Further discussion on glucocorticoid treatment of COVID-19.

To the Editor: The randomized evaluation of coronavirus 2019 (COVID-19) therapy (RECOVERY) [ clinical trial showed that glucocorticoids can affect the prognosis of severe COVID-19 patients, but they have no benefit for mild disease. Other clinical trials, such as COVID-19-associated acute respiratory distress syndrome (ARDS) treated with dexamethasone (CoDEX) and efficacy study of dexameth-asone to treat the ARDS (DEXA-ARDS), have also proven the effectiveness of glucocorticoids. On the basis of these trials, glucocorticoids have been recommended for the treatment of COVID-19, although their mechanism of action is unclear. Diffuse alveolar damage (DAD) is not the only pathological change of ARDS caused by COVID-19. In some cases, organizing pneumonia (OP) or acute fibrinous and organizing pneumonia (AFOP) is the main manifesta-tion.[ Acute patterns of AFOP with AFOP as the main pathological feature often leads to respiratory failure and rapidly progresses to death, whereas subacute patterns of AFOP has a good prognosis. There are two types of COVID-19-related ARDS: type 1 is atypical ARDS, with low elasticity (type L), increased compliance, and imbalance of ventilation/perfusion ratio; and type 2 is classic ARDS, with high elasticity (type H), reduced compliance, and increased right to left diversion, which is mainly related to disease progression (but not absolutely). Some patients with type H ARDS presented with AFOP. Glucocorticoids have little effect on typical DAD, but have a definite therapeutic effect on secondary OP and subacute patterns of AFOP caused by infection (including viral infection). On the basis of current literature, the effectiveness of glucocorticoids for treatment of COVID-19 may be attributable to the pathological changes of OP or AFOP. A meta-analysis of clinical trials of critically ill patients with COVID-19 showed that the administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.[ Therefore, it is important to identify patients who are suitable candidates for glucocorticoid therapy. Computed tomography manifestations that indicate the effectiveness of glucocorticoid therapy are: (1) consolidation dominated by bilateral, peripheral, and lower lung distribution (in line with the characteristics of OP);[ (2) consolidation around the bronchi that may be accompanied by patchy ground-glass opacity in the subpleural area of the lower lobe (in line with the characteristics of OP);[ and (3) focal or diffuse lung parenchymal abnormalities, similar to those of OP (in line with the characteristics of subacute AFOP).[ Identification of suitable patients for glucocorticoid therapy may improve treatment accuracy and prognosis of severe COVID-19 and reduce the adverse effects of glucocorticoids. In COVID-19 patients requiring mechanical ventilation, sufficiently dosed methylprednisolone (≥1 mg kg−1·d−1, ≥3 d) can lead to a further decreased mortality as compared with dexamethasone (≥6mg/d, ≥7 d).[

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