the BioNTech vaccine and some arguments for a third jab in older people. Some more data on breakthrough infections, waning immunity, on immune correlates of protection and on how to identify VITT cases.

 

Vaccines

Bar-On YM, Goldberg Y, Mandel M, et al. Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel. NEJM September 15, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2114255?query=featured_home

Paper of the day, providing important data from the Israeli Ministry of Health on a third shot (“booster”). Among 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (two doses of BNT162b2) at least 5 months earlier, the rate of confirmed infection was lower in the booster group by a factor of 11.3; the rate of severe illness was lower by a factor of 19.5. Though sources of bias may not have been measured or corrected for adequately, these data strongly argue for a third shot in the elderly.

Shown is the factor reduction in the rate of confirmed infection among participants who received a third (booster) dose of the BNT162b2 vaccine as compared with those who did not receive a booster dose, according to the number of days after the administration of the booster dose. Because of wide confidence intervals, only days 1 through 25 are shown.

 

Thomas SJ, Moreira ED, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months. NEJM September 15, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2110345?query=featured_home

Follow up of the large Phase III RCT (published a few months ago), showing a gradual decline in vaccine efficacy over time. Efficacy peaked at 96.2% during the interval from 7 days to less than 2 months after the second dose and declined gradually to 83.7% from 4 months after the second dose to the data cutoff date — an average decline of approximately 6% every 2 months.

 

Rosenberg ES, Holtgrave DR, Dorabawila V, et al. New COVID-19 Cases and Hospitalizations Among Adults, by Vaccination Status — New York, May 3–July 25, 2021. MMWR Morb Mortal Wkly Rep September 15, 2021;70:1306–1311. https://www.cdc.gov/mmwr/volumes/70/wr/mm7037a7.htm?s_cid=mm7037a7_w

Same direction in the “real world”. From May 3–July 25, 2021, the overall age-adjusted vaccine effectiveness against hospitalization in New York was relatively stable. However, the overall age-adjusted vaccine effectiveness against infection for all New York adults declined from 91.8% to 75.0%, coinciding with a period of easing societal public health restrictions and increasing Delta variant circulation.

 

Salih F, Schönborn L, Kohler S, et al. Vaccine-Induced Thrombocytopenia with Severe Headache. NEJM September 15, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2112974?query=featured_home

Small case series, providing some evidence that vaccine-induced thrombocytopenia (VIT) without associated cerebral venous sinus thrombosis and with severe headache as the heraldic symptom may precede VITT (“pre-VITT syndrome”). The authors argue that patients who present with severe headache 5 to 20 days after adenovirus vector vaccination should undergo immediate testing for thrombocytopenia and d-dimer levels.

 

Corbett KS, Nason MC, Flach B, et al. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Science September 17, 2021. Vol 373, Issue 6561. https://www.science.org/doi/10.1126/science.abj0299

In monkeys, S-specific binding antibody induced by the Moderna vaccine was a surrogate marker of protection. Moreover, protection of the lower respiratory tract required lower serum antibody concentrations, possibly explaining why most current vaccines are highly effective against severe lower airway disease.

 

Xia L, Zhang YT, Wang YX, et al. Safety and immunogenicity of an inactivated COVID-19 vaccine, BBIBP-CorV, in people younger than 18 years: a randomised, double-blind, controlled, phase 1/2 trial. Lancet Inf Dis September 15, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00462-X/fulltext

The inactivated COVID-19 vaccine BBIBP-CorV was safe and well-tolerated at all tested dosing levels in 288 participants aged 3–17 years. The vaccine also elicited robust humoral responses.

 

 

17 September

 

Today we have an Immunology Special, mainly on T cells but also on new onset auto-antibodies that are observed in COVID-19, as well as on immune responses to vaccines in patients with complex co-morbidities.

 

Immunology

 

Autoantibodies

Chang SE, Feng A, Meng W, et al. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nat Commun September 14, 2021, 12, 5417. https://www.nature.com/articles/s41467-021-25509-3

Approximately half of hospitalized COVID-19 patients develop serum autoantibodies against one or more antigens. Moreover, a surprisingly large number of anti-cytokine antibodies (ACA) were identified in this study (80%), far more than just the interferon autoantibodies described recently. Some autoantibodies are newly triggered by SARS-CoV-2 infection, suggesting that severe COVID-19 can break tolerance to self.

 

T cells

Mateus J, Dan JM, Zhang Z, et al. Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by cross-reactive T cells. Science September 14, 2021. https://www.science.org/doi/10.1126/science.abj9853

Studying 35 vaccinated subjects out to 7 months, this research group from La Jolla, US found that a two dose 25 μg mRNA-1273 vaccination (Moderna) generated immune memory against spike comparable to that of SARS-CoV-2 infection for antibodies, CD4+ T cells, and CD8+ T cells. Furthermore, immune responses were significantly enhanced by the presence of pre-existing cross-reactive CD4+ T cell memory.

 

Niessl J, Sekine T, Lange J, et al. Identification of resident memory CD8+ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue. Science Immunology September 14, 2021. https://www.science.org/doi/10.1126/sciimmunol.abk0894

This study provides a comprehensive picture of pre-existing SARS-CoV-2-specific mCD4+ and mCD8+ T cell immunity (likely generated via previous encounters with common cold human coronaviruses) in the tonsils, representing key lymphoid organs in the upper respiratory tract and the intravascular circulation. SARS-CoV-2-specific mCD4+ T cells were distributed evenly between these compartments, whereas SARS-CoV-2-specific mCD8+ T cells were almost exclusively present in the tonsils. Earlier studies confined to analyses of peripheral blood samples have therefore likely underestimated the overall prevalence of heterologous mCD8+ T cell responses.

 

Pathogenesis

Lee S, Yu Y, Trimpert J, et al. Virus-induced senescence is driver and therapeutic target in COVID-19. Nature September 13, 2021. https://www.nature.com/articles/s41586-021-03995-1#author-information

Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and composed of pro-inflammatory cytokines, extracellular matrix-active factors and pro-coagulatory mediators. This study marks VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggests senolytic targeting of virus-infected cells as a novel treatment option.

Immune responses in co-morbidities

Le Bourgeois A, Coste-Burel M, Guillaume T, et al. Safety and Antibody Response After 1 and 2 Doses of BNT162b2 mRNA Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant. JAMA Network September 14, 2021. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784061?resultClick=1

A high response rate of 83% was found in this cohort of 117 allogeneic HSCT recipients after 2 doses of BNT162b2 vaccine.

 

Apostolidis SA, Kakara M, Painter MM, et al. Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy. Nat Med September 14, 2021. https://www.nature.com/articles/s41591-021-01507-2

Although most patients with MS treated with anti-CD20 therapy do not generate optimal antibody responses, T cell priming, especially of TH1 and CD8 T cells, is largely intact. However, treatment with anti-CD20 therapy as well as having B cell deficiency were associated with altered coordination of the immune response, and circulating TFH responses were compromised.

 

 

 

16 September

 

Transmission

Adenaiye OO, Lai J, Bueno de Mesquita J, et al. Infectious SARS-CoV-2 in Exhaled Aerosols and Efficacy of Masks During Early Mild Infection. Clinical Infectious Diseases September 14, 2021, ciab797, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab797/6370149

A heroic study and without a doubt the paper of the day. No one can say anymore that masks have not been studied: Oluwasanmi Adenaiye and colleagues recruited 49 COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute (!) breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. Masks reduced viral RNA by 48% in fine aerosols and by 77% in coarse aerosols; cloth and surgical masks were not significantly different. The Alpha variant was associated with a 43-fold increase in fine aerosol viral RNA.

 

Epidemiology

Young BC, Eyre DW, Kendrick S, et al. Daily testing for contacts of individuals with SARS-CoV-2 infection and attendance and SARS-CoV-2 transmission in English secondary schools and colleges: an open-label, cluster-randomised trial. Lancet September 14, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01908-5/fulltext

In this huge controlled study, supervised daily testing with lateral flow devices was non-inferior to self-isolation for close contacts to control SARS-CoV-2 transmission. However, school absence was not significantly reduced due to daily testing.

 

Vaccines

Choi A, Koch M, Wu K, et al. Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. Nat Med September 15, 2021. https://www.nature.com/articles/s41591-021-01527-y

This very preliminary evaluation described the antibody persistence of mRNA-1273 and the safety and immunogenicity of a booster dose of mRNA-1273 and two updated versions (mRNA-1273.351 and mRNA-1273.211) in 80 participants who had been vaccinated 6 months previously with the authorized schedule of mRNA-1273. The bottom line: tolerability was good (“generally similar to (that) observed after the primary series”). More importantly: booster vaccination with all 3 vaccines (seemingly, no big differences between them) induced strong anamnestic responses, indicative of a robust B cell memory response.

 

Van Praet JT, Vandecasteele S, De Roo A, et al. Dynamics of the cellular and humoral immune response after BNT162b2 mRNA Covid-19 vaccination in Covid-19 naive nursing home residents. J Infect Dis September 13, 2021; jiab458, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab458/6369254

Among nursing home residents after BNT162b2 mRNA COVID-19 vaccination, both humoral and cellular responses significantly decreased over the course of 24 weeks and were substantially lower than those of healthcare workers at all time points. The half-life of the antibody response was only 47 days, indicating a quantitatively lower immune reaction and shorter duration of protection for the residents.

 

Treatment

Ader F, Bouscambert-Duchamp M, Hites M, et al. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. Lancet Inf Dis September 14, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00485-0/fulltext

The end for remdesivir? This large RCT conducted in 48 sites in Europe found no clinical benefit in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. The authors believe that the discrepancy observed between the present results and those from the ACTT-19 (which contributed to obtaining its Emergency Use Authorization) might be explained by the differences in study populations. There was also no effect of remdesivir on SARS-CoV-2 viral kinetics, indicating a genuine absence of effect or that treatment was administered too late to be effective.

 

 

15 September

Epidemiology

Love J, Keegan LT, Angulo FJ, et al. Continued need for non-pharmaceutical interventions after COVID-19 vaccination in long-term-care facilities. Sci Rep 11, 18093 (2021). https://doi.org/10.1038/s41598-021-97612-w

A stochastic model to simulate outbreaks in LTCF populations with differing vaccination coverage and NPI adherence to evaluate their interactive effects. Bottom line: to prevent further illness and deaths, there is a continued need for NPIs in LTCFs during vaccine rollout.

 

Davis EL, Lucas TCD, Borlase A, et al. Contact tracing is an imperfect tool for controlling COVID-19 transmission and relies on population adherence. Nat Commun 12, 5412 (2021). https://www.nature.com/articles/s41467-021-25531-5

Well-implemented contact tracing could provide up to a 15% reduction in R but is not currently appropriate as the sole measure of control. Reporting and adherence are the most important predictors of programme impact but tracing coverage and speed also play an important role.

Virology

Arbeitman CR, Rojas P, Ojeda-May P, et al. The SARS-CoV-2 spike protein is vulnerable to moderate electric fields. Nat Commun 12, 5407 (2021). https://www.nature.com/articles/s41467-021-25478-7

The spike protein of SARS-CoV-2 (and especially its RBD) is unusually vulnerable to external electric fields.

 

Vaccine

Schönborn L, Thiele T, Kaderali L, et al. Decline in Pathogenic Antibodies over Time in VITT. NEJM September 8, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2112760?query=featured_home

Anti-PF4 antibodies are transient in most patients with VITT. In 14/15 patients with follow-up of more than 12 weeks, the platelet-activation assay became negative.

 

Variants

Burugorri-Pierre C, Lafuente-Lafuente C, Oasi C, et al. Investigation of an Outbreak of COVID-19 in a French Nursing Home With Most Residents Vaccinated. JAMA Netw Open September 13, 2021; 4:e2125294. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783985?resultClick=1

An outbreak in Biscarrosse, France, due to the B.1.1.7 variant, indicating that SARS-CoV-2 vaccination may not be sufficient as the sole means to prevent COVID-19 in nursing homes. Of 74 residents, 70 were fully and 2 were partially vacccinated.  Among the 17 infected residents, one was unvaccinated, two were partially and were 14 fully vaccinated. Eight residents developed severe disease, 2 were hospitalized, and 1 individual (the unvaccinated resident) died.

 

(No good) Treatment

Dyer O. Covid-19: Hospital may cease giving patient ivermectin, US court rules, as prescriptions soar. BMJ 2021; https://www.bmj.com/content/374/bmj.n2228

Read here how crazy people can be (i.e. people who believe vaccines are too “experimental” and then sue a hospital in order to get ivermectin treatment).

 

 

14 September

Epidemiology

Sanders JG, Spruijt P, van Dijk M, et al. Understanding a national increase in COVID-19 vaccination intention, the Netherlands, November 2020–March 2021. Euro Surveill. 2021;26(36):pii=2100792. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.36.2100792

In March 2021, approximately one in five people in the Netherlands reported having no intention or being unsure of whether to get vaccinated against COVID-19.

 

Vaccines

Thompson MG, Stenehjem E, Grannis S, et al. Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings. NEJM September 8, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2110362?query=featured_home

Real-world data from the US. The effectiveness of mRNA-based vaccines was 88% against a SARS-CoV-2 infection leading to hospitalization and 90% against infection leading to ICU admission. This was also seen in those most at risk for severe COVID-19 (advanced age, underlying medical conditions, race or ethnic group). However, it is of note that during this observation period, the Alpha variant was predominant.

 

Grannis SJ, Rowley EA, Ong TC, et al. Interim Estimates of COVID-19 Vaccine Effectiveness Against COVID-19–Associated Emergency Department or Urgent Care Clinic Encounters and Hospitalizations Among Adults During SARS-CoV-2 B.1.617.2 (Delta) Variant Predominance — Nine States, June–August 2021. MMWR Morb Mortal Wkly Rep 10 September 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e2.htm?s_cid=mm7037e2_w

What about Delta? Here, the same network as above provided data from 187 hospitals and 221 emergency departments (EDs) and urgent care (UC) clinics across nine US states June–August 2021. Vaccine effectiveness (VE) of all three US-authorized COVID-19 vaccines combined remained high against hospitalization (86%) and ED/UC encounters (82%). However, VE among adults aged ≥ 75 years was significantly lower. This decline should be interpreted with caution and might be related to changes in SARS-CoV-2, waning of vaccine-induced immunity, or a combination of factors.

 

Bajema KL, Dahl RM, Prill MM, et al. Effectiveness of COVID-19 mRNA Vaccines Against COVID-19–Associated Hospitalization — Five Veterans Affairs Medical Centers, United States, February 1–August 6, 2021. MMWR Morb Mortal Wkly Rep 10 September 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e3.htm?s_cid=mm7037e3_w

Same direction: mRNA COVID-19 vaccines remain highly effective, even during periods of widespread circulation of the Delta variant. However, VE in preventing COVID-19–related hospitalization was 80% among adults aged ≥ 65 years compared with 95% among adults aged 18–64 years. Growing evidence that the vaccines start to weaken when Delta catches the elderly.

 

Treatment

Murray J, Hogan RJ, Martin DE, et al. Probenecid inhibits SARS-CoV-2 replication in vivo and in vitro. Sci Rep September 10, 2021, 11, 18085. https://www.nature.com/articles/s41598-021-97658-w

Probenecid potently blocked SARS-CoV-2 replication in mammalian cells and virus replication in a hamster model. Plasma concentrations were up to 50-fold higher than the protein binding adjusted IC90 value following a single oral dose, supporting “the potential clinical utility” of probenecid.

 

Beyond Corona

Bulut OC, Oladdokun D, Lippert BM, et al. Can Sex Improve Nasal Function?—An Exploration of the Link Between Sex and Nasal Function. Ear Nose Throat J 2021. https://doi.org/10.1177/0145561320981441

At the 31st First Annual Ig Nobel Prize ceremony, on Thursday, September 9, this milestone work in 18 couples from Heidelberg/Germany won the Ig Nobel Prize in Medicine – quite rightly, as the conclusion gives us an essential insight: “Sexual intercourse with climax can improve nasal breathing to the same degree as application of nasal decongestant for up to 60 minutes in patients having nasal obstruction”. However, please note the main limitation that “the data were only obtained if both individuals experienced sexual orgasm”.

Nasal breathing measured by VAS and rhinometric flow before and after interventions (sexual activity and application of nasal decongestant spray). VAS indicates visual analogue scale.

 

Blavatslyy P. Obesity of politicians and corruption in post-Soviet countries. Econ Transit Institut Change. 2021;29:343–356. https://onlinelibrary.wiley.com/doi/epdf/10.1111/ecot.12259

Ig Nobel Prize in Economics. The median ministers’ body-mass index (estimated from frontal face images) was highly correlated with conventional measures of corruption (based on perception surveys among foreign experts).

 

 

13 September

 

Epidemiology

Shen K, Loomer L, Abrams H, et al. Estimates of COVID-19 Cases and Deaths Among Nursing Home Residents Not Reported in Federal Data. JAMA Netw Open September 9, 2021;4(9):e2122885. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784031

In this cross-sectional study of 15,307 US nursing homes, approximately 44% of COVID-19 cases and 40% of COVID-19 deaths that occurred before the start of reporting were not reported in the first NHSN submission in sample states, suggesting there were more than 68,000 unreported cases and 16,000 unreported deaths nationally.

 

Vaccine

Sauré D, O’Ryan M, Torres JP, et al. Dynamic IgG seropositivity after rollout of CoronaVac and BNT162b2 COVID-19 vaccines in Chile: a sentinel surveillance study. Lancet Inf Dis September 09, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00479-5/fulltext

In this huge study, IgG seropositivity was lower after CoronaVac than after BNT162b2 and declined over time since vaccination for CoronaVac recipients but not BNT162b2 recipients.

 

Transmission

Rebmann T, Loux TM, Arnold LD, Charney R, Horton D, Gomel A. SARS-CoV-2 Transmission to Masked and Unmasked Close Contacts of University Students with COVID-19 — St. Louis, Missouri, January–May 2021. MMWR 2021;70:1245–1248. DOI: https://www.cdc.gov/mmwr/volumes/70/wr/mm7036a3.htm?s_cid=mm7036a3_w

An observational study in a university setting indicating that compared with only masked exposure, close contacts with any unmasked exposure had higher adjusted odds of a positive test result. Each additional exposure was associated with a 40% increase in the odds of a positive test.

