A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data.

Introduction: Thrombotic complications of coronavirus disease 2019 (COVID-19) have received considerable attention. Although numerous conflicting findings have compared escalated thromboprophylaxis doses with a standard dose to prevent thrombosis, there is a paucity of literature comparing clinical outcomes in three different anticoagulation dosing regimens. Thus, we investigated the effectiveness and safety profiles of standard, intermediate, and high-anti-coagulation dosing strategies in COVID-19 critically ill patients. Methodology: This retrospective multicenter cohort study of intensive care unit (ICU) patients from the period of April 2020 to August 2021 in four Saudi Arabian centers. Inclusion criteria were age ≥ 18 years, diagnosis with severe or critical COVID-19 infection, and receiving prophylactic anticoagulant dose within 24-48 h of ICU admission. The primary endpoint was a composite of thrombotic events, with mortality rate and minor or major bleeding serving as secondary endpoints. We applied survival analyses with a matching weights procedure to control for confounding variables in the three arms. Results: A total of 811 patient records were reviewed, with 551 (standard-dose = 192, intermediate-dose = 180, and high-dose = 179) included in the analysis. After using weights matching, we found that the standard-dose group was not associated with an increase in the composite thrombotic events endpoint when compared to the intermediate-dose group {19.8 vs. 25%; adjusted hazard ratio (aHR) =1.46, [95% confidence of interval (CI), 0.94-2.26]} or when compared to high-dose group [19.8 vs. 24%; aHR = 1.22 (95% CI, 0.88-1.72)]. Also, there were no statistically significant differences in overall in-hospital mortality between the standard-dose and the intermediate-dose group [51 vs. 53.4%; aHR = 1.4 (95% CI, 0.88-2.33)] or standard-dose and high-dose group [51 vs. 61.1%; aHR = 1.3 (95% CI, 0.83-2.20)]. Moreover, the risk of major bleeding was comparable in all three groups [standard vs. intermediate: 4.8 vs. 2.8%; aHR = 0.8 (95% CI, 0.23-2.74); standard vs. high: 4.8 vs. 9%; aHR = 2.1 (95% CI, 0.79-5.80)]. However, intermediate-dose and high-dose were both associated with an increase in minor bleeding incidence with aHR = 2.9 (95% CI, 1.26-6.80) and aHR = 3.9 (95% CI, 1.73-8.76), respectively. Conclusion: Among COVID-19 patients admitted to the ICU, the three dosing regimens did not significantly affect the composite of thrombotic events and mortality. Compared with the standard-dose regimen, intermediate and high-dosing thromboprophylaxis were associated with a higher risk of minor but not major bleeding. Thus, these data recommend a standard dose as the preferred regimen.

Tocilizumab effectiveness in mechanically ventilated COVID-19 patients (T-MVC-19 Study): a multicenter real-world evidence.

BACKGROUND: This study aimed to evaluate the effectiveness of tocilizumab in mechanically ventilated patients with coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: This retrospective multicenter study included adults (≥18 years) diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab, and requiring invasive mechanical ventilation during admission. Survival analyses with inverse propensity score treatment weighting (IPTW) and propensity score matching (PSM) were conducted. To account for immortal bias, we used Cox proportional modeling with time-dependent covariance. Competing risk analysis was performed for the extubation endpoint. RESULTS: A total of 556 (tocilizumab = 193, control = 363) patients were included. Males constituted the majority of the participants (69.2% in tocilizumab arm,74.1% in control arm). Tocilizumab was not associated with a reduction in mortality with hazard ratio [(HR) = 0.82,95% confidence interval (95%CI): 0.62-1.10] in the Inverse propensity score weighting (IPTW) analysis and (HR = 0.86,95% CI: 0.64-1.16) in the PSM analysis. However, tocilizumab was associated with an increased rate of extubation (33.6%) compared to the control arm (11.9%); subdistributional hazards (SHR) = 3.1, 95% CI: 1.86-5.16). CONCLUSIONS: Although tocilizumab was not found to be effective in reducing mortality, extubation rate while on mechanical ventilation was higher among tocilizumab treated group.

Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis.

INTRODUCTION: Favipiravir is a repurposed drug to treat coronavirus 2019 (COVID-19). Due to a lack of available real-world data, we assessed its effectiveness and safety in moderately to critically ill COVID-19 patients. METHODS: This retrospective study was conducted in two public/specialty hospitals in Saudi Arabia. We included patients ≥18 years) admitted April-August 2020 with confirmed SARS-CoV-2 diagnosed by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab. Patients received either favipiravir (1800 mg or 1600 mg twice daily loading dose, followed by 800 mg or 600 mg twice daily) or supportive-care treatment. Patients were excluded if they were outside the study period, classified as having a mild form of the disease per WHO criteria, or had an incomplete patient file. Kaplan-Meier (KM) models were used to estimate median time to discharge. Discharge ratios, progression to mechanical ventilation, and mortality outcomes were estimated across the severity spectrum using Cox proportional-hazards models. As a sensitivity analysis, we performed propensity score-matching (PSM) analysis. RESULTS: Overall, median time to discharge was 10 days (95%CI = 9-10) in the favipiravir arm versus 15 days (95%CI = 14-16) in the supportive-care arm. The accelerated discharge benefit was seen across the COVID-19 spectrum of severity. The adjusted discharge ratio was 1.96 (95%CI = 1.56-2.46). Progression to mechanical ventilation was slower with favipiravir (HRadj = 0.10, 95%CI = 0.04-0.29). There was no significant effect on mortality (HRadj = 1.56, 95%CI = 0.73-3.36). There was a statistically non-significant trend toward worse outcomes in the critical category (HRadj = 2.80, 95%CI = 0.99-7.89). Age was an independent risk factor for mortality in mechanically ventilated patients. PSM analyses confirmed these findings. CONCLUSION: Favipiravir was associated with clinical benefits, including accelerated discharge rate and less progression to mechanical ventilation; however, no overall mortality benefits were seen across the severity spectrum.

Mortality, Severity, and Hospital Admission among COVID-19 Patients with ACEI/ARB Use: A Meta-Analysis Stratifying Countries Based on Response to the First Wave of the Pandemic.

BACKGROUND: The use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) is controversial for treating COVID-19 patients. We aimed to estimate pooled risks of mortality, disease severity, and hospitalization associated with ACEI/ARB use and stratify them by country and country clusters. METHODS: We conducted a search in various databases through 4 July 2020 and then applied random-effects models to estimate pooled risks (ORp) across stratifications by country cluster. Clusters were chosen to reflect outbreak times (China followed by Korea/Italy, others subsequently) and mobility restrictions (China and Denmark/France/Spain with stricter lockdowns than the UK/US). RESULTS: Overall analysis showed no increase in mortality; however, a statistical increase in mortality was seen in the US/UK cluster with ORp = 1.28 [95% CI = 1.04; 1.56] and a decrease in China with ORp = 0.65 [95% CI = 0.43; 0.96] and France with OR = 0.31 [95% CI = 0.14; 0.69]. Severity and hospitalization were not statistically significant in the analysis; however, several associations were seen in specific countries but not in country clusters. CONCLUSION: The country-cluster meta-analysis provided a reasonable explanation for COVID-19 mortality among ACEI/ARB users. The analysis did not explain differences in severity and suggested the involvement of other factors. Hospitalization findings among ACEI/ARB users may be considered informative as they may have been subjected to clinical decisions and hospital-bed availability.