García-García D, Vigo MI, Fonfría ES, et al. Retrospective methodology to estimate daily infections from deaths (REMEDID) in COVID-19: the Spain case study. Sci Rep 11, 11274 (2021). https://www.nature.com/articles/s41598-021-90051-7
During the first wave, infection numbers were largely underestimated in Spain. The authors propose a retrospective methodology to estimate daily infections from daily deaths because deaths are usually more accurately documented. They estimate that probable daily infections during the first wave were between 35 and 42 times higher than those officially documented on 14 March, when the national government decreed a national lockdown and still 9 times more than those documented by the updated version of the official data.
Virale J, Mumoli N, Clerici P, et al Assessment of SARS-CoV-2 Reinfection 1 Year After Primary Infection in a Population in Lombardy, Italy. JAMA Intern Med May 28, 2021. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2780557?resultClick=1
In this large observational study, incidence rate ratio (patients with/without prior infection) adjusted for age, sex, ethnicity, and the sanitarian area was 0.07 (95% CI, 0.06-0.08).
Marot S, Malet I, Leducq V, et al. Neutralization heterogeneity of United Kingdom and South-African SARS-CoV-2 variants in BNT162b2-vaccinated or convalescent COVID-19 healthcare workers. Clinical Infectious Diseases, May 29, 2021, ciab492, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab492/6288468
Two findings from this small study, assessing the neutralizing activity of sera from 15 convalescent COVID-19 HCW and from 29 BNT162b2 vaccinated HCW against B.1.1.7 (UK) and B.1.351 (South Africa): 1. One shot is not enough, questioning the timing of the dosing interval of BNT162b2. After two shots, however, most participants displayed a neutralizing activity ≥ 1:10 which could be at least indicative of a potential protection against variants.
Staibano P, Levin L, McHugh T, et al. Association of Tracheostomy With Outcomes in Patients With COVID-19 and SARS-CoV-2 Transmission Among Health Care Professionals: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg. May 27, 2021. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2780431?resultClick=1
Tracheostomy is a relatively effective and safe treatment for patients with COVID-19. It is also safe for the HCPs performing the procedures who are wearing personal protective equipment. Enhanced personal protective equipment is associated with low rates of SARS-CoV-2 transmission during tracheostomy. Early tracheostomy in patients with COVID-19 may reduce ICU stay, but this finding is limited by the observational nature of the studies included.
Loenenbach A, Markus I, Lehfeld AS, et al. SARS-CoV-2 variant B.1.1.7 susceptibility and infectiousness of children and adults deduced from investigations of childcare centre outbreaks, Germany, 2021. Euro Surveill. 2021;26(21):pii=2100433. https://doi.org/10.2807/1560-7917.ES.2021.26.21.2100433
This analysis of three simultaneously occurring outbreaks in childcare facilities (a total of 47 infections), suggests that both susceptibility and infectiousness of children aged between 1 to 6 years are substantially higher compared to the pre-B.1.1.7 period, and may be converging with those among adults.
Yiwen Zhang, Yingshi Chen, Yuzhuang Li, et al. The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι. PNAS May 21, 2021. https://www.pnas.org/content/118/23/e2024202118
This study shows how SARS-CoV-2 utilizes its open reading frame 8 (ORF8) protein to evade T cell responses. ORF8 (which shares the smallest homology with SARS-CoV among all viral proteins) directly interacts with major histocompatibility complex class Ι (MHC-Ι) molecules and mediates their down regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2–infected cells are much less sensitive to lysis by cytotoxic T lymphocytes.
Frenck RW, Klein NP, Kitchin N, et al. Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. NEJM May 27, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2107456?query=featured_home
In 1131 adolescents (12 to 15 years old), the BNT162b2 vaccine had a favorable safety profile. The immune response was non-inferior to that observed in the cohort of 16-to-25-year-old young adults.
Singh J, Rahman SA, Ehtesham NZ, et al. SARS-CoV-2 variants of concern are emerging in India. Nat Med May 27, 2021. https://doi.org/10.1038/s41591-021-01397-4
The sudden surge in COVID-19 cases in India coincides with high prevalence of more transmissible variants, associated with diagnostic test failures and antibody escape. This paper gives an overview.
Schulz C, Wylezich C, Wernike K, Gründl M, Dangel A, Baechlein C, et al. Prolonged SARS-CoV-2 RNA shedding from therapy cat after cluster outbreak in retirement home. Emerg Inf Dis May 26, 2021 https://wwwnc.cdc.gov/eid/article/27/7/20-4670_article
Although an infected and asymptomatic therapy cat in a nursing home in Germany showed prolonged shedding of SARS-CoV-2 RNA up to day 21 after the first detection, genome sequencing found no further role of the cat in human infections on site.
Bodilsen J, Nielsen PB, Søgaard M. Hospital admission and mortality rates for non-covid diseases in Denmark during covid-19 pandemic: nationwide population based cohort study. BMJ 25 May 2021, 373. https://www.bmj.com/content/373/bmj.n1135
Hospital admissions for all major non-COVID-19 disease groups were 30% and 22% lower during the two national lockdowns compared to previous years. Additionally, mortality rates were higher overall and for patients admitted to hospital with conditions such as respiratory diseases, cancer, pneumonia, and sepsis.
Other facts to consider
Ganegoda NC, Wijaya KP, Amadi M, et al. Interrelationship between daily COVID-19 cases and average temperature as well as relative humidity in Germany. Sci Rep 11, 11302, May 28, 2021). https://doi.org/10.1038/s41598-021-90873-5
Well… please correct us if we are wrong: reported daily COVID-19 cases correlated negatively with the average temperature and positively with the average relative humidity. Correct?
However, temperature can only predict incident cases during hot (summer) and cold seasons (winter), not during transitional seasons (spring and fall). Relative humidity, on the other hand, is less likely to predict falling cases during hot seasons.
Leidi A, Koegler F, Dumont R, et al. Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study. Clin Inf Dis 27 May 2021, ciab495, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab495/6287116
Among 8344 serosurvey participants from Geneva, Switzerland, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow up of 35 weeks, there was a 94% (95% CI: 86% to 98%, P < 0.001) reduction in the hazard of having a positive SARS-CoV-2 test in seropositive people.
Revollo B, Blanco I, Toro J, et al. Same-day SARS-CoV-2 antigen test screening in an indoor mass-gathering live music event: a randomised controlled trial. Lancet Inf Dis May 27, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00268-1/fulltext
This RCT assessed the risk of COVID-19 transmission in an indoor mass-gathering live concert done under comprehensive safety measures, including same-day SARS-CoV-2 screening with Ag-RDTs, compulsory wearing of N95 face masks, and optimized air ventilation. The event, held in the Sala Apolo, Barcelona, Spain, on December 12, 2020, lasted for 5 h and included four performances: two DJ sessions and two live music acts. Participants were encouraged to sing and dance in the concert hall room, and no physical distancing was recommended. None of the 465 participants became infected, compared with two of the 495 people in the control arm.
Daniels CJ, Rajpal S, Greenshields JT, et al. Prevalence of Clinical and Subclinical Myocarditis in Competitive Athletes With Recent SARS-CoV-2 Infection. JAMA Cardiol May 27, 2021. https://jamanetwork.com/journals/jamacardiology/fullarticle/2780548?resultClick=1
In this study of aggregate data from 13 Big Ten universities, 1597 athletes who tested positive by PCR underwent comprehensive cardiac evaluation including ECG, echocardiogram, troponin, and CMR imaging. Of these, 2.3% had either clinical or subclinical myocarditis that restricted them from training and competitive play. The authors believe that the role of CMR imaging in routine screening for athletes’ safe return to play should be explored further.
Brueggemann AB, Jansen van Rensburg MJ, Shaw D, et al. Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data. Lancet Digital Health, June 1, 2021. Volume 3, ISSUE 6, e360-e370 https://www.thelancet.com/journals/landig/article/PIIS2589-7500(21)00077-7/fulltext
In this large study including 27 laboratories from 26 countries and territories, all laboratories experienced a significant and sustained reduction in invasive diseases due to S. pneumoniae, H. influenzae, and N. meningitis in early 2020. By contrast, no significant changes in the incidence of invasive S. agalactiae infections were observed. The incidence of reported S. pneumoniae infections decreased by 68% at 4 weeks and 82% at 8 weeks following the week in which significant changes in population movements were recorded.
Al Kaabi N, Zhang Y, Xia S, et al. Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults. A Randomized Clinical Trial. JAMA May 26, 2021. https://jamanetwork.com/journals/jama/fullarticle/2780562?resultClick=24
Interim analysis of an RCT with 40,382 participants from countries in the Middle East who received at least 1 dose of a 2-dose inactivated vaccine series developed from either SARS-CoV-2 WIV04 or HB02 strains or an aluminum hydroxide–only control. Primary endpoint was the incidence of symptomatic COVID-19 at least 14 days after the second injection. The efficacy for the 2 vaccines was 72.8% in the WIV04 group and 78.1% in the HB02 group. Given the young age of the participants (median 36 years), there were only 2 severe infections, both occuring in the control arm.
Salzman MB, Huang C-W, O’Brien CM, Castillo RD. Multisystem inflammatory syndrome after SARS-CoV-2 infection and COVID-19 vaccination. Emerg Infect Dis May 26, 2021. https://wwwnc.cdc.gov/eid/article/27/7/21-0594_article
Three patients from California are described, who experienced multisystem inflammatory syndrome (MIS) after immunization and SARS-CoV-2 infection.
Dhindsa S, Zhang N, McPhail MJ, et al. Association of Circulating Sex Hormones With Inflammation and Disease Severity in Patients With COVID-19. JAMA Netw Open May 25, 2021;4(5):e2111398. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780135?resultClick=24
Unlike the common presumption, testosterone may not be a propagator of COVID-19 severity. On the contrary, it may be protective in men: this single-center cohort study of 152 patients with COVID-19 found that men with severe COVID-19 had 65% to 85% lower testosterone concentrations compared with men with a milder disease course, and this difference was independent of other known risk factors associated with severity, such as age, BMI, co-morbidities, smoking, and race.
Kim MH, Salloum S, Wang JY, et al. Type I, II, and III interferon signatures correspond to COVID-19 disease severity. J Inf Dis May 24, 2021, jiab288, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab288/6283761
Patients with mild COVID-19 exhibited transient type I interferon responses, while ICU patients had prolonged type I interferon responses with hyper-inflammation mediated by interferon regulatory factor 1. Type II interferon responses were compromised in ICU patients. Type III interferon responses were induced in the early phase of SARS-CoV-2 infection, even in convalescent patients.