 

Co-morbidities

Moor MB, Suter-Riniker F, Horn MP, et al. Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study. Lancet Rheumatology September 7, 2021. https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00251-4/fulltext

Further evidence of blunted humoral and cell-mediated immune responses elicited by SARS-CoV-2 mRNA vaccines in patients with a history of CD20 B-cell-depleting treatment. Only 9/66 (14%) patients were double positive for anti-SARS-CoV-2 spike IgG and cell-mediated responses, compared with 21/28 (75%) healthy controls. Lymphocyte subpopulation counts were associated with vaccine response in this highly vulnerable population.

 

Pregnancy

Zauche LH, Wallace B, Smoots AN, et al. Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion. NEJM September 8, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2113891?query=featured_home

Using data of 2456 participants who were enrolled in the CDC COVID-19 pregnancy registry, Lauren Zauche and colleagues provide more evidence that the risk of spontaneous abortion after mRNA COVID-19 vaccination, either before conception or during pregnancy, “is consistent with the expected risk” of spontaneous abortion.

 

 

12 September

 

Transmission

Shah AS, Gribben C, Bishop J, et al. Effect of Vaccination on Transmission of SARS-CoV-2. NEJM September 8, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2106757?query=featured_home

Incredible huge study on 194,362 household members of 144,525 health care workers from Scotland, among them 113,253 HCWs who had received at least one dose of either Pfizer–BioNTech or the AstraZeneca vaccine. The hazard ratio for a household member to become infected was 0.70 (95% CI, 0.63 to 0.78) for the period beginning 14 days after the first dose and 0.46 (95% CI, 0.30 to 0.70) for the period beginning 14 days after the second dose. As not all cases in the household members were transmitted from the health care worker, the effect of vaccination may be larger.

 

Vaccine

To KK, Li Y, Lung DC et al. False COVID-19 cases due to contamination by inactivated virus vaccine. Clin Inf Dis September 9, 2021, ciab684, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab684/6367446

Two individuals whose respiratory specimens were contaminated by inactivated SARS-CoV-2 vaccine strain (CoronaVac), likely at vaccination premises.

 

Variants

Oude Munnink BB, Worp N, Nieuwenhuijse DF, et al. The next phase of SARS-CoV-2 surveillance: real-time molecular epidemiology. Nat Med September 9, 2021. https://www.nature.com/articles/s41591-021-01472-w

This Review summarizes the current knowledge on key viral mutations and variants.

Overview of amino acid changes in specific proteins of VOCs and currently detected and former VOis

 

Diagnostics

Michalakis Y, Sofonea MT, Alizon S, et al. SARS-CoV-2 viral RNA levels are not “viral load”. Trends in Microbiology September 03, 2021. https://www.cell.com/trends/microbiology/fulltext/S0966-842X(21)00208-0#%20

Yannis Michalakis and colleagues argue that current RT-qPCR target amplification does not distinguish replicative from transcriptional RNA. Although analyses of Ct values remain informative, equating them with viral load may lead to flawed conclusions as it is presently unknown whether (and to what extent) variation in Ct reflects variation in viral load or in gene expression.

 

Pediatrics

Somekh I, Stein M, Karakis I, et al. Characteristics of SARS-CoV-2 Infections in Israeli Children During the Circulation of Different SARS-CoV-2 Variants. JAMA Netw Open September 7, 2021. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783851?resultClick=1

In this observational study, transmission rates from children aged 0 to 9 years to other contacts were doubled during the time of B.1.1.7 circulation in Israel. However, hospitalization rates among children decreased.

 

 

11 September

 

Epidemiology

Wilkinson E, Giovanetti M, Tegally H, et al. A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa. Science Sepember 9, 2021. https://www.science.org/doi/10.1126/science.abj4336

Phylogeographic reconstruction of (past) viral dissemination patterns, suggesting a strong epidemiological linkage between Europe and Africa, with 64% of detectable viral imports into Africa originating in Europe and 41% of detectable viral exports from Africa landing in Europe. Strong conclusion: “If the pandemic is not controlled in Africa, we may see the production of vaccine escape variants that may profoundly affect the population in Africa and across the world.”

 

Immunology

Kaplonek P, Wang C, Bartsch Y, et al. Early cross-coronavirus reactive signatures of humoral immunity against COVID-19. Science Immunology September 9, 2021. https://www.science.org/doi/10.1126/sciimmunol.abj2901

Convincing evidence on the importance of cross-coronavirus immunity as a correlate of protection against COVID-19. Individuals who survive COVID-19 may have an advantage as they may be able to rapidly redeploy S2-specific antibodies across coronaviruses in order to combat disease. Early development of SARS-CoV-2-specific immunity occurred in tandem with pre-existing common β-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that developed a paucisymptomatic infection.

 

Clinical

Boyapati A, Wipperman MF, Ehmann PJ, et al. Baseline SARS-CoV-2 Viral Load is Associated With COVID-19 Disease Severity and Clinical Outcomes: Post-Hoc Analyses of a Phase 2/3 Trial. J Inf Dis September 8, 2021. jiab445, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab445/6366357

In this large Phase II/III trial of sarilumab in 1362 COVID-19 hospitalized patients, higher baseline viral load was associated with higher mortality, lower likelihood of improvement in clinical status and supplemental oxygenation requirements, and lower rates of hospital discharge. Viral load was not impacted by sarilumab treatment versus placebo over time.

Survival curves grouped by viral load tertiles for probability of survival (A), clinical improvement (1 point) (B), improvement in oxygen requirements, (C) and hospitalization (D). Viral load tertiles were defined as follows: low (<3.32 log10 copies/mL), middle (3.32–5.09 log10 copies/mL), and high (>5.09 log10 copies/mL).

 

Treatment

Bégin, P., Callum, J., Jamula, E. et al. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial. Nat Med September 8, 2021. https://www.nature.com/articles/s41591-021-01488-2

Huge RCT, providing the last nail in the coffin for convalescent plasma (CP). CP did not reduce the risk of intubation or death in hospitalized patients with COVID-19. Moreover, transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care. “The lack of benefit and the potential concern of harm caution against the unrestricted use of convalescent plasma for hospitalized patients with COVID-19”.

 

Congly SE, Varughese RA, Brown CE, et al. Treatment of moderate to severe respiratory COVID-19: a cost-utility analysis. Sci Rep September 7, 2021, 11, 17787. https://www.nature.com/articles/s41598-021-97259-7

Dexamethasone for moderate-severe COVID-19 infections was the most cost effective strategy and would have minimal budget impact. Based on current data, remdesivir is unlikely to be a cost effective treatment for COVID-19.

 

 

10 September

Variants

Grint DJ, Wing K, Houlihan C, et al. Severity of SARS-CoV-2 alpha variant (B.1.1.7) in England. Clin Infect Dis September 6, 2021, ciab754, https://doi.org/10.1093/cid/ciab754

Using data from 185,234 people who tested positive for SARS-CoV-2 in the community, in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, the authors found alpha associated with 73% higher hazards of all-cause death and 62% higher hazards of hospital admission, compared to wild-type virus.

 

Tostanoski LH, Yu J, Mercado NB, et al. Immunity elicited by natural infection or Ad26.COV2.S vaccination protects hamsters against SARS-CoV-2 variants of concern. Science Translational Medicine September 7, 2021. https://www.science.org/doi/10.1126/scitranslmed.abj3789

See title. The Ad26.COV2.S vaccine (J&J) induced cross-reactive binding and neutralizing antibodies that were reduced against the B.1.351 strain (Beta) compared with wild type, but nevertheless still provided robust protection against B.1.351 challenge, as measured by weight loss and pathology scoring in the lungs.

 

Transmission

Dabisch PA, Biryukov J, Beck K. Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19. PLOS Pathogens August 23, 2021. https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009865

Small study in which 16 healthy, young adult macaques were exposed to small particle aerosols containing SARS-CoV-2, with calculated deposited doses. The probability of seroconversion and fever were both dose-dependent, but the median dose for seroconversion was significantly lower than that of fever. However, the study used an isolate from early in the pandemic (no variant).

Pregnancy

Kharbanda EO, Haapala J, DeSilva M, et al. Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy. JAMA Network September 8, 2021 https://jamanetwork.com/journals/jama/fullarticle/2784193?resultClick=1

In this large surveillance study of 105446 unique pregnancies, 13160 spontaneous abortions and 92286 ongoing pregnancies were identified. Spontaneous abortions did not have an increased odds of exposure to a COVID-19 mRNA vaccination in the prior 28 days compared with ongoing pregnancies (adjusted odds ratio, 1.02; 95% CI, 0.96-1.08).

 

Dagan N, Barda N, Biron-Shental T, et al. Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy. Nat Med September 7, 2021. https://www.nature.com/articles/s41591-021-01490-8

Paper of the day. A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregnant controls using demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. Estimated vaccine effectiveness from 7 through to 56 d after the second dose was 96% (95% confidence interval 89–100%) for any documented infection, 97% (91–100%) for infections with documented symptoms and 89% (43–100%) for COVID-19-related hospitalization.

Cumulative incidence curves of the documented infection outcome in pregnant women, CHS, 20 December 2020 through to 3 June 2021. The main line is the point estimate of the cumulative incidence and the shaded areas are the 95% CIs. The vertical lines at days 28 and 77 demarcate the period when an individual was considered ‘fully vaccinated’ in the manuscript (7 through to 56 d after receipt of the second dose).

 

9 September

 

Transmission

Mishra A, Kumar N, Bhatia S, et al. SARS-CoV-2 Delta variant among Asiatic lions, India. Emerg Infect Dis 2021 August 31, 2021 https://wwwnc.cdc.gov/eid/article/27/10/21-1500_article

Identical SARS-CoV-2 infections in nine lions in a short period of time, indicating the possibility of lion-to-lion transmission.

 

Immunology

Bertoletti A, Le Bert N, Qui M, et al. SARS-CoV-2-specific T cells in infection and vaccination. Cell Mol Immunol September 2, 2021. https://www.nature.com/articles/s41423-021-00743-3

Great review about the function of SARS-CoV-2-specific T cells in patients and in vaccinated individuals.

 

Diagnostics

Torres JR. Are rapid antigen SARS-Cov-2 tests effective for mass screening of travelers at airports? The Olympic experience. Journal of Travel Medicine 03 September 2021, taab135, https://academic.oup.com/jtm/advance-article/doi/10.1093/jtm/taab135/6363815?searchresult=1

Jaime Torres argues that a significant number of asymptomatic carriers will fail to be detected via mass screening of travelers at airports by means of rapid antigenic tests, unless additional strategies, such as supervised quarantine, frequent retesting and close follow up of those who test positive are also carefully implemented.

 

Severe COVID-19

Boscolo A, Pasin L, Sella N, et al. Outcomes of COVID-19 patients intubated after failure of non-invasive ventilation: a multicenter observational study. Scientific Reports September 6, 2021, volume 11, Article number: 17730. https://www.nature.com/articles/s41598-021-96762-1

Among 280 patients who underwent endotracheal intubation, only the length of NIV application before ICU admission (OR 2.03) and age (OR 1.18) were identified as independent risk factors of in-hospital mortality.

 

Co-morbidities

Ghione P, Gu JJ, Attwood K, et al. Impaired humoral responses to COVID-19 vaccination in patients with lymphoma receiving B-cell–directed therapies. Blood, September 2, 2021. https://ashpublications.org/blood/article/138/9/811/476275/Impaired-humoral-responses-to-COVID-19-vaccination?searchresult=1

In this cohort of patients with B-cell lymphoma who were actively receiving B-cell-depleting agents or were within 9 months of completing B-cell-directed therapy, only 6/52 developed antibodies against the SARS-CoV-2 virus, regardless of the type of vaccine used.

 

Treatment

Al Sulaiman K, Aljuhani O, Saleh KB, et al. Ascorbic acid as an adjunctive therapy in critically ill patients with COVID-19: a propensity score matched study. Sci Rep 11 September 3, 2021, 17648. https://www.nature.com/articles/s41598-021-96703-y

Retrospective study in which low dose ascorbic acid as an adjunctive therapy in COVID-19 critically ill patients was not associated with mortality benefits, but was associated with a lower incidence of thrombosis. And yes, “further studies are required to confirm these findings.”

 

8 September

 

Virology

Shan KJ, Wei C, Wang Y, et al. Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process. The Innovation. August 30, 2021. https://www.cell.com/the-innovation/fulltext/S2666-6758(21)00084-9

Some data-driven support for the natural origin of SARS-CoV-2.

 

Transmission

Rosca EC, Heneghan C, Spencer EA, et al. Transmission of SARS-CoV-2 associated with aircraft travel: A systematic review. Journal of Travel Medicine September 3, 2021. taab133, https://doi.org/10.1093/jtm/taab133

Current evidence is very limited. Data suggests SARS-CoV-2 can be transmitted during aircraft travel, but published data do not permit any conclusive assessment of likelihood and/or extent.

 

Vaccine

Klein NP, Lewis N, Goddard K, et al. Surveillance for Adverse Events After COVID-19 mRNA Vaccination. JAMA September 3, 2021. https://jamanetwork.com/journals/jama/fullarticle/2784015

They. Are. Safe. In this interim analysis of surveillance monitoring of more than 11.8 million doses of 2 mRNA vaccines in diverse populations and weekly analyses from December 14, 2020, to June 26, 2021, no vaccine-outcome association met the prespecified threshold for a signal.

 

Seppälä E, Veneti L, Starrfelt J, et al. Vaccine effectiveness against infection with the Delta (B.1.617.2) variant, Norway, April to August 2021. Euro Surveill September 2, 2021;26(35):pii=2100793. https://doi.org/10.2807/1560-7917.ES.2021.26.35.2100793

The adjusted VE against infection with the Delta variant was 22% among those partly vaccinated and 65% among those fully vaccinated, compared with 55% and 84%, respectively, against the Alpha variant.

 

Variants

Mlcochova P, Kemp S, Dhar MS, et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature September 6, 2021. https://www.nature.com/articles/s41586-021-03944-y

This study combined in vitro experimentation and molecular epidemiology, confirming increased replication fitness and reduced sensitivity of SARS-CoV-2 B.1.617.2 (Delta) to neutralizing antibodies.

 

 

7 September

 

Treatment

Kyriazopoulou E, Poulakou G, Milionis H, et al. Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. Nat Med September 3, 2021. https://www.nature.com/articles/s41591-021-01499-z

Paper of the day, presenting encouraging data on anakinra from the SAVE-MORE study, a double-blind randomized controlled trial in 594 patients with COVID-19 at risk of progressing to respiratory failure. It works! With anakinra, an IL-1α/β inhibitor, at day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point WHO scale) was only 0.36 (95% confidence interval 0.26–0.50). The clinical benefit with anakinra was already apparent from day 14 and was maintained until day 28. The magnitude of the efficacy was shown in all multivariate analyses.

Distribution of the WHO-CPS scores at day 28 of patients allocated to placebo and to treatment with anakinra.

 

Epidemiology

Kleynhans J, Tempia S, Wolter N, et al. SARS-CoV-2 seroprevalence in a rural and urban household cohort during first and second waves of infections, South Africa, July 2020–March 2021. Emerg Infect Dis September 3, 2021. https://wwwnc.cdc.gov/eid/article/27/12/21-1465_article

The authors assessed SARS-CoV-2 seroprevalence in 1211 persons living in 2 diverse communities in South Africa and show, not surprisingly, that laboratory-confirmed cases reported from study districts greatly underestimate the actual prevalence. At baseline, seroprevalence was 1% in a rural community and 15% in an urban community, increasing to 7% and 27%, respectively, after the first wave, by March 2021. After the second wave, seroprevalence was 26% (rural) and 41% (urban).

 

Immunology

Smith N, Goncalves P, Charbit B. et al. Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection. Nat Immunol September 1, 2021. https://www.nature.com/articles/s41590-021-01028-7

This study compared systemic and local immune responses during active SARS-CoV-2 infection in a well-characterized COVID-19 cohort. Results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.

 

Galván-Peña S, Leon J, Chowdhary K, et al. Profound Treg perturbations correlate with COVID-19 severity. PNAS September 14, 2021, https://www.pnas.org/content/118/37/e2111315118

Regulatory T cells (Tregs) are essential in maintaining immunologic homeostasis, self-tolerance, and to prevent runaway immune responses. This study found a unique and striking Treg deviation in COVID-19 patients, which results from the effects of several components of the pro-inflammatory storm.

 

Pediatrics

Delahoy MJ, Ujamaa D, Whitaker M, et al. Hospitalizations Associated with COVID-19 Among Children and Adolescents — COVID-NET, 14 States, March 1, 2020–August 14, 2021. MMWR September 3, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7036e2.htm?s_cid=mm7036e2_w

Weekly COVID-19–associated hospitalization rates rose rapidly from late June through mid-August 2021 among US children and adolescents aged 0–17 years; by mid-August, the rate among children aged 0–4 years was nearly 10 times the rate 7 weeks earlier (coincident with widespread circulation of Delta). Hospitalization rates were 10 times higher among unvaccinated than among fully vaccinated adolescents.

 

 

6 September

 

Immunology

Israelow B, Mao T, Klein J, et al. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. Science Immunology September 2021, https://www.science.org/doi/10.1126/sciimmunol.abl4509

More insights into both the immunologic determinants of viral clearance and protection. While T cells were important in the clearance of primary infection, they were not required for protection against reinfection or vaccine-mediated protection, likely due to sufficient antibody-mediated immunity.

 

Vaccine

Klein NP, Lewis N, Goddard K. Surveillance for Adverse Events After COVID-19 mRNA Vaccination. JAMA September 3, 2021. https://jamanetwork.com/journals/jama/fullarticle/2784015?resultClick=1

In this interim analysis of 6.2 million persons who received 11.8 million doses of an mRNA vaccine, event rates for 23 serious health outcomes were not significantly higher for individuals 1 to 21 days after vaccination compared with similar individuals at 22 to 42 days after vaccination.

 

Feder KA, Patel A, Vepachedu VR, et al. Association of E484K spike protein mutation with SARS-CoV-2 infection in vaccinated persons—Maryland, January – May 2021, Clin Inf Dis September 2, 2021, ciab762, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab762/6362726

Among 9048 cases, SARS-CoV-2 viruses carrying the spike protein mutation E484K were disproportionately prevalent among persons infected after full vaccination (adjusted OR 1.96).

 

Collateral damage

Hawrilenko M, Krohus E, Tandon P, et al. The Association Between School Closures and Child Mental Health During COVID-19. JAMA Netw Open September 3, 2021; 4(9):e2124092. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783714?resultClick=1

In this survey study of 2324 adults with at least 1 school-age child, a small association between school closures and worse child mental health outcomes was observed. Children from families with lower income experienced more mental health problems associated with school closures.

