Early Use of Corticosteroid May Prolong SARS-CoV-2 Shedding in Non-Intensive Care Unit Patients with COVID-19 Pneumonia: A Multicenter, Single-Blind, Randomized Control Trial

Abstract

Background: There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia.

Objective: To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia.

Methods: This was a prospective, multicenter, single-blind, randomized control trial. Adult patients with COVID-19 pneumonia who were admitted to the general ward were randomly assigned to either receive methylprednisolone or not for 7 days. The primary end point was the incidence of clinical deterioration 14 days after randomization.

Results: We terminated this trial early because the number of patients with COVID-19 pneumonia in all the centers decreased in late March. Finally, a total of 86 COVID-19 patients underwent randomization. There was no difference of the incidence of clinical deterioration between the methylprednisolone group and control group (4.8 vs. 4.8%, p = 1.000). The duration of throat viral RNA detectability in the methylprednisolone group was 11 days (interquartile range, 6-16 days), which was significantly longer than that in the control group (8 days [2-12 days], p = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3+ T cells, CD8+ T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (p < 0.05).

Conclusions: From this prematurely closed trial, we found that the short-term early use of corticosteroid could suppress the immune cells, which may prolong severe acute respiratory syndrome coronavirus 2 shedding in patients with COVID-19 pneumonia.

Trial registration: ClinicalTrials.gov, NCT04273321.

Keywords: Coronavirus disease 2019; Corticosteroid; Outcome; Pneumonia; Virus shedding.

Fig. 1

Randomization and treatment assignment of patients with COVID-19. COVID-19, coronavirus disease 2019.

Fig. 2

Kaplan-Meier curves of the primary outcome and secondary outcomes between the Met group and Con group. Shown are the probability of clinical deterioration (a), clinical cure (b), discharge (c), and SARS-CoV-2 shedding (d) over time. The Kaplan-Meier approach with the log-rank test was used to assess the primary and secondary outcomes. SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Met, methylprednisolone; Con, control.

Fig. 3

Mass cytometric analysis of CD45⁺ immune cells from peripheral blood. a Representative t-SNE plots of CD45⁺ immune cells on day 0 (at randomization), 7 and 14 days after randomization derived from one COVID-19 patients from the Met group (upper panels) and one from the Con group (bottom panels) are shown. One point represents one cell, and the dark and light colors shows high expression and low expression. The comparisons of the percentages of blood CD3⁺ T cells (b), CD4⁺ T cells (c), CD8⁺ T cells (d), CD19⁺ T cells (e), CD7⁺ NK cells (f), and CD11b⁺ myeloid cells (g) between the Met group and Con group. Data are presented as mean ± SD. *p < 0.05 compared with the Con group on the same time point by repeated measures analysis of the two-way ANOVA followed by Bonferroni's test. †p < 0.05 compared with day 0 in the Met group by repeated measures analysis of the one-way ANOVA followed by Dunnett's test. COVID-19, coronavirus disease 2019; Met, methylprednisolone group; Con, control group.