Efficacy of ribavirin and interferon-α therapy for hospitalized patients with COVID-19: A multicenter, retrospective cohort study.
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ABSTRACT: Objective
To assess the efficacy and safety of ribavirin and interferon-α (RBV/IFN-α) therapy in COVID-19 patients.Methods
A multicenter, retrospective cohort study of COVID-19 patients admitted to 4 hospitals in Hubei Province, China, from 31 December 2019 to 31 March 2020. Patients were divided into 2 groups according to their exposure to RBV/IFN-α therapy within 48 h of admission. Mixed-effect Cox model and Logistic regression were used to explore the association between early treatments of RBV/IFN-α and primary outcomes.Results
Of 2037 patients included, 1281 received RBV/IFN-α (RBV, IFN-α or RBV combined with IFN-α) treatments and 756 received none of these treatments. In a mixed effect model, RBV/IFN-α therapy was not associated with progression from non-severe into severe type (adjusted hazard ratio (aHR) = 1.09, 95% CI: 0.88-1.36) or with reduction in 30-day mortality (aHR = 0.89, 95% CI: 0.61-1.30). However, it was associated with a higher probability of hospital stay >15 days (adjusted odds ratio (aOR) = 2.11, 95% CI: 1.68-2.64) compared with no RBV/IFN-α therapy. The propensity score-matched cohort and subgroup analysis displayed similar results.Conclusion
RBV/IFN-α therapy was not observed to improve clinical outcomes in COVID-19 patients suggesting that RBV/IFN-α therapy should be avoided in COVID-19 treatment.
SUBMITTER: Li H
PROVIDER: S-EPMC7840408 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionCoronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking.MethodsA total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay.Results68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63-1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay.ConclusionsIn hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.
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Project description:Interferons (IFNs) are widely used in treating coronavirus disease 2019 (COVID-19) patients. However, a recent report of ACE2, the host factor mediating SARS-Cov-2 infection, identifying it as interferon-stimulated raised considerable safety concern. To examine the association between the use and timing of IFN-?2b and clinical outcomes, we analyzed in a retrospective multicenter cohort study of 446 COVID-19 patients in Hubei, China. Regression models estimated that early administration (?5 days after admission) of IFN-?2b was associated with reduced in-hospital mortality in comparison with no admission of IFN-?2b, whereas late administration of IFN-?2b was associated with increased mortality. Among survivors, early IFN-?2b was not associated with hospital discharge or computed tomography (CT) scan improvement, whereas late IFN-?2b was associated with delayed recovery. Additionally, early IFN-?2b and umifenovir alone or together were associated with reduced mortality and accelerated recovery in comparison with treatment with lopinavir/ritonavir (LPV/r) alone. We concluded that administration of IFN-?2b during the early stage of COVID-19 could induce favorable clinical responses.
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Project description:ObjectiveCoronavirus disease 2019 (COVID-19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID-19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID-19 patients was lacking.Methods325 patients with laboratory-confirmed critical COVID-19 were enrolled from 4 government-designated COVID-19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28- and 60-day mortality, and the secondary outcomes were the total length of in-hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing.ResultsIn the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28-day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in-hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28-day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60-day mortality in the critical-type patients.ConclusionEarly administration of IVIG with high dose improves the prognosis of critical-type patients with COVID-19. This study provides important information on clinical application of IVIG in the treatment of SARS-CoV-2 infection, including patient selection and administration dosage and timing.
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Project description:IntroductionIFN-α intervention may block SARS-CoV-2 replication and normalize the deregulated innate immunity of COVID-19.AimThis meta-analysis aimed to investigate the efficacy of interferon IFN-α-containing regimens when treating patients with moderate-to-severe COVID-19.Material and methodsPubMed, SCOPUS, and ClinicalTrials.gov were searched from inception to 15 January 2022. A systematic literature search was conducted by applying relevant terms for 'COVID-19' and 'interferon-α'. The primary outcome enclosed the all-cause hospital mortality. The secondary outcomes constituted the length of hospital stay; hospital discharge; nucleic acid negative conversion.ResultsEleven studies are enclosed in the meta-analysis. No significant difference in the all-cause mortality rate was found between the study and control groups (OR 0.2; 95% CI 0.05-1.2; I2 = 96%). The implementation of interferon did not influence such outcomes as the length of hospital stay (OR 0.9; 95% CІ, 0.3-2.6; I2 = 91%), nucleic acid negative conversion (OR 0.8; 95% CI, 0.04-17.2; I2 = 94%). Nevertheless, IFN-α treatment resulted in a higher number of patients discharged from the hospital (OR 26.6; 95% CІ, 2.7-254.3; I2 = 95%).ConclusionsThus, IFN-α does not benefit the survival of hospitalized COVID-19 patients but may increase the number of patients discharged from the hospital.Systematic review registrationwww.crd.york.ac.uk/prospero, identifier (CRD42022374589).