 

Pediatrics

Siegel DA, Reses HE, Cool AJ, et al. Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0–17 Years — United States, August 2020–August 2021. MMWR 3 September 2021. DOI: https://www.cdc.gov/mmwr/volumes/70/wr/mm7036e1.htm?s_cid=mm7036e1_w

Among US children and adolescents aged 0–17 years, COVID-19 cases and associated ED visits and hospital admissions increased from June 2021 through August 2021. During a 2-week period in August 2021, COVID-19–associated ED visits and hospital admissions for children and adolescents with confirmed COVID-19 were highest in states with the lowest vaccination coverage.

 

 

5 September

Epidemiology

Matthias J, Patrick S, Wiringa A, et al. Epidemiologically Linked COVID-19 Outbreaks at a Youth Camp and Men’s Conference — Illinois, June–July 2021. MMWR August 31, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7035e4.htm?s_cid=mm7035e4_w

On June 30, 2021, the Illinois Department of Public Health reported two events sponsored by the same organization: a 5-day overnight church camp for persons aged 14–18 years and a 2-day men’s conference. Believe it or not, neither COVID-19 vaccination nor COVID-19 testing was required before either event. As of August 13, a total of 180 confirmed and probable cases had been identified among attendees at the two events and their close contacts. Among 122 primary cases, 104 (85%) were in persons not fully vaccinated, and 18 (15%) were in fully vaccinated persons. Eight of 38 (21%) close contacts of the 18 fully vaccinated persons subsequently became infected with SARS-CoV-2.

 

Variants

Strålin K, Bruce D, Wahlsttröm E, et al. Impact of the Alpha VOC on disease severity in SARS-CoV-2-positive adults in Sweden. J Infection August 30, 2021. https://www.journalofinfection.com/article/S0163-4453(21)00448-5/fulltext
Large study from Sweden. Alpha positive individuals had significantly higher rates of hospitalization (2.6% vs. 1.2%) and severe illness than variants of concern negative individuals overall, but the numbers were too small to evaluate differences in severity rate among hospitalized individuals.

 

Immunology

Baggen J, Vanstreels E, Jansen S, et al. Cellular host factors for SARS-CoV-2 infection. Nat Microbiol September 1, 2021. https://www.nature.com/articles/s41564-021-00958-0
This review summarizes insights into the proviral host factors that are required for SARS-CoV-2 infection that were mainly obtained using functional genetic and interactome screens.

 

Vaccines

Ben David SSS, Potasman I, Rahamim-Cohen D. Rate of Recurrent Guillain-Barré Syndrome After mRNA COVID-19 Vaccine BNT162b2. JAMA Neurol September 1, 2021; https://jamanetwork.com/journals/jamaneurology/fullarticle/2783708?resultClick=1

In this cohort study of 702 patients, only 1 person needed short medical care for relapse of their previous syndrome, representing a minimal risk.

 

Marlin R, Godot V, Cardinaud S, et al. Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques. Nat Commun September 1, 2021, 12, 5215. https://www.nature.com/articles/s41467-021-25382-0

A new generation of subunit vaccines targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike antigen to the CD40 receptor (αCD40.RBD). Immunogenicity is shown in two different animal models. This vaccine may have advantages for a safe and efficient boosting strategy, without requiring an adjuvant.

 

4 September

Epidemiology

Brooks YM, Gryskwicz B, Sheehan S, Piers S, Mahale P, McNeil S, et al. Detection of SARS-CoV-2 in wastewater at residential college, Maine, USA, August–November 2020. Emerg Infect Dis August 31, 2021. https://wwwnc.cdc.gov/eid/article/27/12/21-1199_article

Wastewater surveillance may help to identify outbreaks. Cumulative increases of > 1 log10 SARS-CoV-2 RNA in consecutive 24-hour composite samples preceded outbreaks. For 76% of cases at a school, RNA was identified in grab samples from residence halls < 7 days before case discovery.

 

Immunology

Loyal L, Braun J, Henze L, et al. Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination. Science August 31, https://www.science.org/doi/10.1126/science.abh1823

This study highlights the functional contribution of pre-existing spike-cross-reactive T cells in SARS-CoV-2 infection and vaccination. Cross-reactive immunity may account for the unexpectedly rapid induction of immunity following primary SARS-CoV-2 immunization and the high rate of asymptomatic/mild COVID-19 disease courses. The S816-830 peptide may serve as a conserved universal coronavirus target in the S2 portion of spike for both B cells and T cells.

 

Vaccine

Flaxman A, Marchevsky NG, Jenkin D, et al. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002). Lancet September 01, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01699-8/fulltext

Sub-study of two trials in which the timing of the second dose varied and allowed for comparisons of immunogenicity between the recommended vaccination schedule and a longer interval. Results: the extended interval between the first two doses (44–45 weeks) resulted in higher antibody titers after the second dose than with a shortened interval. A third dose given 28–38 weeks after the second dose increased the antibody titers to above those after the primary (1-2) series.

 

McQuade ET, Breskin A. Longer intervals and extra doses of ChAdOx1 nCoV-19 vaccine. Lancet September 01, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01817-1/fulltext

But what do these data tell us? In their comment, Elizabeth Rogawski McQuade and Alexander Breskin point out that “the total public health impact of the extended prime-boost interval is unclear given the trade-off between a longer period at the lower level of protection afforded by a single dose and the higher level of protection obtained after a delayed second dose”. However, data may assuage concerns about the potential for impaired responses after repeated use of a replication deficient simian adenoviral vector and suggest that a third dose of the AZ/Oxford vaccine could be successful if necessary.

 

Clinical

Fenton L, Gribben C, Caldwell D, et al.  Risk of hospital admission with covid-19 among teachers compared with healthcare workers and other adults of working age in Scotland, March 2020 to July 2021: population based case-control study. BMJ September 2, 2021, 374 https://www.bmj.com/content/374/bmj.n2060
The risks of COVID-19 among teachers and their household members: neither was shown to be at increased risk of hospital admission or severe COVID-19 at any time, whether compared with healthcare workers or with adults of working age in the general population.

 

Treatment

Strich JR, Tian X, Samour M, et al. Fostamatinib for the treatment of hospitalized adults with COVD-19 A randomized trial. Clinical Infectious Diseases September 1, ciab732.  https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab732/6358811

Fostamatinib is a novel spleen tyrosine kinase inhibitor that could ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. In 59 COVID-19 patients requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared to placebo. According to the authors, this warrants further validation in larger confirmatory trials.

 

3 September

Epidemiology

Soucy JP, Ghasemui A, Sturrock SL, et al. Trends in Interregional Travel to Shopping Malls and Restaurants Before and After Differential COVID-19 Restrictions in the Greater Toronto Area.  JAMA Netw Open August 21, 2021; 4(8):e2123139. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783631

Heterogeneous restrictions or partial lockdowns do not make sense: people/viruses just go shopping somewhere else. In this study from Canada, lockdowns in the urban center were associated with reduced overall visits to shopping malls and restaurants by residents but were not associated with decreased travel to these businesses in peripheral regions, where restrictions permitted indoor dining and shopping for non-essential businesses. The authors observed a large increase in visits to shopping malls in the peripheral regions by residents of the urban center in the week following the lockdown.

 

Keehner J, Horton LE, Binkin NJ, et al. Resurgence of SARS-CoV-2 Infection in a Highly Vaccinated Health System Workforce. NEJM September 1, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2112981?query=featured_home
Rapidly increasing cases among the workforce of the University of California San Diego Health, coinciding with the dominance of the Delta variant, and including cases among fully vaccinated persons. However, the increase was also coincident with the end of California’s mask mandate at the same time.

 

Transmission

Oster Y, Benenson S, Harpaz LY, et al. Association Between Exposure Characteristics and the Risk for COVID-19 Infection Among Health Care Workers With and Without BNT162b2 Vaccination. JAMA Netw Open September 1, 2021;4(9):e2125394. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783675?resultClick=1

This case-control study found that exposure to SARS-CoV-2–positive household members was a risk factor associated with infection among vaccinated HCWs. Household exposure is usually longer and closer than casual exposure or exposure at work and does not include masking or distancing, exposing one to a higher infectious dose and thus being more contagious.

 

Clinical

Boehmer TK, Kompaniyets L, Lavery AM, et al. Association Between COVID-19 and Myocarditis Using Hospital-Based Administrative Data — United States, March 2020–January 2021. MMWR Morb Mortal Wkly Rep. ePub: 31 August 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7035e5.htm

In this study, the occurrence of myocarditis inpatient encounters was 42% higher in 2020 than in 2019. The risk for myocarditis among patients with COVID-19 during March 2020–January 2021 was nearly 16 times as high as the risk among patients without COVID-19, with the association between COVID-19 and myocarditis being most pronounced among children and older adults. Further, in this cohort, approximately 40% of patients with myocarditis had a history of COVID-19.

 

Treatment

Marconi VC, Ramanan AV, de Bono S, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Resp Med September 01, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00331-3/fulltext
Baricitinib “is a potentially effective oral treatment option”. In this huge Phase III trial on 1527 hospitalized COVID-19 patients, the 28-day all-cause mortality was 8% for baricitinib and 13% for placebo (hazard ratio 0.57, 95% CI: 0.41–0.78), a 38% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants.

 

Kailil AC, Stebbing J. Baricitinib: the first immunomodulatory treatment to reduce COVID-19 mortality in a placebo-controlled trial. Lancet Resp Med September 01, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00358-1/fulltext
Comment on the above study. According to Andre Kalil and Justin Stebbing, “the clinical benefits and significant reduction in mortality, as well as the absence of safety concerns found by both the COV-BARRIER and ACTT-2 studies, place baricitinib among the few proven treatments of choice for hospitalised patients with COVID-19”.

 

2 September

Immunology

Lempp FA, Soriaga L, Montiel-Ruiz M, et al. Lectins enhance SARS-CoV-2 infection and influence neutralizing antibodies. Nature August 31, 2021. https://www.nature.com/articles/s41586-021-03925-1

Transmembrane lectins act as attachment receptors, rather than entry receptors for SARS-CoV-2, thus facilitating infection via the canonical ACE2 pathway. This study shows that ranking of SARS-CoV-2 neutralizing antibodies is highly dependent on the level of ACE2 expression and on the presence of attachment receptors, and identifies a mechanism that possibly results in creation of multinucleate viral factories potentially enhanced by specific antibodies.

 

Sulaiman I, Chung M, Angel L, et al. Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome. Nat Microbiol August 31, 2021. https://www.nature.com/articles/s41564-021-00961-5
This study analyzed lower airway microbiome using a metagenomic and metatranscriptomic approach, along with host immune profiling, in critically ill patients with COVID-19. Data suggest that active lower airway SARS-CoV-2 replication and poor SARS-CoV-2-specific antibody responses (but not secondary respiratory infections) are the main drivers of increased mortality in COVID-19 patients requiring ventilation.

 

Vaccine

Shavit R, Maoz-Segal R, Iancovici-Kidon M, et al. Prevalence of Allergic Reactions After Pfizer-BioNTech COVID-19 Vaccination Among Adults With High Allergy Risk. JAMA Netw Open August 31, 2021; 4(8):e2122255. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783626?resultClick=1

In this cohort study of 8102 individuals with a history of allergies, an algorithm was used to define 429 (5%) as “highly allergic”; this group was referred to receive immunization under medical supervision. A total of 98% of the highly allergic individuals had no allergic reaction, 6 (1%) had mild allergic responses, and 3 (0.7%) had anaphylactic reactions.

 

Deepak P, Kim W, Paley MA. Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2. Annals Int Med August 31, 2021. https://www.acpjournals.org/doi/10.7326/M21-1757

This study shows that compared with non-users, patients with chronic inflammatory disease treated with glucocorticoids and B cell depletion therapy seem to have lower SARS-CoV-2 vaccine-induced antibody responses.

 

Pediatrics

Woolford SJ, Sidell M, Li X, et al. Changes in Body Mass Index Among Children and Adolescents During the COVID-19 Pandemic. JAMA August 27, 2021. https://jamanetwork.com/journals/jama/fullarticle/2783690?resultClick=1

Using the huge Kaiser Permanente Southern California (KPSC) electronic health record data, this study revealed a mean gain among 5- through 11-year-olds of 2.30 kg more during the pandemic than during the reference period, 2.31 kg more among 12- through 15-year-olds, and 1.03 kg more among 16- through 17-year-olds.

 

Davies P, du Pré P, Krishnan H, et al. One-Year Outcomes of Critical Care Patients Post–COVID-19 Multisystem Inflammatory Syndrome in Children. JAMA Pediatr August 30, 2021. file:///C:/Users/hoffm/AppData/Local/Temp/jamapediatrics_davies_2021_ld_210022_1629993053.04292.pdf

Small study on 68 children. The majority had good outcomes with no significant medium- or long-term sequelae.

 

1 September

Vaccine

Steensels D, Pierlet N, Penders J, et al. Comparison of SARS-CoV-2 Antibody Response Following Vaccination With BNT162b2 and mRNA-1273. JAMA August 30, 2021. https://jamanetwork.com/journals/jama/fullarticle/2783797?resultClick=1

This large prospective cohort study in Belgian HCWs demonstrated a significantly higher humoral immunogenicity of the mRNA-1273 vaccine (Moderna) compared with the BNT162b2 vaccine (Pfizer-BioNTech), in infected as well as in uninfected participants, and across age categories. According to the authors, the higher mRNA content in mRNA-1273 compared with BNT162b2 and the longer interval between priming (4 weeks vs 3 weeks for BNT162b2) might explain this difference.

 

Knowlton KU. Insights from a murine model of COVID-19 mRNA vaccination-induced myopericarditis: Could accidental intravenous vaccine injection induce myopericarditis? Clin Inf Dis August 28, 2021, ciab741 https://doi.org/10.1093/cid/ciab741

Kirk Knowlton from Salt Lake City believes that the current data suggest that this is plausible and that it would be appropriate to consider further.

 

Transmission

Madewell ZJ, Yang X, Longini Jr IM, et al. Factors Associated With Household Transmission of SARS-CoV-2An Updated Systematic Review and Meta-analysis. JAMA Netw Open August 27, 2021; 4(8):e2122240. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783544?resultClick=1

In this updated systematic review and meta-analysis of 87 studies representing 1,249,163 household contacts from 30 countries, the estimated household secondary attack rate was 19%. The authors observed an increase in household transmission over time, perhaps owing to improved diagnostic procedures and tools, longer follow-up, more contagious variants, and different study locations.

 

Long COVID

Huang L, Yao Q, Gu X, et al. 1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study. Lancet August 28, 2021. Volume 398, ISSUE 10302, P747-758. https://doi.org/10.1016/S0140-6736(21)01755-4

The largest cohort study by far, on 1276 COVID-19 survivors who had been hospitalized and who had a follow up of one year. The proportion of patients with at least one sequelae symptom decreased from 68% at 6 months to 49% at 12 months. 88% of patients who were employed before COVID-19 had returned to their original work at 12 months. However, 12% did not (see below). Fatigue or muscle weakness was still present in 20%.

 

Auwaerter PG. The Race to Understand Post–COVID-19. Ann Int Med August 31, 2021. https://www.acpjournals.org/doi/10.7326/M21-3072

Some thoughts and ideas. “Even if only 10% of patients experience persistent symptoms after COVID-19, the number afflicted will easily be tens of millions.” And, “If science does not move with dispatch in addressing post–COVID-19 care in a multidisciplinary manner, the vacuum will be quickly filled by pseudoscience and quackery.”

 

31 August

Epidemiology

Kephart JL, Delclòs-Alió X, Rodríguez DA, et al. The effect of population mobility on COVID-19 incidence in 314 Latin American cities: a longitudinal ecological study with mobile phone location data. Lancet Dig Health August 26, 2021. https://doi.org/10.1016/S2589-7500(21)00174-6

Interventions to promote social distancing that target specific areas within cities might substantially mitigate SARS-CoV-2 transmission while reducing regional or citywide disruption. A 10% lower weekly mobility was associated with 8.6% (95% CI 7.6–9.6) lower incidence of COVID-19 in the following week.

Immunology

Zhang H, Deng S, Ren L, et al. Profiling CD8+ T Cell Epitopes of COVID-19 Convalescents Reveals Reduced Cellular Immune Responses to SARS-CoV-2 Variants. Cell Reports August 26, 2021. https://doi.org/10.1016/j.celrep.2021.109708

Variants are not only resistant to currently available neutralizing antibodies generated against the original variant. According to this study, evading cellular immunity might also contribute to the increased transmissibility and disease severity associated with the new SARS-CoV-2 variants.

 

Variants

Twohig KA, Nyberg T, Zaidi A, et al. Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study. Lancet Inf Dis August 27, 2021. https://doi.org/10.1016/S1473-3099(21)00475-8

A large national study from England, indicating a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the Delta variant compared with the Alpha variant. The HR of hospital admission within 14 days was 2.26 (95% CI 1.32–3.89) after stratification and regression adjustment for confounders.

 

Lam-Hine T, McCurdy SA, Santora L, et al. Outbreak Associated with SARS-CoV-2 B.1.617.2 (Delta) Variant in an Elementary School — Marin County, California, May–June 2021. MMWR 27 August 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7035e2.htm?s_cid=mm7035e2_w

Delta is fast. An unvaccinated infected teacher continued to work for 2 days before receiving a test. During those two days, the teacher read aloud (unmasked) to the class despite school requirements to mask while indoors. Results: 26 infections. Students were seated in five rows; despite masking, the attack rate in the two rows closest to the teacher’s desk was 80% (8/10) and was 28% (4/14) in the three back rows.

 

Treatment

Kosmopoulos A, Bhatt DL, Meglis G, et al. A Randomized Trial of Icosapent Ethyl in Ambulatory Patients with COVID-19. IScience August 26, 2021. https://www.cell.com/iscience/fulltext/S2589-0042(21)01008-7

IPE is believed to afford potent vasculoprotective effects. This small randomized study provides “possible evidence” of an early anti-inflammatory effect of IPE, including an initial loading dose, in symptomatic COVID-19 outpatients. While the difference in change in hs-CRP between groups was not statistically significant, changes in inflammatory biomarker levels were associated with significant improvement in patient-reported symptoms over a 14+3-day period.

30 August

 

Vaccine

Bates TA, Leier HC, Lyski ZL, et al. Neutralization of SARS-CoV-2 variants by convalescent and BNT162b2 vaccinated serum. Nat Commun August 26, 2021, 12, 5135. https://doi.org/10.1038/s41467-021-25479-6

This study indicates that B.1.1.7 (Alpha) and B.1.351 (Beta) are less well neutralized by serum from vaccinated individuals, and that B.1.351, but not B.1.1.7, is less well neutralized by convalescent serum.