Nasserie T, Hittle M, Goodman SN, et al. Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19A Systematic Review. JAMA Netw Open May 26 2021. 2021;4(5):e2111417. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780376?resultClick=24
This systematic review found that symptoms commonly persisted beyond the acute phase of infection. However, current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.
Jones TC, Biele G, Mühlemann B, et al. Estimating infectiousness throughout SARS-CoV-2 infection course. Science 25 May 2021: eabi5273. https://science.sciencemag.org/content/early/2021/05/24/science.abi5273
Probably the most comprehensive study on infectiousness. Analyzing viral load, cell culture isolation, and genome sequencing data from 25,381 positive samples, the authors estimate 4.3 days from onset of shedding to peak viral load and cell culture isolation probability. Of note, among 2,228 (9%) highly-infectious subjects with a first-positive viral load of at least 9.0 log10, 804 (36.1%) were pre-, asymptomatic or mildly-symptomatic at the time of testing. B.1.1.7 subjects had mean log10 viral load 1.05 higher than non-B.1.1.7, with estimated cell culture replication probability 2.6 times higher.
CDC COVID-19 Vaccine Breakthrough Case Investigations Team. COVID-19 Vaccine Breakthrough Infections Reported to CDC — United States, January 1–April 30, 2021. MMWR Morb Mortal Wkly Rep. ePub: 25 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7021e3.htm?s_cid=mm7021e3_w
As of April 30, 2021, approximately 101 million persons in the US had been fully vaccinated against COVID-19. A total of 10,262 SARS-CoV-2 vaccine breakthrough infections had been reported, among them 6446 (63%) in females. In total, 995 (10%) patients were known to be hospitalized, and 160 (2%) patients died. Sequence data were available from 555 (5%) reported cases, 356 (64%) of which were identified as SARS-CoV-2 variants of concern, including B.1.1.7 (199; 56%), B.1.429 (88; 25%), B.1.427 (28; 8%), P.1 (28; 8%), and B.1.351 (13; 4%).
Giannis D, Allen SL, Tsang J, et al. Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry. Blood May 20, 2021. https://ashpublications.org/blood/article/137/20/2838/475684/Postdischarge-thromboembolic-outcomes-and
Among 4906 patients, post-discharge thromboprophylaxis was prescribed in 13.2%. Venous thromboembolism (VTE) rate was 1.55% and arterial thromboembolism (ATE) was at 1.71%. Post-discharge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54). Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥ 4, and ICU stay increased risk.
Akindele NP, Kuo T, Karaba AH, et al. Hospitalized Children with Acute COVID-19 and Multisystem Inflammatory Syndrome with Similar Levels of Nasopharyngeal SARS-CoV-2 Shedding. J Infect Dis May 24, 2021, jiab285. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab285/6283764
The distinct pattern of heightened cytokine/chemokine dysregulation observed with MIS-C, compared with acute COVID-19, occurs across the pediatric age spectrum and with similar levels of nasopharyngeal SARS-CoV-2 RNA.
Sparrow AK, Brosseau LM, Harrison RJ, et al. Protecting Olympic Participants from Covid-19 — The Urgent Need for a Risk-Management Approach. NEJM May 25, 2021. https://www.nejm.org/doi/full/10.1056/NEJMp2108567?query=featured_home
Bottom line of this perspective: the IOC has no clue, no plan. The authors recommend that the WHO immediately convene an emergency committee that includes experts in occupational safety and health, building and ventilation engineering, and infectious-disease epidemiology, as well as athlete representatives, to advise on a risk-management approach for the Tokyo Olympics.
Wilson N, Baker MG, Blakely T, et al. Estimating the impact of control measures to prevent outbreaks of COVID-19 associated with air travel into a COVID-19-free country. Sci Rep May 24, 2021, 11, 10766. https://www.nature.com/articles/s41598-021-89807-y
This modelling study suggests that the risk of an outbreak in a previously COVID-19-free country is extremely dependent on the source country of the incoming travelers. In some countries, the risk could potentially be reduced to tolerable levels with a package of multi-layered interventions (particularly with repeated testing and mask use) and no quarantine. Nevertheless, quarantine is likely to remain important when the source country has high disease burden.
Gettings J, Czarnik M, Morris E, et al. Mask Use and Ventilation Improvements to Reduce COVID-19 Incidence in Elementary Schools — Georgia, November 16–December 11, 2020. MMWR Morb Mortal Wkly Rep 21 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7021e1.htm
Representatives from 169 (11.6%) of 1461 schools in 51 Georgia counties completed a survey and also had available COVID-19 case data. COVID-19 incidence was 37% lower in schools that required teachers and staff members to use masks and 39% lower in schools that improved ventilation. Ventilation strategies associated with lower school incidence included dilution methods alone (35% lower incidence) or in combination with filtration methods (48% lower incidence).
Ratckliff J, Nguyen D, Fish M, et al. Virological and serological characterization of critically ill patients with COVID-19 in the UK: Interactions of viral load, antibody status and B.1.1.7 variant infection. J Inf Dis 24 May 2021, jiab283, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab283/6283590
Among 1274 subjects, viral loads were higher in B.1.1.7 infected individuals than those infected with wild-type, but only in those who had already seroconverted for anti-SARS-CoV-2 antibody, indicating less effective clearance by innate and adaptive immune responses.
Vayne C, Rollin J, Gruel Y, et al. PF4 Immunoassays in Vaccine-Induced Thrombotic Thrombocytopenia. NEJM May 19. 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2106383?query=featured_coronavirus
It is important to use the right assay in patients with suspected VITT. Rapid immunoassays should be avoided in the detection of PF4-specific antibodies.
Mariette X, Hermine O, Tharaux PL, et al. Effectiveness of Tocilizumab in Patients Hospitalized With COVID-19A Follow-up of the CORIMUNO-TOCI-1 Randomized Clinical Trial. JAMA Network May 24, 2021. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2780021?resultClick=1
Post hoc analysis of a French RCT, including hospitalized patients who were receiving oxygen but did not require high-flow or mechanical ventilation. Results were stratified by CRP. In patients with CRP levels greater than 15.0 mg/dL, the percentage of patients who received ventilation or those who died was 18% and 57% in the tocilizumab and usual care groups, respectively. Day-90 mortality was 9% and 35% in the tocilizumab and usual care groups, respectively.
Hodgson D, Flasche S, Jit M, et al. The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant. Euro Surveill May 20, 2021. 26(20):pii=2100428. https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428
This brilliant modeling study suggests that if highly transmissible variants become dominant in areas with low seroprevalence, control of infection by vaccination, in the absence of non-pharmaceutical interventions, may only be achievable with a vaccine effectiveness against infectiousness of ≥ 80% – as suggested by early data for mRNA vaccines – extended to the full population, including children.
Lanier WA, Babitz KD, Collingwood A, et al. COVID-19 Testing to Sustain In-Person Instruction and Extracurricular Activities in High Schools — Utah, November 2020–March 2021. MMWR Morb Mortal Wkly Rep. ePub: 21 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7021e2.htm?s_cid=mm7021e2_w
Listen up, education policymakers: Utah implemented two high school COVID-19 testing programs to sustain in-person instruction and extracurricular activities. During November 30, 2020–March 20, 2021, of 59,552 students who received testing, 1886 (3.2%) had a positive result. These programs facilitated the completion of approximately 95% of high school extracurricular competition events and saved an estimated 109,752 in-person instruction student-days.
Piñero, P., Marco De La Calle, F., Horndler, L. et al. Flow cytometry detection of sustained humoral immune response (IgG + IgA) against native spike glycoprotein in asymptomatic/mild SARS-CoV-2 infection. Sci Rep 11, 10716 (2021). https://www.nature.com/articles/s41598-021-90054-4
A highly sensitive and specific flow cytometry assay that allows the detection of IgG and IgA antibodies, directed against the native and functional S protein of SARS-CoV-2 exposed on the membrane of a transfected cell line. IgG antibodies remained detectable for at least 8 months from the first PCR+ in virtually all mild or asymptomatic patients.
Singh AK, Singh R, Joshi SR, et al. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes & Metabolic Syndrome: Clinical Research & Review. May 21, 2021. https://www.sciencedirect.com/science/article/pii/S1871402121001570
COVID-19-associated mucormycosis (also called “black fungus”, the association of an aggressive fungal infection with COVID-19) has gained much media attraction during recent days. By May 13, this review found a total of 101 cases of which 82 cases had been reported from India. Diabetes was present in 80% of them, while corticosteroid treatment was given for COVID-19 in 76.3%. The most common organ involved with mucormycosis was the nose and sinuses (89%).
Harrington P, de Lavallade H, Doores KJ, et al. Single dose of BNT162b2 mRNA vaccine against SARS-CoV-2 induces high frequency of neutralising antibody and polyfunctional T-cell responses in patients with myeloproliferative neoplasms. Leukemia May 22, 2021. https://www.nature.com/articles/s41375-021-01300-7
Myeloproliferative neoplasms (MPN), in particular myelofibrosis (MF), are associated with a pro-inflammatory state and dysregulation of the function of pivotal natural killer cells, regulatory T cells and effector T cells. In this unselected cohort of 21 MPN patients, responses to the first injection of BNT162b2 were good: neutralizing antibodies were detected in 86% of patients and a memory T cell response was seen in 80%.
Le Vu, S., Jones, G., Anna, F. et al. Prevalence of SARS-CoV-2 antibodies in France: results from nationwide serological surveillance. Nat Commun May 21, 12, 3025. https://www.nature.com/articles/s41467-021-23233-6
The first wave in France. Testing 11,000 residual specimens for anti-SARS-CoV-2 IgG and neutralizing antibodies, the authors found nationwide seroprevalence of 0.41% mid-March, 4.14% mid-April and 4.93% mid-May 2020. The authors infer that as of 17 May 2020, only 1 in 24 cumulative infections was reported as a confirmed case. Overall infection fatality rate (IFR) was estimated at 0.84% and increased exponentially with age, peaking in those ≥ 80 years old at 9.70%.
Formeister EJ, Chien W, Agrawal Y, et al. Preliminary Analysis of Association Between COVID-19 Vaccination and Sudden Hearing Loss Using US Centers for Disease Control and Prevention Vaccine Adverse Events Reporting System Data. JAMA Otolaryngology–Head & Neck Surgery, May 20, 2021. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2780288?resultClick=1
No association exists between mRNA vaccines and sudden hearing loss.
