Molnupiravir for treating COVID-19

RATIONALE: Five years from the start of the COVID-19 pandemic, morbidity and mortality have subsided. Vaccines have contributed to reducing the risk of infection and severe disease. However, new COVID-19 variants continue to emerge, and the role of oral antivirals such as molnupiravir in preventing progression of disease or hospitalisation must be assessed. OBJECTIVES: To assess the effects of molnupiravir in people with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mild to moderate symptoms. SEARCH METHODS: We identified all relevant randomised controlled trials (RCTs) by searching the Cochrane COVID-19 Study Register, Science Citation Index Expanded, the World Health Organization (WHO) Global Literature on Coronavirus Disease database, and the COVID Network Meta-Analysis database with no language restrictions up to 26 April 2024. ELIGIBILITY CRITERIA: We considered full-text articles, preprints, abstracts, trial registry records, and reports of ongoing trials. Cluster-RCTs were eligible for inclusion, but cross-over trials were ineligible. Participants had confirmed SARS-CoV-2 infection with or without risk factors for severe disease. The intervention was molnupiravir 800 mg taken orally every 12 hours for five days, and control was no treatment, placebo, or standard of care, as defined by the study authors. We excluded studies comparing molnupiravir with treatment strategies that included molnupiravir. OUTCOMES: Our critical outcomes were all-cause mortality and hospitalisation. Our important outcomes were change in clinical status, viral clearance, quality of life, adverse events, and serious adverse events. RISK OF BIAS: Two review authors independently assessed the risk of bias in each included study using the Cochrane risk of bias tool (RoB 2). Disagreements were resolved through discussion. SYNTHESIS METHODS: We conducted a meta-analysis where two or more studies with reasonably similar clinical and methodological characteristics reported the same outcome. We used data from intention-to-treat analysis where available. We analysed all outcomes at the participant level using the generic inverse variance method, applying a random-effects model. We used the GRADE approach to assess the certainty of evidence. INCLUDED STUDIES: This review included 11 studies (31,272 participants). Eight studies recruited outpatients and three recruited inpatients. We did not meta-analyse inpatient studies, as characteristics varied widely. All outpatient studies included participants with mild to moderate COVID-19, with a mean age ranging from 35 years to 57 years and variable prevalences of comorbidities and COVID-19 vaccination. We excluded suboptimal molnupiravir dosing arms in four outpatient studies and one inpatient study. SYNTHESIS OF RESULTS: Outpatients Molnupiravir compared to placebo or usual care probably results in little to no difference in all-cause mortality at 28 to 30 days (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.04 to 0.65; 7 RCTs, 29,238 participants; moderate-certainty evidence). The absolute reduction in mortality is nine fewer deaths per 10,000 people treated (95% CI 10 fewer to four fewer per 10,000), which we consider clinically insignificant. Molnupiravir may result in little to no difference in hospitalisation (RR 0.70, 95% CI 0.43 to 1.12; 6 RCTs, 29,228 participants; low-certainty evidence), symptom resolution by day 14 (RR 1.20, 95% CI 0.84 to 1.71; 3 RCTs, 22,400 participants; low-certainty evidence), and symptom resolution by day 28 (RR 1.06, 95% CI 0.89 to 1.26; 3 RCTs, 24,728 participants; low-certainty evidence). Four studies reported viral clearance by day 5, which was higher in people receiving molnupiravir compared with those receiving placebo or usual care (RR 3.40, 95% CI 2.15 to 5.36; 3067 participants). The effect size decreased by day 10 (RR 1.58, 95% CI 1.07 to 2.34; 2 RCTs, 2438 participants) and indicated little to no difference between molnupiravir and control by day 14 to 15 (RR 1.05, 95% CI 0.98 to 1.13; 4 RCTs, 3062 participants). The results at day 28 to 30 again showed higher virus clearance in the molnupiravir arm (RR 1.11, 95% CI 1.03 to 1.19; 3 RCTs, 397 participants), although there were few participants in this analysis. Molnupiravir probably results in little to no difference in adverse events (RR 1.00, 95% CI 0.87 to 1.15; 7 RCTs, 4304 participants; moderate-certainty evidence). Molnupiravir results in little to no difference in serious adverse events (RR 0.86, 95% CI 0.62 to 1.21; 8 RCTs, 30,009 participants; high-certainty evidence). Inpatients The effect of molnupiravir in inpatients is unclear; substantial heterogeneity precluded meta-analysis. Risk of bias and certainty of the evidence We assigned high risk of bias judgements to one of seven RCTs for all-cause mortality, one of six RCTs for hospitalisation, two of three RCTs for symptom resolution at 14 days and 28 days, three of seven RCTs for adverse events, and three of eight RCTs for serious adverse events. We downgraded the certainty of the evidence for serious indirectness as well as risk of bias, as the populations across trials differed by vaccination status. There was no serious imprecision identified for any outcome. Publication bias is likely high in this review, as we identified 16 unpublished trials. Six were listed as complete, but only one had available data. AUTHORS' CONCLUSIONS: In outpatients with mild to moderate COVID-19, molnupiravir 800 mg taken orally every 12 hours for five days probably results in little to no difference in all-cause mortality and may result in little to no difference in rates of hospitalisation and symptom resolution. There is evidence of increased viral clearance by day 5, but the clinical relevance of this finding is unclear. There is probably little to no difference in adverse events, and there is little to no difference in serious adverse events, with molnupiravir versus placebo or standard care. Inpatient data are lacking, and there is no evidence of benefit of molnupiravir in this population. Further research involving inpatients may change this. FUNDING: The editorial base of the Cochrane Infectious Diseases Group is funded by UK aid from the UK Government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed herein do not necessarily reflect the UK Government's official policies. REGISTRATION: Protocol available at https://doi.org/10.1002/14651858.CD015381.</p

