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By Christian Hoffmann &
Bernd S. Kamps

27 April

Epidemiology

Pearce N, Vandenbroucke JP, VanderWeele TJ, Greenland S. Accurate Statistics on COVID-19 Are Essential for Policy Guidance and Decisions. Am J Public Health. 2020 Apr 23:e1-e3. PubMed: https://pubmed.gov/32324422 . Full-text: https://doi.org/10.2105/AJPH.2020.305708

Review of key epidemiological concepts and discussion of some of the preventable methodologic errors.

 

Mosites E, Parker EM, Clarke KE, et al. Assessment of SARS-CoV-2 Infection Prevalence in Homeless Shelters — Four U.S. Cities, March 27–April 15, 2020. MMWR,  Early Release / April 22, 2020 / 69. Full-text: https://www.cdc.gov/mmwr/volumes/69/wr/mm6917e1.htm?s_cid=mm6917e1_w

Outbreaks in homeless shelters. If you test more than one person to be PCR positive, you have already many positive cases. Overall, 1,192 residents and 313 staff members were tested in 19 shelters from 4 US cities. When testing followed identification of a cluster, high proportions of positive tests were found, ranging from 16-66%. Testing in shelters where only one or no previous case had been identified found low prevalences (1-5%).

 

Arias-Reyes C, Zubieta-DeUrioste N, Poma-Machicao L, et al. Does the pathogenesis of SAR-CoV-2 virus decrease at high-altitude? Respir Physiol Neurobiol. 2020 Apr 22:103443. PubMed: https://pubmed.gov/32333993 . Full-text: https://doi.org/10.1016/j.resp.2020.103443

Interesting idea. Epidemiological data from Tibet, Bolivia and Ecuador suggest that COVID-19 infection is decreased in populations living at an altitude of above 3,000 m. Highland inhabitants may be less susceptible to SARS-CoV-2 virus infection due to physiological acclimatization to hypoxia. High-altitude environmental factors may contribute to reduce the virulence of SARS-CoV-2. But can we trust? The method section of this paper contains one sentence. And the fact that the virus was written incorrectly even in the title, does not enhance credibility.

 

Virology

Cohen J. COVID-19 vaccine protects monkeys from new coronavirus, Chinese biotech reports. Science April 23, 2020. Full-text: https://www.sciencemag.org/news/2020/04/covid-19-vaccine-protects-monkeys-new-coronavirus-chinese-biotech-reports

Preliminary results of an old-fashioned vaccine consisting of a chemically inactivated version of the virus (which could be produced easily and in huge quantities). The vaccine worked in 8 rhesus macaques, while no obvious side effects were observed. Sinovac Biotech, an experienced vaccine maker from China, has now started phase I clinical trials in 144 healthy volunteers to evaluate safety.

 

Transmission

Schwierzeck V, König JC, Kühn J, et al. First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit. Clinical Infectious Diseases, 27 April 2020. Full-text: https://doi.org/10.1093/cid/ciaa491

The next outbreak, occurring in a pediatric dialysis unit in Münster (Germany), comprising a total of 12 cases. After careful investigation, authors found that none of 32 persons with type II exposure became infected (= shared indoor environment without cumulative 15-minutes face-to-face contact, HCWs exposed during treatment or nursing in a distance of > 2 meters, without appropriate personal protective equipment such as surgical masks etc.).

 

Atkinson B, Petersen E. SARS-CoV-2 shedding and infectivity. Lancet. 2020 Apr 25;395(10233):1339-1340. PubMed: https://pubmed.gov/32304647 . Full-text: https://doi.org/10.1016/S0140-6736(20)30868-0

Several reports from China have suggested prolonged shedding of the virus by measuring viral RNA in different body fluids. Authors emphasize an important issue in the current discussion. The presence of nucleic acid alone cannot be used to define viral shedding or infection potential. For many viral diseases including SARS-CoV or MERS-CoV, it is well known that viral RNA can be detected long after the disappearance of infectious virus.

 

Diagnostics

Qu J, Wu C, Li X. Profile of IgG and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical Infectious Diseases. 2020. Full-text: https://doi.org/10.1093/cid/ciaa489

Seroconversion patterns of IgM and IgG antibodies using 347 serum samples from 41 patients. Using combined N and S proteins as capture antigen to increase sensitivity of their in-house assay, IgG and IgM antibodies were found in the majority of the patients during the first three weeks of the disease. Of note, the seroconversion time of IgG antibody was earlier than IgM. IgG antibody reached the highest concentration on day 30, while IgM antibody peaked on day 18, but then began to decline.

 

Severe COVID-19

Matheny Antommaria AH, Gibb TS, McGuire AL, et al. Ventilator Triage Policies During the COVID-19 Pandemic at U.S. Hospitals Associated With Members of the Association of Bioethics Program Directors. Ann Intern Med. 2020 Apr 24. pii: 2765364. PubMed: https://pubmed.gov/32330224 . Full-text: https://doi.org/10.7326/M20-1738

Triage? Nobody is prepared, according to this survey among 67 Bioethics Program Directors from North American hospitals. Over one half of respondents did not have ventilator triage policies. Policies have substantial heterogeneity, and many omit guidance on fair implementation. Of note, among the most frequently cited triage criteria was “lottery” (35%). Well.

 

Treatment

Ledford H. Chloroquine hype is derailing the search for coronavirus treatments. Nature Medicine, 24 April 2020. Full-text https://www.nature.com/articles/d41586-020-01165-3

After hearing politicians touting the potential benefits, many patients are turning away from clinical trials of other therapies that would require them to give up chloroquine treatments. This report reviews these issues which have already led to serious delays in trial enrolment, muddled efforts to interpret data and endangered clinical research on COVID-19.

 

Borrell B. New York clinical trial quietly tests heartburn remedy against coronavirus. Science April 26, 2020. Full-text: https://www.sciencemag.org/news/2020/04/new-york-clinical-trial-quietly-tests-heartburn-remedy-against-coronavirus

Famotidine for COVID-19? By reviewing 6212 Chinese patient records, it became obvious that many survivors had been suffering from chronic heartburn and were on famotidine rather than more expensive omeprazole. On 7 April, the first COVID-19 patients at Northwell Health in the New York City area began receiving famotidine intravenously, at nine times the heartburn dose. Interim results of this clinical trial which has enrolled an incredible huge number of patients, will be available within a few weeks. Don’t tell your politicians.