Copy-editor: Rob Camp
Paper of the Day
Wang P, Nair MS, Liu L, et al. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. Nature March 8, 2021. https://www.nature.com/articles/s41586-021-03398-2
For younger readers: once upon a time, in the stone age (c. 1996), David Ho from the Aaron Diamond Center was deemed “man of the year” (Time Magazine), after explaining the dynamics of HIV replication to the world. Today he explains why B.1.351 is so worrisome. While B.1.1.7 is refractory to neutralization by many mAbs but not more resistant to convalescent plasma (CP) or vaccinee sera (VS), B.1.351 is not only refractory to neutralization by almost all mAbs but also by CP (9.4 fold) and VS (10.3-12.4 fold). SARS-CoV-2 “is traveling in a direction that could ultimately lead to escape from our current therapeutic and prophylactic interventions directed to the viral spike”.
Chen X, Chen Z, Azman AS, et al. Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis. Lancet March 08, 2021. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00026-7/fulltext
After reviewing 404 (!) studies, the authors conclude that antibody-mediated herd immunity is far from being reached in most settings. Of note, the pooled infection-to-case ratio was similar between the region of the Americas (6.9, 95% CI: 2.7–17.3) and the European region (8.4, 95% CI: 6.5–10.7), but higher in India (56.5, 95% CI: 28.5–112.0), the only country in the South-East Asia region with data.
Leung K, Wu JT, Leung GM. Real-time tracking and prediction of COVID-19 infection using digital proxies of population mobility and mixing. Nat Commun 12, 1501 (2021). https://www.nature.com/articles/s41467-021-21776-2
Big Brother is watching you. However, sometimes he can be helpful. Using digital transactions made on Octopus cards (which are ubiquitously used by the Hong Kong population), the authors describe a framework that integrates digital proxies of human mobility and physical mixing into conventional epidemic models. At the end of the day, real-time estimates of Rt (accurate nowcast and short-term forecast of the epidemic) was obtained in Hong Kong.
Ella R, Reddy S, Jogdand H, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. Lancet March 08, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00070-0/fulltext
Inactivated vaccines have the advantage of being easily stored and shipped. BBV152 (COVAXIN) is a whole-virion inactivated SARS-CoV-2 vaccine adjuvanted with Algel-IMDG. An imidazoquinoline molecule (IMDG), a TLR7/8 agonist, is added to augment cell-mediated responses. According to the Phase I/II data from India presented here, BBV152 has shown the potential to provide durable humoral and cell-mediated immune responses (even against variants of concern). The Algel-IMDG formulation was selected for the ongoing Phase III efficacy trial, which involves 25,800 volunteers. BBV152 has received emergency use authorisation in India.
Rapaka RR, Hammershaimb EA, Neuzil KM. Are some COVID vaccines better than others? Interpreting and comparing estimates of efficacy in trials of COVID-19 vaccines. Clinical Infectious Diseases 06 March 2021, ciab213, https://doi.org/10.1093/cid/ciab213
Do you have colleagues who still “prefer” the BioNTech vaccine? Give him this viewpoint to read. Rekha Rapaka and colleagues from Maryland discuss the caveats of cross-trial comparisons. And why it matters how point estimates of efficacy were determined, in what epidemiologic setting, and against what endpoints.
Blumenthal KG, Robinson LB, Camargo Jr CA, et al. Acute Allergic Reactions to mRNA COVID-19 Vaccines. JAMA March 8, 2021; https://jamanetwork.com/journals/jama/fullarticle/2777417?resultClick=1
Of 64,900 vaccine recipients in Massachusetts, anaphylaxis was confirmed in 16 (0.025%). Of note, 15/16 were female, 10 had a prior history of allergies and 5 had a history of anaphylaxis. Mean time to anaphylaxis onset was 17 minutes (range, 1-120). All recovered.
Paul LA, Daneman N, Brown KA, et al. Characteristics associated with household transmission of SARS-CoV-2 in Ontario, Canada: A cohort study. Clinical Infectious Diseases 05 March 2021, ciab186, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab186/6159706
Among 26,714 cases of COVID-19 residing in 21,226 households, longer testing delays (≥ 5 days versus 0 days, OR = 3.02) and male gender (OR = 1.28) were associated with greater odds of household secondary transmission, as well as (not surprisingly) larger average family size and a higher proportion of households with multiple persons per room.
Kompaniyets L, Goodman AB, Belay B, et al. Body Mass Index and Risk for COVID-19–Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death — United States, March–December 2020. MMWR Morb Mortal Wkly Rep. ePub: 8 March 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7010e4.htm
Among 148,494 US adults with COVID-19, a non-linear “dose response” relationship was found between body mass index and COVID-19 severity, with lowest risks at BMIs near the threshold between healthy weight and overweight in most instances, then increasing with higher BMI. Overweight and obesity were risk factors for invasive mechanical ventilation. Obesity was a risk factor for hospitalization and death, particularly among adults aged < 65 years.
Lugon JC, Smit M, Salamun J, et al. Novel outpatient management of mild to moderate COVID-19 spares hospital capacity and safeguards patient outcome: The Geneva PneumoCoV-Ambu study. PLOS One, March 4, 2021. https://doi.org/10.1371/journal.pone.0247774
Calling patients every 48 hours for the first 10 days following diagnosis, with a standardized interview about self-reported symptoms or every 24 hours if patients presented a worsening clinical condition: this small study in relatively young patients shows that such an outpatient management of mild to moderate COVID-19-related pneumonia is possible. Costly and unnecessary hospitalizations were avoided and hospital capacity was spared.
Loffredo M, Lucero H, Chen DY, et al. The in-vitro effect of famotidine on sars-cov-2 proteases and virus replication. Sci Rep March 8, 2021, 11, 5433. https://www.nature.com/articles/s41598-021-84782-w
In silico studies have proposed one of the two SARS-CoV-2 proteases, 3CLpro or PLpro, as potential molecular targets of famotidine activity. Somewhat disappointing: Madeline Loffredo and colleagues show here that the drug neither binds with nor inhibits the functions of these proteases.