Top 10: November 25

Copy-editor: Rob Camp

Epidemiology

Bajema KL, Wiegand RE, Cuffe K, et al. Estimated SARS-CoV-2 Seroprevalence in the US as of September 2020. JAMA Intern Med November 24, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.7976

In this repeated, cross-sectional study of 177.919 residual clinical specimens, the estimated percentage of persons in a US jurisdiction with detectable SARS-CoV-2 antibodies ranged from fewer than 1% to 23%. Over 4 sampling periods in 42 of 49 jurisdictions with calculated estimates, fewer than 10% of people had detectable SARS-CoV-2 antibodies.

 

Kennedy BS, Richeson RP, Houde AJ. Risk Factors for SARS-CoV-2 in a Statewide Correctional System. N Eng J Med November 24, 2020. Full-text: https://doi.org/10.1056/NEJMc2029354

Mass testing by RT-PCR among 10.304 incarcerated persons in the Connecticut (US) statewide correctional system revealed that by far the strongest risk factor for SARS-CoV-2 infection was dormitory housing (odds ratio, 35.3). Social distancing may be more challenging in such settings than in cells that house one or two inmates.

 

Liu M, Thomadsen R, Yao S. Forecasting the spread of COVID-19 under different reopening strategies. Sci Rep 10, 20367 (2020). Full-text: https://doi.org/10.1038/s41598-020-77292-8

Using a modified susceptible-infected-recovered (SIR) model in the United States, the authors found that the incidence of COVID-19 spread is concave in the number of infectious individuals, as would be expected if people have inter-related social networks. This concave shape has a significant impact on forecasted COVID-19 cases. The number of COVID-19 cases would only have an exponential growth for a brief period at the beginning of the contagion event or right after a re-opening, but would quickly settle into a prolonged period of time with stable, slightly declining levels of disease spread. In contrast, if social distancing is eliminated, there will be a massive increase in the cases.

 

Transmission

Sun K, Wang W, Gao L, et al. Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2. Science 24 Nov 2020: eabe2424. Full-text: https://doi.org/10.1126/science.abe2424

Using detailed information on 1178 SARS-CoV-2 infected individuals along with their 15.648 contacts in Hunan, China, Kaiyuan Sun and colleagues dissected the behavioral and clinical drivers of SARS-CoV-2 transmission. They also evaluated the plausibility of SARS-CoV-2 control through individual and population-based interventions. Of note, 80% of secondary infections traced back to 15% of SARS-CoV-2 primary infections. Transmission risk scales positively with the duration of exposure and the closeness of social interactions and is modulated by demographic and clinical factors. Modeling indicates SARS-CoV-2 control requires the synergistic efforts of case isolation, contact quarantine, and population-level interventions, owing to the specific transmission kinetics of this virus.

Figure 1. SARS-CoV-2 transmission chains. | Top: One realization of the reconstructed transmission chains among 1178 SARS-CoV-2 infected individuals in Hunan province. Each node in the network represents a… | Continue reading at https://doi.org/10.1126/science.abe2424. Reproduced with permission.

 

Immunology

Omer SB, Yildirim I, Forman HP. Herd Immunity and Implications for SARS-CoV-2 Control. JAMA November 24, 2020; 324(20):2095-2096. Full-text: https://doi.org/10.1001/jama.2020.20892

Saad B. Omer and colleagues discuss herd immunity in the context of the COVID-19 pandemic and explain the herd immunity threshold as a function of transmissibility (R0), the role of an effective vaccine and vaccination program in sustaining herd immunity, and the risks of an infection-based herd immunity approach. Assuming that less than 10% of the population has been infected so far, with an infection-induced immunity lasting 2 to 3 years (duration unknown), infection-induced herd immunity is not realistic at this point to control the pandemic.

