From NEJM Journal Watch Dexamethasone: first drug found to reduce mortality in people with COVID-19
The reduction in mortality was greatest in those on mechanical ventilation; people who were not on oxygen did not benefit and might have experienced harm.1
Because patients with severe COVID-19 often have evidence of excess inflammation, intense interest has centred on whether anti-inflammatory medications, such as glucocorticoids, have a role in treating COVID-19. In the RECOVERY trial, patients hospitalised with COVID-19 were randomised to receive dexamethasone (6 mg/day for up to 10 days; n=2104) or usual care (n=4321).
Mortality within 28 days was lower with dexamethasone than with usual care (22.9% vs 25.7%; age-adjusted rate ratio [RR], 0.83). Among patients receiving mechanical ventilation at enrolment, dexamethasone recipients had an age-adjusted 36% lower mortality than usual-care recipients (29.3% vs 41.4%; RR, 0.64). Those requiring supplemental oxygen (but not mechanical ventilation) had a smaller but still significant mortality difference between dexamethasone and usual care (23.3% vs 26.2%; RR, 0.82). Among patients not receiving supplemental oxygen, dexamethasone conferred no benefit over usual care; indeed, their results were consistent with potential harm (RR, 1.19).
This landmark trial was designed to evaluate the effect of treatment on major clinical outcomes, like death. It cannot address why dexamethasone worked, whether biomarkers can identify individuals most likely to benefit, and other questions.
Moreover, the mortality in this trial was higher than what is being seen in the current stage of the pandemic, toxicity information is not presented, and the results pertain to only hospitalised patients; ambulatory patients should not receive dexamethasone. Nevertheless, the findings support an emerging paradigm for how different therapies affect COVID-19. The antiviral remdesivir is most beneficial in people with severe COVID-19 who are not yet critically ill, suggesting an important role for viral replication in this disease stage.2 By contrast, dexamethasone’s largest impact is in critically ill people, suggesting that excess inflammation drives much of the damage at this stage. Trials are underway to assess the combination of antiviral and anti-inflammatory therapies in people with severe COVID-19.
From NEJM Journal Watch What’s the duration of immunity to SARS-CoV-2?
Individuals with mild COVID-19 infection have a rapid decline in SARS-CoV-2 antibody levels.
One of the many still unanswered questions regarding COVID-19 is the duration of protective immunity following infection. A recent report from China indicated that individuals with asymptomatic COVID-19 had a less robust immune response to SARS-CoV-2.1 California investigators now report further longitudinal data on antibody levels after mild COVID-19.2
Thirty-four individuals with mild COVID-19 (30 that were polymerase-chain-reaction assay confirmed) had serial anti–SARS-CoV-2 receptor binding domain IgG levels determined at a mean of 37 and 86 days after symptom onset. The estimated mean IgG half-life was 36 days.
The finding of a relatively short anti–SARS-CoV-2 IgG half-life in these two reports has received substantial coverage in the lay press and does raise concerns regarding the duration of protective immunity that is present both after infection and with a COVID-19 vaccine. Still, the present report did not directly assess neutralising antibodies, and neither this nor the report from China assessed either T-cell mediated immunity or the potential for an anamnestic response to this virus.