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By Christian Hoffmann &
Bernd S. Kamps
21 June
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Epidemiology
Twahirwa Rwema JO, Diouf D, Phaswana-Mafuya N, et al. COVID-19 Across Africa: Epidemiologic Heterogeneity and Necessity of Contextually Relevant Transmission Models and Intervention Strategies. Ann Intern Med. 2020 Jun 18. PubMed: https://pubmed.gov/32551812. Full-text: https://doi.org/10.7326/M20-2628
Brief overview on the burden and outcomes associated with COVID-19 in Africa, showing substantial variations across countries. Some explanations why many multiple mathematical models have failed to project the epidemic on the continent.
Han X, Wei X, Alwalid O, et al. Severe Acute Respiratory Syndrome Coronavirus 2 among Asymptomatic Workers Screened for Work Resumption, China. Emerg Infect Dis. 2020 Jun 17;26(9). PubMed: https://pubmed.gov/32553070. Full-text: https://doi.org/10.3201/eid2609.201848
It’s not completely gone. After the outbreak in Wuhan, China, the authors assessed 29,299 workers screened with PCR during March 13–April 25, 2020. They noted 18 (0.06%) cases of asymptomatic infection; 13 turned negative within 8.0 days, and 41 close contacts tested negative. Of 22,633 persons tested for SARS-CoV-2 antibodies, 617 (2.7%) cases had positive IgG but negative IgM; 196 (0.87%) cases had positive IgG and IgM; and 40 (0.18%) cases had negative IgG but positive IgM.
Czeisler MÉ, Tynan MA, Howard ME, et al. Public Attitudes, Behaviors, and Beliefs Related to COVID-19, Stay-at-Home Orders, Nonessential Business Closures, and Public Health Guidance – United States, New York City, and Los Angeles, May 5-12, 2020. MMWR Morb Mortal Wkly Rep. 2020 Jun 19;69(24):751-758. PubMed: https://pubmed.gov/32555138. Full-text: https://doi.org/10.15585/mmwr.mm6924e1
Most people agree: during the week of May 5–12, 2020, a survey among 2,402 adults in New York City and Los Angeles and broadly across the United States found widespread support of stay-at-home orders and nonessential business closures and high degree of adherence to COVID-19 mitigation guidelines. 74-82% reported they would not feel safe if these restrictions were lifted nationwide at the time the survey was conducted. In addition, among those who reported that they would not feel safe, some indicated that they would nonetheless want community mitigation strategies lifted and would accept associated risks (13-17%, respectively).
Virology
Wu KE, Fazal FM, Parker KR, et al. RNA-GPS Predicts SARS-CoV-2 RNA Residency to Host Mitochondria and Nucleolus. Cell Systems, June 20, 2020. Full-text: https://doi.org/10.1016/j.cels.2020.06.008
SARS-CoV-2 genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell’s machinery. But where is the viral RNA localized in the cell? Computational modeling of SARS-CoV-2 viral RNA subcellular residency across eight subcellular neighborhoods, predicted the SARS-CoV-2 RNA genome and sgRNAs to be enriched towards the host mitochondrial matrix and nucleolus. The authors interpret the mitochondrial residency signal as an indicator of intracellular RNA trafficking with respect to double-membrane vesicles, a critical stage in the coronavirus life cycle.
Clinical
Berzuini A, Bianco C, Paccapelo C, et al. Red cell bound antibodies and transfusion requirements in hospitalized patients with COVID-19. Blood. 2020 Jun 19:. PubMed: https://pubmed.gov/32559762. Full-text: https://doi.org/10.1182/blood.2020006695
The direct antiglobulin test (DAT) detects immunoglobulin or complement bound in vivo to red blood cells (RBC), and is widely used to diagnose immune mediated hemolytic anemias. A positive DAT was found in 52 of 113 COVID-19 patients (46%) using the microcolumn screening assay. Thus, anti-RBC antibodies were detectable in almost half of the patients. Although the serologic features of DAT reactivity in COVID-19 patients were somewhat different from those generally observed in autoimmune hemolytic anemia, DAT positivity was associated with increasing frequency of anemia and greater transfusion requirements.
Severe COVID
Colling ME, Kanthi Y. COVID-19-associated coagulopathy: An exploration of mechanisms. Vasc Med. 2020 Jun 19:1358863X20932640. PubMed: https://pubmed.gov/32558620. Full-text: https://doi.org/10.1177/1358863X20932640
Nice review of the laboratory and clinical findings of patients with COVID-19-associated coagulopathy. The authors hypothesize that an imbalance between coagulation and inflammation may result in a hypercoagulable state. Although thrombosis initiated by the innate immune system is hypothesized to limit SARS-CoV-2 dissemination, aberrant activation of this system can cause endothelial injury resulting in loss of thromboprotective mechanisms, excess thrombin generation, and dysregulation of fibrinolysis and thrombosis.
Treatment
Stader F, Khoo S, Stoeckle M, et al. Stopping lopinavir/ritonavir in COVID-19 patients: duration of the drug interacting effect. J Antimicrob Chemother. 2020 Jun 17. PubMed: https://pubmed.gov/32556272. Full-text: https://doi.org/10.1093/jac/dkaa253
The duration of cytochrome P-450 (CYP) 3A inhibition after stopping lopinavir/r treatment is not well understood, leading to some uncertainty as to how long to maintain adjusted doses of co-medications or when to restart drug therapies against comorbidities. The authors investigated the duration of hepatic and intestinal CYP3A inhibition after stopping lopinavir/r treatment by a verified modelling approach. In all age groups, there was more than 80% disappearance of CYP3A inhibition 5 days after stopping lopinavir/r under the consideration of population variability. Complete disappearance of CYP3A inhibition, however, took 21 days in all simulated age groups.
Hegerova L, Gooley T, Sweerus KA, et al. Use of Convalescent Plasma in Hospitalized Patients with Covid-19 – Case Series. Blood. 2020 Jun 19. PubMed: https://pubmed.gov/32559767. Full-text: https://doi.org/10.1182/blood.2020006964
The next case series on early clinical experience of 20 hospitalized patients treated with CP. Compared to 20 matched controls with severe or life-threatening COVID-19 infection, laboratory and respiratory parameters were improved in patients following CP infusion. The 7- and 14-day case fatality rate in CP patients compared favorably to that in controls. However, sample size was small and the study was not randomized. Larger trials are eagerly awaited.
Pediatrics
Otto WR, Geoghegan S, Posch LC, et al. The Epidemiology of SARS-CoV-2 in a Pediatric Healthcare Network in the United States. J Pediatric Infect Dis Soc. 2020 Jun 19. PubMed: https://pubmed.gov/32559282. Full-text: https://doi.org/10.1093/jpids/piaa074
Huge numbers, giving a clearer picture of what happens in children: Of 7,256 children tested for SARS-CoV-2, 424 (6%) tested positive. By race, 10% of black children tested positive vs. 3% of white children. Of the 424 patients who tested positive for SARS-CoV-2, 77 (18%) were hospitalized, of which 24 required respiratory support. Twelve (2.8%) SARS-CoV-2 positive patients developed critical illness requiring mechanical ventilation and 2 patients required ECMO. Two patients died.