 

Immunology

Sarma A, Christenson SA, Byrne A. et al. Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS. Nat Commun August 26, 2021. 12, 5152 (2021). https://doi.org/10.1038/s41467-021-25040-5

Assessing host gene expression in the lower airways, this study reveals distinct immunological features of COVID-19 ARDS. In contrast to a “cytokine storm,” the authors observed a reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes.

 

Co-morbidities

Levy I, Wieder-Finesod A, Litchevsky V, et al. Immunogenicity and safety of the BNT162b2 mRNA Covid-19 vaccine in people living with HIV-1. Clin Microbiol Infection August 23, 2021. https://doi.org/10.1016/j.cmi.2021.07.031

A cohort study of 143 PLWH indicating that the Pfizer/BNT vaccine appears immunogenic and safe in those patients who are on ART with unsuppressed CD4 count and suppressed viral load.

 

Collateral damage

Jarnig G, Jaunig J, van Poppel MN, et al. Association of COVID-19 Mitigation Measures With Changes in Cardiorespiratory Fitness and Body Mass Index Among Children Aged 7 to 10 Years in Austria.  JAMA Netw Open August 26, 2021; 4(8):e2121675. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2783511?resultClick=1

In this cohort study of Austrian children aged 7 to 10 years, fitness levels decreased and BMI increased from September 2019 to September 2020, most likely in association with COVID-19 mitigation measures. The proportion of overweight or obese children increased by 3.1% among girls and 4.5% among boys.

 

Nichter B, Hill ML, Na PJ, et al. Prevalence and Trends in Suicidal Behavior Among US Military Veterans During the COVID-19 Pandemic. JAMA Psychiatry. 2021; https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2783601?resultClick=1

Despite grim forecasts about the COVID-19 pandemic possibly creating a perfect storm for suicidal behavior, the prevalence of suicidality DID NOT increase among military veterans.

 

Pediatrics

Theuring S, Thielecke M, van Loon W, et al. SARS-CoV-2 infection and transmission in school settings during the second COVID-19 wave: a cross-sectional study, Berlin, Germany, November 2020. Euro Surveill. 2021;26(34):pii=2100184. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.34.2100184

SARS-CoV-2 infection activity in Berlin schools during peak transmission in November 2020 appeared to be low. Secondary transmission in class did not happen, and in connected households the attack rate was around 1% (remember – this was prior to Delta).

 

29 August

 

Virology

Holmes EC, Goldstein SA, Rasmussen AL, et al. The Origins of SARS-CoV-2: A Critical Review. Cell August 18, 2021. https://doi.org/10.1016/j.cell.2021.08.017

A “laboratory escape” scenario or zoonotic emergence? According to this comprehensive review, scientific evidence supports a zoonotic origin.

 

Vaccine

Uzun G, Althaus K, Bakchoul T. No Correlation between Anti-PF4 and Anti–SARS-CoV-2 Antibodies after ChAdOx1 nCoV-19 Vaccination. NEJM August 25, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2111305?query=featured_home

This study does not support the hypothesis that the immune response against SARS-CoV-2 proteins leads to the formation of anti-platelet factor 4 antibodies in patients with vaccine-induced immune thrombotic thrombocytopenia.

 

Immunology

Giovannoni F, Li Z, Remes-Lenicov F, et al. AHR signaling is induced by infection with coronaviruses. Nat Commun August 26, 2021, 12, 5148. https://www.nature.com/articles/s41467-021-25412-x

The aryl hydrocarbon receptor (AHR) was recently identified as a host factor for Zika and dengue viruses. This study suggests that AHR activation is a common strategy used by coronaviruses to evade antiviral immunity and promote viral replication, which may also contribute to lung pathology.

 

Diagnostics

Willeit P, Bernar B, Zurl C, et al. Sensitivity and specificity of the antigen-based anterior nasal self-testing programme for detecting SARS-CoV-2 infection in schools, Austria, March 2021. Euro Surveill. 2021;26(34):pii=2100797. https://doi.org/10.2807/1560-7917.ES.2021.26.34.2100797

Data from this nationwide screening program introduced in Austrian schools in January 2021 show that only a (small) subset of infected individuals are detected with antigen-based testing. The authors recommend additional measures such as face masks or ventilation as well as switching to RT-qPCR based approaches.

 

Treatment

Van Blargan LA, Adams LJ, Liu Z, et al. A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope. Immunity August 18, 2021. https://doi.org/10.1016/j.immuni.2021.08.016

Presentation of a new mAb, SARS2-38, that potently neutralizes all SARS-CoV-2 variants of concern tested and protects mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engages a conserved epitope proximal to the receptor binding motif.

 

28 August

 

Epidemiology

Pei S, Yamana TK, Kandula S, et al. Burden and characteristics of COVID-19 in the United States during 2020. Nature August 27, 2021. https://doi.org/10.1038/s41586-021-03914-4

Roughly one third of the US population has been infected. The national infection fatality rate during the latter half of 2020 hovers around 0.30%, well above estimates for both seasonal influenza (< 0.08%) and the 2009 influenza pandemic (0.0076%).

 

Transmission

Wang CC, Prather KA, Sznitman J, et al. Airborne transmission of respiratory viruses. Science August 27, 2021. Vol. 373, Issue 6558, eabd9149. https://science.sciencemag.org/content/373/6558/eabd9149

Forget droplets and fomites. According to this comprehensive review, airborne transmission is the dominant form of transmission. The best arguments? The distinct difference between indoor and outdoor transmission (gravity-driven droplets behave identically indoors and outdoors) and the demonstrated role of poor ventilation (droplets and fomite transmission are not affected by ventilation).

 

Immunology

Sposito B, Broggi A, Pandolfi L, et al. The interferon landscape along the respiratory tract impacts the severity of COVID-19. Cell August 18, 2021. DOI:https://doi.org/10.1016/j.cell.2021.08.016

“Landscape” is the new favorite word of immunologists (for about three years now). This “landscape” study shows that interferons have opposing roles along the respiratory tract, reconciling some of the seemingly contradictory findings on interferons in COVID-19 patients.

 

Vaccines

Barda N, Dagan N, Ben-Shlomo Y, et al. Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. NEJM August 25, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2110475?query=featured_home

This observational data set involving more than 2.4 million vaccinated persons from Israel identified an excess risk of lymphadenopathy (78.4 events per 100,000 persons), herpes zoster infection (15.8 events), appendicitis (5.0 events), and myocarditis (2.7 events). Compared to the risk of adverse events associated with SARS-CoV-2 infection, this is almost meaningless.

 

Hippisley-Cox J, Patone M, Mei XW, et al. Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study. BMJ August 27, 2021; 374 doi: https://doi.org/10.1136/bmj.n1931

Same direction as above. This patient level data obtained for approximately 30 million people vaccinated in England shows that the slightly increased risks of severe hematological and vascular events after the first doses of the Oxford/AZ and Pfizer/BNT vaccines were minimal vs the substantially higher and more prolonged events after SARS-CoV-2 infection in the same population.

 

Clinical

Ge Y, Martinez L, Sun S, et al. COVID-19 Transmission Dynamics Among Close Contacts of Index Patients With COVID-19A Population-Based Cohort Study in Zhejiang Province, China. JAMA Intern Med August 23, 2021. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2783099

Interesting finding: infected contacts of asymptomatic index patients were less likely to present with COVID-19 symptoms, suggesting that amount of exposure may be associated with clinical presentation between close contacts.

 

27 August

 

Epidemiology

Petti S. Undetected and relatively sustained SARS-CoV-2 circulation worldwide during the year 2019. Clinical Infectious Diseases August 2021, ciab727, https://doi.org/10.1093/cid/ciab727

A brief summary on current data suggesting the hypothesis that in 2019, SARS-CoV-2 circulation was already relatively sustained in Europe and America.

 

Transmission

Saretzki C, Bergmann O, Dahmann P, et al. Are small airplanes safe with regards to COVID-19 transmission? Journal of Travel Medicine August 20, 2021, taab105, https://doi.org/10.1093/jtm/taab105

Yes, they are – if the ventilation system is set on ‘high’. In this simulation study (an externally connected ventilation system was used to simulate the cockpit in-flight airflow for a four-seater general aviation aircraft) the airstream was marked with smoke for visualization.

 

Vaccine

Baltas I, Boshier FA, Williams CA, et al. Post-vaccination COVID-19: A case-control study and genomic analysis of 119 breakthrough infections in partially vaccinated individuals. Clinical Infectious Diseases, August 19, 2021, ciab714, https://doi.org/10.1093/cid/ciab714

This matched control study from the UK describes a cohort of Pfizer/BNT or AZ/Oxford vaccinated multimorbid patients developing COVID-19 predominantly from the B.1.1.7 lineage post first vaccination. One life was saved every four to five vaccinations. As mortality benefit from vaccination occurred immediately after COVID-19 infection, these data indirectly question whether pauci-symptomatic/asymptomatic patients should be offered vaccination.

 

Clinical

Narayanan S, Chua CV, Baddley JW. COVID-19 associated Mucormycosis (CAM): risk factors and mechanisms of disease. Clin Inf Dis, August 22, 2021, ciab726, https://doi.org/10.1093/cid/ciab726

High background prevalence of mucormycosis in India, undiagnosed or poorly controlled diabetes, COVID-19 induced immune dysregulation, and therapies like steroids which cause immune suppression in the setting of limited healthcare access amidst a pandemic surge created a perfect storm. This paper reviews currently identified risk factors and pathogenesis of COVID-19 associated mucormycosis.

 

Collateral damage (and benefits)

Burdzovic Andreas J, Scott Brunbirg G. Self-reported Mental and Physical Health Among Norwegian Adolescents Before and During the COVID-19 Pandemic. JAMA Netw Open August 24 2021;4(8):e2121934. doi:10.1001/jamanetworkopen.2021.21934

Most adolescents cope adequately with the pandemic conditions. However, they are at high risk becoming couch potatoes: this large cohort study including 2536 adolescents found that Norwegian adolescents starting high school during the COVID-19 year had lower odds of sports participation than their peers starting high school in preceding years, but no significant differences in depression symptoms, friendships, and physical health.

 

Ujiie M, Tsuzuki S, Nakamoto T, Iwamoto N. Resurgence of respiratory syncytial virus infections during COVID-19 pandemic, Tokyo, Japan. Emerg Infect Dis. 2021 Nov [date cited]. https://wwwnc.cdc.gov/eid/article/27/11/21-1565_article

As of July 2021, however, an unusually high number of respiratory syncytial virus infections were reported in Tokyo. This resurgence (the largest annual increase in cases since monitoring began in 2003) may have resulted from restarting social activities for children.

 

Pregnancy

Badr DA, Picone O, Bevilacqua E, et al. Severe acute respiratory syndrome coronavirus 2 and pregnancy outcomes according to gestational age at time of infection. Emerg Infect Dis. 2021 Oct [date cited]. https://wwwnc.cdc.gov/eid/article/27/10/21-1394_article

A large cohort, indicating that SARS-CoV-2 infection in pregnant women during the late second and early third trimesters is associated with higher risk for adverse outcomes. Of 10,925 pregnant women, 393 (3.6%) were infected with SARS-CoV-2. After matching for possible confounders, statistically significant increases of adverse obstetric outcomes were seen at > 20 weeks gestation and of composite adverse neonatal outcomes at > 26 weeks gestation.

 

26 August

 

Vaccine

Today we have a special on vaccine effectiveness towards the B.1.617.2 (Delta).

 

Fowlkes A, Gaglani M, Groover K, et al. Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Frontline Workers Before and During B.1.617.2 (Delta) Variant Predominance — Eight U.S. Locations, December 2020–August 2021. MMWR Morb Mortal Wkly Rep. ePub: 24 August 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e4.htm?s_cid=mm7034e4_x

In this cohort of 4217 frontline workers (mainly HCW), the vaccine effectiveness (VE) declined from 91% to 66% when the SARS-CoV-2 Delta variant became predominant. However, this trend should be interpreted with caution (increasing time since vaccination, low numbers).

 

Behrens GM, Cossmann A, Stankov MV, et al. SARS-CoV-2 delta variant neutralisation after heterologous ChAdOx1-S/BNT162b2 vaccination. Lancet August 17, 2021. https://doi.org/10.1016/S0140-6736(21)01891-2

Robust inhibition of variants including Delta by the switch vaccination of AZ then Pfizer/BNT.

 

Hammerschmidt SI, Bosnjak B, Bernhardt G, et al. Neutralization of the SARS-CoV-2 Delta variant after heterologous and homologous BNT162b2 or ChAdOx1 nCoV-19 vaccination. Cell Mol Immunol August 23, 2021. https://doi.org/10.1038/s41423-021-00755-z

Same group, same direction. This small study indicates an overall robust inhibition of the Delta variant by heterologous boosting with Pfizer/BNT of vaccinees initially primed with AZ. However, in contrast to Alpha, Beta, and Gamma variants, homologous Pfizer/BNT prime-boost vaccination appeared to be even more efficient in neutralizing the Delta variant.

 

Griffin JB, Haddix M, Danza P, et al. SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status — Los Angeles County, California, May 1–July 25, 2021. MMWR Morb Mortal Wkly Rep. ePub: 24 August 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e5.htm?s_cid=mm7034e5_w

From May 1–July 25, 2021, among 43,127 SARS-CoV-2 infections in residents of Los Angeles County, 25.3% were in fully vaccinated persons, 3.3% were in partially vaccinated persons, and 71.4% were in unvaccinated persons. On July 25, infection and hospitalization rates among unvaccinated persons were 4.9 and 29.2 times, respectively, those of fully vaccinated persons. Of note, in July, when Delta was predominant, cycle threshold values were similar for unvaccinated and vaccinated persons.

 

Ong SW, Chiew CJ, Ang LW, et al. Clinical and virological features of SARS-CoV-2 variants of concern: a retrospective cohort study comparing B.1.1.7 (Alpha), B.1.315 (Beta), and B.1.617.2 (Delta). Clin Inf Dis August 23, 2021; ciab721, https://doi.org/10.1093/cid/ciab721

Retrospective cohort from Singapore, indicating a signal toward increased severity associated with B.1.617.2 (Delta). The association of B.1.617.2 with lower cycle threshold value and longer viral shedding provides a potential mechanism for increased transmissibility. All of 18 vaccinated patients with Delta had mild disease and none developed pneumonia.

 

25 August

 

Transmission

Toumi A, Zhao H, Chhatwal J, et al. Association of Limited In-Person Attendance in US National Football League and National Collegiate Athletic Association Games With County-Level COVID-19 Cases. JAMA Netw Open August 17, 2021;4(8):e2119621. https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2783110

Are football games with limited in-person attendance associated with increased county-level COVID-19 cases? Probably not. This cross-sectional study of US counties that hosted National Football League games suggests that football games held with limited in-person attendance were not associated with increased COVID-19 cases in the counties where they were held.

 

Vaccine

Ranzani OT, Hitchings MD, Durion M, et al. Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of covid-19 in Brazil: test negative case-control study. BMJ August 20, 2021; 374. doi: https://doi.org/10.1136/bmj.n2015

Moderate results with the inactivated whole virus vaccine CoronaVac (from Sinovac Biotech) in older people (> 70 years) in a setting with extensive transmission of the gamma variant: adjusted vaccine effectiveness against symptomatic COVID-19 was 24.7% at 0-13 days and 46.8% at ≥ 14 days after the second dose. Adjusted vaccine effectiveness against hospital admissions was 55.5% (death 61.2%) at ≥ 14 days after the second dose, declining with increasing age.

 

Wan EY, Chui CD, Lai FT, et al. Bell’s palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study. Lancet Inf Dis August 16, 2021. DOI: https://doi.org/10.1016/S1473-3099(21)00451-5

An additional 4.8 cases of this generally self-limiting adverse event per 100,000 people vaccinated with CoronaVac and 2.0 cases per 100,000 people vaccinated with BNT162b2.

 

Clinical

Lehmann M, Allers K, Heldt C et al. Human small intestinal infection by SARS-CoV-2 is characterized by a mucosal infiltration with activated CD8+ T cells. Mucosal Immunol August 21, 2021. https://doi.org/10.1038/s41385-021-00437-z

Intraepithelial CD8+ T cells are activated upon infection of intestinal epithelial cells with SARS-CoV-2, providing one possible explanation for gastrointestinal symptoms associated with COVID-19.

 

Treatment

Ehrmann S, Li J, Ibarra-Estrada M, et al. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. Lancet Resp Med, August 20, 2021. https://doi.org/10.1016/S2213-2600(21)00356-8

This collaborative meta-trial of six randomized controlled open label superiority trials shows that awake prone positioning of patients with hypoxemic respiratory failure due to COVID-19 reduces the need for intubation with no signs of harm. 14 patients treated with awake prone positioning avoids one intubation.

 

 

24 August

 

Epidemiology

Moritz S, Gottschick C, Horn J, et al. The risk of indoor sports and culture events for the transmission of COVID-19. Nat Commun August 2021, 12, 5096. https://www.nature.com/articles/s41467-021-25317-9

The authors conducted an “experimental” pop concert (music was mainstream) on August 22nd 2020, with a total of 1212 individuals in the Leipzig Arena, Germany. They conclude that with an effective ventilation system, indoor mass gathering events with suitable hygiene practices have a very small, if any, effect on epidemic spread. If you are interested in the ventilation system in the arena: the inlet air is blown in laterally on the east- and west side by jet nozzles. https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-021-25317-9/MediaObjects/41467_2021_25317_MOESM7_ESM.mp4

Transmission

Tinker SC, Szablewski CM, Litvintseva AP, Drenzek C, Voccio GE, Hunter MA, et al. Point-of-care antigen test for SARS-CoV-2 in asymptomatic college students. Emerg Infect Dis. 2021 Oct [date cited]. https://wwwnc.cdc.gov/eid/article/27/10/21-0080_article

Bad news for the BinaxNOW COVID-19 Ag Card. In this screening study of 1,540 asymptomatic college students, BinaxNOW missed many infections and showed only 20% overall sensitivity (among participants with culturable virus, sensitivity was 60%).

 

Vaccine

Chung H, He S, Nasreen S, et al. Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study. BMJ August 20, 2021; 374. doi: https://doi.org/10.1136/bmj.n1943

Two doses of mRNA COVID-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose. Of note, a higher effectiveness was seen after one dose of mRNA-1273 (MODERNA) than after one dose of BNT162b2 (BioNTech/Pfizer).

