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By Christian Hoffmann &
Bernd S. Kamps

 

31 July

Transmission

Brown CM, Vostok J, Johnson H, et al. Outbreak of SARS-CoV-2 Infections, Including COVID-19 Vaccine Breakthrough Infections, Associated with Large Public Gatherings — Barnstable County, Massachusetts, July 2021. MMWR Morb Mortal Wkly Rep. ePub: 30 July 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7031e2

Bad news from Barnstable County, Massachusetts. In July 2021, following multiple summer events and large public gatherings, 469 COVID-19 cases were identified among Massachusetts residents who had traveled to the town during July 3–17. Intriguingly, 346 (74%) occurred in fully vaccinated persons. Even more intriguingly: cycle threshold values were similar among specimens from patients who were fully vaccinated and those who were not. The driving force behind the outbreak: the Delta variant.

 

Vaccines

Wu S, Huang J, Zhang Z, et al. Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults: preliminary report of an open-label and randomised phase 1 clinical trial. Lancet Resp Med 2021, published 26 July. Full text: https://doi.org/10.1016/S1473-3099(21)00396-0

Two doses of an aerosolized adenovirus type-5 vector-based COVID-19 vaccine – equivalent to a fifth or two-fifths of an intramuscular dose – were well-tolerated and did not produce serious side effects in healthy adults. They elicited strong IgG and neutralizing antibody responses similar to one dose of an intramuscular injection.

 

Bhuyan P, Medin J, Gomes da Silva H. Very rare thrombosis with thrombocytopenia after second AZD1222 dose: a global safety database analysis. Lancet 2021, published 27 July. Full text: https://doi.org/10.1016/S0140-6736(21)01693-7

Vaccine-induced immune thrombotic thrombocytopenia (VITT or TTS) seems to be rare after the second dose of the AstraZeneca vaccine. A short description of 13 cases: 8 individuals with pulmonary embolism, co-occurring with cerebral venous sinus thrombosis (CVST) in two individuals; one individual with CVST occurring alone; one individual with deep vein thrombosis; one individual with thrombotic stroke; and two individuals with unspecified embolisms.

 

Clinical

Katsoularis I, Fonseca-Rodríguez O, Farrington P. Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet 2021, published 29 July.

86,742 patients with COVID-19 and 348,481 matched controls. The authors find that COVID-19 is a risk factor for acute myocardial infarction and ischemic stroke and that both conditions are part of the clinical picture of COVID-19. See also a commentary by Mafham M, Baigent C. What is the association of COVID-19 with heart attacks and strokes? Lancet 2021, published 29 July. Full text: https://doi.org/10.1016/S0140-6736(21)01071-0

 

Long COVID

Crook H, Raza S, Nowell J, Young M, Edison P. Long covid-mechanisms, risk factors, and management. BMJ. 2021 Jul 26;374:n1648. PubMed: https://pubmed.gov/34312178. Full-text: https://doi.org/10.1136/bmj.n1648

The day after COVID-19: fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, etc. A state-of-the-art review of long COVID, discussing risk factors and possible therapeutic options.

 

Alwan NA. The road to addressing Long Covid. Science 2021, published 30 July. Full text: https://doi.org/10.1126/science.abg7113

“The road to properly addressing Long Covid is long and must be traveled with humility, open mindedness, compassion, and scientific rigor.”

 

Treatment

Tummino TA, Rezelj VV, Fischer B, et al. Phospholipidosis is a shared mechanism underlying the in vitro antiviral activity of many repurposed drugs against SARS-CoV-2. Science, 2021, published 30 July. PubMed: https://pubmed.gov/33791693. Full-text: https://science.sciencemag.org/content/373/6554/541

Why repurposing drugs for COVID-19 has drawn so much attention… and yielded so few results. See also the comment by Edwards A, Hartung IV. No shortcuts to SARS-CoV-2 antivirals. Science 2021, published 30 July. Full text: https://doi.org/ 10.1126/science.abj9488

 

30 July

Vaccines

Bergwerk M, Gonen T, Lustig Y, et al. Covid-19 Breakthrough Infections in Vaccinated Health Care Workers. N Engl J Med. 2021 Jul 28. PubMed: https://pubmed.gov/34320281. Full-text: https://doi.org/10.1056/NEJMoa2109072

Long COVID after breakthrough infections? Most breakthrough infections during the 4-month period after the second vaccine dose (39/1497, 0.4%) were mild or asymptomatic; however, 7 patients (19%) had persistent symptoms (> 6 weeks), including headaches, muscle pain, loss of taste and smell and fatigue), indicating that Long COVID may occur among people who experience breakthrough infections. Note that the study is from the pre-Delta world (20 January through 28 April; 85% of the samples yielded the Alpha strain [B.1.1.7]). Expect the data to be less favorable in settings where Delta (B.1.617.2) is the dominant strain. It may be wise to follow the new CDC guidelines and wear masks indoors in risky situations (see the next paragraph, “Prevention”).

 

Thomas SJ, Moreira ED, Kitchin N, et al. Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. medRxiv 2021, posted 28 July. Full text: https://www.medrxiv.org/content/10.1101/2021.07.28.21261159v1

Six-month efficacy data from the Pfizer/BioNTech vaccine trial: 1) Efficacy declining from 96% at 2 months to 85% at 4-6 months for infection, for an average decline of ~6% every two months; 2) Protection against severe illness was 97% through at least 6 months.

 

Prevention

CDC 20210727. When You’ve Been Fully Vaccinated | How to Protect Yourself and Others. CDC 2021, published 27 July. Full text: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html

Delta is changing the rules of the game. The new CDC mask-wearing guidelines for the smarter part of the population: “To maximize protection from the Delta variant and prevent possibly spreading it to others, wear a mask indoors in public if you are in an area of substantial or high transmission.”

 

Virology

Scudellari M. How the coronavirus infects cells — and why Delta is so dangerous. Nature 2021, published 28 July. Full text: https://www.nature.com/articles/d41586-021-02039-y

Wendy Barclay, Imperial College London: “Two coronavirus variants, Alpha and Delta, have altered furin cleavage sites. In the Alpha variant, the initial proline amino acid is changed to a histidine (P681H); in the Delta variant, it is changed to an arginine (P681R). Both changes make the sequence less acidic, and the more basic the string of amino acids, the more effectively furin recognizes and cuts it.”

 

Treatment

Guimarães PO, Quirk D, Furtado RH, et al. Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021 Jul 29;385(5):406-415. PubMed: https://pubmed.gov/34133856. Full-text: https://doi.org/10.1056/NEJMoa2101643

Now in NEJM’s print edition. Our previous comment on the online publication (16 June): tofacitinib (Wikipedia) is an orally administered selective inhibitor of Janus kinase (Jak), that blocks intracellular transduction pathways after a cytokine is bound to its receptor (as a consequence, no cellular response is triggered, and cytokine production is indirectly suppressed). Among patients hospitalized with COVID-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than did placebo. The cumulative incidence of death or respiratory failure was 18.1% versus 29.0% in the placebo group (risk ratio, 0.63; 95% CI: 0.41 to 0.97; p = 0.04).

 

29 July

Vaccines

Stumpf J, Siepmann T, Lindner T, et al. Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine. Lancet Regional Health Europe 2021, published 22 July. Full text: https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(21)00155-1/fulltext

A prospective study exploring the eight-week time course of specific cellular or/and humoral immune responses after two doses of vaccine. Seroconversion efficacy in dialysis patients was similar to medical personnel (> 95%), but markedly impaired in 368 kidney transplant recipients (42%).

 

Ikegame S, Siddiquey M, Hung CT, et al. Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants. Res Sq. 2021. PubMed: https://pubmed.gov/33851150. Full-text: https://www.nature.com/articles/s41467-021-24909-9

In Argentina, sera from Sputnik vaccine recipients had a median 6.1-fold and 2.8-fold reduction in GMT against B.1.351 and the E484K mutant spike, respectively. “When extrapolated to full serum strength, half of the sera samples failed to achieve an IC₈₀ and only 1 out 12 achieved an IC₉₀ against B.1.351.” The authors conclude that “control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.”

 

Epidemiology

Bindman P. Who has been hit hardest by the UK’s third wave of Covid-19? New Statesman 2021, published 21 July. Full text: https://www.newstatesman.com/politics/health/2021/07/who-has-been-hit-hardest-uk-s-third-wave-covid-19

How the UK’s vaccine roll-out has thus far reduced the number of COVID-19 deaths. What about the coming weeks?

 

Transmission

Schrock JM, Ryan DT, Saber R, et al. Cohabitation With a Known Coronavirus Disease 2019 Case Is Associated With Greater Antibody Concentration and Symptom Severity in a Community-Based Sample of Seropositive Adults. Open Forum Infectious Diseases, Volume 8, Issue 7, 24 July 2021. Full text: https://doi.org/10.1093/ofid/ofab244

The authors find that those who lived with a known COVID-19 case exhibited greater symptom severity compared to those who did not live with a known COVID-19 case. Does the duration of viral exposure explain this relation between household exposure and symptom severity?

 

Prevention

Haelle T. Scientists urge local mask mandates as Delta sweeps the U.S. National Geographic 2021, published 23 July. Full text: https://www.nationalgeographic.com/science/article/scientists-urge-local-mask-mandates-as-delta-sweeps-the-us

Courtesy of the highly transmissible Delta variant, wearing masks in public indoor places will be part of the 2021 Autumn Fashion Collection. Be ready for it.

 

28 July

Vaccines

Paetzold J, Krammer F, van Laer D, et al. The effects of rapid mass vaccination against SARS-CoV-2 and its Variants-of-Concern: Evidence from an early VoCs hotspot. Research Square 2021, posted 24 July. Full text: https://doi.org/10.21203/rs.3.rs-741944/v1

Following a large outbreak of the Beta (B.1.351, “South Africa”) and Alpha variants (B.1.1.7/E484K, “England”) in the district of Schwaz, Austria, more than 70% of the adult population of the district received their first Pfizer/BioNTech vaccine dose within 6 days (11 and 16 March). Result: a 60% reduction in new SARS-CoV-2 infections relative to people residing just outside of the vaccinated district.

 

Lund FE, Randall TD. Scent of a vaccine. Science 2021, published 23 July. Full text: https://science.sciencemag.org/content/373/6553/397

About the advantages of intranasal vaccines: needle-free administration, on-site delivery and mucosal immunity.

 

Transmission

Else H, Baker N. Coronapod: the latest on COVID and sporting events. Nature 2021, published 24 July. Listen at https://www.nature.com/articles/d41586-021-02053-0

“Early in 2021 the United Kingdom, along with several other countries, allowed mass gatherings as part of a series of controlled studies aimed at better understanding the role events could play in the pandemic. The goal was to inform policy – however early results have provided limited data on viral transmission.” But, there were a lot of parties!

 

Bjorkman KK, Saldi TK, Lasda E, et al. Higher viral load drives infrequent SARS-CoV-2 transmission between asymptomatic residence hall roommates. J Infect Dis. 2021 Jul 24:jiab386. PubMed: https://pubmed.gov/34302469. Full-text: https://doi.org/10.1093/infdis/jiab386

Individuals who likely transmitted SARS-CoV-2 had an average viral load ~6.5-fold higher than individuals who did not (mean C_q 26.2 vs 28.9). Longitudinal data of 6408 students and 116 likely transmission events in which a second roommate tested positive within 14 days of the index roommate.

 

Immunology

Fischer DS, Ansari M, Wagner KI, et al. Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’. Nat Commun 12, 4515 (2021). Full text: https://doi.org/10.1038/s41467-021-24730-4

The authors show barcoding through natural T cell receptor sequences can be used to identify SARS-CoV-2 antigen-reactive T cells after differential stimulation with and without antigen, followed by single-cell RNA sequencing.