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Project description:AimTo evaluate interferon-λ3 (IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin (Peg-IFNα/RBV) therapy for genotype 2 (G2) chronic hepatitis C.MethodsBetween January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus (HCV) were treated with response-guided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response (RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype (TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV sub-genotype 2a or 2b.ResultsOf the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response (SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate (96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5% (P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups (80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR (OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.ConclusionIn response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.
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Project description:BackgroundThe waves of COVID-19 infections in Ontario, Canada, were marked by differences in patient characteristics and treatment. Our objectives were to (i) describe patient characteristics, treatment, and outcomes of hospitalized older adults with COVID-19 between waves 1, 2, and 3, (ii) determine if there was an improvement in in-hospital mortality in waves 2 and 3 after adjusting for covariates.MethodsThis retrospective cohort study was done in five acute care hospitals in Toronto, Ontario. Consecutive hospitalized older adults aged ≥65 years with confirmed COVID-19 infection were included. Wave 1 extended from March 11 to July 31, 2020, wave 2 from August 1, 2020 to February 20, 2021, and wave 3 from February 21 to June 30, 2021. Patient characteristics and outcomes were abstracted from charts. A logistic regression model was used to determine the association between COVID-19 and in-hospital mortality in waves 2 and 3 compared with wave 1.ResultsOf the 1671 patients admitted to acute care, 297 (17.8%) were admitted in wave 1, 751 (44.9%) in wave 2, and 623 (37.3%) in wave 3. The median age of our cohort was 77.0 years (interquartile range: 71.0-85.0) and 775 (46.4%) were female. The prevalence of frailty declined in progressive waves. The use of dexamethasone, remdesivir, and tocilizumab was significantly higher in waves 2 and 3 compared with wave 1. In the unadjusted analysis, in-hospital mortality was unchanged between waves 1 and 2, but it was lower in wave 3 (18.3% vs. 27.4% in wave 1). After adjustment, in-hospital mortality was unchanged in waves 2 and 3 compared with wave 1.ConclusionIn-hospital mortality in hospitalized older adults with COVID-19 was similar between waves 1 and 3. Further research should be done to determine if COVID-19 therapies have similar benefits for older adults compared with younger adults.
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Project description:ObjectivesOur study aims at comparing the efficacy and safety of IFN-based therapy (lopinavir/ritonavir, ribavirin, and interferon β-1b) vs. favipiravir (FPV) in a cohort of hospitalized patients with non-critical COVID-19.MethodsSingle center observational study comparing IFN-based therapy (interferon β-1b, ribavirin, and lopinavir/ritonavir) vs. FPV 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 IFN-based therapy and 28-day mortality using Cox regression model with treatment as a time-dependent covariate.ResultsThe 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 FPV group, P <0.0001. IFN-based therapy was associated with a lower 28-day mortality as compared to FPV (6 (9%) vs. 18 (12%)), adjusted hazard ratio [aHR] (95% Cl) = 0.27 (0.08-0.88)). 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 FPV (77%), P = 0.005 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 FPV group (13%) vs. (3%), P = 0.013 and (18%) vs. (3%), P<0.0001, respectively.ConclusionEarly IFN-based triple therapy was associated with lower 28-days mortality as compared to FPV.
