Corticosteroids are widely utilized in the treatment of severe pneumonia, including the Middle East respiratory syndrome and severe acute respiratory syndrome. However, this therapy has been controversial so far. This study revealed that the use of corticosteroids has no effect on the hospitalization stay, SARS-CoV-2 viral shedding or mortality rates of critically ill patients.
At present, there is no specific drug for COVID-19. Critically ill patients often die from the rapid progress of the disease in a short duration of time. The pathogenesis of COVID-19 has not yet been elucidated, but excessive inflammatory response may be one of the reasons for the increased mortality of critically ill patients. Corticosteroids contributes to the patient's outcome through reducing inflammatory factors and relieving the inflammatory response. Our results of study seems not be in line with this view. Considering the limitations of data sample size and possible selection bias, these data and results deserve further integrated analysis.
Some early studies on SARS and MERS have illustrated that proinflammatory factors in serum increased significantly during viral infection, and after 5-8 days corticosteroid treatment of SARS the levels of plasma chemokines (IL-8, IP -10, MCP-1) reduced significantly, thereby relieving chemokine-related lung inflammation of SARS patients【4-5】. At the same time, the article of Craddock about "Hypercortisol" in severe acute diseases demonstrated that the immune response of self-antigens caused by disease or trauma exposure might be suppressed by corticosteroids to offset the possibility of autoimmune attacks【6】. This may explain why corticosteroids can be used in critically ill patients to relieve disease. The results of a retrospective study of Rong-chang Chen on SARS patients also confirmed this view that appropriate administration of corticosteroid therapy in critically ill patients can reduce mortality and shorten hospitalization stay【7】. Although the study of Antoni Torres, MD, PhD and colleagues did not find the effect of the use of corticosteroid on mortality, the corticosteroid group significantly reduced the risk of treatment failure and relieved the inflammatory response【8】. Hilde H.F. Remmelts【9】 and Garcia-Vidal【10】also confirmed the positive side of glucocorticoids. However, corticosteroids are a double-edged sword, which exerts anti-inflammatory and immunosuppressive effects. Prolonged viral shedding, double infection and increased mortality are the most reported adverse events in the literature【11-14】. A small prospective, randomized, double-blind, placebo-controlled trial conducted by Nelson Lee et al also confirmed that patients who received hydrocortisone early had significantly higher concentrations of SARS-Cov RNA in the second and third weeks compared with the control group. It is considered that the virus removal mainly depends on the body's self-immunity. The early use of corticosteroids may coincide with the period of virus replication, which inhibits the body's self-immunity function, resulting in delay in virus removal【15】. No effect of corticosteroid use on length of viral shedding was found in this study, which was considered to be related to the late prevalence of corticosteroid treatment in patients (median time from onset to corticosteroid treatment was 14 days) and effective antiviral treatment. Although the use of corticosteroid therapy in critically ill patients did not increase mortality and lengthen hospitalization stay, this study did not further explore the adverse reactions that may be caused by glucocorticoids such as superinfection and gastrointestinal bleeding. The clinical application still needs to be cautious.
Numerous studies on the application of corticosteroids in pneumonia have described different results. This may be mainly due to the population included in different studies, thedifferent use time and dosage of corticosteroids. In addition, most of the studies are retrospective and observational studies, and there are selection differences and confounding biases. In the future, rigorous, multi-center, and large-scale prospective studies are needed to verify the clinical efficacy of corticosteroids.
Our study also has the following limitations: ① This experiment is a retrospective study, and due to the limitation of sample size and the partial lack of patient data, it is impossible for us to match all baseline characteristics between groups; ②The time for patient nucleic acid testing is determined by the doctor-in-charge, therefore, the length of virus shedding may be limited by the frequency of specimen collection, and at the same time is also limited by the low positive rate of the detection method; ③ Our study only focused on the patients’ short-term partial outcomes, superinfections, complications, and long-term side effects of corticosteroids may require further research to ensure the safety of patients receiving corticosteroid therapy.
The current application of corticosteroids in critically ill patients with COVID-19 is inconclusive. In conclusion, our analysis of 120 critically ill patients with COVID-19 in Wuhan Union Hospital showed that among the critically ill patients, the use of corticosteroids has no effect on length of hospitalization, SARS-CoV-2 viral shedding or mortality rates.