 

27 July

Vaccines

Arunachalam PS, Scott MKD, Hagan T, et al. Systems vaccinology of the BNT162b2 mRNA vaccine in humans. Nature. 2021 Jul 12. PubMed: https://pubmed.gov/34252919. Full-text: https://doi.org/10.1038/s41586-021-03791-x

Booster injections of mRNA vaccines might stimulate a “strikingly enhanced innate immune response” compared to the primary injection.

 

Pathogenesis

Chen S, Yang L, Nilsson-Payant B, et al. SARS-CoV-2 Infected Cardiomyocytes Recruit Monocytes by Secreting CCL2. Res Sq. 2020 Nov 17:rs.3.rs-94634. PubMed: https://pubmed.gov/33236003. Full-text: https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00378-7

The study provides evidence that SARS-CoV-2 infects cardiomyocytes in vivo and suggests a mechanism of immune-cell infiltration and histopathology in heart tissues of COVID-19 patients.

 

Clinical

Public Health England 20210723. SARS-CoV-2 variants of concern and variants under investigation in England | Technical briefing 19. Public Health England 2021, published 23 July. Full text: https://www.gov.uk/government/publications/investigation-of-novel-sars-cov-2-variant-variant-of-concern-20201201

The risk of reinfection with the Delta variant may be 1.46 times higher than with the Alpha variant. Interestingly, the risk of reinfection was not elevated if the primary infection was < 180 days, but was higher for those with a prior infection ≥ 180 days earlier (adjusted odds ratio = 2.37).

 

Co-morbidities

Recalde M, Pistillo A, Fernandez-Bertolin S, et al. Body mass index and risk of COVID-19 diagnosis, hospitalisation, and death: a cohort study of 2 524 926 Catalans. J Clin Endocrinol Metab. 2021 Jul 23:dgab546. PubMed: https://pubmed.gov/34297116. Full-text: https://doi.org/10.1210/clinem/dgab546

In this study from Spain, a body mass index (BMI) of 31kg/m² was associated with a higher risk for diagnosis (hazard ratio, 1.22) and hospitalization (1.88) compared to people with a BMI of 22kg/m². There was also a more pronounced increasing risk of death for BMIs ≥ 40kg/m². The increase in risk for COVID-19 outcomes was particularly pronounced among younger patients.

 

Beyond COVID

Tunyasuvunakool K, Adler J, Wu Z, et al. Highly accurate protein structure prediction for the human proteome. Nature. 2021 Jul 22. PubMed: https://pubmed.gov/34293799. Full-text: https://doi.org/10.1038/s41586-021-03828-1

Baek M, DiMaio F, Anishchenko I, et al. Accurate prediction of protein structures and interactions using a three-track neural network. Science. 2021 Jul 15:eabj8754. PubMed: https://pubmed.gov/34282049. Full-text: https://doi.org/10.1126/science.abj8754

Artificial intelligence programs can determine the three-dimensional structure of human proteins from amino acid sequences. Importantly, the authors of the first paper above are making their predictions freely available to the community via a public database (hosted by the European Bioinformatics Institute at https://alphafold.ebi.ac.uk/). A major advance in life sciences! See also Service RF. New public database of AI-predicted protein structures could transform biology. Science 2021, published 22 July. Full text: https://www.sciencemag.org/news/2021/07/new-public-database-ai-predicted-protein-structures-could-transform-biology

 

26 July

Vaccines

Massa F, Cremoni M. Safety and Cross-Variant Immunogenicity of a Three-Dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant Recipients. Lancet Preprints 2021, posted 22 July. Full text: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3890865

Important study from Nice, France. In kidney transplant recipients (n = 61), a three-dose BioNTech/Pfizer vaccine regimen led to an increase in spike-specific IgG levels, neutralizing activity and number of IFN-γ-secreting cells. However, neutralizing antibody titers remained low even after three doses, especially against new variants. The authors recommend continuation of barrier measures and vaccination of relatives.

 

Benotmane I, Gautier G, Perrin P, et al. Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serologic Response to 2 Doses. JAMA. 2021 Jul 23. PubMed: https://pubmed.gov/34297036. Full-text: https://doi.org/10.1001/jama.2021.12339

Same message as above, now from Strasbourg, France. In kidney transplant recipients (n = 159), a third dose of the Moderna vaccine induced a serologic response in 49% of patients who did not respond after 2 doses. Patients taking tacrolimus, mycophenolate, and steroids were less likely to develop anti–SARS-CoV-2 antibodies than those treated with other regimens (35% vs 63%).

 

Robinson KA, Maimone S, Gococo-Benore DA, Li Z, Advani PP, Chumsri S. Incidence of Axillary Adenopathy in Breast Imaging After COVID-19 Vaccination. JAMA Oncol. 2021 Jul 22. PubMed: https://pubmed.gov/34292295. Full-text: https://doi.org/10.1001/jamaoncol.2021.3127

In this retrospective analysis (n = 750), 23 (3%) patients had axillary adenopathy on mammography. This incidence is higher than axillary adenopathy in otherwise normal mammography (0.02% – 0.04%). The incidence of adenopathy decreased over time with no adenopathy seen in patients who received the vaccine more than 28 days previously. When possible, consider scheduling screening breast imaging 4 to 6 weeks after the second COVID-19 vaccination dose (National Comprehensive Cancer Network, 15 June 2021, Recommendations of the NCCN COVID-19 Vaccination Advisory: https://www.nccn.org/docs/default-source/covid-19/2021_covid-19_vaccination_guidance_v3-0.pdf

 

Co-morbidities

Clift AK, Saatci D, Coupland CAC, et al. Sickle Cell Disorders and Severe COVID-19 Outcomes: A Cohort Study. Ann Intern Med 2021, published 20 July. Full text: https://www.acpjournals.org/doi/10.7326/M21-1375

In this cohort, sickle cell disease was associated with a 4-fold increased risk for COVID-19–related hospitalization and a 2.6-fold increased risk for COVID-19–related death.

 

Collateral Effects

Bernstein AN, Talwar R, Handorf E, et al. Assessment of Prostate Cancer Treatment Among Black and White Patients During the COVID-19 Pandemic. JAMA Oncol. 2021 Jul 22. PubMed: https://pubmed.gov/34292311. Full-text: https://doi.org/10.1001/jamaoncol.2021.2755

During the initial phase of the pandemic only 1% of Black men underwent prostatectomy for untreated nonmetastatic prostate cancer, while 26% of White patients did. Before the pandemic, there was no difference in the rate of prostatectomy between the 2 races. Read also the comment by Vince R Jr. The Intersection of Societal Inequalities and Health Care: Lessons Learned From the COVID-19 Pandemic. JAMA Oncol. 2021 Jul 22. PubMed: https://pubmed.gov/34292296. Full-text: https://doi.org/10.1001/jamaoncol.2021.2750

 

25 July

Vaccines

Mateo-Urdiales A, Spila Alegiani S, Fabiani M, et al. Risk of SARS-CoV-2 infection and subsequent hospital admission and death at different time intervals since first dose of COVID-19 vaccine administration, Italy, 27 December 2020 to mid-April 2021. Euro Surveill. 2021 Jun;26(25):2100507. PubMed: https://pubmed.gov/34169819. Full-text: https://doi.org/10.2807/1560-7917.ES.2021.26.25.2100507

A report on 7,370,008 persons who had received their first dose of vaccine by 4 April 2021 in Italy. As in earlier studies from Israel, a partial protection can be seen as early as two weeks after the first dose.

 

Mazagatos C, Monge S, Olmedo C, et al. Effectiveness of mRNA COVID-19 vaccines in preventing SARS-CoV-2 infections and COVID-19 hospitalisations and deaths in elderly long-term care facility residents, Spain, weeks 53 2020 to 13 2021. Euro Surveill. 2021 Jun;26(24):2100452. PubMed: https://pubmed.gov/34142647. Full-text: https://doi.org/10.2807/1560-7917.ES.2021.26.24.2100452

The same message from a group of elderly residents (aged 65 years and older) in long-term care facilities: partial vaccine effectiveness (VE) of 50% with the first dose of the BioNTech/Pfizer and the Moderna vaccine. After the second dose, VE was 71% against SARS-CoV-2 infection, 88% and 97% against COVID-19 hospitalizations and deaths, respectively.

 

DiPiazza AT, Leist SR, Abiona OM, et al. COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge. Immunity. 2021 Jul 2:S1074-7613(21)00262-4. PubMed: https://pubmed.gov/34270939. Full-text: https://doi.org/10.1016/j.immuni.2021.06.018

The title is the message: vaccination with the Moderna vaccine (mRNA-1273) does not result in disease enhancement following infection with SARS-CoV-2.

 

Virology

Hoffmann M, Pöhlmann S. How SARS-CoV-2 makes the cut. Nat Microbiol. 2021 Jul;6(7):828-829. PubMed: https://pubmed.gov/34194035. Full-text: https://doi.org/10.1038/s41564-021-00931-x

What allows the virus to evade innate antiviral defenses and what is required for transmission? Markus Hoffmann and Stefan Pöhlmann discuss the paper by Peacock TP, Goldhill DH, Zhou J, et al. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat Microbiol. 2021 Jul;6(7):899-909. PubMed: https://pubmed.gov/33907312. Full-text: https://doi.org/10.1038/s41564-021-00908-w

 

Transmission

Else H. COVID and mass sport events: early studies yield limited insights. Nature 2021, published 22 July. Full text: https://www.nature.com/articles/d41586-021-02016-5

Is it safe to attend large gatherings? Maybe not yet.

 

Collateral Effects

Olsen SJ, Winn AK, Budd AP, et al. Changes in Influenza and Other Respiratory Virus Activity During the COVID-19 Pandemic – United States, 2020-2021. MMWR Morb Mortal Wkly Rep. 2021 Jul 23;70(29):1013-1019. PubMed: https://pubmed.gov/34292924. Full-text: https://doi.org/10.15585/mmwr.mm7029a1

Common human coronaviruses, parainfluenza viruses, and respiratory adenoviruses, etc. on the rise again. “Clinicians should be aware of increased circulation, sometimes off-season, of some respiratory viruses and consider multipathogen testing.”

 

24 July

Vaccines

Wei J, Stoesser N, Matthews PC, et al. Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom. Nat Microbiol. 2021 Jul 21. PubMed: https://pubmed.gov/34290390. Full-text: https://doi.org/10.1038/s41564-021-00947-3

In this UK cohort of 45,965 adults, seroconversion rates and antibody levels after a single vaccine dose were lower in older individuals, especially in those aged > 60 years. Low responders were more common among people taking immunosuppressants or corticosteroids, as well as in patients with rheumatoid arthritis, chronic liver disease, cancer, type 2 diabetes, obesity, and asthma.

 

Epidemiology

Ito K, Piantham C, Nishiura H. Predicted dominance of variant Delta of SARS-CoV-2 before Tokyo Olympic Games, Japan, July 2021. Euro Surveill. 2021 Jul;26(27):2100570. PubMed: https://pubmed.gov/34240695. Full-text: https://doi.org/10.2807/1560-7917.ES.2021.26.27.2100570

In many countries, the Delta variant (B.1.671.2) has already replaced other variants. The authors show that in Japan, the replacement is likely to happen mostly before the start of the Tokyo Olympic Games on 23 July 2021. A substantial number of international visitors might be exposed and help spread the Delta variant around the world.

