On the use of corticosteroids for 2019-nCoV pneumonia

In their Comment about the use of corticosteroids to treat 2019 novel coronavirus (2019-nCoV) lung injury, Clark Russell and colleagues¹ summarise the available clinical evidence on corticosteroid to treat patients with severe human coronavirus infections (severe acute respiratory syndrome [SARS] coronavirus and Middle East respiratory syndrome coronavirus), and other severe respiratory virus infections. In accordance with current WHO guidance,² Russell and colleagues¹ recommend that corticosteroids should not be used in 2019-nCoV-induced lung injury or shock, except in the setting of a clinical trial. The Comment¹ contributes to a better understanding of corticosteroid treatment in viral pneumonia. However, as a team of front-line physicians from China, we have a different perspective.

As mentioned by the authors,¹ the studies referred to in the paper were mostly observational studies. In clinical settings, physicians tend to use corticosteroids in the most critically ill patients. Therefore, selection bias and confounders in observational studies might contribute to any observed increased mortality in patient groups treated with corticosteroids. Although attempts were made to adjust for confounding factors in the studies, conclusive inference should not be made. Also, we question the interpretation of the systematic review about effective treatments for SARS.³ Clark and colleagues state that “four studies provided conclusive data, all indicating harm”.¹ These four studies were not definitive and only showed evidence of possible harm, whereas the results of 25 other studies were inconclusive, leading the original authors to state that the totality of data are inconclusive, and because of methodological limitations, it was not possible to make any recommendation. Inconclusive clinical evidence should not be a reason for abandoning corticosteroid use in 2019-nCoV pneumonia.

Moreover, there are studies supporting the use of corticosteroids at low-to-moderate dose in patients with coronavirus infection. For example, in a retrospective study of 401 patients with SARS,⁴ proper use of corticosteroids was found to reduce mortality and shorten the length of stay in hospital for critically ill patients with SARS without causing secondary infection and other complications. Relevant research has also been done for other virus-associated respiratory diseases, such as influenza-associated pneumonia. For example, in a prospective cohort study enrolling 2141 patients with influenza A (H1N1)pdm09 viral pneumonia from 407 hospitals in China,⁵ low-to-moderate dose of corticosteroids (25–150 mg/day methylprednisolone or equivalent) reduced mortality in patients with oxygen index lower than 300 mm Hg. Besides, a systematic review⁶ suggested corticosteroids could reduce mortality and the need for mechanical ventilation in patients with severe community-acquired pneumonia.

Because of methodological limitations in the avialable evidence, the use of corticosteroids remains controversial. We acknowledge the potential risks associated with high-dose corticosteroids in treating 2019-nCoV pneumonia, such as secondary infections, long-term complications, and prolonged virus shedding. However, in critically ill patients, the overwhelming inflammation and cytokine-related lung injury might cause rapidly progressive pneumonia. Given the inconclusive evidence and urgent clinical demand, physicians from the Chinese Thoracic Society have developed an expert consensus statement on the use of corticosteroids in 2019-nCoV pneumonia.⁷ All members of the expert panel participated in treating patients with 2019-nCoV pneumonia. The expert consensus statement is based both on the available published scientific literature and relevant research by panel members, and it was brought together through e-mail correspondence and online meetings.

According to the expert consensus statement, the following basic principles should be followed when using corticosteroids: (1) the benefits and harms should be carefully weighed before using corticosteroids; (2) corticosteroids should be used prudently in critically ill patients with 2019-nCoV pneumonia; (3) for patients with hypoxaemia due to underlying diseases or who regularly use corticosteroids for chronic diseases, further use of corticosteroids should be cautious; and (4) the dosage should be low-to-moderate (≤0·5–1 mg/kg per day methylprednisolone or equivalent) and the duration should be short (≤7 days).

Corticosteroid treatment is a double-edged sword. In line with the expert consensus, we oppose liberal use of corticosteroids and recommend short courses of corticosteroids at low-to-moderate dose, used prudently, for critically ill patients with 2019-nCoV pneumonia. Existing evidence is inconclusive, and even systematic reviews and meta analyses on this topic reach differing conclusions. Therefore, in line with Clark Russell and colleagues,¹ we believe that there is a need for well designed randomised controlled trials in the future to promote a more solid foundation for treatment recommendations.

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