Concern regarding coronavirus (CoV) outbreaks has stayed relevant to global health in the last decades. Emerging COVID-19 infection, caused by the novel SARS-CoV2, is now a pandemic, bringing a substantial burden to human health. Interferon (IFN), combined with other antivirals and various treatments, has been used to treat and prevent MERS-CoV, SARS-CoV, and SARS-CoV2 infections. We aimed to assess the clinical efficacy of IFN-based treatments and combinational therapy with antivirals, corticosteroids, traditional medicine, and other treatments. Major healthcare databases and grey literature were investigated. A three-stage screening was utilized, and included studies were checked against the protocol eligibility criteria. Risk of bias assessment and data extraction were performed, followed by narrative data synthesis. Fifty-five distinct studies of SARS-CoV2, MERS-CoV, and SARS-CoV were spotted. Our narrative synthesis showed a possible benefit in the use of IFN. A good quality cohort showed lower CRP levels in Arbidol (ARB) + IFN group vs. IFN only group. Another study reported a significantly shorter chest X-ray (CXR) resolution in IFN-Alfacon-1 + corticosteroid group compared with the corticosteroid only group in SARS-CoV patients. In a COVID-19 trial, total adverse drug events (ADEs) were much lower in the Favipiravir (FPV) + IFN-α group compared with the LPV/RTV arm (P = 0.001). Also, nausea in patients receiving FPV + IFN-α regimen was significantly lower (P = 0.03). Quantitative analysis of mortality did not show a conclusive effect for IFN/RBV treatment in six moderately heterogeneous MERS-CoV studies (log OR=-0.05, 95% CI: (-0.71,0.62), I2 =44.71%). A meta-analysis of three COVID-19 studies did not show a conclusive nor meaningful relation between receiving IFN and COVID-19 severity (log OR=-0.44, 95% CI: (-1.13,0.25), I2 =31.42%). A lack of high-quality cohorts and controlled trials was observed. Evidence suggests the potential efficacy of several combination IFN therapies such as lower ADEs, quicker resolution of CXR, or a decrease in inflammatory cytokines; Still, these options must possibly be further explored before being recommended in public guidelines. For all major CoVs, our results may indicate a lack of a definitive effect of IFN treatment on mortality. We recommend such therapeutics be administered with extreme caution until further investigation uncovers high-quality evidence in favor of IFN or combination therapy with IFN.
After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon.
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.
OBJECTIVE: To evaluate the efficacy and safety of ribavirin for COVID-19 by systematically reviewing previous clinical studies of coronavirus pneumonia. METHODS: Such databases as Pubmed, EMbase, Cochrane Library, Google Scholar, CNKI, Wanfang Data, VIP and CBM were searched. The date of the latest search was April 29, 2020. Clinical studies on ribavirin used in the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) were included. The literature was screened according to the inclusion and exclusion criteria and the methodological quality of the included studies was assessed by two reviewers independently. Meta-analysis was performed using Review Manager 5.3 software. RESULTS: In total, 7 studies were included, resulting in a sample size of 870 cases. The overall pooled data demonstrated that the difference in mortality rates between the ribavirin group and control group was not statistically significant in the treatment of SARS and MERS[OR=1.10,95％CI（0.79,1.55）,P=0.57]. In the subgroup analysis, the mortality rate was not significantly different between the ribavirin group and control group in the treatment of SARS and MERS whether ribavirin was combined with interferon or not. CONCLUSION: Ribavirin does not make much difference to mortality in the treatment of SARS and MERS, but it can increase drug safety risks. Thus, the applicability of ribavirin in the treatment of COVID-19 remains to be investigated
Objective To systematically evaluate the possibility of ribavirin in treatment of novel coronaviral pneumonia. Method of retrieving PubMed, Embase, The Cochrane Library, and Chinese Journal Full Text Database (CNKI), Wanfang Database (WangFang DATA), Chinese Biomedical Documentation Database (CBM), etc. Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS), while retroactively incorporating the references of the literature. Applying the rapid systematic evaluation method recommended by the World Health Organization (WHO) and evaluating the quality of the literature to evaluate the likelihood of ribavirin for treatment of novel coronavirus pneumonia (COVID-19) in 2019. A total of 437 articles were retrieved and eventually incorporated into During the 18 studies .SARS outbreak, China's mainland, Hong Kong and Canada have experience applying high-dose ribavirin combined with interferon, hormones, lopinavir/ritonavir (LPV/r) treatment. Adverse reactions of high-dose ribavirin include anemia, bradycardia, myalgia, hypoxemia, electrolyte disorders, etc., these adverse reactions may lead to discontinuation of medication or adverse outcomes. Conclusion Ribavirin can be used in COVID-19 based on combined application of interferon, hormone, LPV/r and close monitoring of related adverse reactions, but its clinical effectiveness has yet to be confirmed by more randomized controlled trials.