 

Virology

Rapeport G, Smith E, Gilbert A, Catchpole A, McShane H, Chiu C. SARS-CoV-2 Human Challenge Studies – Establishing the Model during an Evolving Pandemic. N Engl J Med. 2021 Jul 21. PubMed: https://pubmed.gov/34289273. Full-text: https://doi.org/10.1056/NEJMp2106970

Can a SARS-CoV-2 human challenge research program be developed as part of the pandemic response? The authors report about the justification for such research and the management and minimization of risks.

 

Diagnostics

Kahre E, Galow L, Unrath M, et alKinetics and seroprevalence of SARS-CoV-2 antibodies: a comparison of 3 different assays. Sci Rep 11, 14893 (2021). Full text: https://doi.org/10.1038/s41598-021-94453-5

The differences in SARS-CoV-2 antibody kinetics can be astonishing. In this study, seropositivity at baseline differed significantly depended on the assay used (Diasorin 81%, Euroimmun 83%, Abbott 59%). At follow-up there was a significant loss in seropositivity in the Euroimmun and Abbott assays. Only the antibody levels detected in the Diasorin assay were stable.

 

Clinical

Kosiborod M, Berwanger O, Koch GG, et al. Effects of dapagliflozin on prevention of major clinical events and recovery in patients with respiratory failure because of COVID-19: Design and rationale for the DARE-19 study. Diabetes Obes Metab. 2021 Apr;23(4):886-896. PubMed: https://pubmed.gov/33319454. Full-text: https://doi.org/10.1111/dom.14296

“In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin (a SGLT2 inhibitor) did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated.” Or …was well-tolerated but did not result in risk reduction in organ dysfunction or death, or improvement in clinical recovery.

 

23 July

Vaccines

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 Jul 21. PubMed: https://pubmed.gov/34289274. Full-text: https://doi.org/10.1056/NEJMoa2108891

Effectiveness after one dose of the BioNTech/Pfizer or AstraZeneca was lower among individuals infected with the Delta variant (B.1.671.2, “India”) than with the Alpha variant (B.1.1.7, “England”): Delta, 30.7% – Alpha, 48.7% (there was no difference between the two vaccines). After two doses, differences in vaccine effectiveness with the two variants were modest, but the BioNTech/Pfizer vaccine was superior to the AstraZeneca vaccine (BioNTech/Pfizer: Delta, 88.0% – Alpha, 93.7%; AstraZeneca: Delta, 67.0%; Alpha, 74.5%).

 

Transmission

Chu VT, Yousaf AR, Chang K, et al. Household Transmission of SARS-CoV-2 from Children and Adolescents. N Engl J Med. 2021 Jul 21. PubMed: https://pubmed.gov/34289272. Full-text: https://doi.org/10.1056/NEJMc2031915

SARS-CoV-2-infected children coming back from an overnight camp – transmission occurred in 18% of households (35/194); in these households, the secondary attack rate was 45%. The risk of household infection was lower among contacts who had practiced physical distancing (adjusted odds ratio, 0.4). Conclusion: “When feasible, children and adolescents with a known exposure to SARS-CoV-2 or a diagnosis of COVID-19 should remain at home and maintain physical distance from household members.”

 

Immunology

Tortorici MA, Czudnochowski N, Starr TN, et al. Broad sarbecovirus neutralization by a human monoclonal antibody. Nature. 2021 Jul 19. PubMed: https://pubmed.gov/34280951. Full-text: https://doi.org/10.1038/s41586-021-03817-4

A new human monoclonal antibody, designated S2X259, recognized a highly conserved cryptic receptor-binding domain epitope, broadly neutralizing B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.427/B.1.429 and a wide spectrum of human and potentially zoonotic sarbecoviruses. Syrian hamsters were protected against challenge with the historical SARS-CoV-2 strain and the B.1.351 (Beta). The authors suggest that their antibody could be a promising candidate for the prevention and treatment of emergent variants and zoonotic infections.

 

Clinical

García-Azorín D, Sierra Á, Trigo J, et al. Frequency and phenotype of headache in covid-19: a study of 2194 patients. Sci Rep. 2021 Jul 19;11(1):14674. PubMed: https://pubmed.gov/34282206. Full-text: https://doi.org/10.1038/s41598-021-94220-6

Headache may be the presenting symptom of COVID-19. In this study, median headache onset was within 24 h, with a median duration of 7 days. In 13% of patients, the headache persisted after 1 month. Most patients described a bilateral headache with frontal predominance, an oppressive quality, and severe intensity.

 

Collateral Effects

Hillis SD, Unwin HJT, Chen Y, et al. Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study. Lancet 2021, published 20 July. Full text: https://doi.org/10.1016/S0140-6736(21)01253-8

From March 1, 2020, to April 30, 2021, more than one million children lost at least one parent or custodial grandparent.

See also the comment by Kentor RA, Thompson AL. Answering the call to support youth orphaned by COVID-19. Lancet 2021, published 20 July. Full text: Lancet 2021, published 20 July. Full text: https://doi.org/10.1016/S0140-6736(21)01253-8

 

22 July

Vaccines

Ledford H. Should children get COVID vaccines? What the science says. Nature 2021, published 20 July. Full text: https://www.nature.com/articles/d41586-021-01898-9

Vaccinating children. Is it necessary? Is it safe? And how will it affect the pandemic?

 

Mateus J, Dan JM, Zhang Z, et al. Low dose mRNA-1273 COVID-19 vaccine generates durable T cell memory and antibodies enhanced by pre-existing crossreactive T cell memory. medRxiv 2021, posted 5 July. Full text: https://doi.org/10.1101/2021.06.30.21259787

At 25 µg (instead of the four-fold higher 100 µg standard dose), the Moderna vaccine mRNA-1273 vaccine induced a durable and functional T cell and antibody response comparable to natural infection. If these preliminary findings are confirmed, the lower dose could accelerate the global immunization campaign (and perhaps help with side effects?).

 

Virology

Nicastro F, Sironi G, Antonello E, et al. Solar UV-B/A radiation is highly effective in inactivating SARS-CoV-2. Sci Rep 11, 14805 (2021). Full text: https://doi.org/10.1038/s41598-021-94417-9

In temperate regions of the Earth, summer solar radiation at noon is sufficient to inactivate 63% of virions in open-space concentrations in less than 2 min. The authors suggest implementing strategies of confinement during spring/summer months and fully implementing them during low solar irradiation periods.

 

Diagnostics

Ceci A, Muñoz-Ballester C, Tegge AN, et al. Development and implementation of a scalable and versatile test for COVID-19 diagnostics in rural communities. Nat Commun 12, 4400 (2021). Full text: https://doi.org/10.1038/s41467-021-24552-4

The authors show that an academic laboratory can supplement COVID-19 testing needs and help local health departments assess and manage outbreaks.

 

Treatment

Drayman N, DeMarco JK, Jones KA, et al. Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2. Science 2021, published 20 July. Full text: https://doi.org/10.1126/science.abg5827

Masitinib is an orally bioavailable tyrosine kinase inhibitor used in the treatment of canine mast cell tumors. After screening a library of 1900 drugs, the authors show that the drug is a competitive inhibitor of 3Clpro, the SARS-CoV-2 main protease. In vitro, masitinib was effective against the Alfa, Beta and Gamma variants (B.1.1.7, B.1.351, P.1). Mice infected with SARS-CoV-2 and then with masitinib showed a > 200-fold reduction in viral titers in the lungs and nose.

 

21 July

Vaccines

Lucas C, Vogels CBF, Yildirim I, et al. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity in uninfected and previously infected individuals. medRxiv 2021, posted 18 July. Full text: https://www.medrxiv.org/content/10.1101/2021.07.14.21260307v1

Analysis of plasma neutralization using 16 SARS-CoV-2 variants. The Beta (B.1.351, ‘South Africa’) and Gamma (P.1, ‘Brazil’) strains, showed the greatest reduction, followed by the Delta (B.1.617.2, ‘India’) and Alfa (B.1.1.7, ‘England’) strains. Plasma from previously infected vaccinated individuals had a better neutralization than plasma from uninfected vaccinated individuals.

 

Brosh-Nissimov T, Orenbuch-Harroch E, Chowers M, et al. BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully-vaccinated hospitalized COVID-19 patients in Israel. Clin Microbiol Infect. 2021 Jul 7:S1198-743X(21)00367-0. PubMed: https://pubmed.gov/34245907. Full-text: https://doi.org/10.1016/j.cmi.2021.06.036

Retrospective study of 152 individuals who developed COVID-19 more than 7 days after the second BioNTech/Pfizer vaccine dose and required hospitalization. High rate of existing co-morbidities: hypertension (71%), diabetes (48%), congestive heart failure (27%), lung diseases (24%), chronic kidney (24%), dementia (19%) and cancer (24%). Importantly, 60 (40%) patients were immunocompromised. Thirty-four (22%) patients died.

 

Butt AA, Omer SB, Yan P, Shaikh OS, Mayr FB. SARS-CoV-2 Vaccine Effectiveness in a High-Risk National Population in a Real-World Setting. Ann Intern Med 2021, published 20 July. Full text: https://doi.org/10.7326/M21-1577

In this large US veteran cohort (> 108,000), the overall vaccine effectiveness was 97% seven or more days after the second dose of the mRNA vaccine.

 

Transmission

Llibre JM, Videla S, Clotet B, Revollo B. Screening for SARS-CoV-2 Antigen Before a Live Indoor Music Concert: An Observational Study. Ann Intern Med 2021, published 20 July. Full text: https://doi.org/10.7326/M21-2278

Indoor mass-gathering events always have the potential to be super-spreading events. Here, the authors describe the potential of antigen-detecting rapid diagnostic tests (Ag-RDTs) to create safe environments (“same day rapid antigen tests, use of face masks, improved ventilation). More such experiences are needed to provide safe guidelines.

 

Coleman KK, Tay DJW, Tan KS, et al. Viral Load of SARS-CoV-2 in Respiratory Aerosols Emitted by COVID-19 Patients while Breathing, Talking, and Singing. medRxiv 2021, posted 19 July. Full text: https://doi.org/10.1101/2021.07.15.21260561

In this study, fine aerosols (≤ 5μm) produced by talking and singing contained more SARS-CoV-2 copies than coarse aerosols. “The largest proportion of SARS-CoV-2 RNA copies was emitted by singing (53%), followed by talking (41%) and breathing (6%).”

 

20 July

Vaccines

Lim WW, Mak L, Leung GM, Cowling BJ, Peiris M. Comparative immunogenicity of mRNA and inactivated vaccines against COVID-19. Lancet Microbe 2021, published 15 July. Full text: https://doi.org/10.1016/S2666-5247(21)00177-4

Preliminary data from a study by Malik Peiris et al., one of the central figures of the 2002/2003 SARS-CoV-1 epidemic. Health-care workers in Hong Kong who received the BioNTech-Pfizer vaccine (n = 63) had higher antibody concentrations and higher PRNT₅₀ (plaque reduction neutralization test) titers than those who received the Sinovac vaccine (n = 30). The authors conclude that “the difference in concentrations of neutralizing antibodies identified in our study could translate into substantial differences in vaccine effectiveness”.

 

Epidemiology

Guimarães RM, Portela MC, Villela DAM, Matta GC, de Freitas CM. Younger Brazilians hit by COVID-19 – What are the implications? Lancet Regional Health 2021, published 14 July. Full text: https://doi.org/10.1016/j.lana.2021.100014

New variants and incomplete vaccination will lead to increasing numbers of young and middle-aged adults in intensive care units. In the months ahead, how far will the “youthening of the pandemic” go? In Brazil, among patients who died from COVID-19, the median age has dropped 13 years since the beginning of 2021.