Sowerby LJ, Nichols AC, Gibson R, et al. Assessing the Risk of SARS-CoV-2 Transmission via Surgical Electrocautery Plume. JAMA Surgery May 21, 2021. https://jamanetwork.com/journals/jamasurgery/fullarticle/2780434?resultClick=1
SARS-CoV-2 was not detectable in aerosol cautery plume (“surgical smoke”) generated from electrocautery under any of the conditions studied despite the high viral titers used.
Wu CT Lidsky PV, Xiao Y, et al. SARS-CoV-2 infects human pancreatic β-cells and elicits β-cell impairment. Cell Metabolism May 18, 2021. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00230-8
Emerging clinical reports have noted a significant increase in new onset hyperglycemia and diabetes in patients with COVID-19. This study shows that SARS-CoV-2 can directly induce β cell killing. Whereas ACE2 as well as TMPRSS2 were modestly expressed in β cells, selective expression of other critical SARS-CoV-2 entry factors, NRP1 and TFRC, was observed in β cells, indicating that this enrichment is a potential mechanism underlying SARS-CoV-2 tropism for β cells.
Tang X, Uhl S, Zhang T, et al. SARS-CoV-2 Infection Induces Beta Cell Transdifferentiation. Cell Metabolism May 19, 2021. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00232-1
This study shows what happens after ß cell infection: infected beta cells show a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin, respectively, suggesting cellular trans-differentiation.
Grau-Expósito J, Sánchez-Gaona N, Massana N, et al. Peripheral and lung resident memory T cell responses against SARS-CoV-2. Nat Commun May 20, 2021, 12, 3010. https://doi.org/10.1038/s41467-021-23333-3
Some more insights on T cell response to SARS-CoV-2. The acute response of non-hospitalized patients is characterized by CD4+ and, to a lesser extent, CD8+ SARS-CoV-2-specific T cells secreting IL-10. In contrast, hospitalized patients show a bias towards an effector response characterized by IFNγ and IL-4 secretion as the main functions as severity increases. Secondly, depending on the SARS-CoV-2 viral protein targeted, different CD4+ and CD8+ T cell functional profiles are generated. Finally, and most importantly, SARS-CoV-2 resident memory T cells persist for 10 months after infection; nonetheless, the magnitude and profile of the lung SARS-CoV-2-specific T cells strongly differ from the response detected in blood.
Ogata AF, Cheng CA, Desjardins M, et al. Circulating SARS-CoV-2 Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients. Clin Inf Dis May 20, 2021, ciab465, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab465/6279075
In this study, 11/13 participants exhibited S1 antigen in plasma as early as day one after the first vaccine injection, while nucleocapsid concentrations were insignificant in all participants, confirming that the detected S1 originates from vaccination and not natural infection. The presence of S1 was likely due to the nature of the encoded mRNA-1273 spike protein, which contains a cleavable S1-S2 site and enables release of S1 from the spike trimer2. It is hypothesized that release of S1 protein could result from cleavage via mammalian cell proteases or circulating proteases.
Yokota I, Shane PY, Okada K, et al. A novel strategy for SARS-CoV-2 mass screening with quantitative antigen testing of saliva: a diagnostic accuracy study. Lancet Microbe May 19, 2021. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00092-6/fulltext
A chemiluminescent enzyme immunoassay (CLEIA; Lumipulse G SARS-CoV-2 Ag kit, Fujirebio, Tokyo, Japan) was developed that can detect SARS-CoV-2 nucleoproteins in NPS or saliva samples within 35 min. Using self-collected saliva obtained from 2056 participants, CLEIA is shown to be a reliable alternative to RT-qPCR with high concordance.
Daugherty SE, Guo Y, Heath K, et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ May 19, 2021; 373. doi: https://doi.org/10.1136/bmj.n1098
This retrospective study, conducted in a large administrative database, evaluated the excess risk of developing a wide range of clinical sequelae after the acute phase of SARS-CoV-2 infection in commercially insured adults aged 18-65. Around 14% developed at least one new type of clinical sequelae that required medical care after the acute phase of SARS-CoV-2 infection, which was 4.95% higher than the 2020 comparator group and 1.65% higher than individuals diagnosed as having viral lower respiratory tract illness. The risk for incident sequelae increased with age, pre-existing conditions, and admission to hospital for COVID-19, and in adults aged ≤ 50 and those with no pre-existing conditions or not admitted to hospital, the risk for some clinical sequelae was still elevated.
Anand S, Montez-Rath ME, Han J, et al. Serial SARS-CoV-2 Receptor-Binding Domain Antibody Responses in Patients Receiving Dialysis. Ann Int Med May 18. https://www.acpjournals.org/doi/10.7326/M21-0256
In this large cohort of patients receiving maintenance dialysis who were seropositive for total SARS-CoV-2 antibodies in July 2020, most demonstrated an RBD IgG response that persisted for at least 6 months after infection.
Toh ZQ, Higgins RA, Do LAH, Rautenbacher K, Mordant FL, Subbarao K, et al. Persistence of SARS-CoV-2–specific IgG in children 6 months after infection, Australia. Emerg Infect Dis May 20, 2021. https://wwwnc.cdc.gov/eid/article/27/8/21-0965_article
SARS-CoV-2–positive children (n = 15) with no or mild symptoms mounted strong and durable humoral responses that persisted for > 6 months.
Chu DKW, Gu H, Chang LDJ, Cheuk SSY, Gurung S, Krishnan P, et al. SARS-CoV-2 superspread in fitness center, Hong Kong, China, March 2021. Emerg Infect Dis. 2021 Aug [date cited]. https://doi.org/10.3201/eid2708.210833
An asymptomatic 27-year-old male fitness trainer with a positive PCR. About 300 visitors were tested and 101 cases were confirmed (7 staff members and 94 customers). Mask wearing during exercise was not compulsory by law at the time of this outbreak.
Renner K, Schwittay T, Chaabane S, et al. Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes. Nat Commun May 21, 2021, 12, 3006. https://www.nature.com/articles/s41467-021-23334-2
Low polyclonal T cell reactivity is a hallmark of COVID-19 patients and strongly correlated with disease severity. T cell reactivity was much lower in ventilated than in non-ventilated hospitalized patients, which was again somewhat lower than in healthy controls. Of note, T cell hyporeactivity was only detectable in assays with whole blood but not with purified PBMC and could be attributed to suppressive components present in the plasma of COVID-19 patients.
Cheng Y, Ma N, Witt C, et al. Face masks effectively limit the probability of SARS-CoV-2 transmission. Science 20 May 2021. https://science.sciencemag.org/content/early/2021/05/19/science.abg6296
When people see images of millions of respiratory particles exhaled by talking or coughing, they may be afraid that simple masks cannot really protect them. This modeling study explains why wearing simple masks can indeed keep the number of inhaled viruses low. However, unfavorable conditions and the large variability of viral loads may lead to a virus-rich regime in certain indoor environments. In such environments, high efficiency masks and further protective measures like efficient ventilation should be used. The non-linear dependence of mask efficacy on airborne virus concentration also highlights the importance of combining masks with other preventive measures.
Yuan M, Huang D, Lee CC, et al. Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants. Science 20 May 2021:eabh1139. https://science.sciencemag.org/content/early/2021/05/19/science.abh1139
The B.1.1.7 lineage has acquired N501Y, the B.1.351 and P.1 lineages share this mutation plus K417N/T and E484K, and the “California” variants have an L452R mutation that is also present in the Indian variant B.1.617 with E484Q. Binding and neutralization of the two most frequently elicited antibody families are shown to be abrogated by K417N, E484K, or both. These effects can be structurally explained by their extensive interactions with receptor-binding site nAbs. Since nAbs to the more conserved, cross-neutralizing CR3022 and S309 sites were largely unaffected, these sites are promising targets to avoid interference by SARS-CoV-2 mutations observed to date.
Islam N, Shkolnikov VM, Acosta RJ, et al. Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries. BMJ May 19, 2021; 373. https://www.bmj.com/content/373/bmj.n1137
In this international comparative study of excess deaths in relation to the COVID-19 pandemic in 29 high income countries, all countries had excess deaths in 2020, except New Zealand, Norway, and Denmark. The highest excess deaths were in the US, Italy, England and Wales, Spain, and Poland. Accounting for difference in age, the excess death rates were much higher in men than women in almost all countries.
Wang EY, Mao T, Klein J, et al. Diverse Functional Autoantibodies in Patients with COVID-19. Nature May 19, 2021. https://www.nature.com/articles/s41586-021-03631-y
Is it all just dysregulated humoral immunity? This important paper reveals an expansive autoantibody landscape in COVID-19 and identified distinct autoantibodies that exerted striking immunological and clinical outcomes. COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. These autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition.
White EM, Yang X, Blackman C, et al. Incident SARS-CoV-2 Infection among mRNA-Vaccinated and Unvaccinated Nursing Home Residents. NEJM May 19, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2104849?query=featured_coronavirus
This large study on 18,242 residents shows real-world effectiveness of the mRNA vaccines in reducing the incidence of asymptomatic and symptomatic SARS-CoV-2 infections in a vulnerable population in 280 nursing homes.
Meister TL, Fortmann J, Todt D, et al. Comparable environmental stability and disinfection profiles of the currently circulating SARS-CoV-2 variants of concern B.1.1.7 and B.1.351. J Inf Dis 2021, May 16, 2021. https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab260/6276396
Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility to disinfection. Surface stability was comparable on steel, silver, copper and face masks.
Li Y, Tong CH, Bare LA, et al. Assessment of the Association of Vitamin D Level With SARS-CoV-2 Seropositivity Among Working-Age Adults. JAMA Netw Open May 19,2021;4(5):e2111634. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779952?resultClick=1
Have you ever heard about the strong correlation between per capita cheese consumption and the number of people who died by becoming tangled in their bedsheets (r=0.95!)? Between the divorce rate in Maine and the per capita consumption of margarine (r=0.99!)? Then please consult this website: http://www.tylervigen.com/spurious-correlations. Vitamin D and COVID-19 seem to be another nice example. In this large study on 18,148 employees and spouses, SARS-CoV-2–seropositive individuals did have lower vitamin D levels than seronegative individuals. However, low vitamin D levels were not independently associated with the risk of seropositivity. Vitamin D deficiency and insufficiency were more common in individuals who had a BMI equal to or greater than 30. And in people who did not have a college degree, or who were younger. Who were current smokers, hypertensive, or Asian, Black, Hispanic, American Indian or Alaska Native, and Native Hawaiian or other Pacific Islander race/ethnicity. (Bottom line: Correlation does not imply causation)
Cunningham JW, Claggett BL, Jering KS, et al. Prognostic Value of Natriuretic Peptides & Cardiac Troponins in COVID-19. Circulation 17 May 2021, https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.054969
Using data from a large health care company, 48,510 inpatients discharged (alive or dead) between April 1 and November 30, 2020 were analyzed for biomarkers at admission. Despite modest levels in most patients with COVID-19, natriuretic peptides and troponin elevation strongly and independently predicted in-hospital death, including in patients without cardiovascular disease. However, the extent to which biomarker levels reflected pre-existing cardiovascular disease or COVID-19 severity remains unclear.