Attention to menarche, puberty education, and menstrual health monitoring are essential

In August, 2025, Maria Lohan and colleagues reported on the 30 sexual and reproductive health and rights (SRHR) research priorities identified for young adolescents (age 10–14 years), the output of a collaborative global exercise intended to bolster investment and research for this overlooked group.1 We commend their emphasis on young adolescents’ developmental needs, the perspectives of their caregivers, and the underlying determinants of positive SRHR. Among the highlighted areas, strengthening menstrual health programming (priority 11) is especially urgent to promote health and address ongoing gender inequality in this age group. The menstrual cycle typically begins during young adolescence, and early and holistic intervention in menstrual health is an entry point for SRHR throughout the life course

Prevalence and 10-Year Risk of Intracerebral Hemorrhage in Central China Using Estimates From the 1 Million Cross-Sectional Study

Background and Objectives: Intracerebral hemorrhage (ICH) is a common and fatal type of stroke, especially in central China. However, recent epidemiologic data are scarce. The study aimed to investigate the latest prevalence of ICH in central China and assess the risk of ICH in the next 10 years based on the Resident Health Records (RHR) data. Methods First, this cross-sectional study was based on a large-scale face-to-face investigation of ICH, which was launched on residents aged 20 years or older from January 1, 2021, to December 31, 2021, and estimated the prevalence of ICH in Hunan, a representative province in central China. Then, based on the RHR database, we assessed the ICH risk, population attributable fraction (PAF), and effects of ICH prevention under different risk factor control scenarios over the next decade by the China Kadoorie Biobank (CKB)-cardiovascular disease (CVD) model. Results: In 2021, 1.78 million participants enrolled in the investigation (mean age = 50.1 years; 51% male). The age-standardized prevalence rate of ICH was 159.2 (95% CI 153.7-164.9) per 100,000. The prevalence rate of ICH in men was 193.6 (95% CI 185.2-202.5) per 100,000, while in women was 124.0 (95% CI 117.1-131.3) per 100,000, and it increased with age. Spatial aggregation was observed, with the peak prevalence rate of ICH at 327.3 (95% CI 293.1-365.5) per 100,000 in Zhuzhou, followed by Changsha was 215.8 (95% CI 190.6-243.9) per 100,000, while Shaoyang had the lowest rate was 62.8 (95% CI 51.2-77.1) per 100,000. For the assessment of 10-year ICH risk, we included a total of 8.36 million participants aged 30-79 with the RHR database into the CKB-CVD model. We found that there will be 354,146 cases (ICH risk: 4.2%) of ICH among the participants in the next decade. Controlling hypertension showed the highest potential for ICH prevention, with a PAF of 8.6%. By controlling hypertension, smoking, waist circumference, and diabetes, 56,673 ICH cases (PAF 19.1%) can be avoided in the next decade. Discussion: The ICH prevalence in central China remained high. Strict blood pressure control could significantly reduce the risk of ICH in the next 10 years. It is important to continually improve ICH prevention strategies in the general population

Using Model-Based Geostatistics to Refine Population-Based Estimates of Trachoma Prevalence: Update from a Technical Consultation

To explore how model-based geostatistics (MBG) could support trachoma elimination efforts, a technical consultation was held on March 4 and 5, 2024 by the Centre for Health Informatics, Computing, and Statistics at Lancaster University, United Kingdom, a WHO Collaborating Centre on Geostatistical Methods for Neglected Tropical Disease Research. The meeting aimed to foster collaboration for sharing insights on using MBG for decision-making; showcase its applications in assessing trachoma elimination status; address challenges, such as setting the probability threshold for elimination and resolving conflicts between survey and MBG evidence; and discuss considerations for integrating MBG into Tropical Data. Participants, including trachoma program managers, experts, academics, donors, and statisticians, reviewed MBG applications, discussed ongoing studies, identified knowledge gaps, and planned future work. This article summarizes the meeting's presentations, discussions, and outcomes, highlighting current conclusions on and research priorities to evaluate MBG's feasibility and utility in trachoma elimination programs.</p

