Top 10: March 1

Copy-editor: Rob Camp


Paper of the Day

Zhou B, Thi Nhu Thao T, Hoffmann D, et al. SARS-CoV-2 spike D614G change enhances replication and transmission. Nature 26 February 2021.

Extensive study on the first update of SARS-CoV-2, namely the mutation at codon 614 (already partially dominant last spring in many countries). It is shown that the S-614G variant has enhanced binding to human host cell surface receptor ACE2, increased replication in primary human bronchial and nasal airway epithelial cultures as well as markedly increased replication and transmissibility in hamsters and ferrets. It will be interesting to see data on such in vivo competitive advantages with the new variants.



Mensah AA, Sinnathamby M, Zaidi A, et al. SARS-CoV-2 infections in children following the full re-opening of schools and the impact of national lockdown: prospective, national observational cohort surveillance, July-December 2020, England. J Infection February 24, 2021.

In England, childhood cases closely followed adult infection rates and national lockdown whilst keeping schools open was associated with large declines in SARS-CoV-2 infection rates, first in adults and then in school-aged children. There was a strong correlation in weekly infection rates between adults and all three educational cohorts during periods of both low and high community infection rates. Two messages from this paper: Schools are not the drivers but low community infection rates are required to allow schools to remain open safely.


Hyde Z. Difference in SARS-CoV-2 attack rate between children and adults may reflect bias. Clinical Infectious Diseases 26 February 2021, ciab183,

In her brief review, Zoë Hyde from Perth, Australia argues that lower secondary attack rates in children compared to adults may reflect lower testing in children and reduced exposure, rather than a genuine difference in biological susceptibility. Additionally, children may shed infectious virus for a shorter period than adults and their antibody response may be less broad, with implications for both polymerase chain reaction and serological testing. After reviewing the data available so far, she thinks it likely that children are more susceptible to SARS-CoV-2 infection than first thought, and they probably play an important role in community transmission.



Pawlowski C, Puranik A, Bandi H. et al. Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations. Sci Rep 11, 4741 (2021).

Do existing vaccines afford protection against SARS-CoV-2 infection through trained immunity? By analyzing immunization records from 137,037 individuals, Colin Pawlowski and colleagues from Cambridge found that several vaccines such as polio, MMR, flu or hepatitis A/hepatitis B vaccines administered in the past 1-5 years were associated with decreased SARS-CoV-2 infection rates, even after adjusting for geographic SARS-CoV-2 incidence and testing rates, demographics, co-morbidities, and number of other vaccinations. But can we believe this? Can we control for the “healthy user effect” (that persons who have recently had other vaccines may engage in general health-seeking behaviors which decrease their risk of SARS-CoV-2 infection)? The authors say yes. In a “negative control” experiment on patients who have recently taken cancer screens (who may also have lower rates due to the “healthy user effect”), their propensity score matching method was able to correct for confounding.



Metlay JP, Haas JS, Soltoff AE, Armstrong KA. Household Transmission of SARS-CoV-2. JAMA Netw Open. 2021 Feb 1;4(2):e210304. PubMed: Full-text:

In this large hospital and ambulatory care network based in Boston, US, 7262 index cases were linked to 17,917 additional at-risk individuals assigned to the same addresses. Overall household infection risk was 10.1%. Independent factors significantly associated with higher transmission risk included age greater than 18 years and multiple comorbid conditions (adjusted OR for individuals with hypertension, 1.93). In sensitivity analyses limiting the maximum size of the household to as small as 2 persons, the calculated transmission risk increased to only 13.8%.


Kraay ANM, Hayashi MAL, Berendes DM, Sobolik JS, Leon JS, Lopman BA. Risk for fomite-mediated transmission of SARS-CoV-2 in child daycares, schools, nursing homes, and offices. Emerg Infect Dis. February 24, 2021.

SARS-CoV-2 can persist on surfaces, suggesting possible surface-mediated transmission of this pathogen. Using a transmission model to explore the potential for fomite transmission without other pathways, Alicia N.M. Kraay from Atlanta and colleagues found that fomites might be a substantial source of transmission risk, particularly in schools and child daycares. Combining surface cleaning and decontamination with mask wearing can help mitigate this risk.



van Westen-Lagerweij NA, Meijer E, Meeuwsen EG, et al. Are smokers protected against SARS-CoV-2 infection (COVID-19)? The origins of the myth. npj Primary Care Respiratory Medicine February 26, 2021, volume 31, Article number: 10.

Do you believe that alcohol disinfects the stomach? Ok, then you don’t need to read any further. For the rest of us, this commentary dispels a few myths (or, if you will, bullsh*t studies) about smoking and COVID-19.


Struyf T, Deeks JJ, Dinnes J, et al. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19. Cochrane Database Syst Rev. 2021 Feb 23;2:CD013665. PubMed: Full-text:

Are there signs and symptoms predicting COVID-19? This Cochrane review says no.



Janiaud P, Axfors C, Schmitt AM, et al. Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis. JAMA. 2021 Feb 26. PubMed: Full-text:

This review of all RCTs published until January 29 showed that compared with placebo or standard of care, convalescent plasma was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes.


Gupta A, Madhavan MV, Poterucha TJ, et al. Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19. Nat Commun 12, 1325 (2021).

Better take your statins! Among 1296 patients (648 statin users, 648 non-statin users) identified with 1:1 propensity-score matching, statin use was significantly associated with lower odds of in-hospital mortality within 30 days in the propensity-matched cohort (OR 0.47, 95% CI: 0.36–0.62, p < 0.001). The potential benefits from statins extend beyond cholesterol-lowering properties, as there is a robust literature supporting the anti-inflammatory properties of statins, suggesting that these drugs can stabilize and restore endothelial function. Randomized clinical trials are ongoing (and needed).


Herrett E, Williamson E, Brack K, et al. Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials. BMJ. 2021 Feb 24;372:n135. PubMed: Full-text:

And for those patients who supposedly can’t tolerate a statin, it’s probably not the case. In this nice study among 151 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms, no difference in muscle symptom scores was found between the statin and placebo periods. Withdrawals because of intolerable muscle symptoms were 18 participants (9%) during a statin period and 13 (7%) during a placebo period. Two thirds of those completing the trial reported restarting long-term treatment with statins.


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