Low JS, Vaqueirinho D, Mele F, et al. Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2. Science 18 May 2021:eabg8985. https://science.sciencemag.org/content/early/2021/05/17/science.abg8985
COVID-19-recovered individuals display a robust CD4+ T cell response to naturally processed SARS-CoV-2 spike (S) and nucleoprotein (N), including effector, helper, and memory T cells. Using pre- and post-COVID-19 samples and S proteins from endemic coronaviruses, the authors also identified cross-reactive T cells targeting multiple S protein sites, also providing evidence for the recall of pre-existing cross-reactive memory T cells upon SARS-CoV-2 infection.
Prince SE, Chen H, Tong H, et al. Assessing the effect of beard hair lengths on face masks used as personal protective equipment during the COVID-19 pandemic. J Expo Sci Environ Epidemiol May 18, 2021. https://www.nature.com/articles/s41370-021-00337-1
Where is your shaving kit? In bearded men, KF94 and KN95 masks lost up to 40% of their fitted filtration efficiency (FFE). Although N95 respirators showed considerable variability among bearded men, they had the highest FFE for beard lengths of maximum 10 mm.
Haghpanah A, Masjedi F, Salehipour M, et al. Is COVID-19 a risk factor for progression of benign prostatic hyperplasia and exacerbation of its related symptoms?: a systematic review. Prostate Cancer Prostatic Dis May 18, 2021. https://www.nature.com/articles/s41391-021-00388-3
Answer: We don’t know (no studies).
Mayanskiy N, Luchkina P, Fedorova N et al. Seroconversion and dynamics of the anti-SARS-CoV-2 antibody response related to a hospital COVID-19 outbreak among pediatric oncology patients. Leukemia May 18, 2021. https://www.nature.com/articles/s41375-021-01288-0
An outbreak at the hemato-oncology department of a Russian children’s clinical hospital at the end of April 2020. In total, 18 patients with neoplasms (16 with acute lymphoblastic leukemia) receiving multidrug chemotherapy were infected. The majority had a mild course and produced antibodies of different isotypes against the RBD and N target antigens.
Garrido-Pontnou M, Navarro A, Camacho J, et al. Diffuse trophoblast damage is the hallmark of SARS-CoV-2-associated fetal demise. Mod Pathol May 18, 2021. https://www.nature.com/articles/s41379-021-00827-5
SARS-CoV-2-positive placentas show a particular lesion characterized by trophoblast necrosis and intervillous space collapse. It can be seen as tiny foci in the less affected cases or as massively extensive lesions in the more severe ones.
Gao X, Zhu K, Qin B. et al. Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions. Nat Commun May 14, 2021, 12, 2843. https://doi.org/10.1038/s41467-021-23118-8
Orf9b is a unique accessory protein of SARS-CoV-2 and SARS-CoV. It is implicated in immune evasion by targeting mitochondria, where it associates with the versatile adapter TOM70. This study determined the crystal structure of SARS-CoV-2 Orf9b in complex with the cytosolic segment of human TOM70.
BergamaschiL, Mescia F, Turner L, et al. Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease. Immunity May 16, 2021. https://www.cell.com/immunity/fulltext/S1074-7613(21)00216-8
This analysis of serial samples from 207 SARS-CoV-2-infected individuals showed that an early robust bystander CD8+ T cell immune response, without systemic inflammation, characterizes asymptomatic or mild disease. Circulating plasmablasts and CD8+HLA‐DR+CD38+ activated T cells expanded earlier and in higher numbers than in more severe COVID‐19 groups, most notably in the first week after symptom onset.
Roeker LE, Knorr DA, Thompson MC. et al. COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia. Leukemia May 13, 2021. https://www.nature.com/articles/s41375-021-01270-w
Only half of fully vaccinated patients (two doses of mRNA vaccines) with CLL develop detectable anti-SARS-CoV-2 S1/S2 antibodies. There was a significant difference between rates of detectable anti-SARS-CoV-2 S1/S2 antibodies between treatment-naïve patients (17/18, 94%) and those who had received CLL directed therapy (6/26, 23%).
Supaday A, Weber E, Rieder M, et al. Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial. Lancet Resp Med May 14, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00177-6/fulltext
In this small RCT, early initiation of cytokine adsorption (using the CytoSorb adsorber) in patients with severe COVID-19 and venovenous ECMO did not reduce serum IL-6. Of note, cytokine adsorption was associated with an increased mortality risk within 30 days of initiation of ECMO.
Bian H, Zheng ZH, Wei D, et al. Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial. Sig Transduct Target Ther May 17, 2021, 6, 194.
CD147 serves as a novel receptor for SARS-CoV-2 infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection. This small pilot study on 19 COVID-19 patients suggests that meplazumab could accelerate the recovery of patients from pneumonia with a favorable safety profile.
Today we focus on vaccines. There is plenty of good news to share: mRNA vaccines work in real-life, in the US, in Israel, and even after the first shot. These vaccines may offer some protection against the South African variant. However, switching between vaccines (first dose vs second) may also be a reasonable option and although a significant loss in protection from SARS-CoV-2 infection will occur over the first year, protection from severe disease should be largely retained.
Pilishvili T, Fleming-Dutra KE, Farrar JL, et al. Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel — 33 U.S. Sites, January–March 2021. MMWR Morb Mortal Wkly Rep. ePub: 14 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7020e2.htm?s_cid=mm7020e2_w
This large US multisite test-negative design vaccine effectiveness study among HCP found a single dose of Pfizer-BioNTech or Moderna vaccines to be 82% effective against symptomatic COVID-19 and 2 doses to be 94% effective.
Chodick G, Tene L, Rotem RS, et al. The effectiveness of the TWO-DOSE BNT162b2 vaccine: analysis of real-world data. Clinical Infectious Diseases May 17, 2021, ciab438, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab438/6276888
Real life data from Israel. Incidence rate of a SARS-CoV-2 infection between 7 to 27 days after the second dose (the protection period) was compared to days 1 to 7 after the first dose, where no protection by the vaccine is assumed (the reference period). In 1.1 million vaccinated persons, vaccine effectiveness in preventing infection was 90% and 94% against COVID-19. Look at the beautiful Figure 1.
Spencer AJ, McKay PF, Belij-Rammerstorfer S. et al. Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice. Nat commun May 17, 2021. 12, 2893. https://www.nature.com/articles/s41467-021-23173-1
Switching vaccines (first dose vs second) may induce strong immune responses. In mice, antibody responses were high with two-dose heterologous vaccination (first shot with mRNA, second with AstraZeneca, or vice versa) regimens. Neutralizing titers were at least comparable or higher than the titers measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen was dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens. Several trials in humans are underway (https://comcovstudy.org.uk/home).
Bailly B, Guilpain L, Bouiller K, et al. BNT162b2 mRNA vaccination did not prevent an outbreak of SARS COV-2 variant 501Y.V2 in an elderly nursing home but reduced transmission and disease severity. Clinical Infectious Diseases, 16 May 2021. ciab446, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab446/6276392
An outbreak of SARS-CoV-2 1.351 (the South African variant) in a nursing home in Jura, in eastern France. 5/5 non-vaccinated residents versus 13/26 of those vaccinated with BNT162b2 were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease.
Khoury DS, Cromer D, Reynaldi A, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med May 17, 2021. https://www.nature.com/articles/s41591-021-01377-8
Using data from several large vaccine trials (because of the different assays used, neutralization titers were normalized to the mean convalescent titer using the same assay in the same study), the authors estimate the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20% of the mean convalescent level. The estimated neutralization level required for 50% protection from severe infection was significantly lower (3%). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained.
Holmdahl I, Kahn R, Hay JA, et al. Estimation of Transmission of COVID-19 in Simulated Nursing Homes With Frequent Testing and Immunity-Based Staffing. JAMA Netw Open May 14, 2021, 4(5):e2110071. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779870
Frequent and rapid testing! This decision analytical modeling study has evaluated COVID-19 transmission in nursing homes associated with contact-targeted interventions and testing. The testing strategy associated with the greatest estimated reduction in infections was daily antigen testing, indicating that faster results should be prioritized over higher sensitivity.
Wallace M, Woodworth KR, Gargano JW, et al. The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine in Adolescents Aged 12–15 Years — United States, May 2021. MMWR Morb Mortal Wkly Rep. ePub: 14 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7020e1.htm?s_cid=mm7020e1_w#suggestedcitation
On May 10, 2021, the Food and Drug Administration expanded Emergency Use Authorization for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12–15 years. Read why here.
Wu K, Choi A, Koch M, et al. Preliminary Analysis of Safety and Immunogenicity of a SARS-CoV-2 Variant Vaccine Booster. doi: https://doi.org/10.1101/2021.05.05.21256716
Not yet peer reviewed, but important, good news. In total, 40 people who had already been fully vaccinated with mRNA-1273, received a third shot 6 months later. A booster dose of mRNA-1273.351, Moderna’s variant-matched vaccine, achieved higher neutralizing antibody titers against the B.1.351 variant (the “immune escape” variant from South Africa) than a booster dose of mRNA-1273. However, the best news is that the titers were high enough to kill B.1.351 even in those who received the conventional vaccine.
Alkharaan H, Bayati S, Hellström C, et al. Persisting Salivary IgG against SARS-CoV-2 at 9 Months After Mild COVID-19: A Complementary Approach to Population Surveys. J Inf Dis May 12, 2021, jiab256, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab256/6274637
Unlike SARS-CoV-2 salivary IgA that appeared short-lived, the specific IgG in saliva appeared stable even after mild COVID-19 as noted for blood serology. This non-invasive saliva-based antibody test may serve as a complementary alternative to conventional blood serology.
Docherty AB, Mulholland RH, Lone NI, et al. Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK. Lancet Resp Med May 14, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00175-2/fulltext
In this large multi-center prospective observational cohort study at 247 acute general hospitals in the UK, patients who were admitted to hospital in March and early April, 2020, were substantially more unwell at presentation than patients who were admitted in later months (June and July 2020). Mortality declined in all age groups, in all ethnic groups, in men and women, and in patients with and without co-morbidities, over and above contributions from declining severity of illness. After adjustment for these variables, a fifth of the reduction in mortality was explained by changes in the use of respiratory support and steroid treatment.
