Covid-19 Digest 19 July

Covid-19 infections keep rising inexorably. So do Covid-10 publications. Impossible to keep up with the data overload but the following articles have caught my eye. If you have read some other noteworthy ones, do let me know.

My selection includes a considered opinion on the management of acute respiratory distress syndrome ARDS, promising Phase 1 trial news on a Covid-19 mRNA vaccine from the Moderna group, intriguing T-cell immunity to the SARS-Cov-2 virus in unexposed subjects and, finally, the RECOVERY Collaborative Group with a peer-reviewed NEJM paper on dexamethasone (we knew it was good as announced early) and a pre-print on hydroxychloroquine (no good as pre-announced).

ARDS

COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted? Fan, Eddy et al.The Lancet Respiratory Medicine, Volume 0, Issue 0

This viewpoint in The Lancet feels the pendulum has swung too far in direction of phenotypic heterogeneity used to justify differential airways and ventilation management. “Although early reports suggested that COVID-19-associated ARDS has distinctive features that set it apart from historical ARDS, emerging evidence indicates that the respiratory system mechanics of patients with ARDS, with or without COVID-19, are broadly similar. In the absence of evidence to support a shift away from the current paradigm of ventilatory management, we strongly recommend adherence to evidence-based management, informed by bedside physiology, as resources permit.” These are the salient takeaways:

New vaccine hope

The Covid-19 Vaccine-Development Multiverse. Heaton Penny M.. (2020). N Engl J Med DOI: 10.1056/NEJMe2025111. 

The NEJM editorial just marvels at their headline article bringing positive phase 1 news of a mRNA vaccine against Covid-19. “Accelerating the development of Covid-19 vaccine candidates beyond phase 1 depends on continued parallel tracking of activities and fulsome resources. The world has now witnessed the compression of 6 years of work into 6 months. Can the vaccine multiverse do it again, leading to a reality of a safe, efficacious Covid-19 vaccine for the most vulnerable in the next 6?”

An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. Jackson et al. July 14, 2020DOI: 10.1056/NEJMoa2022483

The low down: mRNA-1273 induced binding antibodies to the full length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein (S) in all participants after the first vaccination, with all participants seroconverting by day 15. After the second vaccination, geometric mean titers exceeded those seen in convalescent sera obtained from 38 individuals with confirmed COVID-19 diagnosis. Of these individuals, 15% were classified as having severe symptoms, 22% had moderate symptoms, and 63% had mild symptoms.

T-cell immunity to SARS-Cov-2 in unexposed individuals

SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Le Bert, N., Tan, A.T., Kunasegaran, K. et al Nature (2020). https://doi.org/10.1038/s41586-020-2550-z

This is an exciting paper in Nature that dispels some of the pessimism brought by reports of rapidly falling antibody levels in patients who have recovered from Covid-19. It has found that patients who have recovered from the 1993 SARS-COV-1 virus still have a robust T-cell response to SARS-COV-2 N protein and that some people who have not been exposed to these 2 SARS virus or MERS also have T-cells cross-reacting to SARS-COV-2 N protein. It suggests that exposure to other beta coronaviruses may confer a little protection. A blog post by Derek Lowe in Science Translational Medicine offers a nice analysis.

The RECOVERY trials: DEX in, HCQS out

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report The RECOVERY Collaborative Group July 17, 2020DOI: 10.1056/NEJMoa2021436

The low down: “In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.”

Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial. The RECOVERY Collaborative Group July 16 doi: https://doi.org/10.1101/2020.07.15.20151852

The low down: Another study (RCT, but still in pre-print) that shows that hydroxychloroquine doesn’t help in Covid-19 although it doesn’t cause cardiac arrhythmias.

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