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

RhD alloimmunization in pregnancy and hemolytic disease of the fetus and newborn in Africa: A systematic review and meta-analysis

Although hemolytic disease of the fetus and newborn (HDFN), caused by maternal alloimmunization against fetal erythrocytes, has been nearly eliminated in high-income settings, it likely remains a significant public health problem in low-resource settings in Africa and elsewhere. We performed a comprehensive literature review across six major databases to determine the proportion of RhD-negativity, anti-D immunoprophylaxis utilization, RhD-alloimmunization prevalence, and the burden of RhD-mediated HDFN among pregnant women in Africa. A random-effects model was used to determine pooled estimates. We included 74 studies from 17 countries (42 from Nigeria), published between 1960 and 2024, involving 245,046 pregnancies, mostly from tertiary centers. The proportion of RhD negativity was 4.8 % (95 % CI: 4.1–5.7 %). The proven RhD alloimmunization rate was 5.8 % (95 % CI: 4.1–8.2 %). In multigravida women, the proportion of RhD alloimmunization was 5.7 % (95 % CI: 3.1–10.4 %). Anti-D immunoprophylaxis utilization after a previous pregnancy, reported in 18 studies (1490/3756 women), was 29.7 % (95 % CI: 18.0–45.0 %), with no effect on alloimmunization rate. Nine studies (including 50 neonates from 168 alloimmunized women) provided data on HDFN, with a pooled prevalence of 36.2 % (95 % CI: 16.8–61.4 %). In many papers, the specificity of the alloantibodies was not determined. Data on gravidity and the clinical definition of HDFN were incomplete. We conclude that there is a lack of robust data from Africa, thereby hampering HDFN prevention efforts. To eliminate HDFN in Africa, integrated strategies are urgently needed, including universal RhD typing and antibody screening, access to polyclonal anti-D immunoprophylaxis, and population-based surveillance.</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

Sub-optimal menstrual materials and vaginal microbiome disruption in women relying on sex for livelihood

Background: Sub-optimal menstrual materials (MM), such as using cloths, cotton balls, or tissues, can adversely affect the vaginal microbiome (VMB). Women who rely on sex for economic livelihood often use sub-optimal materials to conceal menstruation and avoid loss of income. We hypothesized that among women who rely on sex for economic livelihood, those using sub-optimal MM would be more likely to have non-optimal VMB than those with adequate MM.Methods: This cross-sectional analysis used baseline data from women participating in a trial assessing the impact of reusable menstrual discs on the VMB, Bacterial vaginosis (BV), and sexually transmitted infections (STIs). Data on sociodemographics, menstrual materials, and sexual practices were collected via interviewer-administered survey. Clinician-collected vaginal samples were tested for BV, STI, and VMB. VMB was assessed via 16S rRNA gene amplicon sequencing. A suite of statistical approaches identified factors associated with sub-optimal MM (use of cotton balls, tissue, or cloth) and VMB composition. Results: 407 women were enrolled February through October 2023, with median age 27 years, 24.7% were HIV-positive, 42.2% had BV, and 21.9% had STI (composite of chlamydia, gonorrhea, trichomoniasis). Vaginal community state type (CST) was primarily diverse (CST-IV; 63.5%), or Lactobacillus iners dominated (CST-III; 28.1%), while CST-I (L. crispatus dominated) was uncommon (7.9%). Sub-optimal MM was reported by 42.0% of participants and in multivariable modeling, was more common among women with indicators of economic strain. In multivariable analyses, alpha diversity was higher with sub-optimal MM and indicators of economic strain. Sub-optimal MM was associated with CST-IV in crude analyses but was attenuated and non-significant when adjusted for age, educational attainment, amount paid at last sexual encounter, number of sex partners, and HSV-2. Non-targeted machine learning algorithms identified non-optimal VMB taxa with greater relative abundance among women with sub-optimal MM.Discussion: Sub-optimal menstrual materials were used commonly and associated with non-optimal VMB composition. Reusable menstrual discs that may be worn during sex may address the economic factors driving sub-optimal MM that are associated with non-optimal VMB.<br/

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

RhD alloimmunization in pregnancy and hemolytic disease of the fetus and newborn in Africa: A systematic review and meta-analysis

Although hemolytic disease of the fetus and newborn (HDFN), caused by maternal alloimmunization against fetal erythrocytes, has been nearly eliminated in high-income settings, it likely remains a significant public health problem in low-resource settings in Africa and elsewhere. We performed a comprehensive literature review across six major databases to determine the proportion of RhD-negativity, anti-D immunoprophylaxis utilization, RhD-alloimmunization prevalence, and the burden of RhD-mediated HDFN among pregnant women in Africa. A random-effects model was used to determine pooled estimates. We included 74 studies from 17 countries (42 from Nigeria), published between 1960 and 2024, involving 245,046 pregnancies, mostly from tertiary centers. The proportion of RhD negativity was 4.8 % (95 % CI: 4.1–5.7 %). The proven RhD alloimmunization rate was 5.8 % (95 % CI: 4.1–8.2 %). In multigravida women, the proportion of RhD alloimmunization was 5.7 % (95 % CI: 3.1–10.4 %). Anti-D immunoprophylaxis utilization after a previous pregnancy, reported in 18 studies (1490/3756 women), was 29.7 % (95 % CI: 18.0–45.0 %), with no effect on alloimmunization rate. Nine studies (including 50 neonates from 168 alloimmunized women) provided data on HDFN, with a pooled prevalence of 36.2 % (95 % CI: 16.8–61.4 %). In many papers, the specificity of the alloantibodies was not determined. Data on gravidity and the clinical definition of HDFN were incomplete. We conclude that there is a lack of robust data from Africa, thereby hampering HDFN prevention efforts. To eliminate HDFN in Africa, integrated strategies are urgently needed, including universal RhD typing and antibody screening, access to polyclonal anti-D immunoprophylaxis, and population-based surveillance.</p

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 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