 

Debes AK, Yiao S, Colantuoni E, et al. Association of Vaccine Type and Prior SARS-CoV-2 Infection With Symptoms and Antibody Measurements Following Vaccination Among Health Care Workers. JAMA Intern Med August 16, 2021; https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2782821

You don’t have to suffer to benefit from COVID vaccination. In this study on HCWs, the vast majority of participants (953 of 954!) developed spike IgG antibodies 14 or more days following dose 2, regardless of vaccine reactions!

 

Co-morbidities

Foote MB, White JR, Lee J, et al. Association of Antineoplastic Therapy With Decreased SARS-CoV-2 Infection Rates in Patients With Cancer. JAMA Oncol August 20, 2021; https://jamanetwork.com/journals/jamaoncology/fullarticle/2783284

Interesting finding. After identifying potential ACE2-lowering anti-neoplastic compounds, including mTOR/PI3K inhibitors (like everolimus) and anti-metabolites (like gemcitabine), these were “validated” in a large retrospective cohort: patients who received potential ACE2-lowering anti-neoplastics were nearly half as likely to have positive results for SARS-CoV-2 compared with patients treated with other active anti-neoplastic therapies.

 

 

23 August

Vaccines

Eliakim-Raz N, Massarweh A, Stemmer A, Stemmer SM. Durability of Response to SARS-CoV-2 BNT162b2 Vaccination in Patients on Active Anticancer Treatment. JAMA Oncol. 2021 Aug 11:e214390. PubMed: https://pubmed.gov/34379092. Full text: https://doi.org/10.1001/jamaoncol.2021.4390

Anti-spike (anti-S) IgG antibody response to the BioNTech/Pfizer vaccine in 95 patients with solid tumors on active anti-cancer treatment after a median of 4 months from the second vaccination. Eighty-three patients (87%) were seropositive for anti-S IgG antibodies. The median titer levels in patients with cancer was significantly lower than those in the control group. There was a 3.6-fold range in median titer values across tumor types and a wider range (8.8-fold) across treatment types. The only variable significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy and immunotherapy plus biological therapy.

 

Epidemiology

Madsen JR, Nielsen JPS, Fogh K, et al. Anti-SARS-CoV-2 Seropositivity Among Medical Students in Copenhagen. Open Forum Infectious Diseases 2021, publshed 19 August. Full text: https://academic.oup.com/ofid/article/8/8/ofab273/6354577

“Medical students have the highest reported seropositivity (34.58%) in the Danish health care system. In this cohort of students at University of Copenhagen, seropositivity was associated with social behavior markers and, to a lesser extent, with self-reported contact with SARS-CoV-2-infected patients.”

 

Transmission

Smith JAE, Hopkins S, Turner C, et al. Public health impact of mass sporting and cultural events in a rising COVID-19 prevalence in England. Public Health England 2021, posted 21 August. Full text: https://khub.net/documents/135939561/338928724/Public+health+impact+of+mass+sporting+and+cultural+events+in+a+rising+COVID-19+prevalence+in+England.pdf/05204895-1576-1ee7-b41e-880d5d6b4f17

“The number of potentially infected persons attending Wembley stadium increased as the [EURO 2020] tournament progressed, reaching more than 2,000 at the EURO 2020 final despite event goers requiring a COVID pass for entry.” In the future, it might be “important to consider including mitigations for spectators to consider such as face coverings when travelling to and from events, minimising crowding in poorly ventilated indoors spaces such as bars and pubs where people may congregate to watch events. It is also important to minimise the risk of transmission from aerosol exposure related to singing and chanting in large groups by improving ventilation in enclosed spaces.” See also the Guardian article: Walker P. 9,000 Covid cases linked to Euro 2020 games in mass events scheme. The Guardian 2021, published 20 August. Full text: https://www.theguardian.com/world/2021/aug/20/9000-covid-cases-linked-to-euro-2020-games-in-mass-events-scheme

 

Prevention

Bartels J, Fairfield C, Chen IC, Neu D. Laboratory Study of Physical Barrier Efficiency for Worker Protection against SARS-CoV-2 while Standing or Sitting. medRxiv 2021, posted 29 July. Full text: https://doi.org/10.1101/2021.07.26.21261146

Masks are better than plexiglass barriers. The authors find a more than 70% reduction in exposure to aerosols from simulated coughs, but barriers increase exposure to other people nearby and may impede proper ventilation. Plexiglass barriers divert aerosols, masks remove them.

 

Collateral Effects

Brink J, Cullen P, Beek K, Peters SAE. Intimate Partner Violence during the Covid-19 pandemic in Western and Southern European countries. Eur J Public Health. 2021 Aug 18:ckab093. PubMed: https://pubmed.gov/34406373. Full text: https://doi.org/10.1093/eurpub/ckab093

“Six countries showed an increase in domestic violence reports (Austria, Belgium, France, Ireland, Spain, and the UK), two countries a drop (Italy and Portugal), two countries showed no change (the Netherlands and Switzerland), and one country did not provide comparative data (Germany).”

 

22 August

Vaccines

Gilbert PB, Montefiori DC, McDermott A, et al. Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial. medRxiv 2021, posted 10 August. Full text: https://doi.org/10.1101/2021.08.09.21261290

Antibody levels (measured as IgG bAbs to spike, IgG bAbs to spike RBD, ID50 and ID80 nAb titer) might be able to predict the level of protection provided by the Moderna vaccine. This is the result of a study which compared levels of neutralizing antibodies in 47 vaccinated individuals who developed breakthrough infections with matched controls.

 

Virology

Resende PC, Naveca FG, Lins RD, et al. The Ongoing Evolution of Variants of Concern and Interest of SARS-CoV-2 in Brazil Revealed by Convergent Indels in the Amino (N)-Terminal Domain of the Spike Protein. Virus Evolution 2021, published 14 August. Full text: https://doi.org/10.1093/ve/veab069

The authors identified that SARS-CoV-2 lineages circulating in Brazil independently acquired convergent deletions and insertions in the amino (N)-terminal domain (NTD) of the S protein. They anticipate that ongoing widespread transmission of SARS-CoV-2 will generate new viral lineages that might be more resistant to antibody neutralization.

 

Prevention

Pagel C. Schools—a gaping hole in the English covid strategy. BMJ Opinion 2021, published 20 August. Full text: https://blogs.bmj.com/bmj/2021/08/20/christina-pagel-schools-a-gaping-hole-in-the-english-covid-strategy

“Schools don’t have to be worse than any other crowded indoor space to be a problem. The problem is simply that they are another crowded indoor space and one where children spend 35 hours a week. We know that Delta spreads easily in such indoor spaces, particular if they are poorly ventilated.”

 

Hammond PS. Will we ever wash our hands of lubrication theory? Physics of Fluids 2021, published 17 August. Full text: https://doi.org/10.1063/5.0060307

The flow physics of hand washing. Why vigorous hand washing for ≥ 20 seconds is optimal. Read more than the abstract, it will be worth your while.

 

Treatment

Korley FK, Durkalski-Mauldin V, Yeatts SD, et al. Early Convalescent Plasma for High-Risk Outpatients with Covid-19. N Engl J Med. 2021 Aug 18. PubMed: https://pubmed.gov/34407339. Full text: https://doi.org/10.1056/NEJMoa2103784

Time to close the chapter on convalescent plasma? In this randomized, multicenter, single-blind trial (257 in the convalescent plasma group and 254 in the placebo group), the administration of COVID-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of COVID-19 did not prevent disease progression.

 

21 August

Vaccines

Morris J. Israeli data: How can efficacy vs. severe disease be strong when 60% of hospitalized are vaccinated? Covid-19 Data Science 2021, posted 17 August. Full text: https://www.covid-datascience.com/post/israeli-data-how-can-efficacy-vs-severe-disease-be-strong-when-60-of-hospitalized-are-vaccinated

“It is important to use infection and disease rates (per 100k, e.g.) and not raw counts to compare unvaccinated and vaccinated groups to adjust for the proportion vaccinated. Use of raw counts exaggerates the vaccine efficacy when vaccinated proportion is low and attenuates the vaccine efficacy when, like in Israel, vaccines proportions are high.”

Copyright: Jeffrey Morris

 

 

Ollila TA, Lu S, Masel R, et al. Antibody Response to COVID-19 Vaccination in Adults With Hematologic Malignant Disease. JAMA Oncol. 2021 Aug 11:e214381. PubMed: https://pubmed.gov/34379085. Full text: https://doi.org/10.1001/jamaoncol.2021.4381

Retrospective study of 160 adults with hematologic malignant disease who were vaccinated with a COVID-19 vaccine. (One hundred and five (66%) patients received a B cell–depleting monoclonal antibody, most commonly rituximab (n = 85)). Sixty-three patients (39%) demonstrated seroconversion. Longer time (greater than or less than 12 months) from last chemotherapy administration to vaccination was associated with increased rates of seroconversion. The quantitative antibody response was also lower among patients with exposure to B cell/plasma cell–depleting antibodies and those with active malignant disease.

 

Epidemiology

Zhang S. The Coronavirus Is Here Forever. This Is How We Live With It. The Atlantic 2021, published 17 August. Full text: https://www.theatlantic.com/science/archive/2021/08/how-we-live-coronavirus-forever/619783

The path from COVID-19 to the common cold.

 

Treatment

Crippa JAS, Zuardi AW, Guimarães FS, et al. Efficacy and Safety of Cannabidiol Plus Standard Care vs Standard Care Alone for the Treatment of Emotional Exhaustion and Burnout Among Frontline Health Care Workers During the COVID-19 Pandemic: A Randomized Clinical Trial. JAMA Netw Open. 2021 Aug 2;4(8):e2120603. PubMed: https://pubmed.gov/34387679. Full text: https://doi.org/10.1001/jamanetworkopen.2021.20603

Randomized trial of 120 frontline health care professionals. “Emotional exhaustion scores were reduced among participants receiving cannabidiol (CBD) [300 mg] plus standard care compared with those receiving standard care alone. Five participants who received CBD plus standard care experienced serious adverse events, with full recovery after discontinuation.”

 

Pediatrics and Obstetrics

Chinn J, Sedighim S, Kirby KA, et al. Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic. JAMA Netw Open. 2021 Aug 2;4(8):e2120456. PubMed: https://pubmed.gov/34379123. Full text: https://doi.org/10.1001/jamanetworkopen.2021.20456

Women with COVID-19 giving birth had increased mortality, need for intubation and ventilation, and intensive care unit admission. This is the result of a cohort study examining 869,079 adult women, including 18,715 women with COVID-19, during 12 months up to February 2021.

 

20 August

Vaccines

Tan CW, Chia WN, Young BE, et al. Pan-Sarbecovirus Neutralizing Antibodies in BNT162b2-Immunized SARS-CoV-1 Survivors. N Engl J Med. 2021 Aug 18. PubMed: https://pubmed.gov/34407341. Full text: https://doi.org/10.1056/NEJMoa2108453

If you had survived SARS-CoV-1 in 2002-2004, the BioNTech/Pfizer vaccine would today give you potent cross-clade pan-sarbecovirus neutralizing antibodies. This study (n = 8) is another proof of concept that a pan-coronavirus vaccine is possible. Such a vaccine might cover not only SARS-CoV-2 and its current and future variants but also other coronaviruses with known potential to cause severe human diseases.

 

Mallapaty S. Delta’s rise is fuelled by rampant spread from people who feel fine. Nature 2021, published 19 August. Full text: https://www.nature.com/articles/d41586-021-02259-2

“People infected with the Delta variant generally do not have COVID-19 symptoms until two days after they start shedding the coronavirus.”

 

Epidemiology

Kupferschmidt K. Evolving Threat. Science 2021, publshed 19 August. Full text: https://www.sciencemag.org/news/2021/08/new-sars-cov-2-variants-have-changed-pandemic-what-will-virus-do-next

“New SARS-CoV-2 variants have changed the pandemic. What will the virus do next?”

 

Immunology

Loske J, Röhmel J, Lukassen S, et al. Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children. Nat Biotechnol (2021). https://doi.org/10.1038/s41587-021-01037-9

The authors provide evidence that the epithelial and immune cells of the upper airways (nose) of children are pre-activated and primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults.

 

Transmission

Branswell H. What’s safe to do during summer’s Covid surge? STAT asked public health experts about their own plans. Stat 2021, published 17 August. Full text: https://www.statnews.com/2021/08/17/whats-safe-to-do-during-summers-covid-surge-stat-asked-public-health-experts-about-their-own-plans/

Experts largely stay put.

 

Paul LA, Daneman N, Schwartz KL, et al. Association of Age and Pediatric Household Transmission of SARS-CoV-2 Infection. JAMA Pediatr. 2021 Aug 16. PubMed: https://pubmed.gov/34398179. Full text: https://doi.org/10.1001/jamapediatrics.2021.2770

In this Ontario study of 6280 households with pediatric index cases, 1717 households (27.3%) experienced secondary transmission.

“Younger children may have greater risk of transmitting SARS-CoV-2 to caregivers and siblings in the household than older children. In this cohort study of 6280 households with pediatric index cases, the adjusted odds of household transmission by children aged 0 to 3 years was 1.43 compared with children aged 14 to 17 years.”

 

Leibowitz AI, Siedner MJ, Tsai AC, Mohareb AM. Association Between Prison Crowding and COVID-19 Incidence Rates in Massachusetts Prisons, April 2020-January 2021. JAMA Intern Med. 2021 Aug 9:e214392. PubMed: https://pubmed.gov/34369964. Full text: https://doi.org/10.1001/jamainternmed.2021.4392

“In this study (…) including all incarcerated persons in 14 Massachusetts state prisons from April 2020 to January 2021 (…), COVID-19 incidence was significantly higher in prisons operating at a higher percentage of their design capacity and was significantly lower in prisons where a higher proportion of incarcerated people were housed in single-cell units.” See also the comment by Clemenzi-Allen AA, Pratt LA. Avoiding COVID-19 Outbreaks in Carceral Settings. JAMA Intern Med. 2021 Aug 9. PubMed: https://pubmed.gov/34369968. Full text: https://doi.org/10.1001/jamainternmed.2021.4389

 

Diagnostics

Congrave-Wilson Z, Lee Y, Jumarang J, et al. Change in Saliva RT-PCR Sensitivity Over the Course of SARS-CoV-2 Infection. JAMA. 2021 Aug 13. PubMed: https://pubmed.gov/34387653. Full text: https://doi.org/10.1001/jama.2021.13967

Prospective study to investigate the testing timeframe that optimizes saliva sensitivity for SARS-CoV-2 detection. “Saliva was sensitive for detecting SARS-CoV-2 in symptomatic individuals during initial weeks of infection, but sensitivity in asymptomatic SARS-CoV-2 carriers was less than 60% at all time points. (…) This study suggests saliva-based RT-PCR should not be used for asymptomatic COVID-19 screening.”

 

19 August

Severe COVID

France 20210817. Triage in Guadeloupe. La Voix du Nord 2021, published 17 August. Full text: https://www.lavoixdunord.fr/1057833/article/2021-08-17/guadeloupe-le-tri-des-patients-covid-en-reanimation-se-fait-desormais-partir-de

Triage in a French overseas territory. French press reports indicate that at the Pointe-à-Pitre hospital in Guadeloupe, “patients over 50 and those below having at least one comorbid factor are no longer intubated.”

 

Epidemiology

Wadman M. A grim warning from Israel: Vaccination blunts, but does not defeat Delta. Science 2021, published 16 August. Full text: https://www.sciencemag.org/news/2021/08/grim-warning-israel-vaccination-blunts-does-not-defeat-delta

“Israel, which has led the world in launching vaccinations and in data gathering, is confronting a surge of COVID-19 cases that officials expect to push hospitals to the brink. Nearly 60% of gravely ill patients are fully vaccinated.”

 

Vaccines

Nanduri S, Pilishvili T, Derado G, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant — National Healthcare Safety Network, March 1–August 1, 2021. MMWR Morb Mortal Wkly Rep. ePub: 18 August 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7034e3

“Two doses of mRNA vaccines were 74.7% effective against infection among nursing home residents early in the vaccination program (March–May 2021). During June–July 2021, when B.1.617.2 (Delta) variant circulation predominated, effectiveness declined significantly to 53.1%.”

 

Madhi SA, Koen AL, Izu A, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. Lancet 2021, published 17 August. Full text: https://doi.org/10.1016/S2352-3018(21)00157-0

A double-blind, placebo-controlled, Phase 1B/2A study of the AstraZeneca vaccine in 104 people with HIV and 70 HIV-negative controls. The authors found similar full-length spike (FLS)-binding and receptor-binding domain (RBD)-binding IgG and SARS-CoV-2 neutralizing response patterns in people with HIV and HIV-negative SARS-CoV-2-naive participants.

 

Schmitz AJ, Turner JS, Liu Z, et al. A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants. Immunity 2021, published 16 August. Full text: https://doi.org/10.1016/j.immuni.2021.08.013

The authors describe an antibody, dubbed 2C08 (a SARS-CoV-2 vaccine-induced mAb cloned from a germinal center B cell isolated from a draining axillary lymph node sampled from a healthy adult after receiving their second dose of an mRNA-based vaccine) which potently neutralizes the Delta, Gamma and Alpha strains and reduces lung viral load and morbidity in hamsters challenged with Delta and Gamma. Clonal analysis identified 2C08-like public clonotypes among B cells responding to SARS-CoV-2 infection or vaccination in 41 out of 181 individuals. Ergo: SARS-CoV-2 vaccines mitigate resistance by circulating variants of concern. Tell your friends to get vaccinated.

 

Treatment

Rizk JG, Gupta A, Sardar P, et al. Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine-Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis: A Review. JAMA Cardiol. 2021 Aug 10. PubMed: https://pubmed.gov/34374713. Full text: https://doi.org/10.1001/jamacardio.2021.3444

The recommendations of this review: treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT) should consist of therapeutic anti-coagulation mostly with non-heparin products and high-dose intravenous immunoglobin (IVIG). In severe cases, plasma exchange should be used for clearing autoantibodies. Routine platelet transfusions, aspirin, and warfarin should be avoided because of the possibility of worsening thrombosis and magnifying risk of bleeding.

 

Pediatrics

Dionne A, Sperotto F, Chamberlain S, et al. Association of Myocarditis With BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children. JAMA Cardiol. 2021 Aug 10:e213471. PubMed: https://pubmed.gov/34374740. Full text: https://doi.org/10.1001/jamacardio.2021.3471

A case series of 15 children who were hospitalized with myocarditis after receiving the BioNTech/Pfizer vaccine.

