By Christian Hoffmann &
Bernd S. Kamps
Virology
Sungnak W, Huang N, Bécavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature Medicine, Published: 23 April 2020. Full-text: https://www.nature.com/articles/s41591-020-0868-6
Elegant paper, confirming the expression of ACE2 in multiple tissues shown in previous studies, with added information on tissues not previously investigated, including nasal epithelium and cornea and its co-expression with TMPRSS2. Potential tropism was analyzed by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. These transcripts were found in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission.
Epidemiology
Giordano G, Blanchini F, Bruno R, et al. Modelling the COVID-19 epidemic and implementation of population-wide interventions in Italy. Nat Med. 2020 Apr 22. pii: 10.1038/s41591-020-0883-7. PubMed: https://pubmed.gov/32322102. Full-text: https://doi.org/10.1038/s41591-020-0883-7
Interesting new model that predicts the course of the epidemic, considering eight stages of infection: susceptible (S), infected (I), diagnosed (D), ailing (A), recognized (R), threatened (T), healed (H) and extinct (E), collectively termed SIDARTHE. The model discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. Authors demonstrate that restrictive social-distancing measures will need to be combined with widespread testing and contact tracing to end the ongoing pandemic.
Peto J, Alwan NA, Godfrey KM, et al. Universal weekly testing as the UK COVID-19 lockdown exit strategy. Lancet. 2020 Apr 20. pii: S0140-6736(20)30936-3. PubMed: https://pubmed.gov/32325027. Full-text: https://doi.org/10.1016/S0140-6736(20)30936-3
They have a dream: These UK researches recommend the evaluation of weekly antigen testing of the whole population after lockdown. As they say, “a voluntary Dunkirk spirit” would be the only way for 10 million tests to be done daily.
Transmission
Park SY, Kim YM, Yi S, et al. Coronavirus Disease Outbreak in Call Center, South Korea. Emerg Infect Dis. 2020 Apr 23;26(8). PubMed: https://pubmed.gov/32324530. Full-text: https://doi.org/10.3201/eid2608.201274
Epidemiologic characteristics of a COVID-19 outbreak centered in a call center in South Korea, indicating an attack rate of 8.5% within the whole building. If results were restricted to one floor, the attack rate was as high as 43.5%. Among the 97 confirmed case-patients, 92% were symptomatic at the time of investigation and 4% were presymptomatic. Only 4% remained asymptomatic after 14 days of isolation.
Keshtkar-Jahromi M, Sulkowski M, Holakouie-Naieni K. Public Masking: An Urgent Need to Revise Global Policies to Protect against Novel Coronavirus Disease (COVID-19). Am J Trop Med Hyg. 2020 Apr 22. PubMed: https://pubmed.gov/32323645. Full-text: https://doi.org/10.4269/ajtmh.20-0305
Brief review. Authors highly recommend mass masking around the world during the pandemic. Whereas surgical masks are the preferred recommendation for the general public, cloth masks should be considered as a substitute if supplies are limited or surgical masks are not available.
Clinical
Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 Apr 20. pii: S0140-6736(20)30937-5. PubMed: https://pubmed.gov/32325026. Full-text: https://doi.org/10.1016/S0140-6736(20)30937-5
The ACE2 receptor is widely expressed on endothelial cells. Three cases, indicating direct viral infection of the endothelial cell and diffuse endothelial inflammation, induced by SARS-CoV-2 infection.
Grillet F, Behr J, Calame P, Aubry S, Delabrousse E. Acute Pulmonary Embolism Associated with COVID-19 Pneumonia Detected by Pulmonary CT Angiography. Radiology. 2020 Apr 23:201544. PubMed: https://pubmed.gov/32324103. Full-text: https://doi.org/10.1148/radiol.2020201544
In 100 patients with severe COVID-19, a high prevalence (23%, 95%CI 15-33%) of acute pulmonary embolism was found. Pulmonary embolus was diagnosed at mean of 12 days from symptom onset. In multivariable analysis, requirement for mechanical ventilation (OR = 3.8, 95%CI 1.02-15) remained associated with acute pulmonary embolus.
Comorbidities
Sriram K, Insel PA. Risks of ACE inhibitor and ARB usage in COVID-19: evaluating the evidence. Clin Pharmacol Ther. 2020 Apr 22. PubMed: https://pubmed.gov/32320478. Full-text: https://doi.org/10.1002/cpt.1863
Nice review. Data from 12 animal studies and from 12 human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. Authors conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.
Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020 Apr 17. PubMed: https://pubmed.gov/32302265. Full-text: https://doi.org/10.1161/CIRCRESAHA.120.317134
Same direction: In this retrospective, multi-center study of 1128 adult patients with hypertension diagnosed with COVID-19, 188 patients taking ACEI/ARB were compared with 940 patients without using ACEI/ARB. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%). In a Cox model, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group (adjusted HR 0.42; 95%CI, 0.19-0.92).
Treatment
Chorin E, Dai M, Shulman E. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin. Nature Medicine. Published: 24 April 2020. Full-Text: https://www.nature.com/articles/s41591-020-0888-2
Check ECG if you do this! In this important study, authors followed the corrected QT (QTc) interval in a consecutive cohort of 84 patients receiving hydroxychloroquine and azithromycin which were administered orally for 5 days. A prolongation of the QTc from a baseline average of 435 ± 24 ms to a maximal average value of 463 ± 32 ms was found, occurring on day 3.6 ± 1.6 of therapy. In a subset of nine (11%) patients, the QTc was severely prolonged to >500 ms, a known marker of high risk of malignant arrhythmia and sudden cardiac death. Five of nine patients with severe QTc prolongation had a normal QTc at baseline.