The prognosis and short-term efficacy of corticosteroid therapy for COVID-19 patients

Dear Editor:

Corticosteroids are widely used in the treatment of critically ill patients for active anti-inflammatory and immunosuppressive effects. However, the therapeutic effects of corticosteroid treatment are still disputable. Some studies have shown that corticosteroids can delay coronavirus RNA clearance^[1], increase mortality^[2] and cause adverse events^[3]. Conversely, other studies have confirmed the clinical value of corticosteroids in shortening hospital stays and decreasing the need for mechanical ventilation^[4]. Similarly, the use of corticosteroids in COVID-19 patients is controversial. Expert consensus in China has indicated that corticosteroids can be used as appropriate in critical patients^[5]. However, World Health Organization interim guidance opposes the routine use of corticosteroids in treatment^[6]. Therefore, we herein discussed the therapeutic effects of corticosteroids in COVID-19 patients based on the experience of front-line physicians and a meta-analysis.

We analyzed the data of 67 difficult and complicated cases from 28 hospitals in 13 regions of Jiangsu Province, including 1 mild, 13 typical, 45 severe, and 8 critical patients. The severity of illness was defined by the expert consensus in China^[5]. All patients were divided into two groups according to whether they used corticosteroids or not. The clinical characteristics, laboratory findings, and treatments are shown in Table 1. Data are presented as numbers (%) or median (IQR). P values were calculated by chi-square test, Fisher's exact test, or Mann-Whitney U test. Multidisciplinary experts guided the therapy by remote consultation through tracking vital signs and examination results and observing the dynamic changes in the patients' conditions. The results showed that the conditions of 18 corticosteroid users were improved or stable and that no patients died. We further analyzed the oxygen and blood indexes of 12 patients with complete data (≥4 consultations, follow-up time ≥10 days). The average course of corticosteroid treatment was 8 days. It was determined that short-term treatment with corticosteroids improved oxygen saturation (SaO₂) and the ratio of arterial oxygen tension (PaO₂) to inspiratory oxygen fraction (FiO₂), and promoted the absorption of pulmonary lesions (Table 2). All statistical analyses were conducted by SPSS software (version 13.0). The results indicated that corticosteroids played a positive role in improving the short-term oxygenation of COVID-19 patients. To include more cases to test the hypothesis, we decided to carry out a meta-analysis.

We carried out a systematic literature search on the PubMed, EMBASE, and Web of Science databases for relevant studies on COVID-19. We used the following keywords in our search: "2019-nCoV", "COVID-19", and "SARS-CoV-2". To avoid literature omission, we did not use "corticosteroids" or other keywords related to treatment. Articles dated up to March 15, 2020 were searched without language limit. Inclusion criteria were as follows: (1) the definite diagnosis of COVID-19; (2) two groups of corticosteroid use and non-corticosteroid use; (3) the clinical data available to extract. Exclusion criteria were as follows: (1) repeated publication; (2) failure to get the full text or detailed abstract; (3) the articles of editorials, reviews, or expert consensus; (4) difficulty in extracting the necessary data. Two researchers independently selected articles and extracted the data by reading the titles, abstracts, and full texts of the articles. The binary data analysis was conducted by Stata software (version 14.1).

A total of 2431 articles were preliminarily retrieved. After deduplication and assessment of titles, abstracts, and full texts, six articles were chosen for study^[7-12] (Fig. 1). We used the Newcastle-Ottawa scale to evaluate the quality of the study^[13] (Table 3). We also included our research data, in which 38 patients used corticosteroids including 32 patients with severe conditions. The conditions of 18 users were improved or stable, while 16 of the non-users achieved the same result. The conditions of the remaining patients were aggravated or even deteriorated. Characteristics of studies included are shown in Table 3.

Figure 1.  Flowchart for study selection.

Finally, a total of 1625 subjects, including 441 corticosteroid users and 1184 non-users, were included from these 7 articles. The forest plot of critical and non-critical patients (Fig. 2A) showed critical patients are more likely to use corticosteroids (OR, 4.82; 95% CI, 3.55–6.54). The result of corticosteroid use (Fig. 2B and C) showed the improvement rate of the corticosteroid group was lower than that of the noncorticosteroid group (OR, 0.54; 95% CI, 0.33–0.88), but corticosteroid use was not associated with mortality of COVID-19 patients (OR, 2.64; 95% CI, 0.86–2.08). Due to the small number of articles, we did not conduct heterogeneity analysis.

Figure 2.  Forest plot of corticosteroid therapy on COVID-19 patients.

Some related meta-analyses of corticosteroid therapy for lung diseases used mortality, need for intensive care unit (ICU) admission or mechanical ventilation as prognostic indicators. In this meta-analysis, we selected only mortality. Because we thought the need for ICU or mechanical ventilation was the evaluation criteria for critical patients who need to use corticosteroids according to the experts consensus. It could not be used as a prognostic indicator simply. However, although the composite endpoints included admission to the ICU, mechanical ventilation, or death, a study by Weijie G et al^[11] was included after discussion due to the large number of subjects and extra subgroups of non-severe and severe patients.