Copy-editor: Rob Camp
Transmission
Manna A. Be Aware of Droplets and Bubbles. Ann Intern Med 2020, published 1 December. Web page: https://doi.org/10.7326/G20-0114
No comment.
Bubbles reproduced with permission.
Vaccine
WHO Ad Hoc Expert Group on the Next Steps for Covid-19 Vaccine Evaluation. Placebo-Controlled Trials of Covid-19 Vaccines — Why We Still Need Them. N Engl J Med 2020, published 2 December. Full-text: https://doi.org/10.1056/NEJMp2033538
In this Perspective, the participants in a World Health Organization ad hoc consultation on the next steps for COVID-19 vaccine evaluation recommend on how to proceed clinically as the first commercial vaccines increasingly become available. Yes, continue with placebo-controlled trials (the bedrock of modern clinical decision-making) because we still need more data on longer-term safety and duration of protection; on whether waning of vaccine-induced protection may lead to vaccine-enhanced disease if a vaccinee becomes infected after exposure to SARS-CoV-2; on information on protection against clinically severe forms of COVID-19; and knowledge of any associations between the degree of protection and the recipient’s age or co-existing conditions. No, refrain from observational studies which are subject to substantial biases and are much less amenable to unambiguous interpretation.
Branswell H. The Covid-19 vaccines are a marvel of science. Here’s how we can make the best use of them. STAT 2020, published 2 December. Full-text: https://www.statnews.com/2020/12/02/how-society-can-make-the-most-of-covid-19-vaccines/
Will 95% efficacy vaccines show the way to a straight road back to Normalville? Or will the route back be a meandering country lane with detours and potholes? Pothole 1: Vaccine skepticism. Pothole 2: Pregnant women. Pothole 3: Children. Pothole 4: How to continue important Phase III randomized trials while vaccines are already on the market? Pothole 5: Understanding SARS-CoV-2 transmission by vaccinated individuals. Have enough time before starting this long-read article.
Diagnostics
Dugdale CM, Anahtar MN, Chiosi JJ, et al. Clinical, laboratory, and radiologic characteristics of patients with initial false-negative SARS-CoV-2 nucleic acid amplification test results. Open Forum Infect Dis 2020, published 24 November. Full-text: https://doi.org/10.1093/ofid/ofaa559
People with COVID-19 symptoms who have a negative PCR test should be retested within two weeks, especially in areas with sustained community transmission of SARS-CoV-2. This is the message Caitlin Dugdale and colleagues from the Massachusetts General Hospital, Boston, after finding 60 positives of 2699 subjects (2,2%) on a second test. Most of these subjects had symptoms (52/60; 87%) and chest radiography (19/32; 59%) consistent with COVID-19. A total of 60% had their initial test either ≤ 1 day (n = 18) or > 7 days (n = 18) after symptom onset.
Treatment
WHO Solidarity Trial Consortium. Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results. N Engl J Med 2020, published 2 December. Full-text: https://doi.org/10.1056/NEJMoa2023184
Harrington DP, Baden LR, Hogan JW (Editorial). A Large, Simple Trial Leading to Complex Questions. N Engl J Med 2020, published 2 December. Full-text: https://doi.org/10.1056/NEJMe2034294
Remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. This is the interim result of the WHO Solidarity Trial which of 11.330 adults at 405 hospitals in 30 countries. 2750 were randomly assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving the control. In the accompanying editorial, David Harrington, Lindsey Baden, and Joseph Hogan try to save the day for remdesivir; however, it is clear that the drug plays in an altogether different league than the powerful anti-HIV and anti-HCV drugs. Also, in future pandemics we will remember that repurposing old antiviral drugs was not successful.
Figure 2. Effects of Remdesivir, Hydroxychloroquine, Lopinavir, and Interferon on In-Hospital Mortality. Reproduced with permission. Shown are Kaplan–Meier graphs of in-hospital mortality at any time (the primary outcome), comparing each treatment with its control without standardization for any initial patient characteristics. Insets show the same data on an expanded y axis. The rate ratios for death were standardized… | Continue reading at https://doi.org/10.1056/NEJMoa2023184. Reproduced with permission.
Drug Development
Cox RM, Wolf JD, Plemper RK. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat Microbiol 2020, published 3 December. Full-text: https://doi.org/10.1038/s41564-020-00835-2
Molnupiravir (MK-4482/EIDD-2801) is able to mitigate SARS-CoV-2 infection and block transmission when therapeutically administered to ferrets. The drug, initially developed as an inhibitor of influenza viruses, is currently in Phase II/III clinical trials (NCT04405570 and NCT04405739).
Wang G, Yang ML, Duan ZL, et al. Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models. Cell Res 2020, published 1 December. Full-text: https://doi.org/10.1038/s41422-020-00450-0
Dalbavancin is a once-a-week antibiotic (plasma half-life: 5–7 days) with activity against a broad range of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and which has been approved for the treatment of acute bacterial skin and skin structure infections. Here, Ren Lai, Gan Wang and colleagues show that the drug effectively prevented SARS-CoV-2 replication in Vero E6 cells with an EC50 of ~12 nM. In both mouse and rhesus macaque models, viral replication and histopathological injuries caused by SARS-CoV-2 infection were significantly inhibited by dalbavancin administration.
Figure 5. Dalbavancin shows significant anti-SARS-CoV-2 effects in rhesus macaque model. a Schematic of rhesus macaque model of SARS-CoV-2 infection. Macaques were randomly assigned to either the saline group (n = 3) or the dalbavancin group (n = 3, administered by intravenous infusion over 0,5 h) and inoculated with… | Continue reading at https://doi.org/10.1038/s41422-020-00450-0. Reproduced with permission.
Education
Rubin EJ, Baden LR, Morrissey S. Caring for Hospitalized Patients with Covid-19. Audio interview (18:39). N Engl J Med 2020; 383: e140. Access: https://doi.org/ 10.1056/NEJMe2034472
The editors discuss the WHO’s Solidarity study and the changing recommendations for the care of hospitalized patients.
Beyond Corona
Callaway E. ‘It will change everything’: DeepMind’s AI makes gigantic leap in solving protein structures. Nature 2020, published 30 November. Full-text: https://www.nature.com/articles/d41586-020-03348-4
Google’s deep-learning program for determining the 3D shapes of proteins might transform biology. Is it truly a game changer? Will it change medicine, research and bioengineering, as suggests Andrei Lupas from MPI Tübingen? Follow Ewen Callaway on this tour around the AI-biology interface.
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Copy-editor: Rob Camp