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 the standard of care for severe coronavirus disease 2019 (COVID-19), but its virological impact is poorly understood. The objectives of this work were to characterize 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 hospitalized patients with severe COVID-19, enrolled between 4th March and 11th December 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 immunoglobulins 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 >10⁶ 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 hospitalized with severe COVID-19.

Keywords: Antibody; COVID-19 nucleic acid testing; Coronavirus disease 2019 (COVID-19); Dexamethasone; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Viral concentration.

Fig. 1

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) concentration kinetics and shedding. (A) Virus concentration over time in upper respiratory tract (URT) samples in two groups of hospitalized COVID-19 patients with comparable disease severity (WHO score ≥ 4), D⁺ patients in orange and D^– in blue. Bold lines and shaded areas indicate the LOWESS fit (smoothing parameter 0.5) and 95% confidence intervals (calculated from 1000 bootstrap replicates of 90 samples, corresponding to ~90% of the full dataset) for the two groups. The grey area indicates the typical time span during which dexamethasone was administered (a median of 1–11 days after admission). (B) Duration of shedding was measured as the time from symptom onset to the last PCR test with a viral load >10⁶ viral copies/mL for D⁺ and D^– patients. Median shedding duration: D⁺ median 17 days (IQR 13–24); D^– median 19 days (IQR 13–29), p 0.37 (Mann–Whitney U test). During their time in hospital, D⁺ patients had a median of three tests (IQR 2–6), a median of 4 days (IQR 2–7) apart, and D^– patients had a median of five tests (IQR 3–8), a median of 4 days (IQR 2–7) apart.

Fig. 2

IgG and IgA S1-ELISA results. (A,B) Time to seroconversion. Time to seroconversion is measured as the time from symptom onset to a reactive S1-ELISA test that is preceded by a non-reactive S1-ELISA test. (A) IgA, median duration to seroconversion: D⁺ 11.5 days (IQR 11–12); D^– 14 days (IQR 11.5–15.75). Seroconversion could be observed in six D⁺ patients and six D^– patients who were included into the study with a non-reactive IgA S1-ELISA result. (B) IgG, median duration to IgG seroconversion, D⁺ 13 days (IQR 12–14.5), D^– 12 days (IQR 11–15). For IgG, 23 D⁺ patients and 15 D^– patients were included into the study with a non-reactive IgG S1-ELISA and later seroconverted. (C, D) Time from symptom onset to the first test reaching the threshold OD ratio ≥5. Only patients with a first test taken no more than 20 days after symptom onset were included. (C) IgA, median duration from symptom onset to first IgA S1-ELISA test with OD ratio ≥5, D⁺ 13 days (IQR 10–16), D^– 13 days (IQR 11–15.5). (D) IgG, median duration from symptom onset to first IgG S1-ELISA test with OD ratio ≥5, D⁺ 15 days (IQR 13–18), D^– 15 days (IQR 12–16). Outliers—defined as patients with >30 days until seroconversion or >30 days to reach the threshold OD ratio of 5—were excluded (n = 5).