COVID-19, corticosteroids and public health: a reappraisal

Abstract

Objectives: To assess whether regulatory guidance on the use of dexamethasone in hospitalised COVID-19 patients is applicable to the larger population of COVID-19 cases. The surge in worldwide demand for dexamethasone suggests that the guidance, although correct, has not emphasised the danger of its wider use.

Study design: Data from the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial and the World Health Organisation (WHO) prospective meta-analysis have been deconstructed and analysed.

Methods: To provide context, relevant publications were identified in PubMed using the following keywords: COVID-19, RECOVERY trial, WHO meta-analysis, variants, immunity, public health.

Results: The WHO guidance 'Corticosteroids for COVID-19' was based on their prospective meta-analysis. This meta-analysis was weighted by data from the RECOVERY trial.

Conclusions: In terms of COVID-19, dexamethasone has value in a narrow indication, namely, in hospitalised patients requiring respiratory support. The media blitz likely resulted in the wider use of dexamethasone in outpatients and as a preventive medication. This is reflected in the surge in worldwide demand for dexamethasone. We ask whether the use of steroids, beyond regulatory indications, may be responsible for the recent increase in mortality and especially the emergence of mucormycosis? From the public health standpoint, the current guidance for use of dexamethasone in COVID-19 could benefit from clarification and the addition of a cautionary note.

Keywords: COVID-19; Immunity; Public health; RECOVERY trial; Variants; WHO meta-analysis.

Fig. 1

In viral infection, the administration of steroids can result in contrasting clinical outcomes. (The Strange Case of Dr Jekyll and Mr Hyde. By, Robert Louis Stevenson. London; Longmans, Green and Company, 1886).

Fig. 2

Innate and adaptive immune response trajectories in COVID-19 (reproduced from Sette and Crotty, with permission). (A) Generic viral infection. (B) Usual SARS-CoV-2 infection. (C) Severe SARS-CoV-2 infection. The initial innate immune response is depicted in green while the later adaptive response consists of antibodies (orange) and T cells (blue). In the usual infection, the coordinated response results in a decrease in the viral load (purple). An uncoordinated and delayed immune response results in an increased and sustained viral load. The latter is likely related to a weak T-cell response. The period of severe COVID-19 clinical disease is shaded grey. Note: T cells refer to virus-specific CD4+ and CD8+ T cells and antibodies refer to virus-specific neutralising antibodies. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)