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Top 10: July 23

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By Christian Hoffmann &
Bernd S. Kamps

23 July

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Epidemiology

Sudharsanan N, Didzun O, Bärnighausen T Geldsetzer P. The Contribution of the Age Distribution of Cases to COVID-19 Case Fatality Across Countries – A 9-Country Demographic Study. Ann Intern Med 2020, published 22 July. Full-text: https://doi.org/10.7326/M20-2973

The overall observed case-fatality rates (CFR) vary widely, with the highest rates in Italy (9.3%) and the Netherlands (7.4%) and the lowest rates in South Korea (1.6%) and Germany (0.7%). This cross-sectional study of population-based data from China, France, Germany, Italy, the Netherlands, South Korea, Spain, Switzerland, and the US finds that age distribution of cases explains 66% of the variation of across countries, with a resulting age-standardized median CFR of 1.9%. See also the editorial by David N. Fisman, Amy L. Greer, and Ashleigh R. Tuite: Age Is Just a Number: A Critically Important Number for COVID-19 Case Fatality; full-text: https://doi.org/10.7326/M20-4048.

 

Fisman DN, Bogoch I, Lapointe-Shaw L, et al. Risk Factors Associated With Mortality Among Residents With Coronavirus Disease 2019 (COVID-19) in Long-term Care Facilities in Ontario, Canada.  JAMA, published July 22, Full-text: https://doi.org/10.1001/jamanetworkopen.2020.15957

The authors compare the risk of death from coronavirus disease 2019 (COVID-19) among residents of long-term care (LTC) homes with that among the general population in long-term care facilities in Ontario, Canada. In the LTC facility setting, the incidence of mortality was more than 13 times greater than that seen in community-living adults older than 69 years during a similar period. Infection among LTC staff was associated with death among residents with a 6-day lag.

 

Immunology

Liu L, Wang P, Nair MS, et al. Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike. Nature (2020). Published: 22 July. Full-text: https://doi.org/10.1038/s41586-020-2571-7

A group of researchers including Yaoxing Huang, Lawrence Shapiro and David D. Ho report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. The list of findings grows. A must-read!

(David H. Ho will remind senior scientists of studies published in the 90’s about HIV and AIDS (see pubmed.gov/10341272, pubmed.gov/10577640, pubmed.gov/11018071, pubmed.gov/15781098, pubmed.gov/16890836, among several hundred other publications). In 2001, he was presented with the Presidential Citizens Medal by President Clinton.)

 

Li J, Guo M, Tian X et al. Virus-host interactome and proteomic survey of PBMCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis. Cell Med, published July 21, 2020. Full-text: https://doi.org/10.1016/j.medj.2020.07.002

The highlights:

  1. Genome-wide screens identify 58 binary interactions between 29 SARS-CoV-2 proteins
  2. Virus-host interactome identifies 286 host targets for SARS-CoV-2 proteins
  3. Quantitative analysis depicts the overall proteome signature in COVID-19 PBMCs
  4. Nsp10 targets NKRF to facilitate IL-8 induction

 

Diagnostics

McCulloch DJ, Kim AE, Wilcox NC. Collected Nasopharyngeal Swabs for Detection of SARS-CoV-2 Infection. JAMA 2020;3(7):e2016382. Full-text: https://doi.org/10.1001/jamanetworkopen.2020.16382

Home self-collected swabs may increase testing access while minimizing exposure risk to health care workers and depletion of personal protective equipment, allowing for early community detection of COVID-19. The authors provided participants with test kits for unsupervised home self-collection of a mid-nasal swab. Home swab performance was compared with clinician-collected nasopharyngeal swabs collected by medical assistants and nurses. Compared with clinician swabs, sensitivity and specificity of home swabs was 80.0% and 97.9%, respectively. Unsupervised home mid-nasal swab collection was comparable to clinician-collected nasopharyngeal swab collection for detection of SARS-CoV-2 in symptomatic patients, particularly those with higher viral loads.

 

Tromberg, BJ, Schwetz TA, Pérez-Stable EJ, et al. Rapid Scaling Up of Covid-19 Diagnostic Testing in the United States — The NIH RADx Initiative. N Engl J Med 2020, published July 22. Full-text: https://doi.org/10.1056/NEJMsr2022263

Earlier in 2020, the COVID-19 epidemic in the US was fueled by a severe (scandalous?) lack of testing capacity. The authors describe the role of the NIH in the effort to increase the range and availability of diagnostic SARS-CoV-2 tests.

 

Treatment

Wang N, Zhan Y, Zhu L, et al. Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients. Cell Host Microb, published July 22. Full-text: https://doi.org/10.1016/j.chom.2020.07.005

A retrospective multicenter cohort study of 446 COVID-19 patients, taking advantage of drug stock disparities between two medical centers in Hubei during the peak of the Chinese COVID-19 outbreak. Early administration (≤ 5 days after admission) of IFN-α2b was associated with reduced in-hospital mortality in comparison with no admission of IFN-α2b, whereas late administration of IFN-α2b was associated with increased mortality. IFN therapy was not associated with recovery time for COVID-19.