Parcha V, Booker KS, Kalra R, et al. A retrospective cohort study of 12,306 pediatric COVID-19 patients in the United States. Sci Rep 11, 10231 (2021). https://www.nature.com/articles/s41598-021-89553-1
In this retrospective cross-sectional analysis of 12,306 pediatric patients, 16.5% presented with respiratory symptoms, 13.9% had gastrointestinal symptoms, 8.1% had dermatological symptoms (rash), 4.8% had neurological (headache), and 18.8% had other non-specific symptoms (fever, malaise, myalgia, arthralgia and disturbances of smell or taste). The hospitalization frequency was 5.3%. Following propensity score matching, the risk of all outcomes was similar between males and females.
Ma S, Zhang F, Zhou F, et al. Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19. Sig Transduct Target Ther May 13, 2021, 6, 191. https://doi.org/10.1038/s41392-021-00614-3
SARS-CoV-2 infection alters the composition of the oropharyngeal microbiota and causes dysbiosis of the local microbiome, which may induce translocation of oral pathogens into the lungs to cause pulmonary co-infections.
Decaro N, Vaccari G, Lorusso A, Lorusso E, De Sabato L, Patterson EI, et al. Possible human-to-dog transmission of SARS-CoV-2, Italy, 2020. Emerg Infect Dis May 12, 2021. https://doi.org/10.3201/eid2707.204959
Pet story, volume one: A female poodle, who was 1.5 years of age, lived with 4 family members in Bitonto, Italy. All five became infected. Full-length genome sequencing showed that the canine and human viruses were identical, suggesting human-to-animal transmission.
Colitti B, Bertolotti L, Mannelli A, et al. Cross-sectional serosurvey of companion animals housed with SARS-CoV-2–infected owners, Italy. Emerg Infect Dis May 11, 2021. 2021 Jul [date cited]. https://doi.org/10.3201/eid2707.203314
Pet story, volume two: Among animals living with SARS-CoV-2–infected owners, 20.4% (11/54) of cats and 3.2% (3/93) of dogs were seropositive. A 13-year-old female cat was hospitalized for a brachial cephalic thrombosis and a 3-year-old male cat was hospitalized for interstitial pneumonia.
Moreno GK, Braun KM, Pray IW, et al. SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing. Clinical Infectious Diseases May 12, 2021, ciab343, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab343/6274297
Antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings.
RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet May 14, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00897-7/fulltext
No, it’s not a matter of titres, antibodies, timing, endpoints etc: convalescent plasma (CP) has NO clinical benefit. In RECOVERY, the by far largest study to date on patients hospitalized with COVID-19, high-titre CP did not improve survival: 1399 (24%) of 5795 patients died in the CP group and 1408 (24%) of 5763 patients died in the usual care group. Of note, there were no differences in other prespecified clinical outcomes and the results were consistent across subgroups of age, sex, ethnicity, duration of symptoms before randomization, level of respiratory support received at randomisation, and use of corticosteroids. Time to face the reality.
Yang Q, Saldi TK, Gonzales PK, et al. Just 2% of SARS-CoV-2−positive individuals carry 90% of the virus circulating in communities. PNAS May 11, 2021. 118 (21) e2104547118; https://doi.org/10.1073/pnas.2104547118
The vast majority of circulating virions in communities are found within the bodies of a small number of individuals. Testing more than 72,500 saliva samples by PCR from individuals who reported no symptoms on the day of collection, 1405 positive cases were identified. Regardless of symptomatic status, ∼ 50% of individuals who test positive for SARS-CoV-2 seem to be in non-infectious phases of the disease, with low viral loads in a range from which live virus has rarely been isolated. At any given time, only 2% of individuals carry 90% of the virions circulating within communities, serving as viral “super-carriers” and possibly also super-spreaders.
Yao L, Wang GL, Shen Y, et al. Persistence of Antibody and Cellular Immune Responses in COVID-19 patients over Nine Months after Infection. J Inf Dis May 12, 2021, jiab255, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab255/6274562
Of 59 COVID-19 patients, approximately 90% of patients had detectable IgG antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~ 60% of patients had detectable IgG antibodies against receptor binding domain and surrogate virus-neutralizing antibodies. Specific IgG + memory B cell and IFN-γ secreting T cell responses were detectable in over 70% of patients.
Romero-Brufau S, Chopra C, Ryu A, et al. Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study. BMJ May 12, 2021; 373 doi: https://www.bmj.com/content/373/bmj.n1087
This simulation modeling study suggests that a delayed second dose vaccination strategy, at least for people aged under 65, could result in reduced cumulative mortality under certain conditions.
Liu Y, Liu J, Xia H, et al. BNT162b2-Elicited Neutralization against New SARS-CoV-2 Spike Variants. NEJM May 12, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2106083?query=featured_home
The newly emerged B.1.526, B.1.429, and B.1.1.7+E484K variants remained susceptible to BNT162b2-elicited immune effector (neutralizing antibody).
Carr J, Wright AK, Leelarathna L, et al. Impact of COVID-19 on diagnoses, monitoring, and mortality in people with type 2 diabetes in the UK. Lancet Diab Endocrin May 11, 2021. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00116-9/fulltext
In April 2020, the rate reduction of new diagnoses of type 2 diabetes in primary care practices in England was 0.70 when compared with 10-year historical trends. Older individuals (65 years and older), men, and people from deprived areas had the greatest reductions in diagnosis rates.
Guagliardo SA, Prasad PV, Rodriguez A, et al. Cruise ship travel in the era of COVID-19: A summary of outbreaks and a model of public health interventions. Clinical Infectious Diseases May 12, 2021, ciab433, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab433/6274545
SARS-CoV-2 outbreaks on cruises in US waters or carrying US citizens: from January 19 to April 16, 2020, 89 voyages on 70 ships had known outbreaks. There were 1669 SARS-CoV-2 infections and 29 confirmed deaths. Mathematical models showed that 7-day voyages had about 70% fewer cases than 14-day voyages. On 7-day voyages, the most effective interventions were reducing the number of individuals onboard (43-49%) and testing passengers and crew (42-43%). Of note, no single intervention or combination eliminated transmission.
Bhatt PR, Scaiola A, Loughran G, et al. Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome. Science May 12, 2021. https://science.sciencemag.org/content/early/2021/05/12/science.abf3546
This study provides a mechanistic description of frameshifting that occurs during translation of the SARS-CoV-2 genome and reveal the features that may be exploited by the virus to finely control the stoichiometry of viral proteins at different stages of infection.
Bernal JL, Andrews N, Gower C, et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ May 13, 2021; 373. https://www.bmj.com/content/373/bmj.n1088
Early real-life data in older people (older than 70 years) from England: with BNT162b2, vaccine effectiveness reached 61% from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards.
Brihn A, Chang J, OYong K, et al. Diagnostic Performance of an Antigen Test with RT-PCR for the Detection of SARS-CoV-2 in a Hospital Setting — Los Angeles County, California, June–August 2020. MMWR Morb Mortal Wkly Rep 2021;70:702–706. https://www.cdc.gov/mmwr/volumes/70/wr/mm7019a3.htm?s_cid=mm7019a3_w
In this analysis of RT-PCR and antigen testing of asymptomatic and symptomatic patients at the time of tertiary hospital admission through the ED, the sensitivity of the Quidel Sofia 2 SARS Antigen FIA test was 66% (72% and 61% in symptomatic and asymptomatic patients, respectively).
Collier AY, McMahan K, Yu J, et al. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. JAMA May 13, 2021. https://jamanetwork.com/journals/jama/fullarticle/2780202?resultClick=1
In this small exploratory analysis of 30 pregnant and 16 lactating women, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and non-pregnant women who were vaccinated developed cross-reactive antibody responses and T cell responses against SARS-CoV-2 variants of concern.
Dispinseri S, Secchi M, Pirillo MF, et al. Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival. Nat Commun 12, 2670 (2021). https://www.nature.com/articles/s41467-021-22958-8
In this study on 169 symptomatic COVID-19 patients, neutralizing antibody titers progressively dropped after 5–8 weeks but well still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities, with IgG to spike antigens providing the best correlate of neutralization.
Johnston MS, Galan A, Watsky KL, et al. Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine A Case Series. JAMA Dermatol May 12, 2021. https://jamanetwork.com/journals/jamadermatology/fullarticle/2779643?resultClick=1
The “COVID vaccine arm”: Delayed localized cutaneous reactions, developing in 16 patients (13 women), a median (range) of 7 (2-12) days after receiving the Moderna COVID-19 vaccine. Reactions occurred near the injection site and were benign and self-limited. These reactions are not a contraindication to subsequent vaccination.
Chou SH, Beghi E, Helbok R, et al. Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19—A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open May 11, 2021. 4(5):e2112131. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779759?resultClick=1
The largest study of neurological manifestations in patients hospitalized with COVID-19. This cohort included 3055 patients with COVID-19 at 28 centers, representing 13 countries and 4 continents. The most prevalent neurological signs and/or syndromes were acute encephalopathy (49%), coma (17%), and stroke (6%), while meningitis and/or encephalitis were rare (0.5%). Neurological symptoms were associated with premature mortality.
McMahon CL, Staples H, Gazi M, et al. SARS-CoV-2 targets glial cells in human cortical organoids. Stem Cell Rep May 11, 2021. Volume 16, ISSUE 5, P1156-1164, May 11, 2021. https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00046-1
SARS-CoV-2 can infect cortical organoids at low titers. There was a preference to glial cells, specifically astrocytes and radial glial progenitor cells. However, replication did not occur.
Bertuzzi AF, Ciccarelli M, Marrari A, et al. Impact of active cancer on COVID-19 survival: a matched-analysis on 557 consecutive patients at an Academic Hospital in Lombardy, Italy. Br J Cancer May 11, 2021). https://www.nature.com/articles/s41416-021-01396-9
Propensity score matching showed a 1.9 × risk of death in active cancer patients compared to non-oncologic patients (p = 0.013), adjusted for ICU-related bias.
Lee LY Rozmanowski S, Pang M, et al. SARS-CoV-2 infectivity by viral load, S gene variants and demographic factors and the utility of lateral flow devices to prevent transmission. Clinical Infectious Diseases May 11, 2021, ciab421, https://doi.org/10.1093/cid/ciab421
This large-scale analysis of combined SARS-CoV-2 contact tracing and testing data from England involving > 2 million contacts of PCR-confirmed cases shows that SARS-CoV-2 infectivity is associated with index case viral load, including after adjustment for demographic factors and type of contact event. SGTF (a proxy for the B.1.1.7 variant), increased transmission by ~ 50% at most viral loads. Except SGTF, there was no significant interaction between Ct values and any other variables in the analysis. Thus, the effect of viral load on infectivity is generalizable across populations and settings.