 

Transmission

Li B, Deng A, Li K, et al. Viral infection and transmission in a large well-traced outbreak caused by the Delta SARS-CoV-2 variant. medRxiv 2021, posted 12 July. Full-text: https://doi.org/10.1101/2021.07.07.21260122

Explaining the forces behind the Delta wave: 1) 1000 times higher viral load and 2) a reduced serial interval, 4 days instead of 6 (the serial interval is defined as the duration of time between a primary case patient having symptom onset and a secondary case patient having symptom onset).

 

Dougherty K, Mannell M, Naqvi O, Matson D, Stone J. SARS-CoV-2 B.1.617.2 (Delta) Variant COVID-19 Outbreak Associated with a Gymnastics Facility – Oklahoma, April-May 2021. MMWR Morb Mortal Wkly Rep. 2021 Jul 16;70(28):1004-1007. PubMed: https://pubmed.gov/34264910. Full-text: https://doi.org/10.15585/mmwr.mm7028e2

In the coming months, avoid gyms. The Delta variant (B.1.617.2, first identified in India) is frighteningly transmissible (see article above) and will lead to increased attack rates, especially in households and in indoor sports settings. In this report, the attack rates at the gymnastics facility and in households were 20% and 53%, respectively.

 

Collateral Effects

Causey K, Fullman N, Sorensen RJD, et al. Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: a modelling study. Lancet 2021, published 14 July. Full text: https://doi.org/10.1016/S0140-6736(21)01337-4

In 2020, tens of millions of children missed DTP3, the third-dose of the diphtheria-tetanus-pertussis vaccine, and MCV1, the first-dose of a measles-containing vaccine.

See also the comment by Abbas K, Mogasale V. Disruptions to childhood immunisation due to the COVID-19 pandemic. Lancet 2021, published 14 July. Full text: https://doi.org/10.1016/S0140-6736(21)01418-5

 

19 July

Diagnostics

Said M, Davis P, Davis P, et al. A Rapid Olfactory Test as a Potential Screening Tool for COVID-19. JAMA Otolaryngol Head Neck Surg July 15, 2021. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2782044?resultClick=1

In this pilot study, a novel olfactory test alone had a sensitivity of 75% and specificity of 95.2% in detecting COVID-19 using PCR testing as the gold standard.

 

Clinical

Drake TM, Riad AM, Fairfield CJ, et al. ^Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study. Lancet July 17, 2021. Volume 398, ISSUE 10296, P223-237, July 17, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00799-6/fulltext

Hospitalization with COVID-19 is associated with high rates of morbidity in adults. In this large prospective cohort study, almost half of the survivors had one or more complications. Rates were high even in young, previously healthy individuals. Acute complications were associated with reduced ability to self-care at discharge, with neurological complications being associated with the worst functional outcomes.

 

Yoshikawa Y, Kawachi I. Association of Socioeconomic Characteristics With Disparities in COVID-19 Outcomes in Japan. JAMA Netw Open July 14. 2021;4(7):e2117060. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781935?resultClick=1

Disparities in COVID-19 outcomes are not unique to the US and Europe: in this cross-sectional study of the 47 prefectures in Japan, a higher burden of COVID-19 cases and deaths was observed in prefectures with lower household incomes; a higher proportion of the population receiving public assistance; a higher unemployment rate; higher numbers of retail, transportation and postal, and restaurant industry workers; more household crowding; and higher smoking and obesity rates.

 

Treatment

Ohl ME, Miller DR, Lund BC, et al. Association of Remdesivir Treatment With Survival and Length of Hospital Stay Among US Veterans Hospitalized With COVID-19. JAMA Netw Open July 15, 2021, 4(7):e2114741. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781959?resultClick=1

In this cohort study of 2344 US veterans hospitalized with COVID-19, remdesivir therapy was not associated with improved 30-day survival but was associated with a significant increase in median time to hospital discharge.

 

Oldenburg CE, Pinsky BA, Brogdon J, et al. Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection – A Randomized Clinical Trial. JAMA July 16, 2021. doi:10.1001/jama.2021.11517

In this randomized trial that included 263 outpatients with SARS-CoV-2 infection, treatment with a single oral dose of azithromycin, 1.2 g, vs placebo resulted in self-reported absence of COVID-19 symptoms at day 14 in 50% vs 50%.

 

Pediatrics

Bogunovic D, Merad M. Children and SARS-CoV-2. Cell Host Microbe July 14, 2021, Volume 29, ISSUE 7, P1040-1042. https://www.cell.com/action/showPdf?pii=S1931-3128%2821%2900297-3

Dusan Bogunovic and Miriam Merad discuss clinical and biological features of SARS-CoV-2 in children and reflect on currently identified (and unknown) immune features.

 

18 July

Vaccine

Barouch DH, Stephenson KE, Sadoff J, et al. Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination. NEJM July 14, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2108829?query=featured_home

This small study indicates that the Ad26.COV2.S vaccine (J&J) elicited durable humoral and cellular immune responses with minimal decreases for at least 8 months. Moreover, there was an expansion of neutralizing antibody breadth associated with improved coverage of SARS-CoV-2 variants over time, including increased neutralizing antibody titers against Delta.

 

Variants

Ferreira I, Kemp S, Datir R, et al. SARS-CoV-2 B.1.617 mutations L452 and E484Q are not synergistic for antibody evasion. J Infect Dis July 14, 2021, jiab368. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab368/6321359

Spike bearing L452R and E484Q (as seen in Delta) confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies. The effect is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone.

 

Immunology

Cohen KW, Linderman SL, Moodie Z, et al. Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells. Cell Rep Med July 14, 2021. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00203-2

Broad and effective immunity may persist long-term in recovered COVID-19 patients. In 254 COVID-19 patients who were followed longitudinally for up to 8 months, neutralizing antibodies showed a bi-phasic decay with half-lives > 200 days. Durable polyfunctional CD4 and CD8 T cells recognized distinct viral epitope regions.

Diagnostics

Nguyen D, Simmonds P, Steenhuis M, et al. SARS-CoV-2 neutralising antibody testing in Europe: towards harmonisation of neutralising antibody titres for better use of convalescent plasma and comparability of trial data. Euro Surveill. 2021;26(27):pii=2100568. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.27.2100568

Substantial heterogeneity in neutralizing antibody testing used to determine antibody content in convalescent plasma donations across Europe. Although the authors observed almost 100-fold differences in raw neutralizing antibody titers between the participating laboratories, these readings could largely be harmonized by adopting the NIBSC international standard.

Clinical

Bennett TD, Moffitt RA, Hajagos JG, et al. Clinical Characterization and Prediction of Clinical Severity of SARS-CoV-2 Infection Among US Adults Using Data From the US National COVID Cohort Collaborative. JAMA Netw Open Jul 13, 2021;4(7):e2116901. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781923?resultClick=1

In this cohort study of 174,568 adults with SARS-CoV-2, 32,472 (18.6%) were hospitalized and 6565 (20.2%) got severely ill, and first-day machine learning models accurately predicted clinical severity. Mortality decreased from 16.4% in March to April 2020 to 8.6% in September to October 2020. In a separate multivariate logistic regression model built for inference, age (odds ratio, 1.03 per year), male sex (OR, 1.60), liver disease (OR, 1.20), dementia (OR, 1.26), African-American (OR, 1.12) and Asian (OR, 1.33) race, and obesity (OR, 1.36) were independently associated with higher clinical severity.

Collateral Damage

Causey K, Fullman N, Sorensen RJ, et al. Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: a modelling study. Lancet July 14, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01337-4/fulltext

Routine immunization services faced stark challenges in 2020, with the COVID-19 pandemic causing the most widespread and largest global disruption in recent history. Although the latest coverage trajectories point towards recovery in some regions, a combination of lagging catch-up immunization services, continued SARS-CoV-2 transmission, and persistent gaps in vaccine coverage before the pandemic still left millions of children under-vaccinated or unvaccinated against preventable diseases at the end of 2020, and these gaps are likely to extend throughout 2021.

 

17 July

Epidemiology

Kimihito I, Chayada P, NHiroshi N. Predicted dominance of variant Delta of SARS-CoV-2 before Tokyo Olympic Games, Japan, July 2021. Euro Surveill. 2021;26(27):pii=2100570. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.27.2100570

It is just a matter of time for the Delta variant to replace other variants in Japan. This study shows that the replacement is likely to happen mostly before the start of the Tokyo Olympic Games on 23 July 2021.

 

Vaccine

Normark J, Vikström L, Gwon YD, et al. Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination. NEJM July 14, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2110716?query=featured_home

This relatively small cohort suggests that the mRNA-1273 vaccine (MODERNA) boost may provide better protection against the B.1.351 variant than a ChAdOx1 nCoV-19 boost. However, the mRNA-1273 boost led to more frequent reports of fever, headache, chills, and muscle aches than the ChAdOx1 nCoV-19 boost.

 

Powell AA, Power L, Westrop S, et al. Real-world data shows increased reactogenicity in adults after heterologous compared to homologous prime-boost COVID-19 vaccination, March−June 2021, England. Euro Surveill. 2021;26(28):pii=2100634. https://doi.org/10.2807/1560-7917.ES.2021.26.28.2100634

Same direction. After the second vaccine dose, previously uninfected adults in both heterologous vaccination groups had significantly higher reactogenicity than their homologous counterparts, with similar rates among those receiving ChAd/BNT (54.4%) and BNT/ChAd (55.2%) compared with ChAd/ChAd (33.5%) or BNT/BNT (33.3%). Severe reactogenicity was 2.4 times (27.8% vs. 11.6%) more likely with heterologous regimens, including increased requirement for medical attention. These findings were irrespective of the reason for receiving a heterologous schedule.

 

Variants

Williams SV, Vusirikala A, Ladhani SN, et al. An outbreak caused by the SARS-CoV-2 Delta (B.1.617.2) variant in a care home after partial vaccination with a single dose of the COVID-19 vaccine Vaxzevria, London, England, April 2021. Euro Surveill. 2021;26(27):pii=2100626. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.27.2100626

The Delta attack rate after the first dose of Astra Zeneca’s vaccine was 35.7% (5/14) for staff and 81.3% (13/16) for residents, indicating lower protection in people who had received only one dose of the Vaxzevria vaccine within 3 months. Reassuringly, though, hospitalisation was uncommon and there were no deaths, providing some evidence that a single dose of vaccine may be protective against severe disease following infection with the Delta variant.

 

Clinical

Williamson EJ, McDonald HI, Bhaskaran K, et al. Risks of covid-19 hospital admission and death for people with learning disability: population based cohort study using the OpenSAFELY platform. BMJ July 14, 2021; 374. https://www.bmj.com/content/374/bmj.n1592

This large population-based cohort study from England indicates that people with learning disability have markedly increased risks of hospital admission and death from covid-19, over and above the risks observed for non-covid causes of death. Down’s syndrome and cerebral palsy were associated with increased hazards for both events; Down’s syndrome to a greater extent.

 

Long COVID-19

Radtke T, Ulyte A, Puhan MA, et al. Long-term Symptoms After SARS-CoV-2 Infection in Children and Adolescents. JAMA July 15, 2021. https://jamanetwork.com/journals/jama/fullarticle/2782164?resultClick=1

Best study title. “Ciao Corona” is a longitudinal cohort study investigating SARS-CoV-2 seroprevalence in 55 randomly selected schools in the canton of Zurich in Switzerland. Prevalence of symptoms compatible with long COVID was low. Between October and November 2020 and March and April 2021, 4 of 109 seropositive children (4%) versus 28 of 1246 seronegative ones (2%) reported at least 1 symptom lasting beyond 12 weeks.

