Impact of dexamethasone on SARS-CoV-2 concentration kinetics and antibody response in hospitalized COVID-19 patients: results from a prospective observational study

Abstract

Objectives Dexamethasone has become standard of care for severe coronavirus disease 2019 (COVID-19), but its virological impact is poorly understood. The objectives of this work were to characterise the kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) concentration in the upper respiratory tract (URT) and the antibody response in patients with (D + ) and without (D - ) dexamethasone treatment. Methods Data and biosamples from hospitalised patients with severe COVID-19, enrolled between March 4 th and December 11 th , 2020, in a prospective observational study, were analysed. SARS-CoV-2 virus concentration in serial URT samples was measured using RT-PCR. SARS-CoV-2-specific Immunoglobulin A and G (IgA and IgG) were measured in serum samples using S1-ELISA. Results We compared 101 immunocompetent patients who received dexamethasone according to the inclusion criteria and dosage determined in the RECOVERY trial to 93 immunocompetent patients with comparable disease severity from the first months of the pandemic, who had not been treated with dexamethasone or other glucocorticoids. We found no inter-group differences in virus concentration kinetics, duration of presence of viral loads >10 6 viral copies/mL (D + : median 17 days (IQR 13-24), D - : 19 days (IQR 13-29)), or time from symptom onset until seroconversion (IgA: D + : median 11.5 days (IQR 11-12), D - : 14 days (IQR 11.5-15.75); IgG: D + : 13 days (IQR 12-14.5), D - : 12 days (IQR 11-15)). Conclusion Dexamethasone does not appear to lead to a change in virus clearance or a delay in antibody response in immunocompetent patients hospitalised with severe COVID-19.

Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

“…The use of dexamethasone caused a boost of virus replication and a significant delay of viral clearance in Syrian hamsters, albeit without significantly worsening the clinical course of disease. In the light of existing literature on the enhanced replication of respiratory viruses upon dexamethasone treatment 42 and data that overall show a tendency toward a boost of SARS-CoV-2 replication in dexamethasone-treated patients, 11,[43][44][45] this result is not unexpected and may imply a risk for increased and/or prolonged transmissibility. Still, dexamethasone exerted the expected anti-inflammatory effects and attenuated inflammatory lung injury.…”

No Impact of Corticosteroid Use During the Acute Phase on Persistent Symptoms Post-COVID-19

“…In line with our results, a retrospective study showed that dexamethasone had no effect on concentration kinetics and antibody response in hospitalized COVID-19 patients. 17 Otherwise, microvascular impairment 18 and autoimmunity 19 have also been discussed as being implicated in persistent symptoms.…”

Presence of Antibodies to Severe Acute Respiratory Syndrome Coronavirus-2 on Admission Is Associated With Decreased Mortality in COVID-19 Critical Illness

“…In a single study in hospitalized, among 38 patients with undetectable anti-S IgG upon study entry, time from symptom onset to detectable anti-S IgG did not differ by receipt of dexamethasone. This study was not conducted in an ICU population limiting generalizability to critical illness, and plasma measurements were only collected every 7 days limiting granularity in this time-to-seroconversion analysis ( 6 ). Here, we extend this analysis to COVID-19 critical illness, and we similarly find that dexamethasone treatment is not associated with time-to-seroconversion.…”

“…Although treatment with dexamethasone is currently considered standard of care for treatment of individuals with severe COVID-19, there is concern that the inhibitory effects of corticosteroids on lymphocytes may impair the serologic response. A single-center study in hospitalized patients found no difference in serologic response following treatment with corticosteroids ( 6 ), and, to our knowledge, no report has focused on critically ill populations.…”