Lund LC, Hallas J, Nielsen H, et al. Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study. Lancet Inf Dis May 10, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00211-5/fulltext
This nationwide cohort study investigated the occurrence of post-acute effects of SARS-CoV-2 infection in individuals who were not admitted to hospital for primary infection. The absolute risk of severe post-acute complications after SARS-CoV-2 infection not requiring hospital admission was low. There was no increased risk of delayed severe acute complications and new onset of chronic disease, except for a slightly increased absolute risk of venous thromboembolism.There was also an increased risk of healthcare encounters caused by dyspnea.
Huang L, Cao B. Post-acute conditions of patients with COVID-19 not requiring hospital admission. Lancet Inf Dis May 10, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00225-5/fulltext
In their comment, Lixue Huang and Bin Cao argue that there is the possibility of greatly underestimating the real prevalence, due to so many reasons that patients with persistent symptoms might not visit a healthcare service, such as symptoms being mild, not having health insurance or access to healthcare, and the risk of re-infection when visiting a health-care facility during the COVID-19 pandemic.
Chou SH, McWilliams A, Murphy S, et al. Factors Associated With Risk for Care Escalation Among Patients With COVID-19 Receiving Home-Based Hospital Care. Ann Int Med May 11, 2021. https://www.acpjournals.org/doi/10.7326/M21-0409
Home care included 24/7 telephone access to nurses; at least daily in-home visits from paramedics; daily virtual visits with someone at the hospital; and therapies that included intravenous fluids and antibiotics, non-invasive oxygen, and respiratory medications as needed. Results: most patients did not require care escalation, with approximately 1 in 5 admitted within 14 days.
Pineles BL, Goodman KE, Pineles L. In-Hospital Mortality in a Cohort of Hospitalized Pregnant and Nonpregnant Patients With COVID-19. Annals Int Med May 11, 2021. https://www.acpjournals.org/doi/10.7326/M21-0974
In this large database including patient discharge data from 853 hospitals, in-hospital death was rare but occurred in 0.8% (n = 9) of pregnant patients. Ages ranged from 23 to 44 years. Eight of the nine were non-Hispanic Black or Hispanic. Six were obese, and 7 had at least 1 co-morbid condition. Gestational ages ranged from 23 to 39 weeks, and 7 of 9 deliveries were live births.
Panda AK, Pati A, Padhi S, et al. Granulin rs5848 (C>T) polymorphism is associated with SARS-CoV-2 infection and mortality. J Inf Dis 5 May 2021, jiab237, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab237/6265298
A common genetic polymorphism in the granulin gene (C>T, rs5848) has been reported to be associated with altered mRNA and protein levels. This preliminary data indicates that the C allele of the progranulin rs5848 polymorphism predisposes to SARS-CoV-2 infection susceptibility and mortality.
Roussel M, Ferrant J, Reizine F, et al. Comparative immune profiling of acute respiratory distress syndrome patients with or without SARS-CoV2 infection. Cell Rep Med May 06, 2021. https://doi.org/10.1016/j.xcrm.2021.100291
The immune landscape in COVID-19-associated ARDS compared to other causes of ARDS: an increase of CD169 positive monocytes, correlated with specific changes of T, plasma, and NK cell subsets, defined COVID-19-associated ARDS and was not found in bacteria-associated ARDS, suggesting a COVID-19-specific immune reprogramming.
Iruzubieta P, Fernández-Lanas T, Rasines L, et al. Feasibility of large-scale population testing for SARS-CoV-2 detection by self-testing at home. Sci Rep 11, 9819 (2021). https://doi.org/10.1038/s41598-021-89236-x
A high level of feasibility and applicability of SARS-CoV-2 serological screening with a rapid antibody self-test. Most participants (96.9%) obtained a valid test result, with 96.2% of them able to correctly perform the self-test procedure without healthcare support. Of note, no differences were found regarding educational level, age above 65 years, and housing area between subjects who performed the self-test correctly vs those who did not.
Staub T, Arendt V, de la Vega EC. Case series of four re-infections with a SARS-CoV-2 B.1.351 variant, Luxembourg, February 2021. Eurosurveillance May 6, 2021. https://www.eurosurveillance.org/content/eurosurveillance/26/18
Four female HCW from the same hospital. All recovered and their re-infections were not severe.
Ram-Mohan N, Zudock EJ, Hashemi MM, et al. SARS-CoV-2 RNAemia predicts clinical deterioration and extrapulmonary complications from COVID-19. Clinical Infectious Diseases 5 May 2021, ciab394, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab394/6265285
In 131 patients, RNAemia was a robust predictor of eventual COVID-19 severity. Initially RNAaemic patients were more likely to manifest severe disease (OR 6.72), worsening of disease severity (OR 2.43), and ICU admission (OR 2.81).
Zhang L, Richards A, Barrasa I, et al. Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues. PNAS May 25, 2021 118 (21) e2105968118; https://doi.org/10.1073/pnas.2105968118
SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of the infected cell and be expressed as chimeric transcripts fusing viral with cellular sequences. Importantly, such chimeric transcripts are detected in patient-derived tissues. Data suggest that, in some patient tissues, the majority of viral transcripts are derived from integrated sequences. This may help explain why patients can continue to produce viral RNA after recovery.
Zheng M, Karki R, Williams EP, et al. TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nature Immunology 07 May 2021. https://www.nature.com/articles/s41590-021-00937-x
TLR2 is a cell surface innate immune sensor with the ability to recognize diverse ligands from viruses, fungi, bacteria and parasites. This study provides the first genetic evidence that TLR2 can sense β-coronavirus infection via recognition of the E protein to induce release of inflammatory cytokines, including TNF-α and IFN-γ. The activation of TLR2 signaling in response to β-coronavirus infection was independent of viral entry and replication.
Dugan HL, Stamper CT, Li L, et al. Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets. Immunity May 6, 2021. https://doi.org/10.1016/j.immuni.2021.05.001
This study characterized the SARS-CoV-2-specific B cell repertoire in 38 COVID-19 patients, both severe acute and convalescent, approximately 1.5–4.5 months post-symptom onset, using oligo-tagged antigen-bait sorting and single-cell RNA sequencing. Memory B cells ((MBC) displayed substantial reactivity toward NP and ORF8 and continued to expand and adapt to these targets over time, particularly in older patients. While SARS-CoV-2 RBD-specific monoclonal antibodies (mAbs) were potently neutralizing and protective, anti-NP and anti-ORF8 mAbs failed to neutralize and provide protection in vivo. Thus, preexisting MBC bias to non-neutralizing targets in SARS-CoV-2 could impact susceptibility to or severity of re-infection.
Cáceres CJ, Cardenas-Garcia S, Carnaccini S et al. Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model. Sci Rep May 4, 2021, 11, 9609. https://www.nature.com/articles/s41598-021-89013-w
GC-376 is a Mpro inhibitor with antiviral activity against SARS-CoV-2 in vitro. In mice challenged with a low virus dose, GC-376 treatment led to milder tissue lesions, reduced viral loads, less presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls.
Bellon M, Baggio S, Bausch FJ, et al. SARS-CoV-2 viral load kinetics in symptomatic children, adolescents and adults. Clinical Infectious Diseases 05 May 2021, ciab396, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab396/6265276
Viral shedding kinetics over the first week of illness for symptomatic children (n = 279), adolescents (n = 639) and adults (n = 7109) show viral loads compatible with infectious virus presence, with slightly lower viral loads in children than adults.
Nunes MC, Baillie VL, Kwatra G, et al. SARS-CoV-2 infection among healthcare workers in South Africa: a longitudinal cohort study. Clinical Infectious Diseases 05 May 2021, ciab398, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab398/6265294
From April to September 2020, 35% of 396 HCWs at Chris Hani Baragwanath Hospital, South Africa had PCR-confirmed SARS-CoV-2 infection, an additional 27 infections were identified by serology. HCWs in the Internal Medicine department had the highest rate of infection (62%).
Angel Y, Spitzer A, Henig O, et al. Association Between Vaccination With BNT162b2 and Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infections Among Health Care Workers. JAMA May 6, 2021. https://jamanetwork.com/journals/jama/fullarticle/2779853
Among 6710 health care workers in Tel Aviv, 757 (11.3%) were not vaccinated. Symptomatic SARS-CoV-2 infection occurred in 8 fully vaccinated and 38 unvaccinated health care workers (adjusted IRR, 0.03). The corresponding numbers for asymptomatic SARS-CoV-2 infections were 19 and 17, respectively (adjusted IRR, 0.14). Results were qualitatively unchanged by the propensity score sensitivity analysis.
Pottegård A, Lund LC, Karlstad Ø, et al. Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. BMJ May 5, 2021; 373. https://www.bmj.com/content/373/bmj.n1114
Among 281,264 people who received ChAdOx1-S, 11 and 2.5 excess events per 100,000 vaccinations were seen for venous thromboembolic events and cerebral venous thrombosis, respectively.
Hui X, Zhang L, Cao L, et al. SARS-CoV-2 promote autophagy to suppress type I interferon response. Sig Transduct Target Ther May 8, 2021. 6, 180. https://www.nature.com/articles/s41392-021-00574-8
Interesting novel finding: SARS-CoV-2 utilizes autophagy to escape host immune defense. SARS-CoV-2 M protein induced mitophagy to break the mitochondria networks to block the downstream innate immunity signaling that inhibits the type I IFN response.
Drake TM, Fairfield CJ, Pius R, et al. Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study. Lancet Rheumatology May 07, 2021. https://doi.org/10.1016/S2665-9913(21)00104-1
Do you remember the rumors surrounding ibuprofen use during the first wave? Forget it. Among 78,674 patients across 255 health-care facilities in England, Scotland, and Wales, NSAID use was not associated with higher mortality or increased severity of COVID-19.
Borchering RK, Viboud C, Howerton E, et al. Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios — United States, April–September 2021. MMWR Morb Mortal Wkly Rep. ePub: 5 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7019e3.htm?s_cid=mm7019e3_w#suggestedcitation
Data from six models indicate that with high vaccination coverage and moderate non-pharmaceutical intervention (NPI) adherence, hospitalizations and deaths will likely remain low nationally, with a sharp decline in cases projected by July 2021. Lower NPI adherence could lead to substantial increases in severe COVID-19 outcomes, even with improved vaccination coverage.