 

18 August

Virology

Liu Y, Liu J, Bryan AJ, et al. Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant. bioRxiv 2021, posted 12 August. Full text: https://doi.org/10.1101/2021.08.12.456173

The Delta spike mutation P681R could be a key mutation in enhancing Delta variant replication via increased S1/S2 cleavage. The authors suggest that Spike mutations that potentially affect furin cleavage efficiency should be closely monitored for future variant surveillance.

 

Vaccines

Wadman M. A grim warning from Israel: Vaccination blunts, but does not defeat Delta. Science 2021, published 16 August. Full text: https://www.sciencemag.org/news/2021/08/grim-warning-israel-vaccination-blunts-does-not-defeat-delta

“Israel, which has led the world in launching vaccinations and in data gathering, is confronting a surge of COVID-19 cases that officials expect to push hospitals to the brink. Nearly 60% of gravely ill patients are fully vaccinated.”

 

Lloyd-Sherlock P, Lasco G, McKee M, Perianayagam A, Sempé L. Does vaccine ageism amount to gerontocide? Lancet. 2021 Aug 11:S0140-6736(21)01689-5. PubMed: https://pubmed.gov/34390657. Full text: https://doi.org/10.1016/S0140-6736(21)01689-5

“In India, more people younger than 45 years are being vaccinated than those 60 years or older, even though about half of those 60 years or older are yet to receive even a single dose. Unlike age-based triage for acute COVID-19 care, this vaccination policy will not save lives: it will contribute to thousands, potentially millions of avertable deaths. In the Philippines, where only 8·5% of people 60 years or older had been fully vaccinated as of June 29, 2021, the focus of vaccination has now shifted to younger so-called working age adults.”

 

Transmission

Subbaraman N. How do vaccinated people spread Delta? What the science says. Nature 2021, published 12 August. Full text: https://www.nature.com/articles/d41586-021-02187-1

The Delta seems to be more likely than other variants to spread via vaccinated people. Although vaccinated people are probably infectious for a shorter period, they need to take precautions, especially in indoor settings. If you cannot avoid crowded indoor settings, see here: CDC 20210406. Improve How Your Mask Protects You. Centers for Disease Control 2021 (updated 6 April, accessed 15 August). Full text: https://www.cdc.gov/coronavirus/2019-ncov/your-health/effective-masks.html

 

Diagnosis

Snell LB, Cliff PR, Charalampous T, et al. Rapid genome sequencing in hospitals to identify potential vaccine-escape SARS-CoV-2 variants. Lancet Infect Dis 2021, published 13 August. Full text: https://doi.org/10.1016/S1473-3099(21)00482-5

Music of the future. The authors sequenced and identified 2 cases of the B.1.621 variant in less than 24 hours and reported them to Public Health England within 72 hours of sampling.

 

Clinical

Liu T, Wu D, Yan W, et al. Twelve-month systemic consequences of COVID-19 in patients discharged from hospital: a prospective cohort study in Wuhan, China. Clin Infect Dis. 2021 Aug 14:ciab703. PubMed: https://pubmed.gov/34390330. Full text: https://doi.org/10.1093/cid/ciab703

The lives of COVID-19 survivors is not easy, as shown by this 12-month follow up of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020. After 3, 6 and 12 months, 257 (51.2%), 169 (40.0%) and 138 (28.4%) patients had at least one symptom. About 5% of patients had restrictions in pulmonary function at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at the 6-month visit and were maintained at a high frequency (242; 49.8%) at the 12-month visit. An increased incidence of abnormal liver and renal function was also found. Patients had a median age of 63, had been severe or critically ill originally (88.1%), 36.1% of whom had a history of smoking, and having at least one pre-existing co-morbidity was common.

 

17 August

Vaccines

Evans SJW, Jewell NP. Vaccine Effectiveness Studies in the Field. N Engl J Med. 2021 Jul 12. PubMed: https://pubmed.gov/34289274. Full-text: https://doi.org/10.1056/NEJMoa2108891.

“Questions crucial to vaccination policy (…) include the effect of new virus variants, the timing between vaccine doses, the effect of vaccines on asymptomatic infection in contrast to severe disease, the waning of vaccine immunity, and the potentially enhanced effectiveness of mix-and-match strategies that might be used with booster shots.” A comment on the paper we presented on 23 July: Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med. 2021 Aug 12;385(7):585-594. PubMed: https://pubmed.gov/34289274. Full text: https://doi.org/10.1056/NEJMoa2108891

 

Diaz GA, Parsons GT, Gering SK, Meier AR, Hutchinson IV, Robicsek A. Myocarditis and Pericarditis After Vaccination for COVID-19. JAMA. 2021 Aug 4. PubMed: https://pubmed.gov/34347001. Full text: https://doi.org/10.1001/jama.2021.13443

Among 2,000,287 individuals receiving at least 1 COVID-19 vaccination (BioNTech/Pfizer: 52.6%, Moderna: 44.1%, Johnson & Johnson: 3.1%), 20 individuals had vaccine-related myocarditis (1 per 100,000) and 37 had pericarditis (1.8 per 100,000). Myocarditis occurred a median of 3.5 days after vaccination. Fifteen individuals (75%) were male. Four persons (20%) developed symptoms after the first vaccination and 16 (80%) after the second one. Nineteen patients (95%) were admitted to the hospital. All were discharged after a median of 2 days. There were no readmissions or deaths. Find more details about pericarditis in the article.

 

FDA 20210812. Coronavirus (COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals. FDA 2021, published 12 August. Full text: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised

The FDA allows a third booster dose in individuals with solid organ transplant or those who have an equivalent level of immunocompromise. The news release also states that “patients should be counseled to maintain physical precautions to help prevent COVID-19. In addition, close contacts of immunocompromised persons should get vaccinated, as appropriate for their health status, to provide increased protection to their loved ones.”

 

Epidemiology

Khullar D. How Will the Coronavirus Evolve? The New Yorker 2021, published 11 August. Full text: https://www.newyorker.com/science/annals-of-medicine/how-will-the-coronavirus-evolve

A nice read about Lenski’s Long-Term Evolution Experiment and possible SARS coronavirus citrate moments, that exceptionally rare, profoundly consequential evolutionary leaps can happen.

 

Transmission

Read JM, Green CA, Harrison EM, et al. Hospital-acquired SARS-CoV-2 infection in the UK’s first COVID-19 pandemic wave. Lancet 20212, published 12 August. Full text: https://doi.org/10.1016/S0140-6736(21)01786-4

Until the end of July 2020, 6.8% of patients with COVID-19 in 314 UK hospitals may have been infected after hospital admission, with a peak of 8.2% in mid-May. The authors conclusion, “As SARS-CoV-2 is likely to persist as an endemic or seasonal virus in coming years, it is critical to use the lessons learned so far in the pandemic to minimise the burden of hospital-acquired infections.”

 

16 August

Vaccines

Hillus D, Schwarz T, Tober-Lau P, et al. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study. Lancet Respir Dis 2021, published 12 August. Full text: https://doi.org/10.1016/S2213-2600(21)00357-X

A new prospective vaccine mixing study comparing “AstraZeneca (AZ) + BioNTech/Pfizer (BP)” with 2 x AZ and 2 x BP. The authors show “AZ first, BP second” elicited a stronger immune response than two doses of either vaccine. Could these data spur a renaissance for the AstraZeneca vaccine? Not sure. The difference might be explained by the longer (and possibly more effective) immunization interval of AZ+BP compared to the typical 3-week interval of the two BP injections.

 

Hou X, Zaks T, Langer R, et al. Lipid nanoparticles for mRNA delivery. Nat Rev Mater (2021). Full text: https://doi.org/10.1038/s41578-021-00358-0

The authors discuss the physiological barriers and possible administration routes for lipid nanoparticle–mRNA systems and highlight preclinical and clinical studies of lipid nanoparticle–mRNA therapeutics for infectious diseases, cancer and genetic disorders.

 

Immunology

Painter MM, Mathew D, Goel RR, et al. Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination. Immunity 2021, published 12 August. Full text: https://doi.org/10.1016/j.immuni.2021.08.001

The authors compiled 26 measures of antigen-specific immunity across CD4 and CD8 T cells, antibodies, and memory B cells. After vaccination, the immune response was different for SARS-CoV-2 naive and recovered individuals. Naive people benefit from receiving both doses, while recovered people only need one. The universal CD4 response to the first dose (Th1 and Tfh) may be critical to overall immunity by amplifying responses to the second dose.

 

Epidemiology

OHA 20210805. COVID-19 Monthly Report | Oregon’s Weekly Surveillance Summary. Oregon Health Authority 2021, published 5 August. Full text: https://www.oregon.gov/oha/covid19/Documents/DataReports/Breakthrough-Report-08-2021.pdf

In Oregon (US), the beginning of the 4th wave of the pandemic is that it is a wave of the unvaccinated. In July 2021, 81% of 12,514 COVID-19 cases were among unvaccinated people, as were 82% of COVID-19-related deaths. Conclusion: “Although the number of vaccine breakthrough cases is increasing, they are very small when compared to the more than 2.3 million people who have completed their COVID-19 vaccination.”

 

Leatherby L. See How Vaccines Can Make the Difference in Delta Variant’s Impact. The New York Times 2021, published 12 August. Infographic: https://www.nytimes.com/interactive/2021/08/12/science/covid-delta-breakthrough.html

As the number of vaccinated people increases, so will the number of breakthrough cases. This doesn’t mean that our vaccines are ineffective. See this very instructional infographic which modeled Delta-driven COVID outbreaks in two communities, one with a high vaccination rate and another with a low rate. Their levels of serious illness and death were starkly different.

 

15 August

Epidemiology

Rozier G. Guadeloupe. CovidTracker 2021, update 13 August. Web page: https://covidtracker.fr/dashboard-departements/?dep=971

Guadeloupe – and to a lesser extent her sister island Martinique (see Google Maps) – are a telling picture of the Delta variant entering a population where less than 20% had their first COVID-19 vaccine shot. For the week 4-10 August, the cumulative incidence in young adults aged 20 to 29 years was… 4248! For these islands, tourism specialists predict a decline in visitor numbers in the next high season (December 2021 – April 2021).

Copyright: Guillaume Rozier – https://twitter.com/GuillaumeRozier

 

Yong E. How the Pandemic Now Ends. The Atlantic 2021, published 12 August. Full text: https://www.theatlantic.com/health/archive/2021/08/delta-has-changed-pandemic-endgame/619726/

Just one of several excellent quotes, “Here, then, is the current pandemic dilemma: Vaccines remain the best way for individuals to protect themselves, but societies cannot treat vaccines as their only defense. And for now, unvaccinated pockets are still large enough to sustain Delta surges, which can overwhelm hospitals, shut down schools, and create more chances for even worse variants to emerge.”

 

Vaccines

Hall VG, Ferreira VH, Ku T, et al. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. N Engl J Med. 2021 Aug 11. PubMed: https://pubmed.gov/34379917. Full text: https://doi.org/10.1056/NEJMc2111462

A double-blind, randomized, controlled trial of a third-dose booster of the Moderna vaccine in 120 organ-transplant recipients (median time from transplantation to the third dose was 3.16 years). After four months, an anti–receptor-binding domain (RBD) antibody level of at least 100 U per milliliter was present in 33 of 60 patients (55%) in the mRNA-1273 group and in 10 of 57 patients (18%) in the placebo group. The median percent virus neutralization was 71% in the Moderna group and 13% in the placebo group. The trial was not powered to detect differences in clinical outcomes.

 

Pathogenesis

Ziegler CGK, Miao VN, Owings AH, et al. Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19. Cell. 2021 Jul 23:S0092-8674(21)00882-5. PubMed: https://pubmed.gov/34352228. Full text: https://doi.org/10.1016/j.cell.2021.07.023

After single-cell transcriptome sequencing of nasopharyngeal swabs from 58 people, the authors suggests that failed nasal epithelial anti-viral immunity might underlie and precede severe COVID-19.

 

Clinical

Sah P, Fitzpatrick MC, Zimmer CF, et al. Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis. Proc Natl Acad Sci U S A. 2021 Aug 24;118(34):e2109229118. PubMed: https://pubmed.gov/34376550. Full text: https://doi.org/10.1073/pnas.2109229118

Systematic review and meta-analysis of over 350 papers. The authors estimate that more than one-third of infections are truly asymptomatic, with greater asymptomaticity in children (46.7%) compared with the elderly (19.7%), and greater asymptomaticity among people with no underlying medical conditions compared with those with co-morbidities.

 

14 August

Vaccines

Ali K, Berman G, Zhou H, et al. Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents. N Engl J Med. 2021 Aug 11. PubMed: https://pubmed.gov/34379915. Full text: https://doi.org/10.1056/NEJMoa2109522

Nothing truly new: the Moderna vaccine had an acceptable safety profile in adolescents, the immune response was similar to that in young adults, and the vaccine prevented COVID-19. Interestingly, in the placebo group, after the first and second injections, study participants experienced injection-site pain (in 34.8% and 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). It’s fascinating how just the thought of getting a vaccine that might give you headache or fatigue is sufficient to give you… headache fatigue. In this trial, about half of all mild adverse events were probably the product of human imagination.

 

Pegu A, O’Connell S, Schmidt SD, et al. Durability of mRNA-1273-induced antibodies against SARS-CoV-2 variants. Science 2021, published 12 PubMed: https://pubmed.gov/34031659. Full text: https://doi.org/10.1126/science.abj4176

Most individuals vaccinated with the Moderna vaccine maintained binding and functional antibodies against SARS-CoV-2 variants for 6 months, including Alpha, Beta, Gamma, B.1.429, and B.1.526. Neutralizing responses were rare after a single Moderna dose, but at the peak of response to the second dose, all individuals had robust responses to all variants. The study included the results from 8 volunteers in each of three age groups: 18-55, 55-70, and 71+ years of age.

 

Malard F, Gaugler B, Gozlan J, et al. Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies. Blood Cancer J. 11, 142 (2021). https://doi.org/10.1038/s41408-021-00534-z

In patients with hematological malignancies, vaccination with two doses of the BioNTech/Pfizer vaccine translates into a significant increase in humoral response, allowing almost half of the patients to achieve immune protection against COVID-19 (retrospective study, n = 237). The use of B cell targeting treatment within the previous 12 months before vaccination, and a low CD19+ B cell level predicted failure in achieving immune protection.

 

Baraniuk C. Covid-19: How effective are vaccines against the delta variant? BMJ. 2021 Aug 9;374:n1960. PubMed: https://pubmed.gov/34373255. Full text: https://doi.org/10.1136/bmj.n1960

49% of people in the UK who died from infection with the SARS-CoV-2 Delta variant up until 19 July had had two vaccine doses – the author is confident about the protection offered by current vaccines. (He’s probably right!)

 

Clinical

Pavord S, Scully M, Hunt BJ, et al. Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis. N Engl J Med. 2021 Aug 11. PubMed: https://pubmed.gov/34379914. Full text: https://doi.org/10.1056/NEJMoa2109908

The mortality associated with vaccine-induced immune thrombocytopenia and thrombosis (VITT) was highest among patients with a low platelet count and intracranial hemorrhage. A prospective study of 170 definite and 50 probable cases of VITT (UK, 22 March – 6 June 2021). The overall mortality was 22%, but 73% among patients with platelet counts < 30,000 and intracranial hemorrhage.

 

13 August

Vaccines

The bad news: Immunity wanes over time

IMH 20210812. Concentration of data on vaccinated in two doses until 31/1/2021 (discussion from 20.7.2021) [ריכוז נתונים על מחוסנים בשתי מנות עד לתאריך 31/1/2021(דיון מ 20.7.2021)]. Israel Ministry of Health (משרד הבריאות) 2021, last modified 12 August. PDF with slides: https://www.gov.il/BlobFolder/reports/vaccine-efficacy-safety-follow-up-committee/he/files_publications_corona_two-dose-vaccination-data.pdf

Effectiveness of the BioNTech/Pfizer vaccine in Israel by 1) outcome and 2) month vaccinated with second dose (slide 8):

 

The good news: Waning immunity is better than no immunity

Jeffey N. Among older Israelis, serious COVID rate six times as high if unvaccinated. The Times of Israel 2021, published 10 August. Full text: https://www.timesofisrael.com/among-older-israelis-serious-covid-rate-six-times-higher-if-unvaccinated/

In the new epidemic wave in Israel, the number of severe COVID-19 cases is far higher among unvaccinated people, both old and young.

 

 

Van Vinh Chau N, Ngoc NM. Transmission of SARS-CoV-2 Delta Variant Among Vaccinated Healthcare Workers, Vietnam. Lancet Preprints 2021, posted 10 August.

In this study of 62 healthcare workers, breakthrough infections with the Delta variant were associated with high viral loads (251 times higher than in people infected with historical strains), prolonged PCR positivity (8–33 days; median: 21), and low levels of vaccine-induced neutralizing antibodies. The authors conclude that physical distancing measures will be critical to reduce the transmission of the Delta variant.

 

Treatment

Yu LM, Bafadhel M, Dorward J, et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet 2021, published 10 August. Full text: https://doi.org/10.1016/S0140-6736(21)01744-X

Inhaled budesonide, 800 μg twice daily for 14 days, might improve time to recovery and possibly reduce hospital admissions or deaths. In this primary analysis of a randomized trial, time to first self-reported recovery was reduced by almost 3 days with budesonide (11.8 vs 14.7 days). For hospital admissions or deaths, the estimated rate was 6.8% in the budesonide group versus 8.8% in the usual care group. See also comment by Mangin D, Howard M. The use of inhaled corticosteroids in early-stage COVID-19. Lancet 2021, published 10 August. Full text: https://doi.org/10.1016/S0140-6736(21)01809-2

 

Tattersall RS, McGonagle D, Manson JJ. A role for interleukin-1 receptor antagonism in severe COVID-19? Lancet Rheumatol 2021, published 9 August. Full text: https://doi.org/10.1016/S2665-9913(21)00249-6

Dexamethasone and tocilizumab, an interleukin (IL)-6 receptor inhibitor, have an established role in the treatment of hyperinflammatory COVID-19. What about anakinra, a recombinant IL-1 receptor antagonist? The authors discuss a paper that finds that anakinra may not be beneficial above and beyond dexamethasone. One possible exception: patients with evidence of a significant inflammatory response, defined as a C-reactive protein concentration higher than 100 mg/L.

