ABSTRACT
Objectives: Our study aims at comparing the efficacy and safety of INF-based therapy (lopinavir/ritonavir, ribavirin, and interferon β-1b) vs. favipiravir (FVP) in a cohort of hospitalized patients with non-critical COVID-19.Methods: Single center observational study comparing INF-based therapy (interferon β-1b, ribavirin, and lopinavir/ritonavir) vs. FVP in non-critical hospitalized COVID-19 patients. Allocation to either treatment group was non-random but based on changes to national treatment protocols rather than physicians’ selection (quasi-experimental). We examined the association between INF-based therapy and 28-day mortality using Cox regression model with treatment as a time-dependent covariate.Results: The study cohort included 222 patients, of whom 68 (28%) received IFN-based therapy. Antiviral therapy was started at a median of 5 days (3-6 days) from symptoms onset in the IFN group vs. 6 days (4-7 days) for the FVP group, P <0.0001. IFN-based therapy was associated with a lower 28-day mortality as compared to FVP (6 (9%) vs. 18 (12%)), adjusted hazard ratio [aHR] (95% Cl) = 0.22 (0.056-0.87)). No difference in hospitalization duration between the 2 groups, 9 (7-14) days vs. 9 (7-13) days, P=0.732 was found. IFN treated group required less use of systemic corticosteroids (57%) as compared to FVP (77%), P=0.023 after adjusting for disease severity and other confounders. Patients in the IFN treated group were more likely to have nausea and diarrhea as compared to FVP group (13%) vs. (3%), P=0.013 and (18%) vs. (3%), P<0.0001, respectively.Conclusion: Early INF-based triple therapy was associated with lower 28-days mortality and less need for systemic corticosteroids as compared to FVP in non-critical hospitalized COVID-19 patients.Funding Statement: None.Declaration of Interests: None.Ethics Approval Statement: KFMC Institutional Review Board (IRB) approved the study and waived the need for informed consent.
Subject(s)
COVID-19 , DiarrheaABSTRACT
BackgroundTo systematically review the literature about the effect of systemic corticosteroid therapy (CST) on outcomes of COVID-19 patients. MethodsWe searched Medline, Embase, EBM Reviews, Scopus, Web of Science, and preprints up to July 20, 2020. We included observational studies and randomized controlled trials (RCT) that assessed COVID-19 patients treated with CST. We pooled adjusted effect estimates of mortality and other outcomes using a random effect model, among studies at low or moderate risk for bias. We assessed the certainty of evidence for each outcome using the GRADE approach. ResultsOut of 1067 citations screened for eligibility, one RCT and 19 cohort studies were included (16,977 hospitalized patients). Ten studies (1 RCT and 9 cohorts) with 10,278 patients examined the effect of CST on short term mortality. The pooled adjusted RR was 0.92 (95% CI 0.69-1.22, I2=81.94 %). This effect was observed across all stages of disease severity. Four cohort studies examined the effect of CST on composite outcome of death, ICU admission and mechanical ventilation need. The pooled adjusted RR was 0.41(0.23-0.73, I2=78.69%). Six cohort studies examined the effect of CST on delayed viral clearance. The pooled adjusted RR was 1.47(95% CI 1.11-1.93, I2=43.38%). ConclusionHeterogeneous and low certainty cumulative evidence suggests that CST lacks efficacy in reducing short-term mortality while possibly delaying viral clearance in patients hospitalized with COVID-19. Because of the discordant results between the single RCT and observational studies, more research should continue to identify the clinical and biochemical characteristics of patients population that could benefit from CST.
Subject(s)
COVID-19ABSTRACT
ImportanceThe antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects. ObjectiveTo systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19. Data SourcesA systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists. Study SelectionStudies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias. Data Extraction and SynthesisStudy characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori. Main Outcomes and MeasuresPooled Incidence of: (1) change in QTc value from baseline [≥] 60 ms, (2) QTc [≥] 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular tachycardia (VT) or cardiac arrest, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias. ResultsA total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of [≥] 60 ms was 7%, 95% CI (3-14), I2=94% (12 studies of 2008 patients). The pooled incidence of QTc [≥] 500 ms was 6%, 95% CI (2-12), I2=95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of [≥] 60 ms or QTc [≥] 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity. Conclusions and RelevanceTreatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring. Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the risks of different cardiac toxicities in patients receiving chloroquine (CQ) or hydroxychloroquine (HCQ) for COVID-19. FindingsIn this systematic review, treatment of COVID-19 patients with CQ or HCQ is associated with a clinically significant risk of drug-induced QT prolongation, and torsades de pointes (TdP) arrhythmia/ventricular tachycardia/cardiac arrest in a relatively higher incidence compared to drugs withdrawn from the market for such adverse effects. MeaningThese agents should be used only in the context of clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.