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By Christian Hoffmann &
Bernd S. Kamps

1 July

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Epidemiology

Tenforde MW, Rose EB, Lindsell CJ, et al. Characteristics of Adult Outpatients and Inpatients with COVID-19 — 11 Academic Medical Centers, United States, March–May 2020. MMWR Morb Mortal Wkly Rep. ePub: 30 June 2020. Full-text:  https://www.cdc.gov/mmwr/volumes/69/wr/mm6926e3.htm?s_cid=mm6926e3_w

Telephone interviews in a random sample of 350 adults aged ≥ 18 years who had positive RT-PCR in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states revealed that only 46% were aware of recent close contact with someone with COVID-19, highlighting a need for increased screening, case investigation, contact tracing, and isolation of infected persons during periods of community transmission. Of note, approximately one third of symptomatic outpatients reported that they had not returned to baseline health by the interview date 14–21 days after testing positive.

 

Vaccine

Dai L, Zheng T, Xu K, et al. A universal design of betacoronavirus vaccines against COVID-19, MERS and SARS. Cell June 28, 2020. Full-text: https://doi.org/10.1016/j.cell.2020.06.035

The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. The authors identified a dimeric form of MERS-CoV RBD that overcomes this limitation and significantly increased the immunogenicity. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. This can be a generalizable strategy for beta-CoV vaccine design.

 

Pathogenesis

Bouhaddou M, Memon DF, Meyer B, et al. The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell June 28, 2020. Full-text: https://www.sciencedirect.com/science/article/pii/S0092867420308114

Nothing to do next weekend? Then read this incredible work of 66 pages (> 400 references!). In brief: proteomics approaches that globally quantify changes in protein abundance and phosphorylation represent a powerful tool to elucidate mechanisms of viral pathogenesis by providing a snapshot of how cellular pathways and processes are rewired upon infection. Using a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, the 78 (!) authors present the global phosphorylation and protein abundance landscape of SARS-CoV-2 infection, map phosphorylation changes to disrupted kinases and pathways, and use these profiles to find drugs with the potential to treat SARS-CoV-2 infection. In total, 87 compounds (10 FDA-approved drugs) were identified.

 

Transmission

Abbas M, Pittet D. Surfing the COVID-19 scientific wave. Lancet June 30, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30558-2

Harsh, relentless (maybe justified?) critical letter on the methodological flaws of the experiment of visualizing speech-generated oral fluid droplets (see below). The authors are “surprised that experiments in one person were published in a leading scientific journal” and state that the experiment had “more to do with sialoquence (spraying saliva when speaking) than with SARS-CoV-2”.

Anfinrud P Stadnytskyi V Bax CE Bax A. Visualizing speech-generated oral fluid droplets with laser light scattering. N Engl J Med. 2020; 382: 2061-2063. Full-text: https://www.nejm.org/doi/full/10.1056/nejmc2007800

 

Clinical

Lavezzo E, Franchin E, Ciavarella C et al. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature 2020, June 30. Full-text: https://doi.org/10.1038/s41586-020-2488-1

On the 21st of February 2020 a resident of the municipality of Vo’, a small town near Padua, Italy, died of pneumonia due to SARS-CoV-2 infection. At the start and the end of the lockdown, NP swabs were performed for 85.9% and 71.5% of the population (n=2,812), yielding to a prevalence of infection of 2.6% (95% CI 2.1-3.3%) and 1.2% (95% CI 0.8-1.8%), respectively. Of note, 42.5% of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic. Viral load of symptomatic versus asymptomatic infections did not differ.

 

Hewitt J, Carter B, Vilches-Moraga A, et al. The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study. Lancet June 30, 2020. Full-text: https://doi.org/10.1016/S2468-2667(20)30146-8

Using the clinical frailty scale (CFS), 1,564 patients from the UK and Italy were grouped according to their score (1–2=fit; 3–4=vulnerable, but not frail; 5–6=initial signs of frailty but with some degree of independence; and 7–9=severe or very severe frailty). Not very surprising: Compared with CFS 1–2, the adjusted hazard ratios for time from hospital admission to death were 1.55 for CFS 3–4, 1.83 for CFS 5–6, and 2.39 for CFS 7–9. Of note, disease outcomes were better predicted by frailty than either age or comorbidity.

 

Severe COVID-19

Goshua G, Pine AB, Meizlish ML, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet June 30, 2020. Full-text: https://doi.org/10.1016/S2352-3026(20)30216-7

In 68 COVID-19 patients, the authors assessed several markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes. Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen and soluble P-selectin. Some were of prognostic value, indicating that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.

 

Comorbidities

Del Amo J, Polo R, Moreno S, et al. Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy – A Cohort Study. Annals Int Med 2020, June 26. Full-text: https://doi.org/10.7326/M20-3689

Is there an effect of TDF? Of 77,590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. However, residual confounding by comorbid conditions cannot be completely excluded.

 

Treatment

Tempestilli M, Caputi P, Avataneo V, et al. Pharmacokinetics of remdesivir and GS-441524 in two critically ill patients who recovered from COVID-19. J Antimicr Chemoth, July 1, 2020. Full-text: https://doi.org/10.1093/jac/dkaa239

Small PK pilot study on remdesivir (Veklury®) and the nucleoside analog GS-441524 (of which remdesivir is a prodrug). After intravenous administration, in both patients remdesivir showed a peak at the end of infusion and a half-life of 1 h, while GS-441524 reached a peak 1 h after infusion and then remained detectable until the next remdesivir administration. GS-441524 plasma concentrations were higher in the patient with renal impairment, indicating that renal excretion was a major route of elimination.

 

Pediatrics

L’Huillier AG, Torriani G, Pigny F, et al. Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, Children, and Adolescents. Emerg Infect Dis 2020, Pub June 29, 2020. Full-text: https://doi.org/10.3201/eid2610.202403

No differences between adults and children. The authors isolated culture-competent virus in vitro from 12 (52%) of 23 SARS-CoV-2–infected children; the youngest was 7 days old. SARS-CoV-2 viral load and shedding patterns of culture-competent virus in the 12 symptomatic children resembled those in adults. Therefore, transmission of SARS-CoV-2 from children is plausible.