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Project description:In patients hospitalized with COVID-19 pneumonia, both tocilizumab and baricitinib have been shown to have clinical benefit compared with placebo. To date, there are few data comparing the two treatments, and their relative benefits and harms are unknown. This study aims to evaluate the effectiveness of tocilizumab versus baricitinib in patients hospitalized with COVID-19 pneumonia and hypoxemia.DesignRetrospective cohort study.SettingSeven inpatient acute-care hospitals in Wisconsin.ParticipantsPatients hospitalized with COVID-19, hypoxemia, and Pao2-to-Fio2 ratio less than or equal to 300 mm Hg, who received either tocilizumab or baricitinib.InterventionsElectronic chart review.Measurements and main resultsPatients were divided into tocilizumab and baricitinib cohorts based on actual medication received. The primary outcome was hospital discharge alive and free from mechanical ventilation within 60 days, assessed by logistic regression. Three hundred eighty-two patients were included: 194 in the tocilizumab cohort and 188 in the baricitinib cohort. Most baseline characteristics in the two cohorts were similar. All patients received dexamethasone. Two patients were lost to follow-up. In the remaining 380 patients, probability of successful discharge in the two cohorts was quantitatively similar in unadjusted, multivariate-adjusted, and propensity score-matched analyses. Hospital length of stay, rates of thromboembolic events, and rates of hospital-acquired infections were all similar in the two cohorts.ConclusionsIn patients hospitalized with COVID-19 pneumonia and hypoxemia who receive dexamethasone, treatment with tocilizumab or baricitinib appears to result in similar outcomes.
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Project description:BackgroundPrevious studies using pegylated interferon (Peg-IFN) and ribavirin (RBV) combination therapy suggested that patients with hepatitis C virus (HCV) genotype 1 and low pretreatment HCV RNA level who achieved rapid virological response (RVR) can be treated for 24 weeks without compromising sustained virological response (SVR) rate.ObjectivesThe current study aimed to investigate the efficacy of Peg-IFN-alfa-2a plus RBV administered for a 24-week treatment course in patients with chronic HCV genotype 1 infection and possessing the following criteria: low baseline serum HCV RNA level, absence of significant fibrosis and achievement of RVR.Patients and methodsIn this case-control study, 20 patients with HCV genotype 1 infection and favorable baseline characteristics and on-treatment response were treated with Peg-IFN and RBV for 24 weeks as the case group. Furthermore, 23 patients with the same characteristics who underwent a 48-week treatment course were selected as the control group.ResultsThe majority of patients had no fibrosis on liver elastography. There was no statistical difference regarding age, gender, alanine transaminase (ALT) level, rs12979860 polymorphism and the level of fibrosis between the two studied groups. All patients in the 24-week treatment course achieved SVR and all the subjects who received the 48-week treatment course achieved SVR as well (P > 0.99).ConclusionsThe current study confirmed that the efficacy of a 24-week regimen of Peg-IFN-alfa-2a plus RBV was similar to the 48-week treatment in the patients infected with HCV genotype 1, and low baseline HCV RNA level who achieved RVR. Response guided therapy can be efficient and cost-effective among the selected HCV genotype 1-infected patients.
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Project description:BackgroundIn the Netherlands, it is customary to discuss directives regarding resuscitation, intubation, and ICU-admission with patients and/or their relatives upon hospital-admission. The outcome of this discussion is documented in a code status. Ideally, these advance care planning (ACP)-related decisions are made by a patient (and/or their relatives) and a professional together in a shared decision-making (SDM) process, to improve patient satisfaction and prevent undesired care. Given the bad outcomes in older COVID-19 patients, it is particularly important to discuss the code status upon admission. This study aims to describe the practice of SDM regarding code status during the COVID-pandemic. Specific aims were to find out to what extend patients took part in this decision-making process and whether all key elements of SDM for a shared decision were documented in medical reports.MethodsIn this retrospective cohort study, we included COVID-19 patients aged 70 years and older, admitted to two large teaching hospitals in the Netherlands, during the first months of the COVID-19 pandemic in 2020. Data about code status and the decision-making process were extracted from electronic healthcare records.ResultsCode status was documented for 274 of 275 included patients. Patient participation in the decision-making process was described in 48%. In 19% all key elements of shared decision-making have been described. Key elements of SDM were defined as the presence of a completed code status form, the presence of clinical notes showing that both patient's wishes and values and the opinion of the healthcare professional about the predicted outcome was taken into consideration and clinical notes of a patient-healthcare professional interaction during the admission.ConclusionOur results show that a proper SDM process regarding code status is possible, even in hectic times like the COVID-19-pandemic. However, shared decision-making was not common practice in older patients with COVID-19 regarding code status (an ACP-related decision) in the early phase of the COVID-19 pandemic. Only in 19% of the patients, all key elements of SDM regarding code status were described.
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