Top 10: February 26

Copy-editor: Rob Camp


Paper of the Day

Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. NEJM February 24, 2021.

No doubt, paper of the day! Encouraging real-life data from Israel: Estimated vaccine effectiveness (> 1 M people vaccinated) during the follow-up period starting 7 days after the second dose was 92% for documented infection, 94% for symptomatic COVID-19, 87% for hospitalization, and 92% for severe COVID-19. Estimated effectiveness days 14 through 20 (after one dose) and days 21 through 27 (gradual shifting between the first and second vaccine doses) was 46% and 60% for documented infection, 57% and 66% for symptomatic COVID-19, 74% and 78% for hospitalization, 62% and 80% for severe COVID-19, and 72% and 84% for COVID-19–related death, respectively.


Kyriakidis NC, López-Cortés A, González EV, et al. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. npj Vaccines 6, 28 (2021).

Comprehensive is right. A fantastic review discusses different strategies used for vaccine development and provides an overview of the current leading vaccine candidates against SARS-CoV-2.



Lendacki FR, Teran RA, Gretsch S, Fricchione MJ, Kerins JL. COVID-19 Outbreak Among Attendees of an Exercise Facility — Chicago, Illinois, August–September 2020. MMWR Morb Mortal Wkly Rep. ePub: 24 February 2021. DOI:

Have you recently met your personal trainer from the local gym? Did he tell you how he disagrees with the lockdown and the closing of the gym, after all they had worked so hard to develop wonderful hygiene management concepts? That all classes would be held at ≤ 25% capacity (i.e., 10–15 persons)? That mask use, temperature checks, symptom screenings would be required on entry (ok, patrons were allowed to remove masks during exercise) and that patrons would bring their own mats and weights and would be stationed ≥ 6 ft apart? Then show him this report. During August 24–September 1, 2020, an exercise facility at Chicago did exactly this. The results: 55 COVID-19 cases were identified among 81 attendees of indoor high-intensity classes. Twenty-two (40%) persons with COVID-19 attended on or after the day symptoms began. Most attendees (76%) wore masks infrequently, including persons with (84%) and without COVID-19 (60%).


Harvey RA, Rassen JA, Kabelac CA, et al. Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection. JAMA Intern Med February 24, 2021. Full-text:

Seropositivity is associated with protection from infection. In this cohort study of more than 3.2 million US patients with a SARS-CoV-2 antibody test, 0.3% of those indexed with positive test results had evidence of a positive nucleic acid amplification test beyond 90 days after index, compared with 3.0% indexed with negative antibody test results. During the follow-up periods, the ratio (95% CI) of positive PCR results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI: 2.73-2.97, consistent with prolonged RNA shedding!) at 0 to 30 days, 0.67 at 31 to 60 days, 0.29 at 61 to 90 days, and 0.10 at more than 90 days.


Katz MH. How to Advise Persons Who Are Antibody Positive for SARS-CoV-2 About Future Infection Risk. JAMA Intern Med February 24, 2021.

In his comment, Mitchell H. Katz still believes that vaccination against SARS-CoV-2 is recommended regardless of antibody status (as nobody knows how long antibody protection due to natural infection will last).


Davido B, Mascitti H, Fortier-Beaulieu M, et al. Blue toes’ following vaccination with the BNT162b2 mRNA COVID-19 vaccine. Journal of Travel Medicine, 23 February 2021, taab024,

COVID toes-like syndrome linked to COVID-19 vaccine: This interesting case report describes a young Caucasian female (aged 41) who presented with chilblain-like skin changes on her toes that appeared 4 days after the first injection with the Pfizer-BioNTech-162b2 vaccine.



Groves LM, Usagawa L, Elm J, et al. Community Transmission of SARS-CoV-2 at Three Fitness Facilities — Hawaii, June–July 2020. MMWR Morb Mortal Wkly Rep. ePub: 24 February 2021. DOI:

Twenty-one COVID-19 cases were linked to an index case in a fitness instructor, who, along with a patient who was also an instructor, taught classes < 1 day, 1 to < 2 days, and ≥ 2 days before symptom onset; aggregate attack rates were 95% (20 of 21), 13% (one of eight), and 0% (zero of 33). Of note, use of masks was not required in the fitness facilities.



Folgueira MD, Luczkowiak J, Lasala F, et al. Prolonged SARS-CoV-2 cell culture replication in respiratory samples from patients with severe COVID-19. Clin Microbiology Inf February 22, 2021. Full-text:

See title. This study from Madrid found a completely different pattern of SARS-CoV-2 viability in upper respiratory tract samples from mild cases, in which viral replication occurs for a short period (10 days), compared with hospitalized patients with severe COVID-19, in whom viable virus can frequently be demonstrated during prolonged periods of up to 4 weeks, both in their upper and lower respiratory tract samples, even in the presence of high levels of neutralizing activity.


Blain H, Gamon L, Tuaillon E, et al. Atypical symptoms, SARS-CoV-2 test results, and immunization rates in 456 residents from eight nursing homes facing a COVID-19 outbreak. Age and Ageing, February 23, 2021, afab050,

A retrospective longitudinal study in eight NHs with at least ten rRT-PCR-positive residents. Among 456 residents, 161 residents had a positive rRT-PCR (35%), 17% of whom were asymptomatic before testing. Temperature > 37.8°C, oxygen saturation < 90%, unexplained anorexia, behavioral change, exhaustion, malaise, and falls before testing were independent predictors of a further positive rRT-PCR. Hubert Blain and colleagues from France conclude that NH residents with unusual fatigue, behavioral change, anorexia, malaise or falls should be tested by rRT-PCR for an early identification of the first SARS-CoV-2 cases.


Gutiérrez-Gutiérrez B, del Toro MD, Borobia AM, et al. Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study. The Lancet Infectious Diseases February 23, 2021.

Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. Using two large cohorts with more than 3500 patients from Spain, the authors developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes, including a total of 16 variables. Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more co-morbidities and even higher inflammatory parameters than phenotype B. These results might help to better classify patients for clinical management. However, whether the model and derived calculator might be helpful in clinical practice is unknown. Moreover, the pathophysiological mechanisms of the phenotypes must be investigated.


Severe COVID-19

Yao Y, Ye F, Li K, et al. Genome and epigenome editing identify CCR9 and SLC6A20 as target genes at the 3p21.31 locus associated with severe COVID-19. Sig Transduct Target Ther February 22, 2021, 6, 85.

Recently, genome-wide association studies (GWASs) have identified chromosome 3p21.31 (sentinel variant: rs11385942) to be associated with severe COVID-19. By utilizing CRISPR/Cas9-mediated genomic deletion, the authors identified CCR9 and SLC6A20 as potential target genes of the 3p21.31 locus.


Feldstein LR, Tenforde MW, Friedman KW, et al. Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19. JAMA Network February 24, 2021. JAMA February 24, 2021.

Incredibly large case series of 1116 patients aged less than 21 years hospitalized between March 15 and October 31, 2020, at 66 US hospitals in 31 states. Comparing children and adolescents with MIS-C vs those with severe COVID-19, MIS-C was distinguished by certain demographic features and clinical presentations including being aged 6 to 12 years, being of non-Hispanic Black race, having severe cardiovascular or mucocutaneous involvement, and having more extreme inflammation.

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