 

Severe COVID

Kon ZN, Smith DE, Chang SH, et al. Extracorporeal Membrane Oxygenation Support in Severe COVID-19. Ann Thorac Surg. 2020 Jul 17:S0003-4975(20)31152-8. PubMed: https://pubmed.gov/32687823. Full-text: https://doi.org/10.1016/j.athoracsur.2020.07.002

The authors describe their institutional practice regarding ECMO support for 27 patients with COVID-19. At the time of paper submission, survival was 96.3% (one death) in over 350 days of total ECMO support. Thirteen patients (48.1%) remained on ECMO support, while 13 patients (48.1%) were successfully decannulated. Seven patients (25.9%) were discharged from the hospital while six patients (22.2%) remained in the hospital, of which four were on (unmodified) room air. The authors rightly conclude that the judicious use of ECMO support may be clinically beneficial.

 

Collateral Effects

Kansagra Ap, Goyal MS, Hamilton S, Albers GW. Collateral Effect of Covid-19 on Stroke Evaluation in the United States. N Engl J Med 2020; 383:400-401. Full-text: https://doi.org/10.1056/NEJMc2014816

Any decrease in care for patients with ischemic stroke may be consequential because timely treatment may decrease the incidence of disability. The authors compare the mean daily counts per hospital of patients in the pre-pandemic 29-day epoch from February 1, 2020, through February 29, 2020, with the mean daily counts per hospital of patients in a 14-day period during the early pandemic, from March 26, 2020, through April 8, 2020. They found a decrease of approximately 39% in the numbers of patients who received evaluations for acute stroke between two recent periods in U.S. hospitals. The decrease in the use of stroke imaging from the pre-pandemic epoch to the early-pandemic period was seen across all ages, sexes, and stroke severity subgroups.

 

Education

Stone JR, Tran KM, Conklin J, Mino-Kenudson M. Case 23-2020: A 76-Year-Old Woman Who Died from Covid-19. N Engl J Med 2020; 383:380-387. Full-text: https://doi.org/10.1056/NEJMcpc2004974

A 76-year-old woman was admitted to the Massachusetts General Hospital because of confusion and hypoxemia (O2 saturation at 87% while breathing ambient air).

 

Rubin EJ, Baden LR, Morrissey S. Dexamethasone and Covid-19. Audio interview (19:56). N Engl J Med 2020; 383:e52. Access: https://doi.org/10.1056/NEJMe2025927

The editors discuss the dexamethasone study by The RECOVERY Collaborative Group (Full-text: https://doi.org/10.1056/NEJMoa2021436) and the implications of corticosteroid use in patients with COVID-19.

 

Society

Egede LE, Walker RJ. Structural Racism, Social Risk Factors, and Covid-19 — A Dangerous Convergence for Black Americans. N Engl J Med 2020, published 22 July. Full-text: https://doi.org/10.1056/NEJMp2023616

Laurencin CT, Walker JM. A Pandemic on a Pandemic: Racism and COVID-19 in Blacks. Cell Systems 2020, published 22 July. Full-text: https://doi.org/10.1016/j.cels.2020.07.002

Racism and COVID-19 represent a pandemic on top of a pandemic for Blacks. Recommended action items for mitigating structural racism proposed by Egede & Walker:

  1. Change policies that keep structural racism in place.
  2. Break down silos and create cross-sector partnerships.
  3. Institute policies to increase economic empowerment.
  4. Fund community programs that enhance neighborhood stability.
  5. Be consistent in efforts by health systems to build trust in vulnerable communities.
  6. Test and deploy targeted interventions that address social risk factors.

 

Beyond COVID-19

Sherwood S, Webb JM, Annan JD, et al. An assessment of Earth’s climate sensitivity using multiple lines of evidence. Reviews of Geophysics 2020. Full-text: https://climateextremes.org.au/wp-content/uploads/2020/07/WCRP_ECS_Final_manuscript_2019RG000678R_FINAL_200720.pdf (166 pages)

By doubling atmospheric carbon dioxide (CO2) from preindustrial levels, planet Earth will eventually warm up to between 2.6°C and 3.9°C. This new estimate by 25 scientists is based on three strands of evidence:

  1. Trends indicated by contemporary warming
  2. The latest understanding of the feedback effects that can slow or accelerate climate change
  3. Lessons from ancient climates

Read also the comment by Paul Voosen, published in Science: After 40 years, researchers finally see Earth’s climate destiny more clearly. Full-text: https://doi.org/10.1126/science.abd9184