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Top 10: April 30

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By Christian Hoffmann &
Bernd S. Kamps

30 April

Virology

Callaway E. The race for coronavirus vaccines: a graphical guide, Eight ways in which scientists hope to provide immunity to SARS-CoV-2. Nature 2020, 28 April 2020. 580, 576-577. https://doi.org/10.1038/d41586-020-01221-y

Fantastic graphical review on current vaccine development. Easy to understand, it explains different approaches such as virus, viral-vector, nucleic-acid and protein-based vaccines.

 

Clinical

Wadhera RK, Wadhera P, Gaba P, et al. Variation in COVID-19 Hospitalizations and Deaths Across New York City Boroughs. April 29, 2020. AMA. Published online April 29, 2020. Full-text: https://doi.org/10.1001/jama.2020.7197

By April 25, the Bronx (which has the highest proportion of racial/ethnic minorities, the most persons living in poverty, and the lowest levels of educational attainment) had higher rates (almost two-fold) of hospitalization and death related to COVID-19 than the other four New York City boroughs Brooklyn, Manhattan, Queens and Staten Island.

 

Comorbidities

Haberman R, Axelrad J, Chen A, et al. Covid-19 in Immune-Mediated Inflammatory Diseases – Case Series from New York. N Engl J Med. 2020 Apr 29. PubMed: https://pubmed.gov/32348641. Full-text: https://doi.org/10.1056/NEJMc2009567

Baseline use of biologics is not associated with worse Covid-19 outcomes. Case series of 86 patients with immune-mediated inflammatory disease (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, inflammatory bowel disease, or related conditions) and symptomatic COVID-19, among them 62 (72%) receiving biologics or Janus kinase (JAK) inhibitors. The percentage of patients who were receiving biologics or JAK inhibitors at baseline was higher among the ambulatory patients than among the hospitalized patient. In contrast, hospitalization rates were higher in patients treated with oral glucocorticoids, hydroxychloroquine and methotrexate.

 

Rangé G, Hakim R, Motreff P. Where have the STEMIs gone during COVID-19 lockdown? European Heart Journal – Quality of Care and Clinical Outcomes, April 29, 2020. Full-text: https://doi.org/10.1093/ehjqcco/qcaa034

Best paper title of the day. Using a French Registry, authors found a spectacular drop of 25% for admission due to STEMI between March 2019 and March 2020. The steep decline was found for both acute (<24hrs) and late presentation (>24 hrs) STEMI. But where have they gone? According to the authors, explanations may be patients’ fear of coming to the hospital or disturbing busy caregivers, especially in case mild STEMI clinical presentation. Other hypothetical reasons are reduced air pollution, better adherence to treatment, limited physical activity or absence of occupational stress during lockdown. When will we ever learn?

 

Baldi E, Sechi GM, Mare C, et al. Out-of-Hospital Cardiac Arrest during the Covid-19 Outbreak in Italy. N Engl J Med. 2020 Apr 29. PubMed: https://pubmed.gov/32348640. Full-text: https://doi.org/10.1056/NEJMc2010418

Avoiding hospitals, staying at home, dying of fear? Using data from the Lombardia Cardiac Arrest Registry for the provinces of Lodi, Cremona, Pavia, and Mantua during the first 40 days of the Covid-19 outbreak (February 21 through March 31, 2020), the authors found a 58 % increase of out-of-hospital cardiac arrest compared to the same period in 2019.

 

Treatment

Ledford H. Hopes rise on coronavirus drug remdesivir. Nature Medicine 29 April 2020. Full-text: https://doi.org//10.1038/d41586-020-01295-8

The next example of “Fauci said”. Anthony Fauci, director of the US National Institute of Allergy and Infectious Disease (NIAID) had announced that a clinical trial of „more than a thousand people showed that people taking remdesivir recovered in 11 days on average, compared to 15 days for those on a placebo“. That’s all. We believe that this is not an appropriate way to share data with the community.

 

Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet, April 29, 2020. Full-text: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext

And here it is, the first randomized, double-blind, placebo-controlled trial of remdesivir (and not the study Fauci was talking about)! This multicenter trial at ten hospitals in Hubei, China enrolled patients with severe COVID-19 to receive 10 days of single infusions or placebo. Clinical improvement up to day 28 was defined as the time (in days) to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. In the 237 patients enrolled between Feb 6 and March 12, remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1.23, 95% CI 0.87–1.75). Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. The trial did not attain the predetermined sample size because the outbreak of COVID-19 was brought under control in China. Disappointing. More data are eagerly awaited.

 

Gates B. Responding to Covid-19 — A Once-in-a-Century Pandemic? NEJM April 30, 2020. N Engl J Med 2020; 382:1677-1679. DOI: https://doi.org/10.1056/NEJMp2003762.

Bill Gates, talking about billions of dollars. He will donate some. According to this perspective, he has comitted “substantial resources”. Well done.

 

Severe COVID-19

Ziehr DR, Alladina J, Petri CR, et al. Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study. Am J Respir Crit Care Med. 2020 Apr 29. PubMed: https://pubmed.gov/32348678. Full-text: https://doi.org/10.1164/rccm.202004-1163LE

Treat it like ARDS! Authors provide a pathophysiologic justification for the use of established ARDS therapies, including low tidal volume and early prone ventilation. In their retrospective cohort of 66 COVID-19 patients (median age 58 years) with respiratory failure, fatality was only 17 %. Authors conclude that their patients exhibit similar gas exchange, respiratory system mechanics, and response to prone ventilation as prior large cohorts of patients with ARDS.

 

Procedures

Bertroche JT, Pipkorn P, Zolkind P, Buchman CA, Zevallos JP. Negative-Pressure Aerosol Cover for COVID-19 Tracheostomy. JAMA Otolaryngol Head Neck Surg. 2020 Apr 28. pii: 2765506. PubMed: https://pubmed.gov/32343299. Full-text: https://doi.org/10.1001/jamaoto.2020.1081

Authors present the creation of a novel negative-pressure aerosol cover made out of readily available operating room materials as an additional barrier to limit the spread of aerosols during tracheostomy. This cover was easy to create and deploy using readily available materials found in operating centers.