Boyarsky NJ, Werbel WA, Avery RK, et al. Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients. JAMA May 5, 2021. https://jamanetwork.com/journals/jama/fullarticle/2779852?resultClick=1
At a median of 29 days after dose 2, antibody was detectable in 357/658 organ recipients (54%). Poor humoral response was persistently associated with use of anti-metabolite immunosuppression.
Lucas C, Klein J, Sundaram ME, et al. Delayed production of neutralizing antibodies correlates with fatal COVID-19. Nat Med May 4, 2021. https://www.nature.com/articles/s41591-021-01355-0
Paper of the day. Although sera from 85% of patients displayed some neutralization capacity during their disease course, generation of neutralizing antibodies (NAb) before day 14 of disease onset emerged as a key factor for recovery. This analysis of 229 COVID-19 patients suggests that mortality does not correlate with the cross-sectional antiviral antibody levels per se but rather with the delayed kinetics of NAb production.
Anand SP, Prévost J, Nayrack M, et al. Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to eight months post-symptom onset. Cell Rep Med May 4, 2021. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00118-X
Longitudinal assessment of humoral immune responses on 32 donors up to 8 months post-symptom onset indicate that anti-spike and anti-RBD IgM in plasma decay rapidly, whereas the reduction of IgG is less prominent.
Wu X, Liu X, Zhou Y, et al. 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. Lancet Resp Med May 05, 2021. https://doi.org/10.1016/S2213-2600(21)00174-0
One year later. In 135 patients who recovered from severe COVID-19, dyspnea scores and exercise capacity improved over time; however, at 12 months, pulmonary function tests (ie, diffusing capacity of the lungs for carbon monoxide, DLCO) remained impaired at 12% and radiographic changes were found in 24%.
Today, we present five papers focusing on variants: the Novavax Phase II study in South Africa, important real-life data on BNT162b2 (BioNTech/Pfizer) from Israel and Quatar indicating protection from B.1.1.7. and B.1.351, and some data on new variants (“California” and “New York”) circulating in the US.
Shiinde V, Bhikha S, Hoosain Z, et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant. NEJM May 5, 2021, https://www.nejm.org/doi/full/10.1056/NEJMoa2103055?query=featured_home
Early findings on the efficacy of a randomized, placebo-controlled, Phase IIa/b trial of Novavax’ nanoparticle vaccine NVX-CoV2373. The trial was conducted in 4347 predominantly young and healthy people in South Africa during a period of predominant circulation of the B.1.351 variant. Vaccine efficacy among HIV-negative participants was 60% (B.1.351: 51%). Severe COVID-19 was rare. Of note, previous infection with wild type viruses did not appear to reduce the risk of COVID-19 due to subsequent infection with B.1.351 variants among placebo recipients during the first 2 months of follow-up.
Haas EJ, Angulo FJ, McLaughlin JM, et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. The Lancet May 05, 2021. DOI:https://doi.org/10.1016/S0140-6736(21)00947-8
By April 3, 2021, 4.7 M people aged 16 years and older were fully vaccinated with two doses of BNT162b2 in Israel. Vaccine effectiveness at 7 days or longer after the second dose was 95% against SARS-CoV-2 infection, 97% against symptomatic COVID-19, 97% against hospitalization, and 98% against severe or critical disease. In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined. Estimated prevalence of the B.1.1.7 variant was 95%.
Abu-Raddad LJ, Chemaitelly H, Butt AA. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. NEJM May 5, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2104974?query=featured_home
Following a mass immunization campaign with BNT162b2 in Qatar, as of March 31, 2021, a total of 385,853 persons had received at least one vaccine dose and 265,410 had completed both doses. The estimated effectiveness against any documented infection with the B.1.1.7 variant was 89.5% at 14 days or more after the second dose. The effectiveness against any documented infection with the B.1.351 variant was 75%. Of note, effectiveness against severe, critical, or fatal disease (with the B.1.1.7 and B.1.351 variants being predominant in Qatar) was very high, at 97%.
Thompson CN, Hughes S, Ngai S, et al. Rapid Emergence and Epidemiologic Characteristics of the SARS-CoV-2 B.1.526 Variant — New York City, New York, January 1–April 5, 2021. MMWR Morb Mortal Wkly Rep. ePub: 5 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7019e1.htm?s_cid=mm7019e1_w#suggestedcitation
The “New York variant”: although the SARS-CoV-2 B.1.526 variant emerged rapidly in NYC, early evidence suggests that this variant, even with the E484K mutation (found in 40%), does not lead to more severe disease and is not associated with increased risk for breakthrough infection or re-infection compared with other sequenced SARS-CoV-2 viruses.
Martin Webb L, Matzinger S, Grano C, et al. Identification of and Surveillance for the SARS-CoV-2 Variants B.1.427 and B.1.429 — Colorado, January–March 2021. MMWR Morb Mortal Wkly Rep. ePub: 5 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7019e2.htm?s_cid=mm7019e2_w#suggestedcitation
The arrival of the two “California” variants B.1.427/B.1.429 in Colorado: the proportion of sequenced specimens increased from 3%–4% in late January to 20%–22% in early March. Some (very) preliminary data indicate that B.1.427/B.1.429 might more frequently cause discernible and severe illness than do other circulating lineages.
Voss WN, Hou YJ, Johnson NV, et al. Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes. Science 04 May 2021: https://science.sciencemag.org/content/early/2021/05/03/science.abg5268
Important paper on the molecular composition and binding epitopes of the convalescent plasma IgG response to SARS-CoV-2. This response is oligoclonal and directed overwhelmingly toward non-receptor-binding domain (RBD) epitopes in the SARS-CoV-2 spike ectodomain, including public, near-germline, and potently neutralizing antibodies against the N-terminal domain (NTD). Genetic, structural, and functional characterization of a multi-donor class of “public” antibodies revealed an NTD epitope that is recurrently mutated among emerging SARS-CoV-2 variants of concern.
Garrett ME, Galloway J, Chu HY, et al. High resolution profiling of pathways of escape for SARS-CoV-2 spike-binding antibodies. Cell May 04, 2021. https://www.cell.com/cell/fulltext/S0092-8674(21)00580-8
This brilliant study provides a granular view of potential antibody escape pathways: the authors tested all possible mutations on the S protein to provide a map of escape pathways within immunodominant linear epitopes targeted by the plasma of convalescent COVID-19 patients. The responses within an individual were consistent over time, but there were many unique pathways of escape that differed between individuals, even within the same epitope region. Findings suggest that the pattern of viral evolution within the growing pandemic is not likely to be driven by a single antibody escape mutation, which may explain the lack of emergence of circulating strains with mutations that disrupt antibody binding identified here.
Salto-Alejandre S, Jiménez-Jorge S, Sabé N, Ramos-Martínez A, Linares L, Valerio M, et al. Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study. PLoS ONE 16(4): e0250796. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250796
In this prospective observational cohort study of 210 consecutive solid organ transplant recipients hospitalized with COVID-19 in 12 Spanish centers, four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis.
Riou C, Du Bruyn E, Stek C, et al. Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and Tuberculosis co-infection. J Clin Inv May 4, 2021. https://www.jci.org/articles/view/149125
This study shows that HIV-1 and TB co-infection may skew the SARS-CoV-2 T cell response. HIV-1 mediated CD4 T cell depletion is associated with suboptimal T cell and humoral immune responses to SARS-CoV-2; an active TB is associated with a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4 T cells.
Pavone P, Ceccarelli M, Marino S, et al. SARS-CoV-2 related Paediatric Acute-onset Neuropsychiatric Syndrome. Lancet Child Adolesc Health May 04, 2021. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00135-8/fulltext
Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) presents with a sudden onset of obsessive-compulsive disorder or a severely restricted food intake, and concurrent neuropsychiatric symptoms and motor dysfunction. The authors report two unrelated adolescents with PANS that started 2 weeks after a positive COVID-19 nasopharyngeal swab.
Hilt EE, Boocock J, Trejo M, et al. Retrospective Detection of SARS-CoV-2 in Symptomatic Patients prior to Widespread Diagnostic Testing in Southern California. Clin Inf Dis May 3, 2021, ciab360, https://doi.org/10.1093/cid/ciab360
The authors found SARS-CoV-2 in 7 specimens from 6 patients dating back to mid-January, indicating community spread of SARS-CoV-2 in the Los Angeles area well before widespread diagnostic testing was being performed in early 2020.
Fabiani M, Ramigni M, Gobbetto V, et al. Effectiveness of the Comirnaty (BNT162b2, BioNTech/Pfizer) vaccine in preventing SARS-CoV-2 infection among healthcare workers, Treviso province, Veneto region, Italy, 27 December 2020 to 24 March 2021. Eurosurveillance May 3, 2021. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.17.2100420
In this study on 6423 HCW from northern Italy, vaccine effectiveness (VE) was high. VE in preventing symptomatic infections during the time intervals 1–14 days and 15–28 days from administration of the first dose were 40% (95% CI: 9–60) and 86% (95% CI: 33–97), respectively.
Diao B, Wang C, Wang R, et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection. Nat Commun May 4, 2021, 12, 2506. https://doi.org/10.1038/s41467-021-22781-1
SARS-CoV-2 virus can directly infect human renal cells. Both viral NP and S protein antigens were found in the kidneys from 6 COVID-19 autopsies, accumulating in ACE2+ kidney tubules.
De la Puerta R, Montoro J, Aznar C, et al. Common seasonal respiratory virus infections in allogeneic stem cell transplant recipients during the SARS-COV-2 pandemic. Bone Marrow Transplant May 4, 2021. https://www.nature.com/articles/s41409-021-01319-5
Through a prospective common seasonal respiratory virus (CSRV) survey program conducted from 2016, a significant drop in CSRV activity during the SARS-COV-2 pandemic was observed in allo-HSCT recipients, supporting the idea that prevention measures for the general population are highly effective in reducing CSRV prevalence and its complications in immunocompromised patients.
Fernández-de-las-Peñas C, Torres Macho J, Velasco-Arribas M, et al. Similar Prevalence of Long-Term Post-COVID Symptoms in Patients with Asthma: A Case-Control Study. J Infection May 2, 2021. https://doi.org/10.1016/j.jinf.2021.04.034
In this study from Madrid, from 800 randomized COVID-19 patients hospitalized during the first wave of the pandemic, 61 patients with asthma and 122 age- and sex-matched patients without asthma were recruited. From the total sample, only 34 (18.6%) were completely free of any post-COVID symptom 7 months after hospital discharge. Individuals with pre-existing asthma showed similar numbers of post-COVID symptoms than those without asthma.