 

16 July

Vaccine

Rossi AH, Ojeda DS, Varese A, et al. Sputnik V Vaccine Elicits Seroconversion and Neutralizing Capacity to SARS CoV-2 after a Single Dose. Cell Rep Med July 13, 2021. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00208-1

Of 227 seronegative healthcare workers in Argentina, 94% developed spike-specific IgG antibodies at day 21 after the first dose. A single Sputnik V dose elicited higher antibody levels and virus neutralizing capacity in 67 previously infected individuals than in naïve ones receiving the full two-dose schedule.

 

Immunology

Bui LT, Winters NI, Chung MIm et al. Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity. Nat Commun Jul 14, 2021, 12, 4314. https://www.nature.com/articles/s41467-021-24467-0

Chronic lung disease AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response.

 

Co-morbidities

Anand S, Monte-Rath M, Han J, et al. Estimated SARS-CoV-2 Seroprevalence in US Patients Receiving Dialysis 1 Year After the Beginning of the COVID-19 Pandemic. JAMA Netw Open July 12, 2021 2021;4(7):e2116572. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781907?resultClick=1

In this cross-sectional study of patients receiving dialysis in the US, less than 1 in 4 patients had evidence of SARS-CoV-2 antibodies 1 year after the first case of SARS-CoV-2 infection was detected in the US. Results standardized to the US population indicate similar prevalence of antibodies.

 

Treatment

Dougan M, Nirula A, Azizad M, et al. Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19. for the BLAZE-1 Investigators. NEJM July 14, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2102685?query=featured_home

This RCT shows the clinical benefit of early testing for SARS-CoV-2 infection coupled with prompt intervention with neutralizing antibody therapy in high-risk ambulatory patients: By day 29, 11/518 patients (2.1%) in the bamlanivimab–etesevimab group had a COVID-19–related hospitalization or death from any cause, as compared with 36/517 patients (7.0%) in the placebo group. At day 7, a greater reduction from baseline (difference from placebo in the change from baseline, −1.20; P<0.001).

 

Mura C, Preissner S, Nahles S, et al. Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients. Sig Transduct Target Ther July 14, 2021, 6, 267. https://www.nature.com/articles/s41392-021-00689-y

In this analysis of 22,560 COVID-19 patients taking H1/H2 receptor antagonists, the combination of famotidine and aspirin exhibited a significant synergistic survival benefit (OR 0.55, CI 0.39–0.78). The RR for death decreased by 32.5%—an immense benefit. The authors anticipate that at least three prospective RCTs that have been underway (NCT04504240, NCT04370262, and NCT04545008) will illuminate famotidine’s potential therapeutic profile.

 

15 July

Epidemiology

Kofman A, Kanto R, Adashi EY. Potential COVID-19 Endgame Scenarios. JAMA July 8, 2021. https://jamanetwork.com/journals/jama/fullarticle/2781945

Eradication, elimination, cohabitation, or conflagration? This viewpoint describes four potential scenarios that may constitute the resolution of the COVID-19 pandemic.

 

Vaccine

Barros-Martins J, Hammerschmidt SI, Cossmann A, et al. Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination. Nat Med Jul 14, 2021. https://www.nature.com/articles/s41591-021-01449-9

ChAdOx1 (AstraZeneca/Oxford)-primed immune responses before and 3 weeks after booster with ChAd (n = 32) or BioNTech/Pfizer’s BNT162b2 (n = 55): although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4+ and CD8+ T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants.

 

Co-morbidities

John BV, Deng Y, Scheinberg A, et al. Association of BNT162b2 mRNA and mRNA-1273 Vaccines With COVID-19 Infection and Hospitalization Among Patients With Cirrhosis. JAMA Intern Med July 13, 2021. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2782121?resultClick=1

This large cohort study of > 20,000 US veterans with cirrhosis found that mRNA vaccine administration was associated with a delayed but modest reduction in COVID-19 infection but an excellent reduction in COVID-19–related hospitalization or death.

 

Treatment

Starr TN, Czudnochowski N, Liu Z, et al. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Nature Jul 14, 2021. https://www.nature.com/articles/s41586-021-03807-6

The authors have identified neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a previously undescribed cryptic epitope and prophylactically protects hamsters from viral challenge. Another RBM antibody (S2E128) had an unusual breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape.

 

Pregnancy

Goldshtein I, Nevo D, Steinberg DM, et al. Association Between BNT162b2 Vaccination and Incidence of SARS-CoV-2 Infection in Pregnant Women. JAMA Jul 12, 2021; https://jamanetwork.com/journals/jama/fullarticle/2782047?resultClick=1

This cohort included 7530 vaccinated and 7530 matched unvaccinated women, 46% and 33% in the second and third trimester, respectively. Adjusted hazard ratio for infection of 0.22 (95% CI, 0.11-0.43), corresponding to an estimate of vaccine effectiveness of 78%. The authors argue that benefit from the vaccine may be somewhat attenuated because pregnant women had already been generally advised to take extra precautions during the pandemic.

 

14 July

Immunology

Janneh AH, Kassir MF, Dwyer CJ, et al. Alterations of lipid metabolism provide serologic biomarkers for the detection of asymptomatic versus symptomatic COVID-19 patients. Sci Rep July 7, 2021, 11, 14232. https://www.nature.com/articles/s41598-021-93857-7

While most asymptomatic donors had a slight increase in their serum sphingosine, symptomatic COVID-19 patients exhibited a robust decrease in their serum sphingosine levels, an almost 15-fold reduction, compared to asymptomatic donor levels.

 

Zhang Q, Ju B, Ge J, et al. Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2. Nat Commun July 7, 2021, 12, 4210. https://www.nature.com/articles/s41467-021-24514-w

Analyzing a total of 165 antibodies from eight COVID-19 patients, the authors found that potent NAbs from different patients have disproportionately high representation of IGHV3-53/3-66 usage (termed as “public” antibodies). Crystal structural comparison of these antibodies reveals that they share a similar angle of approach to RBD, overlap in buried surface and binding residues on RBD, and have substantial spatial clash with receptor ACE2 with regards to binding to RBD.

 

Clinical

COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature July 8, 2021. https://www.nature.com/articles/s41586-021-03767-x

An individual’s genetics can influence their risk of infection and the severity of disease symptoms. This large international study has identified parts of the human genome that can affect the risk of severe COVID-19. Three genome-wide association meta-analyses comprised of up to 49,562 COVID-19 patients from 46 studies identified a total of 13 genome-wide significant loci associated with SARS-CoV-2 infection (n = 4) or severe manifestations of COVID-19 (n = 9). Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases.

 

Long COVID-19

Barizien N, Le Guen M, Russel S, et al. Clinical characterization of dysautonomia in long COVID-19 patients. Sci Rep July 7, 2021, 11, 14042. https://www.nature.com/articles/s41598-021-93546-5

A small study, indicating that dysautonomia (the failure or the increase of the sympathetic or para-sympathetic components activities in the autonomic nervous system) may explain the persistent symptoms observed in long COVID-19 patients, such as fatigue and hypoxia.

 

Treatment

Koehler J, Ritzer B, Weidlich S, et al. Use of monoclonal antibody therapy for nosocomial SARS-CoV-2 infection in patients at high risk for severe COVID-19: experience from a tertiary-care hospital in Germany. Infection July 6, 2021. https://doi.org/10.1007/s15010-021-01657-y

Because of an in-house transmission of SARS-CoV-2 infection, 11 patients received monoclonal antibodies shortly after an infection (eight cases received bamlanivimab, three received the combination of casirivimab and imdevimab), and prior to symptoms. Despite many risk factors, none of these 11 patients were admitted to the intensive care unit or died from any causes.

 

13 July

Immunology

Pan Y, Jiang X, Yang L, et al. SARS-CoV-2-specific immune response in COVID-19 convalescent individuals. Sig Transduct Target Ther July 7, 2021, 6, 256. https://www.nature.com/articles/s41392-021-00686-1

In a total of 212 samples from 171 COVID-19 convalescent individuals, NAbs were significantly correlated with the number of SARS-CoV-2-specific T and NK cells. This study indicates that B, T, and NK cells are involved in immune-mediated protection against viral infection.

 

Variants

Souza WM, Amorim MR, Sesti-Costa R, et al. Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study. Lancet Microbe July 08, 2021. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00129-4/fulltext

SARS-CoV-2 lineage P.1 (gamma) might escape neutralization by antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Plasma from individuals previously infected with SARS-CoV-2 had an 8.6 times lower neutralizing capacity against the P.1 isolates.

 

Vaccine/co-morbidities

Mahil SK, Bechman K, Raharja A, et al. The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2: a cohort study. Lancet Rheumatology July 08, 2021. https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00212-5/fulltext

Seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression. In 84 patients with psoriasis receiving immunosuppressive drugs, seroconversion rates were lower in patients receiving immunosuppressants (78%), compared to 17 controls (100%), with the lowest rate in those receiving methotrexate (47%). However, cellular responses were preserved in almost all patients.

 

Goshen-Lago T, Waldhorn I, Holland R, et al. Serologic Status and Toxic Effects of the SARS-CoV-2 BNT162b2 Vaccine in Patients Undergoing Treatment for Cancer. JAMA Oncol July 8, 2021. https://jamanetwork.com/journals/jamaoncology/fullarticle/2781608?resultClick=1

This cohort study compared serologic status and safety of the BNT162b2 vaccine in 232 patients receiving active treatment for cancer and 261 health care workers who served as controls. After the first dose of the vaccine, only 29% of the patients were seropositive compared with 84% of the controls; after the second dose, the seropositive rate of the patients reached 86%, and reported adverse events resembled those of healthy individuals.

 

Clinical

Jassat W, Mudara C, Ozougwu L, et al. Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study. Lancet Global Health July 09, 2021. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00289-8/fulltext

Increased mortality in the second wave could be partly explained by more admissions in older individuals and in the public sector, and by higher volumes of hospital admissions. However, the residual 31% increased mortality could possibly be associated with the new beta variant.

Treatment

Hinks TS, Cureton L, Knight R, et al. Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial. Lancet Resp Med July 09, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00263-0/fulltext

In patients with mild-to-moderate COVID-19, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospital admission or death.

 

Pediatrics

Malshe N, Patnaik SK, Lalwani S, et al. Perinatal transmission of SARS-CoV-2 and transfer of maternal IgG/neutralizing anti-SARS-CoV-2 antibodies from mothers with asymptomatic infection during pregnancy. Infection July 7, 2021. https://link.springer.com/article/10.1007/s15010-021-01650-5

In this large study, perinatal SARS-CoV-2 transmission was 3.6% with only 21.6% neonates receiving maternal antibodies. Predominant asymptomatic SARS-CoV-2 infection during pregnancy led to effective transfer of antibodies in 51% neonates. Around 75% of the IgG positives exhibited neutralizing potential suggestive of protection in early life.

 

12 July

Variants

Today a Delta special. Delta, also known as lineage B.1.617.2 (first seen in India), has some mutations in the spike protein (see below), which enhance transmissibility and decrease recognition of the immune system. In many countries, Delta has become the predominant variant. We’ll have encouraging data on effectiveness of several vaccines and of molnupiravir, as well as a pessimistic outbreak in a gym.

 

Chemaitelly H, Yassine HM, Benslimane FM, et al. mRNA-1273 COVID-19 vaccine effectiveness against the B.1.1.7 and B.1.351 variants and severe COVID-19 disease in Qatar. Nat Med July 7, 2021. https://www.nature.com/articles/s41591-021-01446-y

Real world effectiveness of Moderna’s vaccine against SARS-CoV-2 variants of concern in Qatar, using a matched case-control study design. Effectiveness against B.1.1.7 infection (alpha) was 88% ≥ 14 days after the first dose but before the second dose and was 100% ≥ 14 days after the second dose. Analogous effectiveness against B.1.351 infection (beta) was 61% after the first dose and 96% after the second dose. Effectiveness against any severe, critical or fatal COVID-19 disease due to SARS-CoV-2 infection was 82% and 96% after the first and second dose, respectively. Compared to beta (64%) and alpha (10%), the percentage of delta was low (3%). However, it is encouraging to see the high effectiveness against beta which constitutes the variant of the greatest concern in regard to immune escape (much more so than delta).

