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Interferon therapy in patients with SARS, MERS, and COVID-19: A systematic review and meta-analysis of clinical studies.

ABSTRACT: 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.

SUBMITTER: Saleki K

PROVIDER: S-EPMC8195694 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:(1) Background: The use of corticosteroids in critical coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS), or Coronavirus disease 2019 (COVID-19), has been controversial. However, a meta-analysis on the efficacy of steroids in treating these coronavirus infections is lacking. (2) Purpose: We assessed a methodological criticism on the quality of previous published meta-analyses and the risk of misleading conclusions with important therapeutic consequences. We also examined the evidence of the efficacy of corticosteroids in reducing mortality in SARS, MERS and COVID-19. (3) Methods: PubMed, MEDLINE, Embase, and Web of Science were used to identify studies published until 25 April 2020, that reported associations between steroid use and mortality in treating SARS/MERS/COVID-19. Two investigators screened and extracted data independently. Searches were restricted to studies on humans, and articles that did not report the exact number of patients in each group or data on mortality were excluded. We calculated odds ratios (ORs) or hazard ratios (HRs) under the fixed- and random-effect model. (4) Results: Eight articles (4051 patients) were eligible for inclusion. Among these selected studies, 3416 patients were diagnosed with SARS, 360 patients with MERS, and 275 with COVID-19; 60.3% patients were administered steroids. The meta-analyses including all studies showed no differences overall in terms of mortality (OR 1.152, 95% CI 0.631-2.101 in the random effects model, p = 0.645). However, this conclusion might be biased, because, in some studies, the patients in the steroid group had more severe symptoms than those in the control group. In contrast, when the meta-analysis was performed restricting only to studies that used appropriate adjustment (e.g., time, disease severity), there was a significant difference between the two groups (HR 0.378, 95% CI 0.221-0.646 in the random effects model, p < 0.0001). Although there was no difference in mortality when steroids were used in severe cases, there was a difference among the group with more underlying diseases (OR 3.133, 95% CI 1.670-5.877, p < 0.001). (5) Conclusions: To our knowledge, this study is the first comprehensive systematic review and meta-analysis providing the most accurate evidence on the effect of steroids in coronavirus infections. If not contraindicated, and in the absence of side effects, the use of steroids should be considered in coronavirus infection including COVID-19.

Project description:Objective:The aim of this systematic review was to report pregnancy and perinatal outcomes of coronavirus spectrum infections, and particularly coronavirus 2019 (COVID-19) disease because of severe acute respiratory syndrome-coronavirus-2 infection during pregnancy. Data Sources:Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched electronically utilizing combinations of word variants for coronavirus or severe acute respiratory syndrome or SARS or Middle East respiratory syndrome or MERS or COVID-19 and pregnancy. The search and selection criteria were restricted to English language. Study Eligibility Criteria:Inclusion criteria were hospitalized pregnant women with a confirmed coronavirus related-illness, defined as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), or COVID-19. Study Appraisal and Synthesis Methods:We used meta-analyses of proportions to combine data and reported pooled proportions, so that a pooled proportion may not coincide with the actual raw proportion in the results. The pregnancy outcomes observed included miscarriage, preterm birth, preeclampsia, preterm prelabor rupture of membranes, fetal growth restriction, and mode of delivery. The perinatal outcomes observed were fetal distress, Apgar score <7 at 5 minutes, neonatal asphyxia, admission to a neonatal intensive care unit, perinatal death, and evidence of vertical transmission. Results:Nineteen studies including 79 hospitalized women were eligible for this systematic review: 41 pregnancies (51.9%) affected by COVID-19, 12 (15.2%) by MERS, and 26 (32.9%) by SARS. An overt diagnosis of pneumonia was made in 91.8%, and the most common symptoms were fever (82.6%), cough (57.1%), and dyspnea (27.0%). For all coronavirus infections, the pooled proportion of miscarriage was 64.7% (8/12; 95% confidence interval, 37.9-87.3), although reported only for women affected by SARS in two studies with no control group; the pooled proportion of preterm birth <37 weeks was 24.3% (14/56; 95% confidence interval, 12.5-38.6); premature prelabor rupture of membranes occurred in 20.7% (6/34; 95% confidence interval, 9.5-34.9), preeclampsia in 16.2% (2/19; 95% confidence interval, 4.2-34.1), and fetal growth restriction in 11.7% (2/29; 95% confidence interval, 3.2-24.4), although reported only for women affected by SARS; 84% (50/58) were delivered by cesarean; the pooled proportion of perinatal death was 11.1% (5/60; 95% confidence interval, 84.8-19.6), and 57.2% of newborns (3/12; 95% confidence interval, 3.6-99.8) were admitted to the neonatal intensive care unit. When focusing on COVID-19, the most common adverse pregnancy outcome was preterm birth <37 weeks, occurring in 41.1% of cases (14/32; 95% confidence interval, 25.6-57.6), while the pooled proportion of perinatal death was 7.0% (2/41; 95% confidence interval, 1.4-16.3). None of the 41 newborns assessed showed clinical signs of vertical transmission. Conclusion:In hospitalized mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, preterm birth is the most common adverse pregnancy outcome. COVID-19 infection was associated with higher rate (and pooled proportions) of preterm birth, preeclampsia, cesarean, and perinatal death. There have been no published cases of clinical evidence of vertical transmission. Evidence is accumulating rapidly, so these data may need to be updated soon. The findings from this study can guide and enhance prenatal counseling of women with COVID-19 infection occurring during pregnancy, although they should be interpreted with caution in view of the very small number of included cases.

Project description:INTRODUCTION:Several antiretroviral drugs are being considered for the treatment of COVID-19, the disease caused by a newly identified coronavirus, (SARS-CoV-2). We systematically reviewed the clinical outcomes of using antiretroviral drugs for the prevention and treatment of coronaviruses and planned clinical trials. METHODS:Three databases were screened from inception to 30 March 2020 for studies reporting clinical outcomes of patients with SARS, MERS or COVID-19 treated with antiretrovirals. RESULTS:From an initial screen of 433 titles, two randomized trials and 24 observational studies provided clinical outcome data on the use of antiretroviral drugs; most studies reported outcomes using LPV/r as treatment. Of the 21 observational studies reporting treatment outcomes, there were three studies among patients with SARS, six studies among patients with MERS and 12 studies among patients with COVID-19. In one randomized trial 99 patients with severe COVID-19 illness were randomized to receive LPV/r (400/100 mg twice a day) and 100 patients to standard of care for 14 days: LPV/r was not associated with a statistically significant difference in time to clinical improvement, although LPV/r given within 12 days of symptoms was associated with shorter time to clinical improvement; 28 day mortality was numerically lower in the LPV/r group (14/99) compared to the control group (25/100), but this difference was not statistically significant. The second trial found no benefit. The certainty of the evidence for the randomized trials was low. In the observational studies 3 out of 361 patients who received LPV/r died; the certainty of evidence was very low. Three studies reported a possible protective effect of LPV/r as post-exposure prophylaxis. Again, the certainty of the evidence was very low due to uncertainty due to limited sample size. CONCLUSIONS:On the basis of the available evidence it is uncertain whether LPV/r and other antiretrovirals improve clinical outcomes or prevent infection among patients at high risk of acquiring COVID-19.

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Interferon therapy in patients with SARS, MERS, and COVID-19: A systematic review and meta-analysis of clinical studies.

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