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By Christian Hoffmann &
Bernd S. Kamps
21 August
Transmission
Hoehl S, Karaca O, Kohmer M, et al. Assessment of SARS-CoV-2 Transmission on an International Flight and Among a Tourist Group. JAMA Netw Open August 18, 2020, 3(8). Full-text: https://doi.org/10.1001/jamanetworkopen.2020.18044
Two likely SARS-CoV-2 transmissions on a 4.5-hour flight from Tel Aviv to Frankfurt, with 7 index cases. Both passengers were seated within two rows of an index case. According to the authors, it could be speculated that the rate may have been reduced further had the passengers worn masks.
Bhaskar ME, Arun S. SARS-CoV-2 Infection Among Community Health Workers in India Before and After Use of Face Shields. JAMA August 17, 2020. Full-text: https://doi.org/10.1001/jama.2020.15586
This observational study describes transmission before and after the use of face shields (made of polyethylene terephthalate) in health workers in Chennai, India. Before the introduction of face shields, 12/62 workers were infected, while visiting 5,880 homes with 31,164 persons (222 positive for SARS-CoV-2). After the introduction, among 50 workers (previously uninfected) who continued to provide counseling, visiting 18,228 homes with 118,428 persons (2682 positive), no infection occurred.
Diagnosis
Kiran U, Gokulan CG, Kuncha SK, et al. Easing diagnosis and pushing the detection limits of SARS-CoV-2. Biology Methods and Protocols, August 20, 2020. Full-text: https://doi.org/10.1093/biomethods/bpaa017
A more effective and reliable method of SARS-CoV-2 detection. Udan Kiray and colleagues show that the currently used and most reliable RT-PCR based SARS-CoV-2 procedure can be further simplified to make it faster, safer, and economical by eliminating the RNA isolation step.
Clinical
Tucker NR, Chaffin M, Bedi KC Jr, et al. Myocyte-Specific Upregulation of ACE2 in Cardiovascular Disease: Implications for SARS-CoV-2-Mediated Myocarditis. Circulation. 2020 Aug 18;142(7):708-710. PubMed: https://pubmed.gov/32795091 . Full-text: https://doi.org/10.1161/CIRCULATIONAHA.120.047911
Nathan Tucker and colleagues assessed ACE2 expression by performing bulk and single nucleus RNA-Seq on the left ventricles of 11 individuals with dilated cardiomyopathy, 15 individuals with hypertrophic cardiomyopathy, and 16 controls with non-failing hearts. Data suggest that previous cardiovascular disease is a predominant driver of cardiomyocyte-specific increased transcription of ACE2, providing a pathologic link for SARS-CoV–associated viral myocarditis.
Severe COVID-19
Hanley B, Naresh KN, Roufosse C, et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. Lancet Microbe August 20, 2020. Full-text: https://doi.org/10.1016/S2666-5247(20)30115-4
Ten cases of fatal COVID-19 showed diffuse alveolar damage, thrombosis, hemophagocytosis, and immune cell depletion. The authors report several novel autopsy findings including pancreatitis, pericarditis, adrenal micro-infarction, secondary disseminated mucormycosis, and brain microglial activation.
Comorbidities
Cheng X, Liu YM, Li H, et al. Metformin Use Is Associated with Increased Incidence of Acidosis but not Mortality in Individuals with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metabol August 20, 2020. Full-text: https://doi.org/10.1016/j.cmet.2020.08.013
Retrospective cohort study of 1,213 hospitalized individuals with COVID-19 and pre-existing type 2 diabetes (T2D). Metformin use was significantly associated with a higher incidence of acidosis, particularly in cases with severe COVID-19, but not with 28-day COVID-19-related mortality. Furthermore, metformin use was significantly associated with reduced heart failure and inflammation. These findings provide some evidence in support of continuing metformin treatment in individuals with COVID-19 and pre-existing T2D, but acidosis and kidney function should be carefully monitored.
Treatment
Karlsen APH, Wiberg S, Laigaard J, Pedersen C, Rokamp KZ, Mathiesen O. A systematic review of trial registry entries for randomized clinical trials investigating COVID-19 medical prevention and treatment. PLoS One. 2020 Aug 20;15(8):e0237903. PubMed: https://pubmed.gov/32817689 . Full-text: https://doi.org/10.1371/journal.pone.0237903
A global snapshot overview of COVID-19 interventions: Anders Peder Højer Karlsenand and colleagues systematically screened trial registry entries via the WHO ICTR Platform and 33 trial registries up to June 23, 2020. In total, 1,303 RCTs from 71 countries were identified (47% blinded), planning to include a total of 611,364 participants. Recruitment was ongoing in 54% of trials and completed in 8%. The five most frequent investigational categories were immune modulating drugs (20%), unconventional medicine (13%), antimalarial drugs (9%), antiviral drugs (8%) and respiratory adjuncts (6%). The five most frequently tested unimodal interventions were: chloroquine/hydroxychloroquine (113 trials with 199,841 participants); convalescent plasma (64 trials with 11,840 participants); stem cells (51 trials with 3,370 participants); tocilizumab (19 trials with 4,139 participants) and favipiravir (19 trials with 3,210 participants).
Park JJ, Decloedt EH, Rayner CR. Clinical trials of disease stages in COVID 19: complicated and often misinterpreted. Lancet August 20, 2020. Full-text: https://doi.org/10.1016/S2214-109X(20)30365-X
Important comment, emphasizing the nuances and differences of COVID-19 disease states in clinical trials. Although it is clear that some therapies have no clinical benefits in patients admitted to hospital, Jay JH Park and colleague argue that there is much uncertainty, and thus clinical equipoise, to justify continuing clinical trials in other COVID-19 disease states.
Lin DY, Zeng D, Eron JJ. Evaluating the Efficacy of Therapies in COVID-19 Patients. Clinical Infectious Diseases, August 21, 2020. Full-text: https://doi.org/10.1093/cid/ciaa1231
Some thoughts on clinical endpoints. To provide a full picture of the clinical course of a patient and make complete use of available data, the authors consider the trajectory of clinical status over the entire follow-up period. They also show how to combine the evidence of treatment effects on the occurrences of various clinical events and compare the proposed and existing endpoints through extensive simulation studies.
Pediatrics
Yonker LM, Neilan AM, Bartsch Y, et al. Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and Immune Responses. J Pediatrics August 19, 2020. Full-text: https://doi.org/10.1016/j.jpeds.2020.08.037
Lael Yonker and colleagues from Massachusetts General Hospital in Boston postulate that children may be a potential source of contagion in the SARS-CoV-2 pandemic in spite of milder disease or lack of symptoms. A total of 192 children (mean age 10.2 years) were enrolled, among them 49 children with acute SARS-CoV-2 infection. Nasopharyngeal viral load was highest in children in the first 2 days of symptoms, significantly higher than hospitalized adults with severe disease. Age did not impact viral load, but younger children had lower ACE2 expression.