Baseline characteristics of 214 COVID-19 patients
214 patients were included in this study, and 34 patients were treated with corticosteroid. The comparison of baseline characteristics from the two group were shown in Table 1. The median age of the two groups (non-corticosteroid and corticosteroid) was 60 (IQR 52-67) and 65 (IQR 55-73) years old, respectively. The median time from illness onset to admission was 12.0 days (IQR 8.0–15.0). Of the 214 patients, 117 (54.4%) had 1 or more comorbidities. Hypertension (73[33.6%]), diabetes (32[15.0%]), chronic obstructive lung disease (8[3.7%]), coronary heart disease (33[15.4%]), malignancy (15[7.0%]), Chronic kidney disease (6[12.8%]) and Chronic liver disease (4[1.9%]). The most common symptoms of patients were fever (177[82.7%]), dry cough (153[71.4%]), sputum production (74[34.6%]), dyspnea (97[45.3%]) and diarrhea (43[20.1%]).
There was no significant difference of age, sex, comorbidities and clinical symptoms between the two groups. However, the median time from illness onset to admission in corticosteroid groups was significantly shorter than that of non-corticosteroid groups (P=0.007), which may be the result of the faster progress of COVID-19.
Laboratory parameters
Major laboratory parameters were tracked from illness onset (Table 2). Creatinine, blood urea nitrogen, AST, ALT, total bilirubin, ESR, white blood cell, neutrophil, lymphocyte, hemoglobin, platelet, eosinophils count, FIB, D-Dimer, total lymphocytes, CD4, CD8, B cells and NK cells did not differ between patients who received corticosteroid treatment and patients who did not receive corticosteroid treatment.
Lactate dehydrogenase (LDH) was significantly higher in corticosteroid group than non-corticosteroid group (P=0.036), as well as higher levels of CD4+/CD8+ cells (P=0.046). Virus clearance time (P=0.007) and hospital length of stay (P<0.001) were significantly prolonged in corticosteroid compared with non-corticosteroid group throughout the clinical course. And patients who required corticosteroid treatment were more likely to have higher levels of inflammatory indicators, including CRP (P=0.017), PCT (P=0.043), and IL-6 (P=0.029).
Treatment
According to the medication use of 214 patients, the patients generally received antiviral, antibiotic, traditional Chinese medicine (including Lianhua qingwen capsule and traditional Chinese medicine decoction), immune enhancer, intestinal microecological regulator and sedative hypnotic drugs (Table 3).
All of the 214 patients received antiviral treatment, of which 35(16.4%) treated with chloroquine phosphate, 209(97.7%) patients received arbidol tablets, 54(25.2%) patients administered lopinavir/ritonavir, 69(32.2%) patients received ribavirin injection and 56(26.2) received interferon alfa inhalation. 144(67.3%) patients received antibiotic (moxifloxacin, levofloxacin, carbapenems) therapy. Most of the patients were treated with traditional Chinese medicine for consolidation therapy. 205(95.8%) patients received traditional Chinese medicine decoction, 111(51.9%) patients received Lianhua qingwen capsule. 160(74.8%) patients received immune enhancer therapy and 70(32.7%) received intestinal microecological regulator treatment. 30(14.0%) patients need to take sedative hypnotics therapy.
Compared with patients who did not receive corticosteroid treatment, the usage rate of chloroquine phosphate patients in corticosteroid group were significantly higher in patients given corticosteroid (P=0.002). Moreover, the usage of antibiotic was also significantly higher in corticosteroid group (P<0.001). However, patients in non-corticosteroid group were more likely to received traditional Chinese medicine therapy, including Lianhua qingwen capsule (P=0.035) and traditional Chinese medicine decoction (P=0.017).
To detect the effect of corticosteroid on secondary infections, we analyzed the antibiotic treatment of these patients. As shown in Table 4, the antibiotics duration in patients given corticosteroid was significantly longer than those of non-corticosteroid. And the usage of multiple antibiotics in corticosteroid group was also significantly higher. These indicated that patients treated by corticosteroid were more likely to get secondary infections.
As corticosteroid was recommended to use in COVID-19 patients in low dose and short term (3-5 days), we analyzed the patients given corticosteroid beyond 5 days and those less than 5 days. As Table 5 showed, patients who treated by corticosteroid beyond 5 days showed a significantly longer antibiotics duration. However, there were no statistic difference in the virus clearance time and multiple antibiotics between the two groups. These results suggested that short-term use of corticosteroid may not increase the risk of secondary infections, but do prolong the virus clearance time.
Univariate analysis of virus clearance time
In univariable analysis, sex, longer time from illness onset to hospital admission, sputum production symptom, chloroquine phosphate therapy, non-Lianhua qingwen capsule therapy, immune enhancer, intestinal microecological regulator, corticosteroid, and sedative hypnotic therapy, higher levers of LDH, CRP, ESR, IL-6 and FIB, as well as lower lymphocyte count were associated with longer virus clearance time (Table 4).
Prognostic factors of virus clearance time
We included 15 significant variables in univariable analysis for multiple linear regression. The results showed that patients with sputum production and higher IL-6 at admission, or treated with corticosteroid therapy were associated with prolonged virus clearance time. Whereas, patients treated with lianhua qingwen capsule were more likely to shorten virus clearance time.