ARDS is a pulmonary manifestation of a severe systemic inflammatory response. A variety of inflammatory cells, inflammatory mediators and cytokines are involved in this complex pathophysiological process[9].ARDS are mainly manifested as inflammatory disorders, inappropriate accumulation and activation of leukocytes and platelets, uncontrolled coagulation activation and permeability of the alveolar-capillary barrier damage.
Methylprednisolone is the most commonly used corticosteroid therapy for ARDS, and many studies have controversy on using of Methylprednisolone. Despite improvements some parameters in the cardiopulmonary, a study published in the new england journal of medicine[10] suggested that it is not routine use of methylprednisolone for persistent ARDS. In addition, the research found that methylprednisolone treatment more than two weeks after the onset of ARDS may increase the risk of death. One research have even found that[11], long-term application of used a methylprednisolone dose of 0.125-2 mg/kg/day reduced patient immunity. Other research found that[12], using high-dose methylprednisolone(1 g/d) could not improve the prognosis of patients, or even increase the 60-day mortality and decrease the number of ventilator-free days of patients. There was no difference in the number of mechanical ventilation, blood and biochemical parameters between SARS induced high-dose pulse methylprednisolone ( > = 500 mg/day) and nonpulse (< 500 mg/day) [13]. In our study, methylprednisolone was used at a low dose of 0.5-2 mg/kg/day. The methylprednisolone dose used of this study was 0.5-2 mg/kg/day. Our results showed low-dose methylprednisolone did not decrease the intubation rate of patients. It may be due to the new coronavirus is different from previous pathogens.
The mechanism of COVID-19 leading to ARDS is not clear. The most common manifestations of patients are fever, weakness, respiratory distress and respiratory failures[1, 14]. A few of anatomical results [12] showed that the pathological changes of COVID-19 were associated with ARDS. The lungs showed diffuse alveolar injury and pulmonary hyaline membrane formation, which were similar to ARDS. The pulmonary pathology are similar to SARS and MERS. Lymphocyte-dominated mononuclear cells infiltration of inflammatory infiltration were in both pulmonary interstitium. In the alveolus cavity, multinucleated giant cells and atypically enlarged alveolar cells appear. Among them, the atypically enlarged alveolar cells have a larger nucleus, amphiphilic intracytoplasmic particles and obvious nucleoli, showing viral cytopathy Like change. The current research can only confirm that the final performance of COVID-19 is similar to ARDS, but it is not certain that it has the same pathophysiological mechanism.
In addition to treating severe patients, it is also important to choose appropriate treatments for patients with milder symptoms to prevent disease progression[15, 16]. Similar studies of viral pneumonia showed that the use of corticosteroid did not improve their prognosis[17–19].
From our results, the study show that the non-invasive ventilation time between the two groups is different, which may indicate that the corticosteroid has the potential to delay the invasive ventilation, but it does not improve the prognosis.
One of the characteristics of COVID-19 are a series of immunosuppression, including lymphopenia as the main manifestation[1, 14, 20]. Whether the timing and dose of corticosteroid would cause further immunosuppression and delay the elimination of the virus may be a question worthy of our more attention[19]. A significant increase in DD dimer was also suggested in our data analysis, which may be due to extensive endothelial cell damage caused by COVID-19 pneumonia. Corticosteroid may have coagulation effect, and whether it would further aggravate the disorder of coagulation function also needs attention.
This study only analyzed the phenomenon and the possible pathophysiological effects of corticosteroid therapy based on the current retrospective analysis, does not involve the analysis of the pathophysiology of COVID-19.
We are aware of some limitations in this study. First, The sample size of this clinic research is small. Jin yin tan Hospital is the designated Grade III hospital for critically ill patients and our results may not be applied in the patient populations with milder symptoms. Second, at present, the disease develops rapidly from occurrence to development, our treatment and observation time is short, therefore, we could not use the 28-day mortality rate as the main result. Instead, we used the intubation rate after the use of corticosteroid as the main observation result. This main result may also lead to erroneous evaluations of the potential therapeutic effects of corticosteroid. Additionally, the pathophysiology of COVID-19 is unclear. The current speculation on pathophysiology is mainly based on a small amount of anatomical research and limited epidemiological investigations. It can also interfere with the interpretation of the results. Moreover, in the current data, there are insufficient cases with high-dose steroid pulse therapy, thus the effects of different dosages on intubation rate have not been evaluated.