Visceral fat-to-muscle mass ratio to predict cardiovascular events and mortality in patients with chronic obstructive pulmonary disease A prospective cohort study

Background: Chronic obstructive pulmonary disease (COPD) patients can have increased cardiovascular events risk, which might be impacted by an imbalance between fat and muscle mass. This study explores the relationships between visceral fat-to-muscle mass ratio (VMR) and cardiovascular events and mortality in COPD patients. Methods: A prospective cohort study was performed on COPD patients from May 2018 to December 2023. Baseline information and VMR were collected. The primary outcome was major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, stroke, and exacerbation of congestive heart failure. Secondary outcomes were non-fatal cardiovascular events and mortality. Cox regression models, Kaplan–Meier curves, and restricted cubic splines were applied to assess the relationship between VMR and outcomes. Results: Of 1045 COPD patients, 138 (13.2 %) experienced MACE, and 169 (16.2 %) experienced non-fatal cardiovascular events and mortality during an average of 62-month follow-up period. VMR was nonlinearly associated with MACE (P = 0.023), with one-standard-deviation VMR increase leading to a 50 % increase in MACE risk (hazard ratio, HR, = 1.50, 95 % confidence interval, CI = 1.17–1.93) and 20 % increase in non-fatal cardiovascular event and mortality risk (HR = 1.20, 95 % CI = 1.08–1.34). The cumulative MACE incidence rose with higher VMR categories (log-rank P &lt; 0.0001). In the fully adjusted model, the highest VMR quartile was significantly associated with a greater MACE risk than the lowest VMR (HR = 5.18, 95 % CI = 2.75–9.75). Sensitivity analyses confirmed the robustness of these findings. Subgroup analyses indicated a more significant VMR impact in those below 60. Conclusions: Elevated VMR was associated with increased MACE among COPD patients.</p

The mediating effects of resilience and the symptoms of depression and anxiety on social frailty and quality of life in older heart failure patients

Objectives: To investigate the relationship between social frailty (SF) and quality of life (QoL) in older heart failure individuals and to verify the mediating effect of resilience and the symptoms of depression and anxiety (DA) on this relationship. Methods: A cross-sectional study was implemented to collect data from 443 old HF patients from three tertiary hospitals based on convenient sampling. The measurement tools included a general information questionnaire, the Social Frailty Scale, the 10-item Connor-Davidson Resilience Scale, the Hospital Anxiety and Depression Scale, and the Minnesota Living with Heart Failure Questionnaire. The SPSS PROCESS Marco Plug-in was used to conduct mediation analysis. Results: The regression analysis showed that place of residence, the number of hospitalizations, and New York Heart Association (NYHA) classes were influencing factors of the QoL in older HF patients. The mediation analysis indicated that resilience and the symptoms of DA mediated the relationship between SF and QoL in older HF individuals, with mediating effect sizes of 45.95 % and 64.94 %, respectively. Conclusion: SF was significantly associated with QoL in older HF patients, and resilience and the symptoms of DA mediated the relationship. Interventions paying attention to reducing SF and the symptoms of DA or enhancing resilience are beneficial for improving the QoL in older HF individuals.</p

The migratory behaviour of salt marsh mosquitoes: Revisiting the evidence

In the early 1950s, approximately 1.5 million radiolabelled black salt marsh mosquitoes (Diptera: Culicidae, Aedes taeniorhynchus Wiedemann) were released from a point source on Sanibel Island, part of an archipelago of barrier islands and mangrove swamps off the southwest coast of Florida, during one evening in June (Provost, 1957). Carefully synchronising the timing of larval hatch in outdoor tanks filled with water from local marshlands, the research team orchestrated a mass emergence of adults and witnessed that “wisps of mosquitoes took off spontaneously in puffs”. After sunset, newly emerged Ae. taeniorhynchus adults resting on nearby surfaces gradually departed, and before dawn “the great mass of mosquitoes had gone”. In the following days, adults were recaptured using light traps distributed across the archipelago (Figure 1). Recapture rates of females marked with radiolabelled phosphorous-32 (p32) vastly outweighed those of marked males, with the latter concentrated within just a few kilometres. Marked females, however, were found up to 40 km from the release point, mostly downwind, and significant numbers made open-water crossings at least three kilometres in length shortly after release

Timing of Screening Benefit for Lung Cancer With Low-Dose CT Imaging

BackgroundIncreasing evidence supports lung cancer screening with low-dose CT (LDCT) imaging. However, the benefits of LDCT screening for lung cancer may not be immediate, making it unlikely to benefit patients with limited life expectancy.Research QuestionWhat is the time to benefit (TTB) from LDCT screening for individuals at high risk for lung cancer

