Clinical Outcome and 7-Day Virological Clearance in High-Risk Patients with Mild-Moderate COVID-19 Treated with Molnupiravir, Nirmatrelvir/Ritonavir, or Remdesivir.

INTRODUCTION: We compared the effectiveness and virological clearance (VC) at day 7 (T7) post-treatment with molnupiravir, nirmatrelvir/ritonavir, and remdesivir in SARS-CoV-2-infected patients at high risk (HR) for clinical progression. METHODS: We conducted a retrospective study enrolling HR patients with mild-to-moderate COVID-19 (Jan-Oct 2022) treated with nirmatrelvir/ritonavir or molnupiravir or 3 days of remdesivir. We investigated clinical recovery at T7 (resolution of symptoms for ≥ 72 h or all-cause death), VC at T7 (PCR/antigenic negative nasopharyngeal swab), and median time to VC (days from symptom onset to the first negative swab). Factors associated with VC were investigated by logistic regression. RESULTS: In the study, 92/376 (43.8%) patients received molnupiravir, 150/376 (24.7%) nirmatrelvir/ritonavir, and 134/376 (31.5%) remdesivir. Forty-nine (13%) patients were unvaccinated or incompletely vaccinated. Patients treated with nirmatrelvir/ritonavir were younger and presented immunodeficiencies more frequently; remdesivir was used more commonly in patients hospitalized for other diseases. A high proportion of patients obtained clinical recovery without differences among the therapies (97.5% for molnupiravir, 98.3% for nirmatrelvir/ritonavir, and 93.6% for remdesivir); 12 (3.7%) patients died. Nirmatrelvir/ritonavir was associated with a higher proportion of T7 VC and a shorter time to VC compared to molnupiravir/remdesivir, also after adjustment for age and immunodeficiency (AOR 0.445 RDV vs. NMV-r, 95% CI 0.240-0.826, p = 0.010; AOR 0.222 MNP vs. NMV-r, 95% CI 0.105-0.472, p < 0.001). CONCLUSIONS: SARS-COV-2 antiviral treatments are an excellent therapeutic strategy in HR patients. Nirmatrelvir/ritonavir showed a higher proportion of VC as early as 7 days after treatment, confirming its likely superiority in indirect comparisons.

Nirmatrelvir-ritonavir, molnupiravir, and a 3-day course of remdesivir are antiviral therapies recommended in patients with a mild-to-moderate COVID-19 disease at high risk of clinical progression. Randomized controlled trials and observational studies have shown their efficacy in reducing all-cause mortality and clinical progression. Few data are available about a direct comparison among the three drugs; furthermore, the possible role of nirmatrelvir-ritonavir in increasing viral clearance and in reducing the duration of viral shedding needs to be further elucidated. We thus investigated the effectiveness, safety, and virological clearance 7 days after treatment with these three antivirals in our retrospective cohort. We included in the analysis patients that have received these treatments from January 2022 and October 2022; we observed that patients receiving nirmatrelvir-ritonavir displayed a shorter median time from symptoms' onset to virological clearance and a higher proportion of virological clearance at day 7, also after adjustment for possible confounders, compared to molnupiravir and remdesivir. Our data might help in understanding which COVID-19 patients may benefit mostly from antiviral therapies and in the choice of antiviral therapy.

Performance evaluation of a self-administered point-of-care test for anal HPV screening in PrEP users: data from a community-based PrEP service.

OBJECTIVES: In this study, we compared the performance of a self-administered point-of-care test (POCT) for anal human papillomavirus (HPV) screening with laboratory gold-standard test in pre-exposure prophylaxis (PrEP) users and evaluated its feasibility. METHODS: We enrolled PrEP users from a local community-based PrEP service. Each participant self-collected an anal swab to test anal HPV with a PCR POCT capable of detecting 14 high-risk HPV genotypes. Anonymous questionnaires on self-sampling feasibility were completed. Participants were then referred to local clinics to undergo standard viral genotyping. Concordance between POCT and gold-standard test was measured with absolute agreement and Cohen's kappa. Receiver operating characteristic (ROC) curves were used to calculate POCT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: 179 subjects got a valid POCT result, most of them men (98.3%) and men who have sex with men (90.4%). 68.2% tested positive for at least one high-risk HPV genotype on POCT. 150 feasibility questionnaires were collected: 92.7% of compilers found the self-swab easy to perform. For 178 subjects, a gold-standard test valid result was also available: 77% tested positive for at least one high-risk HPV genotype. The median time elapsed between the two tests was 9.8 months, due to COVID-19-related service interruptions. Agreement between POCT and gold-standard test was 79.3% (Cohen's kappa=0.49). POCT showed a sensitivity of 81.0%, a specificity of 73.8%, a PPV of 91.0% and an NPV of 54.4%. CONCLUSIONS: POCT showed a moderate agreement with gold-standard test and a discrete sensitivity and specificity, suggesting that it could be a useful and feasible additional tool for HPV screening, especially in low-resource and community-based settings.

Declining Mortality Rate of Hospitalised Patients in the Second Wave of the COVID-19 Epidemics in Italy: Risk Factors and the Age-Specific Patterns.

BACKGROUND: Mortality rate from COVID-19 in Italy is among the world's highest. We aimed to ascertain whether there was any reduction of in-hospital mortality in patients hospitalised for COVID-19 in the second-wave period (October 2020-January 2021) compared to the first one (February-May 2020); further, we verified whether there were clusters of hospitalised patients who particularly benefitted from reduced mortality rate. METHODS: Data collected related to in-patients' demographics, clinical, laboratory, therapies and outcome. Primary end-point was time to in-hospital death. Factors associated were evaluated by uni- and multivariable analyses. A flow diagram was created to determine the rate of in-hospital death according to individual and disease characteristics. RESULTS: A total of 1561 patients were included. The 14-day cumulative incidence of in-hospital death by competing risk regression was of 24.8% (95% CI: 21.3-28.5) and 15.9% (95% CI: 13.7-18.2) in the first and second wave. We observed that the highest relative reduction of death from first to second wave (more than 47%) occurred mainly in the clusters of patients younger than 70 years. CONCLUSIONS: Progress in care and supporting therapies did affect population over 70 years to a lesser extent. Preventive and vaccination campaigns should focus on individuals whose risk of death from COVID-19 remains high.