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

<b><i>Background:</i></b> There is still no clinical evidence available to support or to oppose corticosteroid treatment for coronavirus disease 2019 (COVID-19) pneumonia. <b><i>Objective:</i></b> To investigate the efficacy and safety of corticosteroid given to the hospitalized patients with COVID-19 pneumonia. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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%, <i>p</i> = 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], <i>p</i> = 0.030). There were no significant differences between the 2 groups in other secondary outcomes. Mass cytometry discovered CD3<sup>+</sup> T cells, CD8<sup>+</sup> T cells, and NK cells in the methylprednisolone group which were significantly lower than those in the control group after randomization (<i>p</i> < 0.05). <b><i>Conclusions:</i></b> 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. <b><i>Trial Registration:</i></b> ClinicalTrials.gov, NCT04273321.

Usage of Compromised Lung Volume in Monitoring Steroid Therapy on Severe COVID-19

“…This nding was supported by recent studies [2,40,41], in which corticosteroid therapy led to different clinical outcomes according to severity of illness. We speculated that the absence of bene t in the low CL group may be partially explained by the delayed viral clearance [42][43][44]. In the present study, patients in the low CL group receiving steroids had relatively longer viral shedding duration than those who were not receiving steroids, although the difference was not statistically signi cant.…”

Corticosteroid therapy for COVID-19

“…All included studies had data regarding mortality. Of note, 1 study evaluated mortality at 30 days, [ 21 ] 3 studies evaluated mortality at 28 days, [ 16 – 18 ] 1 study evaluated mortality at 21 days, [ 15 ] 1 study evaluated mortality at 14 days, [ 19 ] and 2 studies did not specify a date for mortality (time of death). [ 20 , 22 ] Across all available studies, the overall mortality rate in the steroids group was 22.9% (95% CI: 13.0%; 37.1%), while the overall mortality rate for the SOC group was 31.0% (95% CI: 20.3%; 44.3%).…”

“…Of the studies included in the quantitative meta-analysis, 5 had data regarding mechanical ventilation rates. [ 15 , 17 , 18 , 20 , 21 ] Across all available studies, the overall mechanical ventilation rate in the steroids group was 14.0% (95% CI: 5.6%; 30.4%), while the overall mechanical ventilation rate for the SOC group was 16.3% (95% CI: 4.6%; 44.3%). The need for mechanical ventilation in the steroids group was significantly lower compared to the SOC group (OR = 0.76 [95% CI: 0.59; 0.97], P = .030; Fig.…”

“…Four of the other 7 studies were terminated early following publication of the RECOVERY results or due to a lack of patients. [ 15 , 16 , 19 , 21 ] The varying quality of studies included in our meta-analysis may have also impacted the conclusions of our study, with only 2 studies being considered high quality, double-blinded RCTs while the rest were either moderate or low quality open-label studies. Nevertheless, each study was deemed to be applicable to the target population and were of sufficient quality for inclusion based on the SIGN methodology for assessing the risk of bias and quality of evidence of individual RCTs.…”

Systemic Corticosteroid Administration in Coronavirus Disease 2019 Outcomes: An Umbrella Meta-Analysis Incorporating Both Mild and Pulmonary Fibrosis–Manifested Severe Disease

“…Similar results in a retrospective study suggested corticosteroids were associated with delayed MERS coronavirus RNA clearance ( Arabi et al, 2018 ). Additionally, studies also showed corticosteroid use was associated with longer throat viral RNA detectability and acute respiratory syndrome coronavirus 2 shedding in mild-to-moderate COVID-19 patients, and clinical benefits on these patients were limited ( Jamaati et al, 2021 ; Tang et al, 2021 ). Immune response and CD8 + T cell infiltration were involved in the COVID-19 pathological process, and reduction of CD4 + T cells, CD8 + T cells, and NK cells was observed on day 7 after corticosteroid use ( Du et al, 2020 ).…”