 

Vaccine

Ma X, Zou F, Yu F, et al. Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses. Immunity November 25, 2020. Full-text: https://doi.org/10.1016/j.immuni.2020.11.015

A promising new vaccination approach: Xiancai Ma and colleagues from Guangdong, China developed nanoparticle vaccines by covalently conjugating the self-assembled 24-mer ferritin to the receptor binding domain (RBD) and/or heptad repeat (HR) subunits of spike (S) protein. Compared to monomer vaccines, nanoparticle vaccines elicited more robust neutralizing antibodies and cellular immune responses. hACE2 transgenic mice vaccinated with RBD and/or RBD-HR nanoparticles exhibited reduced viral load in the lungs after SARS-CoV-2 challenge. RBD-HR nanoparticle vaccines also promoted neutralizing antibodies and cellular immune responses against other coronaviruses. The nanoparticle vaccination of rhesus macaques induced neutralizing antibodies, and T and B cell responses prior to boost immunization; these responses persisted for longer than three months.

Graphical abstract. Reproduced with permission.

 

Clinical

Bilinski A, Emanuel EJ. COVID-19 and Excess All-Cause Mortality in the US and 18 Comparison Countries. JAMA 2020; 324(20):2100-2102. Full-text: https://doi.org/10.1001/jama.2020.20717

Compared with other countries, the US experienced high COVID-19–associated mortality and excess all-cause mortality into September 2020. After the first peak in early spring, US death rates from COVID-19 and from all causes remained exceptionally high. This may have been a result of several factors, including weak public health infrastructure and a decentralized, inconsistent US response to the pandemic.

 

Fodoulian L, Tuberosa J, Rossier D, et al. SARS-CoV-2 receptors and entry genes are expressed in the human olfactory neuroepithelium and brain. iScience November 24, 2020. Full-text: https://doi.org/10.1016/j.isci.2020.101839

More on anosmia: Leon Fodoulian and colleagues from Geneva, Switzerland asked whether specific cells present in the human olfactory neuroepithelium may represent targets for SARS-CoV-2, by looking at the molecular players involved in infection, both at the RNA and protein levels. They found that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. These cells represent a potential way in for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.

Graphical abstract. Reproduced with permission.

Treatment

Simonovich VA, Burgos Pratx LD, Scibona P, et al for the PlasmAr Study Group. A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. N Eng J Med, November 24, 2020. Full-text: https://doi.org/10.1056/NEJMoa2031304

A crushing failure for convalescent plasma (CP): this study from Argentina randomly assigned 338 hospitalized adult patients with severe COVID-19 pneumonia in a 2:1 ratio to receive CP or placebo. No significant differences were observed in clinical status or overall mortality and prespecified subgroup analyses failed to suggest any credible subgroup effects. Moreover, the trial ensured that more than 95% of the transfused CP units had a total anti–SARS-CoV-2 antibody titer of at least 1:800 and that the plasma volume infused had a correction factor according to the participant’s weight. The authors “believe the use of CP as a standard of care in such patients should be reevaluated”. Well said.

Figure 3. Time to Death or to Improvement after Treatment with Convalescent Plasma or Placebo. | Shown are the Kaplan–Meier failure estimates of the time from intervention (administration of convalescent plasma or placebo) to death or to… | Continue reading at https://doi.org/10.1056/NEJMoa2031304 . Reproduced with permission.

 

Fan H, Hong B, Luo Y et al. The effect of whey protein on viral infection and replication of SARS-CoV-2 and pangolin coronavirus in vitro. Sig Transduct Target Ther 5, 275 (2020). Full-text: https://doi.org/10.1038/s41392-020-00408-z

Human breastmilk inhibits SARS-CoV-2 virus infection in Vero E6 and A549 cell lines. Huaghao Fan and colleagues show for the first time that whey protein from human breastmilk effectively inhibited SARS-CoV-2 by blocking viral attachment and viral replication at entry and even post-entry. Moreover, human whey protein inhibited infectious virus production, as proved by a plaque assay. Whey protein from different species, such as cow and goat, also showed anti-coronavirus properties. Commercial bovine formula milk also showed similar anti-SARS-CoV-2 activity.

 


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