Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients to prevent hospitalization or death during the Omicron era: a propensity score-matched study.

Background: Even though worldwide death rates from coronavirus disease 2019 (COVID-19) have decreased, the threat of disease progression and death for high-risk groups continues. Few direct comparisons between the available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antivirals have been made. Objective: We aimed to compare two SARS-CoV-2 antivirals (nirmatrelvir/ritonavir and remdesivir) against all-cause hospitalization or death. Design: This is a propensity score-matched cohort study. Methods: We included all high-risk outpatients with COVID-19 in a tertiary referral center in Mexico City from 1 January 2022 to 31 July 2023. The primary outcome was all-cause hospitalization or death 28 days after symptom onset. The secondary outcome was COVID-19-associated hospitalization or death 28 days after symptom onset. Logistic regression analysis for characteristics associated with the primary outcome and a multi-group comparison with Kaplan-Meier survival estimates were performed. Results: Of 1566 patients analyzed, 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. The median age was 60 years (interquartile range: 46-72), 62.5% were female and 97.8% had at least one comorbidity. The use of nirmatrelvir/ritonavir was associated with an absolute risk reduction of 8.8% and a relative risk reduction of 90% for all-cause hospitalization or death. The use of remdesivir was associated with an absolute risk reduction of 6.4% and a relative risk reduction of 66% for all-cause hospitalization or death. In multivariable analysis, both antivirals reduced the odds of 28-day all-cause hospitalization or death [nirmatrelvir/ritonavir odds ratio (OR) 0.08 - 95% confidence interval (CI): 0.03-0.19, remdesivir OR 0.29 - 95% CI: 0.18-0.45]. Conclusion: In high-risk COVID-19 outpatients, early antiviral treatment with nirmatrelvir/ritonavir or remdesivir was associated with lower 28-day all-cause hospitalization or death.

Nirmatrelvir/ritonavir and remdesivir against symptomatic treatment in high-risk COVID-19 outpatients In this study, we included high-risk non-hospitalized patients with confirmed mild COVID-19. We compared those who received antiviral treatment (nirmatrelvir/ritonavir or remdesivir) against those who only received symptomatic treatment. The aim was to detect differences in hospitalization or death 28 days after symptom onset. We analyzed 1566 patients: 783 did not receive antiviral treatment, 451 received remdesivir, and 332 received nirmatrelvir/ritonavir. Most patients were female and over 60 years old. The most common comorbidities were chronic hypertension (44%), diabetes mellitus (26%), and autoimmune diseases (25%); systemic immunosuppression was registered in 35% of patients. Hospitalization or death 28 days after symptom onset occurred in 168 patients (136 in the symptomatic treatment group, 27 in the remdesivir group, and 5 in the nirmatrelvir/ritonavir group). Considering multiple variables like age, sex, comorbidities, and previous vaccination, both antivirals significantly reduced the odds of hospitalization or death (nirmatrelvir/ritonavir odds ratio 0.08, 95% confidence interval 0.03-0.19; remdesivir odds ratio 0.29, 95% confidence interval 0.18-0.45).

Clinical, molecular, and histological characteristics of severely necrotic and fatal mpox in HIV-infected patients.

BACKGROUND: This case series of 5 patients with severely necrotic mpox highlights the predominantly necrotic nature of lesions seen in cases of severe mpox as shown by skin and lung biopsy, as well as the extensive dissemination of the infection, as shown by polymerase chain reaction (PCR) assessment in different body sites. CASE PRESENTATIONS: Patients were male, the median age was 37, all lived with HIV (2 previously undiagnosed), the median CD4+ cell count was 106 cells/mm3, and 2/5 were not receiving antiretroviral treatment. The most common complication was soft tissue infection. Skin and lung biopsies showed extensive areas of necrosis. Mpox PCR was positive in various sites, including skin, urine, serum, and cerebrospinal fluid. The initiation of antiretroviral treatment, worsened the disease, like that seen in immune reconstitution syndrome. Three patients died due to multiple organ failure, presumably associated with mpox since coinfections and opportunistic pathogens were ruled out. CONCLUSIONS: Severely necrotic manifestations of mpox in people living with advanced and untreated HIV are related to adverse outcomes.