By Christian Hoffmann &
Bernd S. Kamps
Vaccine
Callaway E. Hundreds of people volunteer to be infected with coronavirus. Nature 22 April 2020. Full-text: https://www.nature.com/articles/d41586-020-01179-x
What about a ‘human challenge’ vaccine study? Such a trial would be much faster: a much smaller group of young, healthy volunteers would receive a candidate vaccine and then be intentionally infected with the virus, to judge the efficacy of the immunization. No trial is yet planned, but the debate is on. The approach is also gaining some political support.
Epidemiology
Cowling BJ, Ali ST, Ng TWY, et al. Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study. Lancet Public Health. 2020 Apr 17. pii: S2468-2667(20)30090-6. PubMed: https://pubmed.gov/32311320. Full-text: https://doi.org/10.1016/S2468-2667(20)30090-6
Detailed paper from Hong Kong modelling the effects of non-pharmaceutical interventions (NPIs, including border restrictions, quarantine and isolation, distancing, and changes in population behaviour). NPIs were associated with reduced transmission of COVID-19 and were also likely to have substantially reduced influenza transmission. Findings strongly suggest that social distancing and population behavioural changes – that have a social and economic impact that is less disruptive than a total lockdown – can meaningfully control COVID-19.
Wu X, Fu B, Chen L, Feng Y. Serological tests facilitate identification of asymptomatic SARS-CoV-2 infection in Wuhan, China. J Med Virol. 2020 Apr 20. PubMed: https://pubmed.gov/32311142. Full-text: https://doi.org/10.1002/jmv.25904
Forget herd immunity! Overall prevalence is still incredibly low. Even in hotspots like Wuhan! From April 3 to 15, SARS-CoV-2-specific IgG positive rate among 1,021 people applying for a permission of resume, only 98 (9.60%) were IgG positive and IgM and NAT (SARS‐CoV‐2 nucleic acid test) negative.
Diagnostics
Wilson NM, Norton A, Young FP, Collins DW. Airborne transmission of severe acute respiratory syndrome coronavirus-2 to healthcare workers: a narrative review. Anaesthesia. 2020 Apr 20. PubMed: https://pubmed.gov/32311771. Full-text: https://doi.org/10.1111/anae.15093
Evidence suggestive of airborne spread is growing. Authors discuss several ‘aerosol-generating procedures’ and current evidence (limited). A precautionary approach should be considered to assure healthcare worker safety.
Marty M, Chen K, Verrill KA. How to Obtain a Nasopharyngeal Swab Specimen. NEJM 2020. April 17, 2020. Full-text: https://www.nejm.org/doi/full/10.1056/NEJMvcm2010260?query=featured_home
It’s not that trivial to obtain a NP-Swab. Watch this video on protection, preparation, equipment, handling, removing personal protective equipment etc.
Xiang F, Wang X, He X, et al. Antibody Detection and Dynamic Characteristics in Patients with COVID-19. Clin Infect Dis. 2020 Apr 19. pii: 5822173. PubMed: https://pubmed.gov/32306047. Full-text: https://doi.org/10.1093/cid/ciaa461
More on antibodies, as a complement approach for PCR. The seroconversion of specific IgM and IgG antibodies were observed as early as the 4th day after symptom onset. In the confirmed patients with COVID-19, sensitivity, specificity, positive predictive value of IgM were 77.3% (51/66), 100% and 100%, and those of IgG were 83.3% (55/66), 95.0% and 94.8%. Both antibodies performed well in serodiagnosis for COVID-19 rely on great specificity. The antibodies against SARS-CoV-2 can be detected in the middle and later stage of the illness.
Clinical
Effenberger M, Grabherr F, Mayr L, et al. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut. 2020 Apr 20. pii: gutjnl-2020-321388. PubMed: https://pubmed.gov/32312790. Full-text: https://doi.org/10.1136/gutjnl-2020-321388
Faecal calprotectin (FC) has evolved as a reliable faecal biomarker allowing detection of intestinal inflammation in inflammatory bowel diseases and infectious colitis. This report on 40 patients provides some evidence that SARS-CoV-2 infection instigates an inflammatory response in the gut, as elevated FC (largely expressed by neutrophil granulocytes) and diarrhea.
Severe COVID-19
Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med. 2020 Jun 1;217(6). pii: 151683. PubMed: https://pubmed.gov/32302401. Full-text: https://doi.org/10.1084/jem.20200652
Case report of a patient who succumbed to COVID-19. Hypothesis that a powerful function of neutrophils – the ability to form neutrophil extracellular traps (NETs) – may contribute to organ damage and mortality in COVID-19. Targeting NETs directly and/or indirectly with existing drugs may reduce clinical severity.
Spiezia L, Boscolo A, Poletto F, et al. COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure. Thromb Haemost. 2020 Apr 21. PubMed: https://pubmed.gov/32316063. Full-text: https://doi.org/10.1055/s-0040-1710018
Case series of 22 patients with acute respiratory failure present a severe hypercoagulability rather than consumptive coagulopathy. Fibrin formation and polymerization may predispose to thrombosis and correlate with a worse outcome.
Treatment
Bhimray A, Morgan RL, Shumaker. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Published by IDSA, 4/11/2020. Full-text: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
Evidence-based guidelines which are, in the absence of large RCTs, not very helpful. Recommendations for all drugs acknowledge the current “knowledge gap”. HCQ, lopinavir/r, tocilizumab and convalescent plasma should be given “only in the context of a clinical trial”. Well.