Community views on mass drug administration for soil-transmitted helminths: a qualitative evidence synthesis

Background: Soil-transmitted helminth (STH) infections are amongst the most common infectious diseases worldwide, with an estimated 24% of the world's population currently infected. Mass drug administration (MDA) is the periodic medicinal treatment, without prior individual diagnosis, of at-risk people living in endemic areas. The World Health Organization currently recommends MDA for STHs. MDA programmes are complex health interventions; achieving adherence is important to their success. Adherence is influenced by the target population's perceptions of the drug, the programme, and those delivering it.Objectives: To synthesize qualitative research evidence about community experiences and perceptions of mass drug administration programmes for soil-transmitted helminths. To assess whether our findings confirm, extend, enrich, or conflict with those of a 2022 Cochrane qualitative evidence review of mass drug administration programmes for lymphatic filariasis.Search methods: We searched CENTRAL, MEDLINE, Embase, and four other databases up to 11 November 2024, together with reference checking, and citation searching.Selection criteria: We synthesized qualitative and mixed-methods studies. We included studies exploring community experiences and perceptions of MDA programmes for STHs in any country, conducted between 2001 and 2024. We included all participants of MDA programmes, regardless of disease status, individual participation, or other demographic information. We also included lay healthcare workers and formally qualified healthcare workers, if their perspectives were clearly separated from those of the general population.Data collection and analysis: We collected data on study characteristics and programme delivery, including country, endemicity, drug regimen, how the drugs were delivered, use of health education and sensitization, and adherence monitoring. We conducted thematic analysis using a 'best-fit' framework synthesis based on a framework developed in a 2022 Cochrane review exploring community views on mass drug administration for filariasis (a parasitic infection caused by filarial worms). We conducted a deductive phase, accommodating our data within the existing model, followed by an inductive phase, during which we explored data not accommodated by the framework. We used the GRADE-CERQual approach to assess our confidence in the findings, and updated the filariasis review's conceptual model to display our findings.Main results: We included 17 studies, conducted in Bangladesh, Benin, India, Kenya, Malawi, Nigeria, the Philippines, and Turkey. Four themes emerged, three of which were identified in the review of MDA for lymphatic filariasis. People weigh up the benefits and harms in their decision to participate in MDA, though some may not have a choice. Outcomes of individual participation in MDA may be positive, negative, or both. The decision to partake is a careful balance of risk, benefit, and feasibility (high confidence). Unpleasant associations become part of the narrative and spread rapidly through the community (moderate confidence). Physical and social barriers prevent some people from being able to access MDA even if they want to participate (moderate confidence). Many people are suspicious of MDA programmes, although trust may be built over time. Factors such as historical legacies, rumours, and mistrust of people involved in the programme affect overall trust in drug distribution and influence whether people choose to participate. Past experiences can have a profound effect on people, and negative experiences are likely to deter people from future participation (high confidence). Careful management of the relationships between people implementing the programme and people receiving the programme is important to building trust over time (moderate confidence). The drug distributor's status in the community is often low, and they are not well-equipped to answer the communities' questions. People employed to distribute the drugs during STH treatment campaigns often lack a healthcare background and in-depth training around the drug or the disease itself (moderate confidence). Some community members prefer distribution from people they know or trust (high confidence). However, others place value on the knowledge or status of the drug distributors, and may not participate if the community drug distributors (CDDs) cannot answer their programme-related questions (moderate confidence). Many community members have ideas to improve delivery and want more involvement in the programme. Although some programmes conduct education and sensitization activities prior to drug distribution, many community members still lack awareness of the timing and purpose of the distribution (high confidence). People value distribution strategies that make it easy for everyone to participate, and express a desire for adults in the community to be included in the programme (moderate confidence). Many community members believe a more comprehensive health campaign, which includes improved sanitation, is necessary to tackle STH burden (moderate confidence). One theme that the filariasis review identified was not substantiated by the findings in this review (Programmes expect compliance: this can result in coercion and blame).Authors' conclusions: Despite the prevalence and undoubted impact of MDA programmes over the past 10 years, endemic hotspots and continued transmission are common, due in part to poor community adherence. The 2022 Cochrane review outlined several key community concerns and doubts that hinder the effective implementation of MDA for lymphatic filariasis. This review shows that most of these concerns and doubts are shared by communities targeted for MDA for STHs, indicating that there are fundamental challenges in the overall conceptualization and design of MDA programmes that need to be addressed.Funding: TF, MT, RK, and the Cochrane Infectious Diseases Group editorial base were funded by UK aid from the UK Government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed do not necessarily reflect the UK Government's official policies.Registration: The protocol for this review was published in January 2024 on the Cochrane Database of Systematic Reviews. Available at doi.org/10.1002/14651858.CD015794