 

Lazarevic I, Pravica V, Miljanovic D, et al. Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far? Viruses June 22, 2021,13, 1192. https://www.mdpi.com/1999-4915/13/7/1192

Nice review on variants of concern, summarizing current knowledge. A must read.

 

Yadav PD, Sapkal GN, Ella R, et al. Neutralization of Beta and Delta variant with sera of COVID-19 recovered cases and vaccinees of inactivated COVID-19 vaccine BBV152/Covaxin. Journal of Travel Medicine Jul 6, 2021, taab104, https://academic.oup.com/jtm/advance-article/doi/10.1093/jtm/taab104/6316247?searchresult=1

An inactivated SARS-CoV-2 vaccine, BBV152, was rolled out under the national COVID-19 vaccination program in India. BBV152 was found to confer significant protection against delta (and beta).

 

Planas D, Veyer D, Baidaliuk A. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature July 8, 2021. https://www.nature.com/articles/s41586-021-03777-9

Delta partially but significantly escapes neutralizing mAbs, and polyclonal antibodies elicited by previous SARS-CoV-2 infection or vaccination. Sera from individuals having received one dose of either the Pfizer or AstraZeneca vaccines barely inhibited the delta variant. Administration of two doses generated a neutralizing response in 95% of individuals, with titers 3-to-5-fold lower against delta than alpha.

 

Abdelnabi R, Foo CS, De Jonghe S, et al. Molnupiravir inhibits the replication of the emerging SARS-CoV-2 variants of concern (VoCs) in a hamster infection model. The Journal of Infectious Diseases Juily 9, 2021, jiab361, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab361/6318434

Molnupiravir, currently in Phase II clinical trials, has worked well in hamsters infected with either Wuhan strain, with the delta or alpha variants.

 

Dougherty K, Mannell M, Naqvi O, Matson D, Stone J. SARS-CoV-2 B.1.617.2 (Delta) Variant COVID-19 Outbreak Associated with a Gymnastics Facility — Oklahoma, April–May 2021. MMWR Morb Mortal Wkly Rep. ePub: 9 July 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7028e2.htm?s_cid=mm7028e2_w

This delta outbreak may indicate that return to gym in 2021 is probably not the best idea. During April 15–May 3, 2021, 47 COVID-19 cases (all 21 tested cases were delta) were linked to a gymnastics facility. The overall facility and household attack rates were 20% and 53%, respectively. Of note, four persons (9%) had received 2 doses of either the Moderna or Pfizer-BioNTech or a single dose of the Johnson & Johnson vaccine ≥ 14 days before a positive test result. Several potential risk factors for transmission were identified, including not using masks among active participants, coupled with increased respiration during active sport participation (further, facility policy was that all persons not actively participating wear masks, but this policy was not always followed); poor facility ventilation; staff members training multiple cohorts, etc.

 

11 July

Virology

Zhang Z, Zhang Y, Liu K, et al. The molecular basis for SARS-CoV-2 binding to dog ACE2. Nat Commun Jul 7, 2021, 12, 4195. https://www.nature.com/articles/s41467-021-24326-y

How can SARS-CoV-2 infect dogs? The present study solved the crystal structure of the RBD/dACE2 complex, and revealed the molecular basis for the recognition of SARS-CoV-2 receptor in dogs.

 

Immunology

Moriyama S, Adachi Y, Sato T, et al. Temporal Maturation of Neutralizing Antibodies in COVID-19 Convalescent Individuals Improves Potency and Breadth to Circulating SARS-CoV-2 Variants. Immunity July 02, 2021. https://www.cell.com/immunity/fulltext/S1074-7613(21)00259-4

Antibodies from late convalescents exhibited increased neutralization potency to variants of concern, suggesting persistence of cross-neutralizing antibodies in plasma. Maturation of the antibody response to SARS-CoV-2 potentiates cross-neutralizing ability to circulating variants, suggesting that declining antibody titers may not be indicative of declining protection.

 

Li C, Yu D, Wu X, et al. Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan. Nat Commun Jul 6, 2021, 12, 4144. https://www.nature.com/articles/s41467-021-24230-5

This 12-month longitudinal study using 1,782 plasma samples from 869 convalescent plasma donors shows that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreased with time, with the titer stabilizing at 64.3% of the initial level by the 9th month.

 

Clinical

Kadri SS, Sun J, Lawandi A, et al. Association Between Caseload Surge and COVID-19 Survival in 558 U.S. Hospitals, March to August 2020. Ann Int Med July 6, 2021. https://www.acpjournals.org/doi/10.7326/M21-1213

Nearly 1 in 4 COVID-19 deaths was potentially attributable to hospitals strained by surging caseload. Bolstering preventive measures and supporting surging hospitals will save many lives.

 

Long COVID

Nehme M, Braillard O, Chappuis F, et al. Prevalence of Symptoms More Than Seven Months After Diagnosis of Symptomatic COVID-19 in an Outpatient Setting. Annals Int Med July 6, 2021. https://www.acpjournals.org/doi/10.7326/M21-0878

Residual symptoms after SARS-CoV-2 infection are common among otherwise young and healthy persons followed in an outpatient setting. Of the 629 participants who completed the baseline interviews, 410 completed follow-up at 7 to 9 months after COVID-19 diagnosis; 39.0% reported residual symptoms. Fatigue (20.7%) was the most common symptom reported, followed by loss of taste or smell (16.8%) and dyspnea (11.7%).

 

Radin JM, Quer G, Ramos E, et al. Assessment of Prolonged Physiological and Behavioral Changes Associated With COVID-19 Infection. JAMA Netw Open July 7, 2021;4(7):e2115959. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781687?resultClick=1

Huge study, indicating a prolonged physiological impact of COVID-19 infection, lasting approximately 2 to 3 months, on average, but with substantial intraindividual variability, which may reflect various levels of autonomic nervous system dysfunction or potentially ongoing inflammation.

 

10 July

Virology

Kang L, He G, Sharp AK, et al. A selective sweep in the Spike gene has driven SARS-CoV-2 human adaptation. Cell July 06, 2021. https://www.cell.com/cell/fulltext/S0092-8674(21)00833-3

S protein residue 372 is critical for replication in human cells. The threonine-to-alanine change may have enabled the putative ancestral virus to replicate more efficiently in human cells, thus possibly enabling efficient human-to-human transmission.

 

Variants

Tarke A, Sidney J, Methot N, et al. Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals. Cell Rep July 01, 2021. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00204-4

The SARS-CoV-2 variants B.1.1.7, B.1.351, P.1 and CAL.20C do not significantly disrupt the total SARS-CoV-2 T cell reactivity. T cells of exposed donors or vaccinees effectively recognized SARS-CoV-2 variants.

 

Treatment

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19A Meta-analysis. JAMA July 6, 2021. https://jamanetwork.com/journals/jama/fullarticle/2781880?resultClick=1

This prospective meta-analysis of 27 randomized trials included 10,930 patients. The 28-day all-cause mortality was lower among patients who received IL-6 antagonists compared with those who received usual care or placebo (summary odds ratio, 0.86). Administration of IL-6 antagonists was also associated with lower progression to IMV or death, cardiovascular support or death.

 

Pediatrics/Pregnancy

Gaythorpe KA, Bhatia S, Mangal T, et al. Children’s role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility. Sci Rep Jul 6, 2021, 11, 13903. https://www.nature.com/articles/s41598-021-92500-9

Children’s susceptibility to infection and onward transmissibility relative to adults is still unclear and varies widely between studies.

 

Vouga M, Favre G, Martinez-Perez O, et al. Maternal outcomes and risk factors for COVID-19 severity among pregnant women. Sci Rep Jul 6, 2021, 11, 13898. https://www.nature.com/articles/s41598-021-92357-y

In this large study, several risk factors for developing severe complications of SARS-CoV-2 infection among 926 pregnant women were identified including pulmonary co-morbidities, hypertensive disorders and diabetes. Obstetric and neonatal outcomes appear to be influenced by the severity of maternal disease.

 

9 July

Today another vaccine special, including data on effectiveness of the inactivated vaccine CoronaVac and of mRNA vaccines against delta. New US recommendations on how to deal with myocarditis in young men receiving mRNA vaccines and some new data on the mechanisms of vaccine-induced immune thrombotic thrombocytopenia (VITT) and on treatments.

Vaccine

Effectiveness

Jara A, Undurraga EA, González C, et al. Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile. NEJM July 7, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2107715?query=featured_home

A countrywide mass vaccination campaign with the use of an inactivated vaccine (CoronaVac) was conducted in > 10 million people in Chile starting on February 2, 2021. Among persons who were fully immunized, the adjusted vaccine effectiveness was 66% for the prevention of COVID-19 and 87.5% for the prevention of hospitalization, and 86.3% for the prevention of COVID-19–related death.

 

Variants

Edara VV, Pinksy BA, Suthar MS, et al. Infection and Vaccine-Induced Neutralizing-Antibody Responses to the SARS-CoV-2 B.1.617 Variants. NEJM July 7, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2107799?query=featured_home

Good news: the protective immunity conferred by the mRNA vaccines is most likely retained against the B.1.617.1 and B.1.617.2 variants. Although the B.1.617.1 variant was 6.8 times less susceptible (and the B.1.617.2 variant 2.9 times less so) to neutralization by serum from recovered or vaccinated persons, the majority of the convalescent serum samples (19/24) against B.1.617.1 (23/24 against B.1.617.2) and all serum samples from vaccinated persons still had detectable neutralizing activity.

Adverse events

Gargano JW, Wallace M, Hadler SC, et al. Use of mRNA COVID-19 Vaccine After Reports of Myocarditis Among Vaccine Recipients: Update from the Advisory Committee on Immunization Practices — United States, June 2021. MMWR Morb Mortal Wkly Rep. ePub: 6 July 2021. DOI: https://www.cdc.gov/mmwr/volumes/70/wr/mm7027e2.htm?s_cid=mm7027e2_w

The committee concluded that the benefits of COVID-19 vaccination to individual persons and at the population level clearly outweigh the risks of myocarditis after vaccination. Even in young men: per million second doses of mRNA COVID-19 vaccine administered to males aged 12–29 years, 11,000 COVID-19 cases, 560 hospitalizations, 138 ICU admissions, and six deaths due to COVID-19 were prevented, compared with 39–47 expected myocarditis cases after COVID-19 vaccination.

 

Huynh A, Kelton JG, Arnold DM, et al. Antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia. Nature July 7, 2021. https://www.nature.com/articles/s41586-021-03744-4

VITT antibodies can mimic the effect of heparin by binding to a similar site on PF4, allowing PF4 tetramers to cluster and form immune complexes, which in turn cause FcγRIIa-dependent platelet activation.

 

Patriquin CJ, Laroche V, Selby R, et al. Therapeutic Plasma Exchange in Vaccine-Induced Immune Thrombotic Thrombocytopenia. NEJM July 7, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2109465?query=featured_home

Three cases from Canada, indicating that therapeutic plasma exchange may be effective for the treatment of refractory VITT. Two recovered despite their severe presentation.

 

8 July

Variants

Widera M, Wilhelm A, Hoehl S, et al. Limited neutralization of authentic SARS-CoV-2 variants carrying E484K in vitro. The Journal of Infectious Diseases 05 July 2021, jiab355, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab355/6314691

This in vitro study using authentic SARS-CoV-2 confirms that, in contrast to vaccine-elicited sera, bamlanivimab and casirivimab may not provide efficacy against SARS-CoV-2 variants B.1.351 (beta) and P.2 (zeta), both harboring the E484K substitution. Since imdevimab was able to efficiently neutralize both variants, therapeutical treatment with the REGN-COV-2 combination remains effective.

