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By Christian Hoffmann &
Bernd S. Kamps
3 September
Epidemiology
Self WH, Tenforde MW, Stubblefield WB, et al. Seroprevalence of SARS-CoV-2 Among Frontline Health Care Personnel in a Multistate Hospital Network — 13 Academic Medical Centers, April–June 2020. MMWR. Full-text: http://dx.doi.org/10.15585/mmwr.mm6935e2
Many appear to go undetected: among 3,248 HCWs who routinely cared for COVID-19 patients in 13 US academic medical centers from February 1, 2020, 194 (6%) had evidence of previous SARS-CoV-2 infection, with considerable variation by location that generally correlated with community cumulative incidence. Among 194 participants who had SARS-CoV-2 antibodies, 56 (29%) did not recall any symptoms consistent with an acute viral illness in the preceding months and 133 (69%) did not have a previous positive test result demonstrating an acute SARS-CoV-2 infection. Prevalence of SARS-CoV-2 antibodies was lower among personnel who reported always wearing a face covering while caring for patients (6%), compared with those who did not (9%).
Vaccine
Keech C, Albert G, Cho I, et al. Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. NEJM September 2, 2020, Full-text: https://doi.org/10.1056/NEJMoa2026920
NVX-CoV2373 is a recombinant SARS-CoV-2 nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant. In 83 participants younger than 60 years of age, two injections of NVX-CoV2373 delivered in the deltoid muscle on day 0 and 21 appeared to be safe. Immune responses exceeded levels in COVID-19 convalescent serum, showing high neutralizing antibody responses and T cells with a predominant Th1 phenotype. Phase 2 has started.
Clinical
Yelin D, Wirtheim E, Vetter P, et al. Long-term consequences of COVID-19: research needs. Lancet Inf Dis September 01, 2020. Full-text: https://doi.org/10.1016/S1473-3099(20)30701-5
Weeks and months after the onset of acute COVID-19, people continue to suffer. But how many? In their important comment on the trajectory of people recovering from COVID-19, Dana Yelin addresses the key issues. A clear definition of patient inclusion criteria, a common protocol, and uniform definitions of outcomes and ways to measure them are required.
Buetti N, Patrier J, Le Hingrat Q, et al. Risk factors for SARS-CoV-2 detection in blood of critically ill patients. Clinical Infectious Diseases, 02 September 2020. Full-text: https://doi.org/10.1093/cid/ciaa1315
Of 81 blood samples for SARS-CoV-2 detection (from 42 critically ill patients), 30 (37%) were positive. Immunosuppression (OR 12.16, 95% CI 1.74-84.93, p = 0.013) and chronic renal failure (OR 5.98) increased the risk for SARS-CoV-2 detection in the blood. In contrast to previous reports, SARS-CoV-2 detection in the blood was not associated with 6-week mortality.
Comorbidities
Keller N, Chantrel F, Krummel T. Impact of first-wave COronaVIrus disease 2019 infection in patients on haemoDIALysis in Alsace: the observational COVIDIAL study. Nephrology Dialysis Transplantation, September 2, 2020. Volume 35, Issue 8, August 2020, Pages 1338–1411. Full-text: https://doi.org/10.1093/ndt/gfaa170
Prospective observational study conducted in eight HD facilities in Alsace, France. Among 1,346 HD patients, 123 tested positive for COVID-19. Case fatality rate was 24%. While patients presented severe forms of the disease, they often displayed atypical symptoms, with the CRP level being highly associated with risk of death.
Treatment
The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. NEJM July 17, 2020. Full-text: https://doi.org/10.1056/NEJMoa2021436
With a press release on June 16, 2020 reporting the results of the UK-based RECOVERY trial, treatment of COVID-19 underwent a major change. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Why is this mentioned here again? Because the RECOVERY results had a huge impact on other randomized clinical trials (RCTs) around the world. Many trials were stopped prematurely following the press release and are now, unfortunately, underpowered. Three of them were now published in the JAMA:
Dequin PF, Heming N, Meziani F, et al. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19A Randomized Clinical Trial. JAMA September 2, 2020. Full-text: https://doi.org/10.1001/jama.2020.16761
- CAPE COD trial (France). Multicenter double-blinded RCT, in 149 (290 planned) critically-ill patients admitted to the intensive care unit (ICU) for COVID-19–related acute respiratory failure. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (p = 0.29).
Tomazini BM, Maia IS, Cavalcanti AB. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19. The CoDEX Randomized Clinical Trial. JAMA September 2, 2020. https://doi.org/10.1001/jama.2020.17021
- CoDEX (Brazil). Multicenter, open-label RCT in 299 COVID-19 patients (350 planned) with moderate-to-severe ARDS. Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n = 151) or standard care alone (n = 148). Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days during the first 28 days vs 4.0 ventilator-free days in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; p = 0.04). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days.
The Writing Committee for the REMAP-CAP Investigators. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19. JAMA September 2, 2020. https://doi.org/10.1001/jama.2020.17022
- REMAP-CAP (different countries). In this Bayesian RCT, 384 patients were randomized to fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone. Treatment with a 7-day fixed-dose course or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority, respectively, with regard to the odds of improvement in organ support–free days within 21 days. However, due to the premature halt of the trial, no treatment strategy met pre-specified criteria for statistical superiority, precluding definitive conclusions.
The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19. A Meta-analysis. JAMA September 2, 2020. doi:10.1001/jama.2020.17023
A prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The fixed-effect summary odds ratios for the association with mortality were 0.64 (95% CI, 0.50-0.82; p < 0.001) for dexamethasone compared with usual care or placebo, 0.69 (95% CI, 0.43-1.12; p = 0.13) for hydrocortisone and 0.91 (95% CI, 0.29-2.87; p = 0.87) for methylprednisolone, respectively. There was no suggestion of an increased risk of serious adverse events. See also the editorial: Prescott HC, Rice TW. Corticosteroids in COVID-19 ARDS: Evidence and Hope During the Pandemic. JAMA 2020, published 2 September. Full-text: https://jamanetwork.com/journals/jama/fullarticle/2770275
Sterne J, Rice T, Diaz J. Corticosteroids for COVID-19 – New Evidence of Benefit. Jama Network 2020, published 2 September. Link: https://www.youtube.com/watch?v=XfDWjPxhKcE
A conversation with Jonathan Sterne, Todd Rice and Janet Diaz on the latest research supporting the use of hydrocortisone and dexamethasone for treatment of COVID-19 ARDS.