The effect of oral antiviral therapy for COVID-19 in managing non-hospitalized patients with lung cancer.

BACKGROUNDS: The effectiveness of oral antiviral therapy including nirmatrelvir plus ritonavir and molnupiravir in managing COVID-19 among individuals with pre-existing lung cancer was unclear. Therefore, this study was conducted to evaluate the usefulness of antiviral agents in the management of COVID-19 among patients with lung cancer. METHODS: Utilizing data from the TriNetX - a global health research network, a retrospective cohort study was conducted involving 2484 patients diagnosed with both lung cancer and COVID-19. Propensity score matching (PSM) was employed to create well-balanced cohorts. The study assessed the primary outcome of all-cause hospitalization or mortality within a 30-day follow-up. RESULTS: After PSM, the oral antiviral group exhibited a significantly lower risk of the primary composite outcome compared to the control group (6.1 % vs. 9.9 %; HR: 0.60; 95 % CI: 0.45-0.80). This association was consistent across various subgroups according to age, sex, vaccine status, type of oral antiviral agent, and lung cancer characteristics. Additionally, the oral antiviral group showed a lower risk of all-cause hospitalization (HR: 0.73; 95 % CI: 0.54-0.99) and a significantly lower risk of mortality (HR: 0.16; 95 % CI: 0.06-0.41). CONCLUSION: The study suggests a favorable impact of oral antiviral therapy on the outcomes of COVID-19 in individuals with lung cancer and support the potential utility of oral antiviral agents in improving outcomes in this vulnerable population.

Effectiveness of recently-approved oral antiviral medications on the outcome of patients with mild-to-moderate COVID-19 and pre-existing chronic obstructive pulmonary diseases.

OBJECTIVES: This study assessed the effectiveness of the oral antiviral agents nirmatrelvir - ritonavir (NMV-r) and molnupiravir (MOV) for treating mild-to-moderate coronavirus disease 2019 (COVID-19) in patients with COPD. METHODS: This retrospective cohort study extracted data from the TriNetX platform and examined 94,984 COVID-19 patients with preexisting COPD from 1 January 2022, to 1 October 2023. Patients receiving NMV-r or MOV (study group) were compared with those not receiving oral antiviral agents (control group) after propensity score matching (PSM). RESULTS: After PSM, 7,944 patients were classified into the study and control groups. The primary composite outcome of all-cause hospitalization, or death in 30 days was reported in 458 (5.7%) patients in the study group and 566 (7.1%) patients in the control cohort, yielding a hazard ratio [HR] of 0.79 (95% confidence interval [CI]: 0.70-0.89; Table 2). Compared with the control group, the study group had a significantly lower risk of all-cause hospitalization (HR, 0.87; 95% CI: 0.76-0.99) and death (HR: 0.21, 95% CI: 0.13-0.35). CONCLUSIONS: This study revealed that oral antivirals - NMV-r or MOV might improve clinical outcomes in patients with preexisting COPD and COVID-19. However, only a small proportion of preexisting COPD patients with COVID-19 received oral antiviral treatment.

Optimizing myocardial cell protection with xanthine derivative KMUP-3 potentiates autophagy through the PI3K/Akt/eNOS axis.

BACKGROUND: Autophagy can have either beneficial or detrimental effects on various heart diseases. Pharmacological interventions improve cardiac function, which is correlated with enhanced autophagy. To assess whether a xanthine derivative (KMUP-3) treatment coincides with enhanced autophagy while also providing cardio-protection, we investigated the hypothesis that KMUP-3 treatment activation of autophagy through PI3K/Akt/eNOS signalling offered cardioprotective properties. METHODS: The pro-autophagic effect of KMUP-3 was performed in a neonatal rat model targeting cardiac fibroblasts and cardiomyocytes, and by assessing the impact of KMUP-3 treatment on cardiotoxicity, we used antimycin A-induced cardiomyocytes. RESULTS: As determined by transmission electron microscopy observation, KMUP-3 enhanced autophagosome formation in cardiac fibroblasts. Furthermore, KMUP-3 significantly increased the expressions of autophagy-related proteins, LC3 and Beclin-1, both in a time- and dose-dependent manner; moreover, the pro-autophagy and nitric oxide enhancement effects of KMUP-3 were abolished by inhibitors targeting eNOS and PI3K in cardiac fibroblasts and cardiomyocytes. Notably, KMUP-3 ameliorated cytotoxic effects induced by antimycin A, demonstrating its protective autophagic response. CONCLUSION: These findings enable the core pathway of PI3K/Akt/eNOS axis in KMUP-3-enhanced autophagy activation and suggest its principal role in safeguarding against cardiotoxicity.

The effectiveness of novel oral antiviral treatment for non-hospitalized high-risk patients with COVID-19 during predominance of omicron XBB subvariants.

OBJECTIVES: This study investigated the association between nirmatrelvir plus ritonavir (NMV-r) or molnupiravir and the outcomes of non-hospitalized high-risk patients with COVID-19 during Omicron XBB subvariants. METHODS: The retrospective cohort study used the TriNetX US collaborative network to identify non-hospitalized high-risk adult patients with COVID-19 between 1 February 2023, and 31 August 2023. Propensity score matching (PSM) was used to match patients receiving NMV-r or MOV (the study group) with those not receiving antivirals (the control group). RESULTS: Using PSM, two cohorts of 17,654 patients each with balanced baseline characteristics were identified. During the follow-up period, the study group had a lower risk of all-cause hospitalization, or death (3.2% [n = 564] versus 3.8% [n = 669]; HR, 0.796; 95% confidence interval [CI], 95% CI, 0.712-0.891). Compared with the control group, the study group had a significantly lower risk of all-cause hospitalization (3.1% vs. 3.4%; HR, 0.847; 95% CI, 0.754-0.950) and mortality (0.1% vs. 0.4%; HR, 0.295; 95% CI, 0.183-0.476). CONCLUSION: The use of novel oral antiviral including NMV-r or MOV can be associated with a lower risk of all-cause hospitalization, or death in non-hospitalized high-risk patients with COVID-19 during Omicron XBB wave.

Clinical effectiveness of nirmatrelvir plus ritonavir in the treatment of COVID-19 in patients with cirrhosis.

OBJECTIVES: This retrospective cohort study assessed the clinical effectiveness of nirmatrelvirplus ritonavir (NMV-r) in treating COVID-19 in patients with liver cirrhosis(LC). METHODS: The data of non-hospitalized adult patients with LC who had COVID-19 were selected from the TriNetX platform for the period between 1 March 20201 March 2020, and 31 December 202231 December 2022. Propensity score matching was used to match patients receiving NMV-r (theNMV-r group) with those not receiving NMV-r (the control group). Hazard ratios(HRs) along with 95% confidence intervals (CIs) for the primary outcome - a composite of all-cause hospitalization or mortality during the 30-day follow-up period - were calculated and compared. RESULTS: Two cohorts of 2,369 patients each with balanced baseline characteristics were identified.During the follow-up period, the NMV-r group had a lower risk of all-cause hospitalization or mortality (HR, 0.642;95% CI, 0.503-0.819) than did the control group.NMV-r was also associated with a reduced risk of individual all-cause hospitalization (HR 0.681, 95% CI 0.530-0.876])and all-cause mortality (HR, 0.270; 95% CI,0.129-0.562). This association was consistently observed in the subgroups of age, sex, vaccination status, and LC severity. CONCLUSIONS: NMV-r can reduce all-cause hospitalization and mortality among patients with LC who have COVID-19.