COVID-19 has become a major issue in recent months with respect to its treatment and recovery, due to increased mortality rate. No effective clinical protocols and drug regime is currently available in the treatment of COVID-19. In recent months, application of glucocorticoids in treating COVID-19 has been ventured by different hospitals based on their application during SARS . Down-regulation of immune responses induced by cytokine storm and reduction of lymphocytes has been considered as an important mechanism of severe COVID-19 . Our study retrospectively analyzed the data of 66 COVID-19 patients, and found that the more patients were with chest distress in GC group than control group, but the duration of chest distress was shorter. Similarly, fever duration in the GC group was significantly shorter than control group. Also, the CRP and IL-6 levels in the GC group were lower than control group at 7 d after hospitalization.
Our study demonstrated that GC helped improving the chest distress and fever in the patients. The pathogenic investigations showed that COVID-19 infection activated the innate immunity and adaptive immunity of the system , consequently inducing the release of cytokines and aggregation of inflammatory cells, which not only damaged the mucosal-epithelial barrier of airway [15,16], but also could induce diffuse alveolar damages, including apoptosis of alveolar cells, hyaline membrane formation, and pulmonary edema . They not only cause dyspnea, but also secondary infection. So, COVID-19 not only activates the immune responses of patients, but also causes adverse outcomes due to excessive immune responses. However, glucocorticoids could down-regulate these inflammatory responses, which can alleviate clinical symptoms.
To further investigate whether glucocorticoids could influence the immune and inflammatory status of COVID-19 patients, changes in the immune-related indicators and inflammatory factors during the treatment in both groups were compared. The count of lymphocytes and absolute count of CD4+ and CD8+ T lymphocytes were significantly lower shortly after hospitalization than before allotting them in both groups, but their differences between the two groups were not statistically significant. So, glucocorticoids were not the cause of decreased lymphocytes in the patients. To rule out the influence of hospitalization time on the outcomes, the time from symptom appearing to hospitalization was compared between the two groups, which showed no statistically significant difference. Another study showed that corticosteroid treatment did not influence hospital length of stay, or duration of symptoms in patients with mild COVID-19 . The secretion of cytokines and chemokines after COVID-19 infection, induced the migration of immune cells, mainly include monocytes and lymphocytes, but not neutrophils, to the sites of infection . Some studies reported decreased LYM and increased NLR in about 80% of COVID-19 patients [18,19]. In addition, NLR could be an independent predictor for the severity of COVID-19 . NLR not only reflects the systemic immune status , but also associates with the immune function impairment of the system. Our study findings showed that the changes of NLR were not significantly different between the two groups. Also, the 28-d prognoses of patients were also not significantly different between the two groups, suggesting that short-term application of low- to moderate- dose glucocorticoids did not aggravate the disease conditions.
The findings of this study showed that the CRP and IL-6 levels in the GC group were lower than control group at 7 d after hospitalization, suggesting the glucocorticoids role in reducing the levels of inflammatory factors. CRP and IL-6 levels of patients treated with low- to moderate- dose glucocorticoids decreased, which reached the lowest levels at 5 d after hospitalization. To rule out the timing of drug application on the results, the time from hospitalization to the first dosing of glucocorticoids was analyzed, which showed that the median time from hospitalization to the first dosing of glucocorticoids was 3 days, and the median time from symptom appearing to the first dosing of glucocorticoids was 6 days, which were generally in agreement with the time of inflammatory mediator reduction shown in the comparisons between the two groups. These findings suggested that the application of glucocorticoids reduced the levels of inflammatory mediator . However, the inflammatory mediator levels were not significantly different between the two groups on day 14, suggesting that the inflammatory mediator levels could decrease with the improvement of disease conditions, and glucocorticoids may only accelerate the decrease in a certain degree. More clinical studies are needed to verify and further provide evidence for the standardization of glucocorticoids treatment.
This study was a retrospective study, and there were several limitations in this study. Missing data, relatively small sample size, and no further analysis for the clinical subtypes limited the extrapolation of the findings. Therefore, more clinical trials with rigorous study design is essential to investigate further the timing and doses of glucocorticoids and understand their clinical outcome.