BackgroundThe COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children.
MethodsElectronic databases from their inception to March, 31 2020 were searched for randomized controlled trials, clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19.
ResultsA total of 23 studies of indirect evidence with 6008 patients were included. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality (risk ratio [RR]= 0.77, 95% confidence interval [CI] 0.45 to 1.30) and probability of negative PCR test (RR=0.98, 95 CI% 0.82 to 1.18). Arbidol had no benefit on probability of negative PCR test (RR=1.27, 95% CI 0.93 to 1.73). Hydroxychloroquine was not associated with increasing the probability of negative PCR result (RR=0.93, 95% CI 0.73 to 1.18). For adults with SARS, interferon was associated with reduced corticosteroid dose (weighted mean difference [WMD]=-0.14 g, 95% CI -0.21 to -0.07) but had no effect on mortality (RR=0.72, 95% CI 0.28 to 1.88); ribavirin did not reduce mortality (RR=0.68, 95% CI % 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR=0.87, 95% CI 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions.
ConclusionsThere is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials.
BackgroundTo identify safe and effective medical countermeasures (e.g., antivirals/antibodies) to address the current outbreak of a novel coronavirus (COVID-19)
MethodsComprehensive literature searches were developed by an experienced librarian for MEDLINE, EMBASE, the Cochrane Library, and biorxiv.org/medrxiv.org; additional searches for ongoing trials and unpublished studies were conducted in clinicaltrials.gov and the Global Infectious Diseases and Epidemiology Network (GIDEON). Title/abstract and full-text screening, data abstraction, and risk of bias appraisal were carried out by single reviewers.
Results54 studies were included in the review: three controlled trials, 10 cohort studies, seven retrospective medical record/database studies, and 34 case reports or series. These studies included patients with severe acute respiratory syndrome (SARs, n=33), middle east respiratory syndrome (MERS, n=16), COVID-19 (n=3), and unspecified coronavirus (n=2). The most common treatment was ribavirin (n=41), followed by oseltamivir (n=10) and the combination of lopinavir/ritonavir (n=7). Additional therapies included broad spectrum antibiotics (n=30), steroids (n=39) or various interferons (n=12). No eligible studies examining monoclonal antibodies for COVID-19 were identified. One trial found that ribavirin prophylactic treatment statistically significantly reduced risk of MERS infection in people who had been exposed to the virus. Of the 21 studies reporting rates of ICU admission in hospitalized SARS or MERS patients, none reported statistically significant results in favour of or against antiviral therapies. Of the 40 studies reporting mortality rates in hospitalized SARS or MERS patients, one cohort study (MERS) and one retrospective study (SARS) found a statistically significant increase in the mortality rate for patients treated with ribavirin. Eighteen studies reported potential drug-related adverse effects including gastrointestinal symptoms, anemia, and altered liver function in patients receiving ribavirin.
ConclusionThe current evidence for the effectiveness and safety of antiviral therapies for coronavirus is inconclusive and suffers from a lack of well-designed prospective trials or observational studies, preventing any treatment recommendations from being made. However, it is clear that the existing body of evidence is weighted heavily towards ribavirin (41/54 studies), which has not shown conclusive evidence of effectiveness and may cause harmful adverse events so future investigations may consider focusing on other candidates for antiviral therapy.
OBJECTIVE: Subsequent to a global outbreak of the Middle East Respiratory Syndrome (MERS) in 2012, a novel human coronavirus, known as Corona Virus Disease 2019 (COVID-19) has caused a major disease outbreak. The aim of this study was to perform a systematic review to compare epidemiological, clinical, and laboratory features of COVID-19 and MERS-COV populations.
MATERIALS AND METHODS: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials database to identify potential studies that have reported COVID-19 or MERS-COV disease. Epidemiology, clinical, and laboratory outcomes, intensive care unit (ICU) admission rates, discharge rates, and fatality rates were evaluated using Graph-Pad Prism software.
RESULTS: A total of forty-two studies were included in our research, involving in 4,720 patients (COVID-19 = 2,012, MERS-COV = 2,708). The present study revealed that main clinical manifestations of both COVID-19 and MERS-COV populations are fever, cough and generalized weakness or myalgia, and Acute Respiratory Distress Syndrome (ARDS) is the main complication. The COVID-19 population has a lower rate of ICU admissions, discharges, fatalities, and shorter incubation periods than those of MERS-COV population.
CONCLUSIONS: The main clinical features of both COVID-19 and MERS-COV populations are fever, cough and generalized weakness or myalgia. ARDS is the main complication of both populations. COVID-19 cases have a shorter incubation period and lower rate of ICU admissions, discharges and fatalities compared to MRES-COV population.