Tan AX, Hinman JA, Magidf HS, et al. Association Between Income Inequality and County-Level COVID-19 Cases and Deaths in the US. JAMA Netw Open. May 3, 2021. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779417?resultClick=1
This ecological cohort study found that there was a positive correlation between Gini coefficients (a measure of unequal income distribution) and county-level COVID-19 cases and deaths during the study period. Of note, the association varied over time and was strongest in the summer months of 2020.
Solforosi L, Kuipers H, Jongeneelen M, et al. Immunogenicity and efficacy of one and two doses of Ad26.COV2.S COVID vaccine in adult and aged NHP. J Exp Med April 28 2021. https://rupress.org/jem/article/218/7/e20202756/212032/Immunogenicity-and-efficacy-of-one-and-two-doses?searchresult=1
In rhesus macaques, spike protein–specific immune responses were better with two-doses of the Ad26.COV2.S vaccine. In humans, a two-dose regimen is currently evaluated in a Phase 3 study (ENSEMBLE 2).
Issakhov A, Zhandaulet Y, Omarova P et al. A numerical assessment of social distancing of preventing airborne transmission of COVID-19 during different breathing and coughing processes. Sci Rep May 3, 2021, 11, 9412. https://www.nature.com/articles/s41598-021-88645-2
Paper of the day. This study looked at the transport of droplets or particles generated by the respiratory system in a room during various scenarios. Results: Social distance of 2 m is sufficient for simple breathing for all cases (without ventilation and with ventilation). However, when coughing or sneezing, this distance is clearly not enough and it needs at least 5 m social distance in order not to get into the zone of exposure to these particles.
Sharov KS. 8806 Russian patients demonstrate T cell count as better marker of COVID-19 clinical course severity than SARS-CoV-2 viral load. Sci Rep 11, 9440, May 3, 2021. https://www.nature.com/articles/s41598-021-88714-6
Congrats to Konstantin S. Sharov. He is the sole author of this impressive paper, indicating that T lymphocyte count may be a perspective marker of COVID-19 course severity and prognosis, more unambiguous than SARS-CoV-2 VL in the upper respiratory tract or respiratory index PaO2/FiO2. Using T cell count in clinical practice may provide an opportunity of early prediction of deteriorating a patient’s state.
Roth GAA, Emmons-Bell S, Alger HM. Trends in Patient Characteristics and COVID-19 In-Hospital Mortality in the United States During the COVID-19 Pandemic. JAMA Netw Open May 3, 2021; 4(5):e218828. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779415?resultClick=1
Again, a learning curve. In this large cohort study, the high rates of in-hospital COVID-19 mortality among US registry patients in March and April 2020 fell by 38% by May and June with a modest further decrease by November. This difference persisted even after adjusting for age, sex, medical history, and COVID-19 disease severity.
Wiens KE, Mawien PN, Rumunu J, Slater D, Jones FK, Moheed S, et al. Seroprevalence of severe acute respiratory syndrome coronavirus 2 IgG in Juba, South Sudan, 2020. Emerg Infect Dis April 27, 2021 Jun [date cited]. https://wwwnc.cdc.gov/eid/article/27/6/21-0568_article
Relatively few coronavirus cases and deaths have been reported from sub-Saharan Africa. After performing a huge cross-sectional survey in South Sudan (August–September 2020), the authors estimate that 38% (95% CI: 32%–47%) of the population had been infected with SARS-CoV-2. For each PCR–confirmed SARS-CoV-2 infection officially reported, 103 infections went unreported.
Feder KA, Pearlowitz M, Goode A, et al. Linked Clusters of SARS-CoV-2 Variant B.1.351 — Maryland, January–February 2021. MMWR Morb Mortal Wkly Rep 2021;70:627–631. https://www.cdc.gov/mmwr/volumes/70/wr/mm7017a5.htm?s_cid=mm7017a5_w#suggestedcitation
The first clusters of B.1.351 infections in the US with no identified link to international travel. The two linked clusters included 17 patients. Four cases were sequenced; all had the B.1.351 variant.
Hause AM, Gee J, Johnson T, et al. Anxiety-Related Adverse Event Clusters After Janssen COVID-19 Vaccination — Five U.S. Mass Vaccination Sites, April 2021. MMWR Morb Mortal Wkly Rep. ePub: 30 April 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7018e3.htm?s_cid=mm7018e3_w#suggestedcitation
Anxiety-related events, including fainting, can occur immediately after vaccination with any vaccine and might be caused by anxiety about receiving an injection. The stress of an ongoing pandemic might increase anxiety: Reports of syncope (fainting) are approximately 164 times more common after the Janssen COVID-19 vaccination (8.2 per 100,000) than after influenza vaccination (0.05 per 100,000).
Thell R, Zimmermann J, Szell M, et al. Standard blood laboratory values as a clinical support tool to distinguish between SARS-CoV-2 positive and negative patients. Sci Rep 11, 9365 (2021). https://doi.org/10.1038/s41598-021-88844-x
In this large study from Vienna, Austria, leukopenia, eosinopenia, elevated erythrocytes, hemoglobin and ferritin were detected to be among the best standard laboratory parameters to distinguish between COVID-19-positive and -negative patients.
Van Kemoen ZL, Strijbis EM, Al MM, et al. SARS-CoV-2 Antibodies in Adult Patients With Multiple Sclerosis in the Amsterdam MS Cohort. JAMA Neurol April 30, 2021. https://jamanetwork.com/journals/jamaneurology/fullarticle/2779734?resultClick=1
A lower SARS-CoV-2 antibody response was found in patients with MS who were depleted of B cells.
Carter RL, Rose D, Sabo R, et al. Widespread SARS-CoV-2 Transmission Among Attendees at a Large Motorcycle Rally and their Contacts, 30 US Jurisdictions, August–September, 2020. Clinical Infectious Diseases 29 April 2021, ciab321, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab321/6257584
A major event, the Sturgis Motorcycle Rally, held in Meade County, South Dakota, August 7–16, 2020, with approximately 462,000 persons attending a variety of outdoor and indoor activities. South Dakota had implemented few restrictions and there were no state, county, or city mask mandates in effect. Attendance at the rally led to widespread SARS-CoV-2 transmission to 463 people in 30 jurisdictions, with 17 jurisdictions reporting subsequent transmission to 186 household and workplace contacts (it is likely that the true numbers are largely underestimated). No comment.
See I, Su JR, Lale A, et al. US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021. JAMA April 30, 2021. https://jamanetwork.com/journals/jama/fullarticle/2779731?resultClick=1
Twelve US cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia following vaccination with Ad26.COV2.S, the COVID-19 vaccine produced by Janssen/J&J. All were women, younger than 60 years, and had symptom onset ranging from 6 to 15 days after vaccination that required hospitalization.
Reynolds CJ, Pade C, Gibbons JM, et al. Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose. Science 30 Apr 2021: eabh1282. https://science.sciencemag.org/content/early/2021/04/29/science.abh1282
T and B cell responses after first dose vaccination with the Pfizer/BioNTech vaccine were followed longitudinally in healthcare workers (HCW), with (n = 23) or without (n = 23) prior SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351.
Spinelli MA, Lynch KL, Yun C, et al. SARS-CoV-2 seroprevalence, and IgG concentration and pseudovirus neutralising antibody titres after infection, compared by HIV status: a matched case-control observational study. Lancet HIV April 29, 2021. https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(21)00072-2/fulltext
Among 31 people with HIV (PWH) and 70 people without HIV who had evidence of past infection, the odds of severe COVID-19 were 5.52 times higher among PWH. Adjusting for time since PCR-confirmed infection, SARS-CoV-2 IgG concentrations and pseudovirus neutralising antibody titers were lower in PWH.
Bartoszko JJ, Siemieniuk RA, Kum E, et al. Prophylaxis against covid-19: living systematic review and network meta-analysis. BMJ April 26, 2021; 373. https://www.bmj.com/content/373/bmj.n949
Bottom line of this review, including 9 RCTs: HCQ (hydroxychloroquine) is not protective and probably increases adverse effects, and any effect of ivermectin is “highly uncertain”.
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet May 01, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00676-0/fulltext
Paper of the day: The RECOVERY results do support the use of tocilizumab (TCZ)! Overall, 621 (31%) of the 2022 patients allocated to TCZ and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0.85; 95% CI: 0.76–0.94; p = 0.0028). TCZ patients were more likely to be discharged from hospital within 28 days (57% vs 50%). Benefits were consistent across all patient groups studied, including those receiving invasive mechanical ventilation, non-invasive respiratory support, or no respiratory support other than simple oxygen. The benefits were also clearly seen among those also receiving steroids. Of note, the RECOVERY trial contains around four times as much information as all previous trials combined.
Melms JC, Biermann J, Huang H, et al. A molecular single-cell lung atlas of lethal COVID-19. Nature April 29, 2021. https://doi.org/10.1038/s41586-021-03569-1
Single-nucleus RNA-sequencing of ~116,000 nuclei of lungs from 19 COVID-19 decedents and 7 control lungs, providing insights into the biology of lethal COVID-19: interplay among aberrantly activated monocytes/macrophages producing IL-1β, inflammation-induced impairment of alveolar epithelial regeneration, and expansion of pathological fibroblasts that promote fibrosis. Data also suggest that despite a potentially sufficient humoral immune response, T cell response was inadequate.
Delorey TM, Ziegler CG, Heimberg G, et al. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature April 29, 2021. https://doi.org/10.1038/s41586-021-03570-8
Complementing the above sister lung atlas above, these single-cell atlases of 23 lung, 16 kidney, 16 liver and 19 heart COVID-19 autopsy donor tissue samples, and spatial atlases of 14 lung donors elucidate the biological impact of severe SARS-CoV-2 infection across the body.
Koskinen A, Tolvi M, Jauhiainen M, et al. Complications of COVID-19 Nasopharyngeal Swab Test. JAMA Otolaryngol Head Neck Surg April 29, 2021. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2779393?resultClick=1
The risk for a severe complication requiring specialist-level care after SARS-CoV-2 nasopharyngeal swab testing is extremely low. During the 7-month study period (643,284 PCR tests performed), there were 8 complication-related visits: 4 nasal bleeds and 4 broken swabs, all occurring immediately after sampling.
Norman M, Navér L, Söderling J, et al. Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes. JAMA April 29, 2021. https://jamanetwork.com/journals/jama/fullarticle/2779586?resultClick=1
Among 88,159 infants in Sweden, 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. Maternal infection was associated with higher risk of any neonatal respiratory disorder (2.8% vs 2.0%; odds ratio, 1.42, 95% CI: 1.50-3.84). Neonatal mortality was also slightly higher but this was not statistically significant (0.30% vs 0.12%; odds ratio, 2.55, 95% CI: 0.99-6.57).