 

Diagnostics

Melo AK, Milby KM, Caparroz AL, et al. Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis. PLOS ONE, June 29, 2021. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253894

According to this review, elevated levels of interleukin-6 and hyperferritinemia should be considered red flags of systemic inflammation and poor prognosis in COVID-19.

 

Immunology

Vanderbeke, L., Van Mol, P., Van Herck, Y. et al. Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity. Nat Commun Jul 5, 2021, 12, 4117. https://www.nature.com/articles/s41467-021-24360-w

In this prospective, case-control study of 61 patients with varying degrees of disease severity and 31 control patients, a quantitative and integrative qualitative immunophenotyping approach was used to characterize the cytokine responses. The authors identified a myeloid-driven atypical cytokine storm that is distinctly different from the so-called macrophage activation syndrome (MAS), with specific contributions of classical pro-inflammatory monocytes and neutrophils dominating COVID-19 immunopathology in the most critical cases.

 

Grandjean L, Saso A, Ortiz AT, et al. Long-Term Persistence of Spike Antibody and Predictive Modeling of Antibody Dynamics Following Infection with SARS-CoV-2. Clinical Infectious Diseases July 4, 2021. ciab607, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab607/6314536

A total of 1163 monthly samples were provided from 349 seropositive participants. S antibody was predicted to remain detectable in 95% of participants until 465 days. N antibodies decayed rapidly with a half-life of 60 days.

 

Pediatrics

Golan Y, Prahl M, Cassidy A, et al. Evaluation of Messenger RNA From COVID-19 BTN162b2 and mRNA-1273 Vaccines in Human Milk. JAMA Pediatr July 6, 2021. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2781679?resultClick=1

Vaccine-associated mRNA was not detected in 13 milk samples collected 4 to 48 hours after vaccination from 7 breastfeeding individuals.

 

7 July

Vaccine

Tran KC, Andronico A, Bosetti P, et al. Benefits and risks associated with different uses of the COVID-19 vaccine Vaxzevria: a modelling study, France, May to September 2021. Euro Surveill. 2021;26(26):pii=2100533. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.26.2100533

A modeling study, indicating that for individuals 55 years and older, the benefits of distributing AstraZeneca’s Vaxzevria largely outweighs the risks in a range of possible scenarios. In contrast, in young adults, the risks were similar or higher than the benefits.

 

Sangli S, Virani A, Cheronis N, et al. Thrombosis With Thrombocytopenia After the Messenger RNA–1273 Vaccine. Annals Int Med, June 29, 2021. https://www.acpjournals.org/doi/10.7326/L21-0244

A 65-year-old man with vaccine-induced thrombosis with thrombocytopenia (VITT) developing a few days after administration of the mRNA-1273 vaccine from Moderna: most of his clotting and other relevant work-up was consistent with the syndrome. This report complicates the hypothesis that implicates adenoviral vectors as the sole cause of VITT or TTS.

 

Variants

Lustig Y, Zuckerman N, Nemet I, et al. Neutralising capacity against Delta (B.1.617.2) and other variants of concern following Comirnaty (BNT162b2, BioNTech/Pfizer) vaccination in health care workers, Israel. Euro Surveill Jul 1, 2021;26(26):pii=2100557. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.26.2100557

Using micro-neutralization assays with sera obtained after Comirnaty (BNT162b2, BioNTech/Pfizer) vaccination in 36 healthcare workers, the authors show that, despite somewhat reduced neutralization capacity, mRNA vaccination induces a substantial antibody response for the Delta VOC as well.

 

Diagnostics

Bradley BT, Bryan A, Fink SL, et al. Anti-SARS-CoV-2 antibody levels measured by the Advise Dx SARS-CoV-2 assay are concordant with previously available serologic assays but are not fully predictive of sterilizing immunity. Journal of Clinical Microbiology 24 June 2021. https://journals.asm.org/doi/10.1128/JCM.00989-21

In this small study, protection against SARS-CoV-2 infection could not be predicted exclusively using in vitro antibody assays against wildtype SARS-CoV-2 spike. Further work is required to establish protective correlates for SARS-CoV-2 infection.

 

Long COVID

Seeßle J, Waterboer T, Hippchen T, et al. Persistent symptoms in adult patients one year after COVID-19: a prospective cohort study. Clinical Infectious Diseases July 5, 2021, ciab611, https://doi.org/10.1093/cid/ciab611

Is autoimmunity a co-factor in the etiology of long COVID? Of 96 patients who were included 5 months after acute COVID-19 in this prospective, non-interventional study, only 23% of patients were completely free of symptoms at 12 months. The most frequent symptoms were reduced exercise capacity (56%) and fatigue (53%). Females showed significantly more neurocognitive symptoms than males. ANA titers were ≥ 1:160 in 44% of patients at 12 months, and neurocognitive symptom frequency was significantly higher in the group with an ANA titer ≥ 1:160 compared to < 1:160.

 

6 July

Vaccines

Maneikis K, Šablauskas K, Ringelevičiūtė U, et al. Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study. Lancet Hematology July 02, 2021. https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(21)00169-1/fulltext

According to this large cohort, patients actively treated with BTKIs, ruxolitinib, venetoclax, or anti-CD20 antibody therapies seem to be the most negatively affected and unprotected from SARS-CoV-2 infection.

 

Nathan A, Rossin EJ, Kaseke C, et al. Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses. Cell June 29, 2021. https://www.cell.com/cell/fulltext/S0092-8674(21)00797-2

The development of immunogens that can induce CD8+ T cell responses to mutationally constrained epitopes could greatly augment current vaccines for SARS-CoV-2 given the emergence of variants that escape convalescent plasma and vaccine-induced antibody responses. This study elucidates key mutationally constrained regions and immunogenic epitopes in the SARS-CoV-2 proteome for a global T cell-based vaccine against emerging variants and sarbecoviruses.

Immunology

Liu W, Russell RM, Bibollet-Ruche F, Skelly AN, Sherrill-Mix S, Freeman DA, et al. Predictors of nonseroconversion after SARS-CoV-2 infection. Emerg Infect Dis June 30, 2021. https://wwwnc.cdc.gov/eid/article/27/9/21-1042_article

Non-seroconversion was associated with younger age and higher reverse transcription PCR cycle threshold values. Patients with low SARS-CoV-2 viral loads in their respiratory tract were less likely to mount a systemic antibody response.

 

Diagnostics

Pickering S, Batra R, Merrick B, et al. Comparative performance of SARS-CoV-2 lateral flow antigen tests and association with detection of infectious virus in clinical specimens: a single-centre laboratory evaluation study. Lancet Microbe June 30, 2021. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00143-9/fulltext

A head-to-head comparison of six LFDs commercially available in the UK: Innova Rapid SARS-CoV-2 Antigen Test, Spring Healthcare SARS-CoV-2 Antigen Rapid Test Cassette, E25Bio Rapid Diagnostic Test, Encode SARS-CoV-2 Antigen Rapid Test Device, SureScreen COVID-19 Rapid Antigen Test Cassette, and SureScreen COVID-19 Rapid Fluorescence Antigen Test. All LFDs showed high specificity (≥ 98.0%), except for the E25Bio (86.0%). Sensitivities of the LFDs on clinical samples ranged from 65.0% to 89.0%. These sensitivities increased to greater than 90% for samples with Ct values of lower than 25 for all tests except the SureScreen fluorescence test.

 

Co-morbidities

Lupo-Stanghellini MT, Xue E, Mastaglio S, et al. COVID-19 in recipients of allogeneic stem cell transplantation: favorable outcome. Bone Marrow Transplant Jul 1, 2021. https://www.nature.com/articles/s41409-021-01278-x

This small study suggests that being a recipient of HSCT should not be considered a priori a determinant of dismal prognosis on diagnosis of COVID-19.

 

Pediatrics

Schmidt A, Peters S, Knaus A, et al. TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19. npj Genom Med Jul 1, 2021. https://www.nature.com/articles/s41525-021-00220-w

A rare case of a 3.5-year-old girl with an unusually severe presentation. The authors suggest that the identified gene variants, the autoinflammatory disorder (of unknown etiology) and its treatment (prednisolone and methotrexate), or a combination of these factors probably pre-disposed her to COVID -19 being lethal.

 

Treatment

Leach DA, Mohr A, Giotis ES, et al. The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells. Nat Commun Jul 1, 2021, 12, 4068. https://www.nature.com/articles/s41467-021-24342-y

Treatment with the anti-androgen enzalutamide—a well-tolerated drug widely used in advanced prostate cancer—reduces TMPRSS2 levels in human lung cells and in mouse lungs. Anti-androgens significantly reduced SARS-CoV-2 entry and infection in lung cells.

 

5 July

Epidemiology

Lemey P, Ruktanonchai N, Hong SL, et al. Untangling introductions and persistence in COVID-19 resurgence in Europe. Nature June 30, 2021. https://www.nature.com/articles/s41586-021-03754-2

The authors estimate that in many countries over half of the lineages circulating in late summer 2020 resulted from new variant introductions since June 15^th.

 

Vaccines

Lustig Y, Sapir E, Regev-Yochay G, et al. BNT162b2 COVID-19 vaccine and correlates of humoral immune responses and dynamics: a prospective, single-centre, longitudinal cohort study in health-care workers. Lancet Resp Med Jul 2, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00220-4/fulltext

A lot of data from Israel. A high correlation (r=0.92) was seen between IgG against the receptor-binding domain and neutralizing antibody titers. First-dose induced IgG response was significantly lower in individuals aged 66 years and older and immunosuppressed individuals. Of note, this disparity was partly abrogated following the second dose.

 

Variants

McCallum M, Bassi J, De Marco A, et al. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. Science 01 Jul 2021: eabi7994. https://science.sciencemag.org/content/early/2021/06/30/science.abi7994

How the B.1.427/B.1.429 variant (“California”) evades immune responses. The L452R mutation reduced neutralizing activity of 14 out of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 out of 10 NTD-specific mAbs. In this case, the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and formation of a new disulfide bond, as revealed by mass spectrometry and structural studies.

 

Transmission

Lindsley WG, Derk RC, Coyle JP, et al. Efficacy of Portable Air Cleaners and Masking for Reducing Indoor Exposure to Simulated Exhaled SARS-CoV-2 Aerosols — United States, 2021. MMWR Morb Mortal Wkly Rep. ePub: 2 July 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7027e1.htm?s_cid=mm7027e1_w

A simulated infected meeting participant who was exhaling aerosols was placed in a room with two simulated uninfected participants and a simulated uninfected speaker. Using two high efficiency particulate air (HEPA) cleaners close to the aerosol source reduced the aerosol exposure of the uninfected participants and speaker by up to 65%. A combination of HEPA air cleaners and universal masking reduced exposure by up to 90%.

 

Immunology

Efrati S, Catalogna M, Abu Hamed R, et al. Early and long term antibody kinetics of asymptomatic and mild disease COVID-19 patients. Sci Rep July 2, 2021, 11, 13780. https://www.nature.com/articles/s41598-021-93175-y

Of 135 study participants, 97% were seropositive during the study. Two distinct clusters were identified that were significantly different in their inflammatory related symptoms. Systemic symptoms (i.e., fever, fatigue, pain, dry cough) were associated with higher antibody titers in mild symptomatic patients. Interestingly, the decay rate in antibody concentrations during the study period was similar in both clusters.

