Safety of Treatments Recommended by Guidelines for SARS-CoV-2 and Other β-Coronaviruses Associated Respiratory Diseases: A Systematic Review and Meta-Analysis

BACKGROUND:

The pandemic of COVID-19 has brought unprecedented disaster. We aimed to evaluate the safety of treatments for SARS-CoV-2 and other β-coronaviruses.

METHODS:

We did a systematic review and meta-analysis. We searched PubMed, Embase, Web of Science, Cochrane library, SinoMed, China National Knowledge Infrastructure, WanFang Database between 2003 and 2020. We included random controlled trials (RCTs), cohort studies, quasi-random controlled trials (quasi-RCTs) of eight categories treatments for patients infected five β-coronaviruses. We excluded non-comparative studies or studies without sufficient data. We extracted data following a predefined criteria and group-level data were used. Primary outcomes were overall adverse events (OAEs) rate, acute respiratory distress syndrome (ARDS) incidence rate. We did meta-analysis with random effects. This study is registered with PROSPERO, CRD42020168178.

FINDINGS:

A total of 59 studies with 9598 participants met the inclusion criteria (49 studies on SARS-CoV-2: 27 RCTs, 19 cohort studies, three quasi-RCTs; nine studies on SARS-CoV: seven RCTs, two cohort studies; one cohort study on MERS-CoV). Only the following results of studies were significant or concerned. In SARS-CoV-2 patients, lopinavir/ritonavir (LPV/r) (RR=2·68, 95% CI.:1·48–4·85, I 2 =34·3%, low quality) and high-dose hydroxychloroquine or chloroquine (CQ) (RR=3·43, 95% CI.: 1·55–7·58, moderate quality) were associated with more overall adverse events (OAEs) than standard of care (SOC). Remdesivir 10 days vs placebo (RR=0·94, 95%CI: 0·80–1·11, I 2 =28·8%, moderate quality) and Traditional Chinese Medicine (TCM) vs SOC (RR=0·77, 95%CI: 0·53–1·10, I 2 =0·0%, low quality) reported no significant differences. In SARS-CoV patients, TCM was associated with lower OAEs than SOC (RR=0·38%, 95%CI: 0·21–0·71, I 2 =0·0%, low quality).

INTERPRETATION:

For treating against SARS-CoV-2, LPV/r and high-dose CQ showed OAE issues, while no significant safety problems among safety outcomes are found in remdesivir and TCM. Traditional Chinese Medicine may be an alternative treatment with less safety issue for SARS-CoV patients. These results can provide reference for clinical practice and more high-quality studies are required in the future.