 

Co-morbidities

Klineova S, Harel A, Straus Farber R, et al. Outcomes of COVID-19 infection in multiple sclerosis and related conditions: one-year pandemic experience of the multicenter New York COVID-19 Neuroimmunology Consortium (NYCNIC). Mult Scler Relat Disord. 2021, published 18 July. Full text: https://doi.org/10.1016/j.msard.2021.103153

Anti-CD20 therapies blunt the humoral responses to COVID-19 in patients with multiple sclerosis. Of 474 patients, only 39.5% of patients treated with anti-CD20 therapies were positive for SARS-CoV-2 antibodies.

 

12 August

Vaccines

Puranik A, Lenehan PJ, Silvert E, et al. Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence. medRxiv 2021, posted 9 August. Full text: https://doi.org/10.1101/2021.08.06.21261707

Data from the Mayo Clinic Health System from January to July 2021 find that the mRNA vaccines produced by BioNTech/Pfizer and Moderna are highly effective against SARS-CoV-2 infection (BioNTech/Pfizer: 76%; Moderna: 86%) and COVID-19 associated hospitalization (85% vs. 91.6%). Surprise in July: while vaccine effectiveness against hospitalization remained high (75% vs 81%), effectiveness against infection was lower for both vaccines (42% vs 76%), with a more pronounced reduction for the BioNTech/Pfizer vaccine. To be taken with a grain of salt. (BioNTech/Pfizer vaccine administered earlier than the Moderna vaccine?) Note that this is a pre-print paper that has not yet been reviewed.

 

Hadjadj J, Planas D, Ouedrani A, et al. Immunogenicity of BNT162b2 vaccine Against the Alpha and Delta Variants in Immunocompromised Patients. medRxiv 2021, posted 9 August. Full text: https://doi.org/10.1101/2021.08.08.21261766

Prospective study in 64 patients with systemic inflammatory diseases and 21 controls receiving two doses of the BioNTech/Pfizer vaccine. The Delta variant fully escaped the humoral response of individuals treated with rituximab. See also how they differentially impacted the immunogenicity of the BioNTech/Pfizer vaccine, by impairing B cell (rituximab) and T cell (methotrexate) responses.

 

Epidemiology

Rocklöv J, Liu Y. The reproductive number of the Delta variant of SARS-CoV-2 is far higher compared to the ancestral SARS-CoV-2 virus. J Travel Med 2021, published 9 August. Full text: https://doi.org/10.1093/jtm/taab124

Don’t throw your masks away, even if you are vaccinated. Here, the authors summarize 5 studies that estimate the basic reproductive number for the Delta variant ranging from 3.2 to 8, with a mean of 5.08. This is almost double the R0 of the historical strain which is 2.79. Vaccination alone may not be sufficient until well into 2022.

 

Immunology

Vora SM, Lieberman J, Wu H. Inflammasome activation at the crux of severe COVID-19. Nat Rev Immunol (2021). Full text: https://doi.org/10.1038/s41577-021-00588-x

Obesity, diabetes, heart disease, hypertension and ageing, which may be etiologically linked through overactive inflammasome signaling, are prognostic of poor COVID-19 outcome. The authors discuss potential mechanisms of inflammasome activation and the implications for therapy.

 

Beyond COVID

IPCC 20210810. Sixth Assessment Report, Working Group I. The Intergovernmental Panel on Climate Change 2021, published 9 August. Full text: https://www.ipcc.ch

Infinitely larger than COVID-19. See also the short Nature comment by Tollefson J. IPCC climate report: Earth is warmer than it’s been in 125,000 years. Nature 2021, published 9 August. Full text: https://www.nature.com/articles/d41586-021-02179-1

 

11 August

Vaccines

Moline HL, Whitaker M, Deng L, et al. Effectiveness of COVID-19 Vaccines in Preventing Hospitalization Among Adults Aged ≥65 Years — COVID-NET, 13 States, February–April 2021. MMWR Morb Mortal Wkly Rep. ePub: 6 August 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7032e3

Among adults aged ≥ 65, the effectiveness of full vaccination for preventing hospitalization was 96% for the BioNTech/Pfizer and Moderna vaccines (exception: 91% for the BioNTech/Pfizer vaccine in age ≥ 75 years) and 84% for the Janssen vaccine. Note that these data are from the pre-Delta era.

 

Nirenberg E. Myocarditis and COVID-19 mRNA vaccines. Deplatformdisease.com 2021, published 10 July. https://www.deplatformdisease.com/blog/myocarditis-and-covid-19-mrna-vaccines?format=amp

Not a scientific paper, but worth reading. The author mentions that compared to mRNA vaccine-induced myocarditis, leaving children unprotected or incompletely protected from COVID-19 is currently the bigger risk.

 

Pepe S, Gregory AT, Denniss AR. Myocarditis, Pericarditis and Cardiomyopathy After COVID-19 Vaccination. Heart Lung Circ. 2021 Jul 30:S1443-9506(21)01156-2. PubMed: https://pubmed.gov/34340927. Full text: https://doi.org/10.1016/j.hlc.2021.07.011

Among 2,000,287 individuals receiving at least one dose of vaccine, 20 had vaccine-related myocarditis (1.0/100,000; median age: 36) and 37 had pericarditis (1.8/100,000; median age: 59). Myocarditis occurred a median of 3.5 days after vaccination, pericarditis developed after a median of 20 days. All patients were discharged after a median of 1 to 2 days. No one died.

 

Epidemiology

Wallace-Wells D. Too Many People Are Dying Right Now. “It’s hard to look at these indicators and feel at all optimistic,” explains scientist Eric Topol. Intelligencer 2021, published 8 August. Full text: https://nymag.com/intelligencer/2021/08/too-many-people-are-dying-of-covid-19-right-now.html

There is much uncertainty about how the Delta wave will evolve in the United States. An interview with Eric Topol, director of the Scripps Research Translational Institute.

 

Collateral Effects

Kidman R. Use HIV’s lessons to help children orphaned by COVID-19. Nature 2021, published 9 August. Full text: https://www.nature.com/articles/d41586-021-02155-9

“Young people who have lost parents to the pandemic need urgent support and long-term study to avert the cascade of adversity that can follow. Decades of research into the HIV epidemic provide(s) a solid foundation.”

 

10 August

Vaccines

Boekel L, Steenhuis M, Hooijberg F, et al. Antibody development after COVID-19 vaccination in patients with autoimmune diseases in the Netherlands: a substudy of data from two prospective cohort studies. Lancet Rheumatology 2021, published 6 August. Full text: https://doi.org/10.1016/S2665-9913(21)00222-8

Two prospective studies of 3682 patients with rheumatic diseases, 546 patients with multiple sclerosis, and 1147 healthy controls. Seroconversion after first vaccination was significantly lower in patients than in controls, but after the second vaccination, seroconversion exceeded 80% in all patient treatment subgroups, except among those treated with anti-CD20 therapies (three [43%] of seven patients). We all know the final message: don’t delay the second shot in patients receiving immunosuppressive drugs.

 

Clinical

Chauhan K, Soni D, Sarkar D, et al. Mucormycosis after COVID-19 in a patient with diabetes. Lancet 2021, published 4 August. Full text: https://doi.org/10.1016/S0140-6736(21)01641-X

Ten days after starting a treatment with supplemental oxygen, intravenous antibiotics, and corticosteroids due to a moderately severe pneumonia caused by SARS-CoV-2, this patient presents with a blackish patch—extending from just below his left eye to the left side of his face to the level of his mouth—that had developed 2 days earlier. The authors explain that “COVID-19 followed by mucormycosis carries a very high mortality rate and timely detection, antifungal therapy, and aggressive surgical debridement remain key factors in the management.” See also the video at https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01641-X/fulltext#sec1

 

Co-morbidities

Jassat W, Cohen C, Tempia S, et al. Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study. Lancet HIV 2021, published 4 August. Full text: https://doi.org/10.1016/S2352-3018(21)00151-X

In South Africa, between March 5, 2020, and March 27, 2021, increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio [OR] 1.34), past tuberculosis (OR 1.26), current tuberculosis (OR 1.42) and both past and current tuberculosis (OR 1.48) compared with never tuberculosis (as well as other common COVID-19 risk factors, such as male sex, non-White race, hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years). See also the comment by Madhi SA, Nel J. Epidemiology of severe COVID-19 from South Africa. Lancet HIV 2021, published 4 August. Full text: https://doi.org/10.1016/S2352-3018(21)00183-1

 

Bitan DT, Kridin K, Cohen AD, Weinstein O. COVID-19 hospitalisation, mortality, vaccination, and postvaccination trends among people with schizophrenia in Israel: a longitudinal cohort study. Lancet Psychiatry 2021, published 5 August. Full text: https://doi.org/10.1016/S2215-0366(21)00256-X

A longitudinal cohort study with a year-long estimation of differences in hospitalization and mortality among 25,539 patients with schizophrenia and 25,539 controls. People with schizophrenia showed a higher risk for COVID-19 hospitalization (hazard ratio [HR] 4.81) and mortality (HR 2.52) and showed a sharper decline in survival as time progressed. Diabetes, hypertension, obesity, and ischemic heart disease were significant predictors of vaccination rates among patients with schizophrenia but not among controls. See also the comment by De Picker LJ. Closing COVID-19 mortality, vaccination, and evidence gaps for those with severe mental illness. Lancet Psychiatry 2021, published 5 August. Full text: https://doi.org/10.1016/S2215-0366(21)00291-1

 

Severe COVID

Perkins G, Bronwen CJ, Connolly BA, et al. An adaptive randomized controlled trial of non-invasive respiratory strategies in acute respiratory failure patients with COVID-19. medRxiv 2021, posted 4 August. Full text: https://doi.org/10.1101/2021.08.02.21261379

Over 13 months, 1272 participants were randomized to continuous positive airway pressure (CPAP; n = 380, 29.9%), high-flow nasal oxygenation (HFNO; n = 417, 32.8%) and conventional oxygen therapy (n = 475, 37.3%). Neither CPAP nor HFNO, when compared with conventional oxygen therapy, reduced mortality at any point. In a comment by Elisabeth Mahase (Covid-19: CPAP reduces need for invasive mechanical ventilation in patients requiring oxygen, study finds. BMJ. 2021 Aug 4;374:n1950. PubMed: https://pubmed.gov/34353810. Full text: https://doi.org/10.1136/bmj.n1950), the study’s chief investigator Danny McAuley is cited, saying that “CPAP reduces the pressure on the need for invasive mechanical ventilation and the pressure on intensive care unit beds. HFNO uses a large amount of oxygen and can cause issues with limited oxygen therapy, and we’ve found that it doesn’t really add anything above conventional therapy.”

 

9 August

Collateral Effects

Sansone A, Mollaioli D, Ciocca G, et al. “Mask up to keep it up”: Preliminary evidence of the association between erectile dysfunction and COVID-19. Andrology. 2021 Jul;9(4):1053-1059. PubMed: https://pubmed.gov/33742540. Full text: https://onlinelibrary.wiley.com/doi/10.1111/andr.13003 | See also the informal discussion at https://theconversation.com/covid-19-could-cause-male-infertility-and-sexual-dysfunction-but-vaccines-do-not-164139

Erectile dysfunction (ED) could be a short‐ or long‐term complication of COVID‐19. In this analysis of 100 people (25 COVID‐positive and 75 COVID‐negative), the prevalence of ED was significantly higher in the COVID+ group (28% vs. 9.33%; p = 0.027).

 

Vaccines

Cavanaugh AM, Spicer KB, Thoroughman D, Glick C, Winter K. Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination — Kentucky, May–June 2021. MMWR Morb Mortal Wkly Rep. ePub: 6 August 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7032e1

The immunological response elicited by vaccines might be better than the response elicited by natural SARS-CoV-2 infection. In Kentucky residents infected by COVID in 2020, those who were not vaccinated had a 2.34 times higher risk of reinfection than those who were fully vaccinated.

 

Perry RJ, Tamborska A, Bhagteshwar S, et al. Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study. Lancet 2021, published 6 August. Full text: https://doi.org/10.1016/S0140-6736(21)01608-1

An analysis of 95 patients from more than 40 hospitals across the UK. Seventy patients had vaccine-induced immune thrombotic thrombocytopenia (VITT) and 25 did not. Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed than non-VITT patients; they also more frequently had extracranial thrombosis. Death or dependency occurred in 47% of patients with VITT-associated cerebral venous thrombosis. Non-heparin anticoagulants and immunoglobulin treatment might improve VITT outcome.

 

Callaway E. COVID vaccine boosters: the most important questions. Nature 2021, published 5 August. Full text: https://www.nature.com/articles/d41586-021-02158-6

“Concerns over waning immunity and SARS-CoV-2 variants have convinced some countries to deploy extra vaccine doses — but it’s not clear to scientists whether most people need them.”

 

Immunology

Ortega N, Ribes M, Vidal M, et al. Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses. Nat Commun 12, 4740 (2021). https://doi.org/10.1038/s41467-021-24979-9

Many studies have reported a lack of protection from infection with human coronaviruses causing common cold (HCoVs). The authors don’t agree. They analyzed data from a cohort of 578 health care workers followed up to 7 months and found that IgG and IgA to HCoV were significantly higher in asymptomatic than symptomatic SARS-CoV-2 seropositive individuals.

 

8 August

Vaccines

Public Health England 202100806. SARS-CoV-2 variants of concern and variants under investigation in England | Technical briefing 20. UK Government 2021, 6 August. https://www.gov.uk/government/publications/investigation-of-novel-sars-cov-2-variant-variant-of-concern-20201201 | PDF: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1009243/Technical_Briefing_20.pdf

Again, for Delta variant infections, the viral load cycle threshold (Ct) is described as being similar for unvaccinated individuals (17.8) and those with a full vaccination schedule (18.0). The authors conclude that “similar Ct values (…) suggest limited difference in infectiousness.” Note that there is still the possibility that vaccinated people shed the virus for a shorter period of time. Vaccination may also reduce an individual’s overall risk of becoming infected. In any case, vaccination should be expected to reduce SARS-CoV-2 transmission, even of the Delta variant. Interesting discussions ahead.

 

Liu X, Shaw RH, Stuart ASV, et al. Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Lancet 2021, published 6 August. Full text: https://doi.org/10.1016/S0140-6736(21)01694-9

BioNTech/Pfizer vs AstraZeneca ­– the first immunogenicity comparison of heterologous vaccine schedules. After measuring the SARS-CoV-2 anti-spike IgG concentrations (measured by ELISA) at 28 days after the vaccine boost, the authors find the following values for homologs and heterologs schedules (BNT: BioNTech/Pfizer; AZ: AstraZeneca):

BNT/BNT: 14,080 ELU/mL

AZ/BNT: 12,906 ELU/mL

BNT/AZ: 7133 ELU/mL

AZ/AZ: 1392 ELU/mL

 

Bok K, Sitar S, Graham BS, Mascola JR. Accelerated COVID-19 vaccine development: milestones, lessons, and prospects. Immunity. 2021 Aug 3:S1074-7613(21)00303-4. PubMed: https://pubmed.gov/34348117. Full text: https://doi.org/10.1016/j.immuni.2021.07.017

SARS-CoV-2 vaccines have been developed and approved in time frames never before seen, a feat that bodes well for future advancements in medicine, not only in infectious diseases. The authors review the milestones, methods and outcomes of this effort and provide a perspective for how partnership and preparedness can be better utilized in response to future public-health pandemic emergencies.

 

Transmission

Chen PZ, Koopmans M, Fisman DN, Gu FX. Understanding why superspreading drives the COVID-19 pandemic but not the H1N1 pandemic. Lancet Infect Dis 2021, published 2 August. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00406-0/fulltext

With SARS-CoV-2, fewer cases cause the majority of infections, and a greater proportion of infections tend to be linked to large clusters via superspreading events. Why is this phenomenon, called over-dispersion in transmissibility (k), a characteristic of the SARS-CoV-2 pandemic, not part of the 2009 influenza H1N1 pandemic? The authors discuss which virological factors mediate k.

 

Pediatrics

Molteni E, Sudre CH, Canas LS, et al. Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. Lancet Child Adolesc Health 2021, published 3 August. https://doi.org/10.1016/S2352-4642(21)00198-X

In this study of more than 1700 children age 5-17 that analyzed data reported by an adult proxy via a mobile application, 62% of children suffered from headaches and 55% from exhaustion. Among the younger children (5 to 11 years old), fever (44%), sore throat (36%) and stomach pain (28%) were also common. Among the older children, other symptoms included sore throat (51%), anosmia (48%), fever (35%) and persistent cough (26%). Younger and older children were sick for a median of five and seven days, respectively. 4.4% of the children had symptoms for at least 28 days; this was more commonly in older than younger children (5.1% and 3.1%, respectively).

 

7 August

Vaccines

Israel A, Merzon E, Schäffer AA, et al. Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort. medRxiv 2021, posted 5 August. Full text: https://doi.org/10.1101/2021.08.03.21261496

A retrospective study from Israel describing 33,993 fully vaccinated adults tried to answer one of the bigger questions these days: is the amount of time since the second injection of the BioNTech/Pfizer vaccine significantly associated with a risk of post-vaccination COVID-19 infection? Yes, it is. Those who received their second dose of vaccine at least 146 days before a new RT-PCR test (Group 1) had a higher risk of infection that those who received their vaccine less than 146 days before (Group 2). The absolute numbers are somewhat less scary: among people older than 60, 182/7021 (2.6%) tested positive in Group 1 and 19/2164 (0.9%) in Group 2.

 

Elliott P, Haw D, Wang H, et al. REACT-1 round 13 final report: exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant in England during May to July 2021. Imperial College London 2021, published 4 August. https://spiral.imperial.ac.uk/handle/10044/1/90800

First, the good news: fully vaccinated people have lower viral loads (median Ct: 27.6) than unvaccinated or partially vaccinated people (23.1), so vaccines are likely to decrease the potential for the transmission of the Delta variant. Now, the bad news: between 24 June and 12 July 2021, with the Delta variant already firmly established in the UK, 44% of infections occurred in fully vaccinated individuals. The authors estimate vaccine effectiveness against infection to be 49%. Sex, ethnicity, household size and local levels of economy also jointly contributed to the risk of higher prevalence. The authors anticipate that increased mixing during the autumn in the presence of the Delta variant may lead to a new wave of the pandemic, even at high levels of vaccination. [Note that men had higher odds of infection than women, a finding not seen in a previous analysis (20 May and 7 June). The reason? Increased social mixing during England’s progression in the Euro 2020 football competition during June and July 2021…]

 

Clinical

Hakimian S, Raines D, Reed G, et al. Assessment of Video Capsule Endoscopy in the Management of Acute Gastrointestinal Bleeding During the COVID-19 Pandemic. JAMA Netw Open. 2021 Jul 1;4(7):e2118796. PubMed: https://pubmed.gov/34328500. Full text: https://doi.org/10.1001/jamanetworkopen.2021.18796

The authors suggest that “video capsule endoscopy can serve as a safe alternative to the standard endoscopic evaluation of gastrointestinal bleeding because it reduces the number of invasive procedures, personnel involved, and use of personal protective equipment.”