 

Severe COVID

Estenssoro E, Loudet CI, Ríos FG, et al. Clinical characteristics and outcomes of invasively ventilated patients with COVID-19 in Argentina (SATICOVID): a prospective, multicentre cohort study. Lancet Resp Med July 02, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00229-0/fulltext

A large study of 1909 invasively ventilated patients with COVID-19. In-hospital mortality was 57.7% and ICU mortality was 57.0%.

 

4 July

Epidemiology

Bosco-Lauth AM, Root JJ, Porter SM, Walker AE, Guilbert L, Hawvermale D, et al. Peridomestic mammal susceptibility to severe acute respiratory syndrome coronavirus 2 infection. Emerg Infect Dis June 29, 2021. https://wwwnc.cdc.gov/eid/article/27/8/21-0180_article

Watch out, pet owners: deer mice, bushy-tailed woodrats, and striped skunks are susceptible to infection and can shed the virus in respiratory secretions. In contrast, cottontail rabbits, fox squirrels, Wyoming ground squirrels, black-tailed prairie dogs, house mice, and racoons were not susceptible to SARS-CoV-2 infection!

 

Vaccines

Thompson MG, Burgess JL, Naleway AL, et al. Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines. NEJM June 30, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2107058?query=featured_home

This prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers shows that mRNA vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination.

 

Ropper AH, Klein JP. Cerebral Venous Thrombosis. NEJM Jul 1, 2021. https://www.nejm.org/doi/full/10.1056/NEJMra2106545?query=featured_home

Nice review. Allan H. Ropper and Joshua P. Klein summarize current knowledge on how to diagnose and how to treat cerebral venous thrombosis.

 

Sánchez van Kammen M, Brodard J, Scutelnic A, et al. Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic. JAMA July 2, 2021. https://jamanetwork.com/journals/jama/fullarticle/2781791?resultClick=1

In 865 patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon (8.4%), and heparin-induced thrombocytopenia (0.1%) and platelet factor 4/heparin antibodies were rare.

 

Treatment

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

The authors identified four receptor-binding domain targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526 and B.1.617 VOCs. Two antibodies were ultrapotent, with sub-nanomolar neutralization titers. The structural and functional determinants of binding for all four VOC-targeting antibodies were determined. Combinations of two antibodies decreased the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.

 

Roman YM, Burela PA, Pasupuleti V, et al. Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials. Clinical Infectious Diseases June 28, 2021, ciab591, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab591/6310839

In comparison to standard of care or placebo, ivermectin did not reduce all-cause mortality, length of stay or viral clearance in this review of 10 RCTs in COVID-19 patients with mostly mild disease. Ivermectin is not a viable option for treating COVID-19 patients.

 

3 July

Virology

Zhang Q, Gefter J, Sneddon WB et al. ACE2 interaction with cytoplasmic PDZ protein enhances SARS-CoV-2 invasion. iScience June 23, 2021. https://www.cell.com/iscience/fulltext/S2589-0042(21)00738-0

This study bridges gaps in understanding SARS-CoV-2 entry into the cell. Intracellular factors are identified, involved in mediating SARS-CoV-2 internalization.

 

Immunology

Neidleman J, Luo Y, George AF, et al. Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19. Cell Reports June 28, 2021. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00827-5

This study indicates that lung-homing T cells activated through bystander effects contribute to immunopathology, while a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19.

 

Vaccine

Heath PT, Galiza EP, Baxter DN, et al. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. NEJM Jun 30, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2107659?query=featured_home

Paper of the day. The next vaccine! Large RCT of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant. Among 14039 participants, the two-dose regimen conferred 89.7% protection. A post hoc analysis showed an efficacy of 86.3% against the B.1.1.7 (or alpha) variant and 96.4% against non-B.1.1.7 variants.

 

Clinical

Lee SA, Park R, Yang JH. et al. Increased risk of acute kidney injury in coronavirus disease patients with renin–angiotensin–aldosterone-system blockade use: a systematic review and meta-analysis. Sci Rep Jun 30, 2021, 11, 13588. https://www.nature.com/articles/s41598-021-92323-8

This meta-analysis of published retrospective and prospective cohort studies observed that the exposure to RAAS blockade was associated with a higher risk of incident acute kidney injury in patients with laboratory-confirmed or clinically diagnosed COVID-19. Odds ratio were 2.45 for ACEI use and 2.32 for ARB use. However, a causal relationship cannot be ascribed to the RAAS blockade and practice changing recommendations cannot be made on the basis of these data.

 

Collateral damage (and benefits)

Pieh C, Plener PL, Probst T, et al. Assessment of Mental Health of High School Students During Social Distancing and Remote Schooling During the COVID-19 Pandemic in Austria. JAMA Netw Open June 28, 2021; 4(6):e2114866. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781462?resultClick=1

This cross-sectional study suggests that the COVID-19 pandemic was associated with impaired mental health. The mental well-being and life satisfaction in adolescents in Austria were significantly lower in 2021 compared with 2018. However, owing to the online nature of the study, a self-selection bias toward higher participation of adolescents with a higher mental health burden may be possible.

 

2 July

Epidemiology

Knabl L, Mitra T, Kimpel J. et al. High SARS-CoV-2 seroprevalence in children and adults in the Austrian ski resort of Ischgl. Commun Med June 30, 2021, 1, 4. https://www.nature.com/articles/s43856-021-00007-1

In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe. Local seroprevalence was high, reaching 42.4%.

 

Immunology

Jung JH, Rha MS, Sa M, et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nat Commun June 30, 2021, 12, 4043. https://www.nature.com/articles/s41467-021-24377-1

In the present study, it is demonstrated that SARS-CoV-2-specific memory T cell responses were maintained in COVID-19 convalescent patients 10 months post-infection regardless of disease severity. Notably, SARS-CoV-2-specific stem cell-like memory T (TSCM) cells were successfully developed, indicating that T cell memory may be long-lasting in COVID-19 convalescent patients.

 

Variants

Hoffmann M, Hofmann-Winkler H, Krüger N, et al. SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination. Cell Reports June 28, 2021. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00828-7

The spike protein of B.1.617 (delta) harbors two mutations in the receptor-binding domain, which interacts with the ACE2 receptor and constitutes the main target of neutralizing antibodies. The B.1.617 spike protein can facilitate entry into lung cells with slightly increased efficiency and shows that entry can be blocked by soluble ACE2 and camostat. B.1.617 also evades antibodies induced by infection or vaccination, although less so than the B.1.351 variant.

 

Diagnostics

Smolinska A, Jessop DS, Pappan KL. et al. The SARS-CoV-2 viral load in COVID-19 patients is lower on face mask filters than on nasopharyngeal swabs. Sci Rep June 29, 2021, 11, 13476. https://www.nature.com/articles/s41598-021-92665-3

This study investigated whether, in addition to preventing SARS-CoV-2 virus spread, filters embedded in some types of face masks and respirators could be used for SARS-CoV-2 detection. However, the sensitivity of SARS-CoV-2 detection when using samples extracted from filters was less than 10% of that of nasopharyngeal swab samples.

 

Clinical

Castro MC, Gurzenda S, Turra CM, et al. Reduction in life expectancy in Brazil after COVID-19. Nat Med June 29, 2021. https://www.nature.com/articles/s41591-021-01437-z

The authors estimate a decline in 2020 life expectancy from birth of 1.3 years, a mortality level not seen since 2014. Life expectancy in the presence of COVID-19 was equivalent to levels observed in Brazil as far back as 20 or more years in some states.

 

1 July

Today we have another vaccine special: some new data on CoronaVac in children, on the vaccine effect on household transmission, as well as on antibody response in older patients, in patients with prior COVID-19 and in patients with myeloma. Some new cases of myocarditis cases after mRNA vaccine.

 

Vaccine special

Effectiveness

Harris RJ, Hall JA, Zaidi A, et al. Effect of Vaccination on Household Transmission of SARS-CoV-2 in England. NEJM June 23, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2107717?query=featured_home

Overall, the likelihood of household transmission was approximately 40 to 50% lower in households of index patients who had been vaccinated 21 days or more before testing positive than in households of unvaccinated index patients; the findings were similar for the two vaccines from Pfizer/BioNTech and AstraZeneca.

 

Pawlowski C, Lenehan P, Puranik A, et al. FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system. Med June 28, 2021. https://www.cell.com/med/fulltext/S2666-6340(21)00238-5

This retrospective analysis of 136,532 individuals in the Mayo Clinic health system shows comparable real-world vaccine effectiveness in preventing SARS-CoV-2 infection for BNT162b2 (BioNTech/Pfizer, 86.1%) and mRNA-1273 (Moderna, 93.3%). BNT162b2 and mRNA-1273 were 88.8% and 86.0% effective in preventing COVID-19 associated hospitalization.

 

Collier DA, Ferreira IA, Kotagiri P, et al. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature June 30, 2021. https://www.nature.com/articles/s41586-021-03739-1

This study analyzed immune responses following vaccination with the mRNA vaccine BNT162b22 in elderly participants and younger health care workers. Serum neutralization and binding IgG/IgA after the first vaccine dose diminished with increasing age, with a marked drop in participants over 80 years old. Of note, a greater proportion of individuals in the over 80 age group lost all neutralizing activity to P.1 and B.1.1.7 following the first dose compared to the wild type.

 

Variants

Lustig Y, Nemet I, Kliker L, et al. Neutralizing Response against Variants after SARS-CoV-2 Infection and One Dose of BNT162b2. N Engl J Med June 24, 2021; 384:2453-2454.  https://www.nejm.org/doi/full/10.1056/NEJMc2104036?query=featured_home

In this study, one dose of the BNT162b2 vaccine increases neutralizing activity against the B.1.1.7, B.1.351, and P.1 variants in six persons previously infected with SARS-CoV-2. This highlights the importance of vaccination even in previously infected patients, given the added benefit of an increased antibody response to the variants tested.

 

Co-morbidities

Van Oekelen O, Gleason CR, Agte S, et al. Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma. Cancer Cell June 28, 2021. https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00336-6

Of note, 15.8% of myeloma patients (41/260) failed to develop any SARS-CoV-2 spike-binding IgG antibodies despite having received both doses of mRNA vaccines.

 

Safety

Montgomery J, Ryan M, Engler R, et al. Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military. JAMA Cardiol, June 29, 2021; doi: https://jamanetwork.com/journals/jamacardiology/fullarticle/2781601?resultClick=1

A total of 23 male patients (20-51 years) presented with acute onset of marked chest pain within 4 days after receipt of an mRNA COVID-19 vaccine. Eight patients had cMRI findings consistent with myocarditis. More than 2.8 million doses of mRNA COVID-19 vaccine were administered in this period.

 

Kim HW, Jenista ER, Wendell DC, et al. Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination. JAMA Cardiol June 29, 2021. https://jamanetwork.com/journals/jamacardiology/fullarticle/2781602?resultClick=1

In this study of 7 patients with acute myocarditis, 4 occurred within 5 days of COVID-19 vaccination between February 1 and April 30, 2021. Fortunately, the hospital courses of the 4 patients with myocarditis following COVID-19 vaccination were uneventful.

 

New vacccines

Han B, Song Y, Li C, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial. Lancet Inf Dis June 28, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00319-4/fulltext

CoronaVac was well-tolerated and safe and induced humoral responses in 550 children and adolescents aged 3–17 years. Neutralizing antibody titers induced by the 3.0 μg dose were higher than those of the 1.5 μg dose.

 

Bricker TL, Darling TL, Hassan AO, et al. A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters. Cell Reports June 28, 2021. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00798-1

In Golden Syrian hamsters, intranasal delivery of a chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike protein (ChAd-SARS-CoV-2-S) was better than intramuscular delivery.

 

 

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