Background: The COVID-19 outbreak presents a new, life-threatening disease. Our aim was to assess the potential effectiveness and safety of antiviral agents for COVID-19 in children. Methods: Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane library, CBM, CNKI, and Wanfang Data) from their inception to March 31, 2020 were searched for randomized controlled trials (RCTs), clinical controlled trials and cohort studies of interventions with antiviral agents for children (less than 18 years of age) with COVID-19. Results: A total of 23 studies with 6,008 patients were included. There was no direct evidence and all of evidence were indirect. The risks of bias in all studies were moderate to high in general. The effectiveness and safety of antiviral agents for children with COVID-19 is uncertain: For adults with COVID-19, lopinavir/ritonavir had no effect on mortality [risk ratio (RR) =0.77; 95% confidence interval (CI), 0.45 to 1.30]. Arbidol and hydroxychloroquine (HCQ) had no benefit on probability of negative PCR test (RR =1.27; 95% CI, 0.93 to 1.73; RR =0.93; 95% CI, 0.73 to 1.18) respectively. For adults with SARS, interferon was associated with reduced corticosteroid dose [weighted mean difference (WMD) = -0.14 g; 95% CI, -0.21 to -0.07] but had no effect on mortality (RR =0.72; 95% CI, 0.28 to 1.88); ribavirin did not reduce mortality (RR =0.68; 95% CI, 0.43 to 1.06) and was associated with high risk of severe adverse reactions; and oseltamivir had no effect on mortality (RR =0.87; 95% CI, 0.55 to 1.38). Ribavirin combined with interferon was also not effective in adults with MERS and associated with adverse reactions. Conclusions: There is no evidence showing the effectiveness of antiviral agents for children with COVID-19, and the clinical efficacy of existing antiviral agents is still uncertain. We do not suggest clinical routine use of antivirals for COVID-19 in children, with the exception of clinical trials.
Available animal and cell line models have suggested that specific therapeutics might be effective in treating Middle East respiratory syndrome (MERS). We conducted a systematic review of evidence for treatment with pharmacologic and supportive therapies. We developed a protocol and searched 5 databases for studies describing treatment of MERS and deaths in MERS patients. Risk of bias (RoB) was assessed by using ROBINS-I tool. We retrieved 3,660 unique citations; 20 observational studies met eligibility, and we studied 13 therapies. Most studies were at serious or critical RoB; no studies were at low RoB. One study, at moderate RoB, showed reduced mortality rates in severe MERS patients with extracorporeal membrane oxygenation; no other studies showed a significant lifesaving benefit to any treatment. The existing literature on treatments for MERS is observational and at moderate to critical RoB. Clinical trials are needed to guide treatment decisions.
Concern regarding coronavirus (CoV) outbreaks has stayed relevant to global health in the last decades. Emerging COVID-19 infection, caused by the novel SARS-CoV2, is now a pandemic, bringing a substantial burden to human health. Interferon (IFN), combined with other antivirals and various treatments, has been used to treat and prevent MERS-CoV, SARS-CoV, and SARS-CoV2 infections. We aimed to assess the clinical efficacy of IFN-based treatments and combinational therapy with antivirals, corticosteroids, traditional medicine, and other treatments. Major healthcare databases and grey literature were investigated. A three-stage screening was utilized, and included studies were checked against the protocol eligibility criteria. Risk of bias assessment and data extraction were performed, followed by narrative data synthesis. Fifty-five distinct studies of SARS-CoV2, MERS-CoV, and SARS-CoV were spotted. Our narrative synthesis showed a possible benefit in the use of IFN. A good quality cohort showed lower CRP levels in Arbidol (ARB) + IFN group vs. IFN only group. Another study reported a significantly shorter chest X-ray (CXR) resolution in IFN-Alfacon-1 + corticosteroid group compared with the corticosteroid only group in SARS-CoV patients. In a COVID-19 trial, total adverse drug events (ADEs) were much lower in the Favipiravir (FPV) + IFN-α group compared with the LPV/RTV arm (P = 0.001). Also, nausea in patients receiving FPV + IFN-α regimen was significantly lower (P = 0.03). Quantitative analysis of mortality did not show a conclusive effect for IFN/RBV treatment in six moderately heterogeneous MERS-CoV studies (log OR=-0.05, 95% CI.: (-0.71,0.62), I2 =44.71%). A meta-analysis of three COVID-19 studies did not show a conclusive nor meaningful relation between receiving IFN and COVID-19 severity (log OR=-0.44, 95% CI.: (-1.13,0.25), I2 =31.42%). A lack of high-quality cohorts and controlled trials was observed. Evidence suggests the potential efficacy of several combination IFN therapies such as lower ADEs, quicker resolution of CXR, or a decrease in inflammatory cytokines; Still, these options must possibly be further explored before being recommended in public guidelines. For all major CoVs, our results may indicate a lack of a definitive effect of IFN treatment on mortality. We recommend such therapeutics be administered with extreme caution until further investigation uncovers high-quality evidence in favor of IFN or combination therapy with IFN.