 

Co-morbidities

Corey L, Beyrer C, Cohen MS, Michael NL, Bedford T, Rolland M. SARS-CoV-2 Variants in Patients with Immunosuppression. N Engl J Med. 2021 Aug 5;385(6):562-566. PubMed: https://pubmed.gov/34347959. Full text: https://doi.org/10.1056/NEJMsb2104756

Is viral evolution in immunocompromised patients an important factor in the emergence of SARS-CoV-2 variants of concern? Read this nice summary of our current knowledge.

 

Treatment

O’Brien MP, Forleo-Neto E, Musser BJ, et al. Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19. N Engl J Med. 2021 Aug 4. PubMed: https://pubmed.gov/34347950. Full text: https://doi.org/10.1056/NEJMoa2109682

Normally, articles published in the New England Journal of Medicine provide relevant and important information for the improvement of medical care. This one might fail to reach that benchmark. You would need to treat 753 people to prevent 48 household infections with SARS-CoV-2. That is, 16 people treated to prevent one infection. Disappointingly, apart from the ‘duration of symptoms’, this study doesn’t present any clinical data on the 70 people who got infected. The combination of vaccines and – later on – cheap antiviral drugs will help combat the COVID-19 pandemic, monoclonal antibodies won’t.

 

6 August

Vaccines

Zhang H, Liu Y, Liu D, et al. Time of day influences immune response to an inactivated vaccine against SARS-CoV-2. Cell Res. 2021 Aug 2. PubMed: https://pubmed.gov/34341489. Full text: https://doi.org/10.1038/s41422-021-00541-6

Should you better go early in the morning to get your vaccine shot? The authors analyzed 63 health care workers who received the inactivated BBIBP-CorV vaccine (Sinopharm) either between 9 and 11 o’clock in the morning or between 3 and 5 o’clock in the afternoon. Strikingly, participants vaccinated in the morning showed significantly higher level of NAbs in the sera, 34.70 vs 19.35. Early birds also had stronger B cell and Tfh responses. Interesting path to follow.

 

Keeton R, Richardson SI, Moyo-Gwete T, et al. Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner. medRxiv 2021, posted 28 July. Full text: https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1

Therefore, vaccination with the J&J vaccine following previous infection, even > 6 months previously, may result in substantially enhanced protection against COVID-19. The authors conclude that this finding may be of particular relevance in settings of high SARS-CoV-2 seroprevalence.

 

Emanuel EJ, Skorton DJ. Mandating COVID-19 Vaccination for Health Care Workers. Ann Intern Med. 2021 Jul 30. PubMed: https://pubmed.gov/34328365. Full text: https://doi.org/10.7326/M21-3150

The Delta variant is paving the way for mandating COVID-19 vaccination, not only for health care workers.

 

Variants

Kimura I, Kosugi Y, Wu J, et al. SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance. bioRxiv 2021, posted 28 July. Full-text: https://doi.org/10.1101/2021.07.28.454085

More about the Lambda variant (also known as the C.37 lineage which is now spreading in South American countries such as Peru, Chile, Argentina, and Ecuador).
The authors describe three mutations or variants, the RSYLTPGD246-253N, L452Q and F490S mutations, which respectively confer resistance to vaccine-induced antiviral immunity. Additionally, the T76I and L452Q mutations contribute to enhanced viral infectivity.

 

Clinical

Vousden N, Ramakrishnan R, Bunch K, et al. Impact of SARS-CoV-2 variant on the severity of maternal infection and perinatal outcomes: Data from the UK Obstetric Surveillance System national cohort. medRxiv 2021, posted 25 July. Full text: https://doi.org/10.1101/2021.07.22.21261000

In this prospective cohort study on 3371 hospitalized pregnant women with symptoms of confirmed SARS-CoV-2, the proportion of pregnant women with moderate to severe COVID has increased with each successive appearance of new variants: 24% during the ‘wild-type period’ (1st March to 30th November 2020); 36% during the ‘Alpha period’ (1 December 2020 to 15 May 2021); and 45% during the ‘Delta period’ (16 May to 11 July 2021).

 

Treatment

REMAP-CAP, et al. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med 2021, published 4 July. Full text: https://doi.org/10.1056/NEJMoa2103417

No benefit for critically ill patients with COVID-19 from routine therapeutic-dose anticoagulation with unfractionated or low-molecular-weight heparin. See also the comment by ten Cate H. Surviving Covid-19 with Heparin? N Engl J Med 2021, published 4 July. Full text: https://doi.org/10.1056/NEJMe2111151

 

5 August

Vaccines

Hause AM, Gee J, Baggs J, et al. COVID-19 Vaccine Safety in Adolescents Aged 12–17 Years — United States, December 14, 2020–July 16, 2021. MMWR Morb Mortal Wkly Rep. ePub: 30 July 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7031e1

As of July 16, 2021, almost 9 million US adolescents aged 12–17 years had received the BioNTech/Pfizer vaccine. The Vaccine Adverse Event Reporting System (VAERS) received 9246 reports, 90.7% of which were for non-serious adverse events while 9.3% were for serious adverse events, including around 400 cases of myocarditis (4.3%; about 1:25,000 vaccinees; see also https://www.cdc.gov/mmwr/volumes/70/wr/mm7027e2.htm). Systemic reactions were more common after the second dose.

 

Pinto D, Sauer MM, Czudnochowski N, et al. Broad betacoronavirus neutralization by a stem helix–specific human antibody. Science 2021, 3 August. Full text: https://science.sciencemag.org/content/early/2021/08/03/science.abj3321

On our way to a universal betacoronavirus vaccine? The authors describe 5 monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple β coronavirus spike glycoproteins isolated from COVID-19 convalescent individuals.

 

Immunology

Hasenkrug KJ, Feldmann F, Myers L, et al. Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques. mBio. 2021 Jul 27:e0150321. PubMed: https://pubmed.gov/34311582. Full text: https://doi.org/10.1128/mBio.01503-21

What is the role of T cells in protection against SARS-CoV-2 reinfection? The authors inoculated macaques and rechallenged them 6 weeks later. Their conclusion: T cells might not be critical for recovery from acute SARS-CoV-2 infections while B cell responses and antibodies could be the essential mediators of protection from re-exposure. The discussion about the importance of T cells continues.

 

Virology

Mendonça L, Howe A, Gilchrist JB, et al. Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress. Nat Commun 12, 4629 (2021). https://doi.org/10.1038/s41467-021-24887-y

The authors report a multi-modal, multi-scale cryo-correlative platform to image SARS-CoV-2 infection in Vero cells, describing viral RNA transport portals, virus assembly intermediates, viral egress pathway, and native virus spike structures, in the context of whole cell volumes revealing drastic cytopathic changes.

 

Pathogenesis

Xydakis MS, Albers MW, Holbrook EH, et al. Post-viral effects of COVID-19 in the olfactory system and their implications. Lancet Neurol. 2021 Jul 30:S1474-4422(21)00182-4. PubMed: https://pubmed.gov/34339626. Full text: https://doi.org/10.1016/S1474-4422(21)00182-4

Why do we lose our smell with COVID-19? And what might be the consequences? The authors postulate that, “in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term.” See also the comment by Doty RL. The mechanisms of smell loss after SARS-CoV-2 infection. Lancet Neurol. 2021 Jul 30:S1474-4422(21)00202-7. PubMed: https://pubmed.gov/34339627. Full text: https://doi.org/10.1016/S1474-4422(21)00202-7

 

4 August

Vaccines

Chia PY, Ong S, Chiew CJ, et al. Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study. medRxiv 2021, posted 31 July. Full text: https://doi.org/10.1101/2021.07.28.21261295

Singapore, 218 patients admitted to hospital with Delta (B.1.617.2) SARS-CoV-2 infection. Vaccination (mostly with the BioNTech/Pfizer or Moderna vaccines) was associated with a faster decline in RNA viral load. The odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07, p = 0.001). PCR cycle threshold (Ct) values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals.

 

Parry H, McIlroy G, Bruton R, et al. Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia. Blood Cancer J. 11, 136 (2021). https://doi.org/10.1038/s41408-021-00528-x

In 267 patients with B cell chronic lymphocytic leukemia (CLL), one dose of vaccine generated detectable spike-specific antibody responses in 34% of patients with CLL compared to 94% of healthy donors. After the second dose of vaccine, antibody responses increased to 75% (n = 55), but titers remained lower than in controls. Current treatment with Bruton’s tyrosine kinase (BTK) inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine.

 

Medeiros-Ribeiro AC, Aikawa NE, Saad CGS, et al. Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial. Nat Med (2021). https://doi.org/10.1038/s41591-021-01469-5

In 910 adults with autoimmune rheumatic diseases (ARD) vaccinated with the Chinese CoronaVac vaccine, all had lower IgG seroconversion rates, and lower neutralizing antibody titers were lower than in 182 age- and sex-matched healthy adults.

 

Immunology

Muecksch F, Weisblum Y, Barnes CO, et al. Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations. Immunity. 2021 Jul 29:S1074-7613(21)00294-6. PubMed: https://pubmed.gov/34331873. Full text: https://doi.org/10.1016/j.immuni.2021.07.008

The authors suggest that “increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses.”

 

Pathogenesis

Chen KG, Park K, Spence JR. Studying SARS-CoV-2 infectivity and therapeutic responses with complex organoids. Nat Cell Biol (2021). https://doi.org/10.1038/s41556-021-00721-x

A review of the roles of complex organoids in the study of SARS-CoV-2 infection, modeling of COVID-19 disease pathology and of drug, antibody and vaccine development. The authors anticipate valuable lessons for the study of other viral diseases as well.

 

3 August

Vaccines

DREES 20210729. Entrées hospitalières et décès de patients Covid-19 selon le statut vaccinal et la présence de la mutation L452R. DREES 2021 (Direction de la recherche, des études, de l’évaluation et des statistiques), published 29 July. Full text : https://solidarites-sante.gouv.fr/IMG/pdf/2021-07-23_-_sivic-sidep-vacsi_premiers_resultats_-_drees-2.pdf

In France, between 31 May and 11 July 2021, unvaccinated people represented around 85% of COVID-19 patients hospitalized, both in ICU units and non-ICU units. Fully vaccinated patients made up only 7% of admissions.

 

Merrill ED, Kashem SW, Amerson EH, et al. Association of Facial Pustular Neutrophilic Eruption With Messenger RNA-1273 SARS-CoV-2 Vaccine. JAMA Dermatol. 2021 Jul 28. PubMed: https://pubmed.gov/34319363. Full text: https://doi.org/10.1001/jamadermatol.2021.2474

The authors report a facial eruption that developed within 24 hours after receiving the Moderna vaccine in 2 patients without a history of known allergies, rosacea, facial/dental fillers, or prior SARS-CoV-2 infection.

 

Transmission

Sikkens JJ, Buis DTP, Peters EJG, et al. Serologic Surveillance and Phylogenetic Analysis of SARS-CoV-2 Infection Among Hospital Health Care Workers. JAMA Netw Open. 2021 Jul 1;4(7):e2118554. PubMed: https://pubmed.gov/34319354. Full text: https://doi.org/10.1001/jamanetworkopen.2021.18554

In this cohort study of 801 hospital health care workers (HCWs), the risk of getting infected with SARS-CoV-2 was nearly 4-fold higher among HCWs on COVID-19 wards compared with HCWs not in patient care. There was no evidence for patient-to-HCW transmission but several occurrences of HCW-to-HCW transmission.

 

Diagnosis

Schuit E, Veldhuijzen IK, Venekamp RP, et al. Diagnostic accuracy of rapid antigen tests in asymptomatic and presymptomatic close contacts of individuals with confirmed SARS-CoV-2 infection: cross sectional study. BMJ. 2021 Jul 27;374:n1676. PubMed: https://pubmed.gov/34315770. Full-text: https://doi.org/10.1136/bmj.n1676

The sensitivities of the Veritor and Biosensor lateral flow rapid antigen tests in asymptomatic and pre-symptomatic close contacts tested on day 5 onwards after close contact with an index case were more than 85% after a viral load cut-off was applied as a proxy for infectiousness.

 

Treatment

Abbasi J. Überantibodies From Recovered COVID-19 Patients Could Spur New Therapeutics and Vaccines. JAMA. 2021 Jul 28. PubMed: https://pubmed.gov/34319350. Full text: https://doi.org/10.1001/jama.2021.12915

A comment on the Wang paper that described antibodies with sub-nanomolar neutralization titers: Wang L, Zhou T, Zhang Y. Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Science 01 Jul 2021: eabh1766. https://science.sciencemag.org/content/early/2021/06/30/science.abh1766

 

2 August

Vaccines

Corbett KS, Nason MC, Flach B, et al. Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates. Science 2021, published 29 July. PubMed: https://pubmed.gov/33907752. Full text: https://science.sciencemag.org/content/early/2021/07/29/science.abj0299

In Rhesus macaques, viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following a SARS-CoV-2 challenge in vaccinated animals and strongly correlated with levels of anti-S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway.

 

Fallah M. Remember Ebola: stop mass death in Africa. Nature. 2021 Jul;595(7869):627. PubMed: https://pubmed.gov/34316054. Full text: https://doi.org/10.1038/d41586-021-01964-2

“Rich countries are hoarding vaccines, allowing doses to expire while unvaccinated people who want to be immunized die.”

 

Clinical

Araujo-Silva CA, Marcos AAA, Marinho PM, et al. Presumed SARS-CoV-2 Viral Particles in the Human Retina of Patients With COVID-19. JAMA Ophthalmol. 2021 Jul 29. PubMed: https://pubmed.gov/34323931. Full text: https://doi.org/10.1001/jamaophthalmol.2021.2795

Post-mortem analysis of enucleated eyes of three patients with confirmed COVID-19 infection revealed presumed S and N COVID-19 proteins within endothelial cells close to the capillary flame and cells of the inner and the outer nuclear layers. This finding may explain some of the infection’s ocular clinical manifestations.

 

Treatment

Butler CC, Yu LM, Dorward J, et al. Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet Resp Med 2021, published 27 July. Full text: https://doi.org/10.1016/S2213-2600(21)00310-6

Don’t use doxycycline as a routine treatment for COVID-19! In patients with suspected COVID-19 who were at high risk of adverse outcomes, treatment with doxycycline was not associated with clinically meaningful reductions in time to recovery, hospital admissions or deaths related to COVID-19.

 

Collateral Effects

Burki K. Tobacco industry capitalises on the COVID-19 pandemic. Lancet Resp Med 2021, published 29 July. Full text: https://doi.org/10.1016/S2213-2600(21)00361-1

“Ever since the tobacco industry started marketing its products, it has attempted to hitch them to key trends and events. Adverts during World War One associated tobacco with victory. The industry would subsequently deploy the rhetoric of the suffragette movement with the “torches of freedom” campaign. Virginia Slims introduced the tagline “you’ve come a long way, baby” in the late 1960s, playing on the feminist themes of the era. “Today, we see the industry paying influencers on social media to push e-cigarettes, which they claim are harmless and cool, when in fact the whole point is to get a new generation addicted to nicotine. (…) As soon as COVID-19 arrived, they recognized the opportunity that the pandemic presented.”

 

1 August

Vaccines

Krantz MS, Kwah JH, Stone CA Jr, et al. Safety Evaluation of the Second Dose of Messenger RNA COVID-19 Vaccines in Patients With Immediate Reactions to the First Dose. JAMA Intern Med. 2021 Jul 26. PubMed: https://pubmed.gov/34309623. Full text: https://doi.org/10.1001/jamainternmed.2021.3779

All 159 patients with an immediate allergic reaction to the first dose of the Pfizer/BioNTech or Moderna vaccine, including 19 individuals with first-dose anaphylaxis, tolerated the second dose. (Antihistamine pre-medication had been given to 47 patients [30%] before the second dose). Thirty-two patients (20%) reported immediate and potentially allergic symptoms that were associated with the second dose that were self-limiting, mild, and/or resolved with antihistamines alone.

 

Stampfer SD, Goldwater MS, Jew S, et al. Response to mRNA vaccination for COVID-19 among patients with multiple myeloma. Leukemia (2021). Full text: https://doi.org/10.1038/s41375-021-01354-7

Study of 103 multiple myeloma (MM) patients (96 patients with active MM and 7 with smoldering (asymptomatic) disease). Smoldering MM patients responded better than those with active disease. Only 45% of active MM patients developed an adequate response, while 22% had a partial response. Lower spike antibody levels were associated with older age, impaired renal function, low lymphocyte counts, reduced uninvolved immunoglobulin levels, > second line of treatment, and among those not in complete remission.

 

Pathogenesis

Cohen CA, Li APY, Hachim A, et al. SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection. Nat Commun 12, 4678 (2021). Full text: https://doi.org/10.1038/s41467-021-24938-4

Could a reduced prior β coronavirus immunity and reduced T cell activation in children drive a milder COVID-19 pathogenesis? The authors found that infected children have lower CD4+ and CD8+ T cell responses to SARS-CoV-2 structural and ORF1ab proteins compared to infected adults.

 

Prevention

Schooley RT. Introduction to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) Supplement, Clinical Infectious Diseases, Volume 73, Issue Supplement_2, 1 August 2021, Page S119, https://doi.org/10.1093/cid/ciab524

Eight manuscripts about the scientific underpinning of non-biological interventions. Among other topics: 1) the importance of aerosols and pre-symptomatic shedding; 2) the impact of distancing and masking on preventing ongoing viral transmission; 3) initial overestimation of the role of fomites and of droplets in viral transmission.

 

Chowell G, Dahal S, Bono R, et al. Harnessing testing strategies and public health measures to avert COVID-19 outbreaks during ocean cruises. Sci Rep 11, 15482 (2021). Full text: https://doi.org/10.1038/s41598-021-95032-4

A cruise ship is not a good place to be during a pandemic of a respiratory pathogen. This study finds that PCR testing at embarkation and daily testing of all individuals aboard, together with increased social distancing, might be able to reduce the probability of onboard COVID-19 community spread. At the personal level, there might be an even more promising strategy: avoid cruise ships until the pandemic is under control.

 

 


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By Christian Hoffmann &
Bernd S. Kamps


By Christian Hoffmann &
Bernd S. Kamps

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