ABSTRACT
Introduction: Lung transplant recipients (LTR) are at significant risk for severe covid-19 disease. The oral combination therapy Nirmatrelvir plus Ritonavir (Paxlovid) has been shown to reduce the risk for disease progression. Due to drug interactions with calcineurin inhibitors (CNI), significant concern exists in treating LTR with Paxlovid. We describe safety related outcomes of Paxlovid use among our LTR. Method(s): We retrospectively collected data of all LTR with a positive COVID-19 test since Paxlovid was available in Israel from January 2022 - May 2022. During this time, Paxlovid was the drug of choice, unless contraindicated. Data collection included: demographics, hospitalization for covid-19, death of any cause and drug related adverse events. Result(s): A total of 96 LTR tested positive for covid-19 during this period. View inline There was no evidence of posterior reversible encephalopathy (PRES), seizures, kidney failure or ED visits in any of the paxlovid treated patients. Conclusion(s): Despite significant drug related interactions between CNI and Paxlovid, the drug can be administrated safely in LTR. Given the high risk for severe covid-19 disease among LTR and the demonstrated safety of this study, use of paxlovid among this population should be considered.
ABSTRACT
BACKGROUND: Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19). AIM: To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients. DESIGN: A systematic review and meta-analysis. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28-30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses. RESULTS: Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28-30-day mortality compared to placebo/control (RR = 0.89, 95% CI 0.82-0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR = 0.94, 95% CI 0.74-1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR = 0.57, 95% CI 0.35-0.93). CONCLUSION: The treatment with TCZ reduces 28-30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19.