Age-specific mortality and immunity patterns of SARS-CoV-2.

Estimating the size of the coronavirus disease 2019 (COVID-19) pandemic and the infection severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is made challenging by inconsistencies in the available data. The number of deaths associated with COVID-19 is often used as a key indicator for the size of the epidemic, but the observed number of deaths represents only a minority of all infections1,2. In addition, the heterogeneous burdens in nursing homes and the variable reporting of deaths of older individuals can hinder direct comparisons of mortality rates and the underlying levels of transmission across countries3. Here we use age-specific COVID-19-associated death data from 45 countries and the results of 22 seroprevalence studies to investigate the consistency of infection and fatality patterns across multiple countries. We find that the age distribution of deaths in younger age groups (less than 65 years of age) is very consistent across different settings and demonstrate how these data can provide robust estimates of the share of the population that has been infected. We estimate that the infection fatality ratio is lowest among 5-9-year-old children, with a log-linear increase by age among individuals older than 30 years. Population age structures and heterogeneous burdens in nursing homes explain some but not all of the heterogeneity between countries in infection fatality ratios. Among the 45 countries included in our analysis, we estimate that approximately 5% of these populations had been infected by 1 September 2020, and that much higher transmission rates have probably occurred in a number of Latin American countries. This simple modelling framework can help countries to assess the progression of the pandemic and can be applied in any scenario for which reliable age-specific death data are available.

Seasonal Patterns of Mpox Index Cases, Africa, 1970-2021.

Across 133 confirmed mpox zoonotic index cases reported during 1970-2021 in Africa, cases occurred year-round near the equator, where climate is consistent. However, in tropical regions of the northern hemisphere under a dry/wet season cycle, cases occurred seasonally. Our findings further support the seasonality of mpox zoonotic transmission risk.

Source of SARS-CoV-2 infection: results from a series of 584,846 cases in France from October 2020 to August 2022.

BACKGROUND: We aimed to study the source of infection for recently SARS-CoV-2-infected individuals from October 2020 to August 2022 in France. METHODS: Participants from the nationwide ComCor case-control study who reported recent SARS-CoV-2 infection were asked to document the source and circumstances of their infection through an online questionnaire. Multivariable logistic regression was used to identify the factors associated with not identifying any source of infection. RESULTS: Among 584,846 adults with a recent SARS-CoV-2 infection in France, 46.9% identified the source of infection and an additional 22.6% suspected an event during which they might have become infected. Known and suspected sources of infection were household members (30.8%), extended family (15.6%), work colleagues (15.0%), friends (11.0%), and possibly multiple/other sources (27.6%). When the source of infection was known, was not a household member, and involved a unique contact (n = 69,788), characteristics associated with transmission events were indoors settings (91.6%), prolonged (> 15 min) encounters (50.5%), symptomatic source case (64.9%), and neither the source of infection nor the participant wearing a mask (82.2%). Male gender, older age, lower education, living alone, using public transportation, attending places of public recreation (bars, restaurants, nightclubs), public gatherings, and cultural events, and practicing indoor sports were all independently associated with not knowing the source of infection. CONCLUSION: Two-thirds of infections were attributed to interactions with close relatives, friends, or work colleagues. Extra-household indoor encounters without masks were commonly reported and represented avoidable circumstances of infection. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT04607941.

SARS-CoV-2 seroprevalence and associated factors of infection before and after the Delta wave in French Polynesia: a cross-sectional study.

BACKGROUND: French Polynesia (FP) comprises 75 inhabited islands scattered across five archipelagos. Between July and October 2021, the SARS-CoV-2 Delta variant triggered a much stronger second epidemic wave in FP than the original Wuhan strain, which was dominant from August 2020 to March 2021. Although previous seroprevalence surveys made it possible to determine the proportion of the population infected by SARS-CoV-2 on the two most populated islands (Tahiti and Moorea) after the first (20.6% in Tahiti and 9.4% in Moorea) and second (57.7% in Tahiti) epidemic waves, no data are available for more remote islands. We used blood samples and personal data collected before, during, and after the second wave from inhabitants of several islands within the five archipelagos to assess the prevalence of SARS-CoV-2 infections and identify associated factors. METHODS: Blood samples and personal data were collected between April and December 2021 as part of the MATAEA study, a cross-sectional survey conducted on a random sample of the adult population representative of the five FP archipelagos and stratified by age and gender. IgG antibodies targeting the SARS-CoV-2 nucleocapsid (N) protein were detected using a recombinant antigen-based microsphere immunoassay. Factors associated with anti-SARS-CoV-2-N seropositivity were identified using logistic regression models. RESULTS: Of 1,120 participants, 503 (44.9%) tested positive for anti-SARS-CoV-2-N antibodies, corresponding to a weighted prevalence of 56.8% for the FP population aged 18-69 years. The seroprevalence increased from 21.9% to 62.1% before and during/after the Delta wave. Of these infections, only 28.4% had been diagnosed by health professionals. The odds of being seropositive were lower in males, participants recruited before the Delta wave, those who had never been married, those with a diagnosed respiratory allergy, smokers, and those vaccinated against COVID-19. CONCLUSIONS: Our results confirm the high impact of the Delta wave in FP. By the end of 2021, 56.8% of the FP population aged 18-69 years had been infected by SARS-CoV-2; the majority of these infections went undetected. Individuals with respiratory allergies were found to be less susceptible to SARS-CoV-2 infection.

Epidemiological Evidence of Nosocomial and Zoonotic Transmission of Human T-Cell Leukemia Virus-1 in a Large Survey in a Rural Population of Central Africa.

BACKGROUND: Central Africa is one of the largest areas of high endemicity for human T-cell leukemia virus-1 (HTLV-1). However, no preventive measures are yet implemented to reduce its transmission, which can be sexual, from mother-to-child, or through contaminated blood products. Rare zoonotic transmissions from nonhuman primates (NHPs) have also been reported in this region. Here we investigated the HTLV-1 prevalence and associated risk factors in a rural population in Cameroon. METHODS: From 2019 to 2021, we performed a cross-sectional survey in the eastern region of Cameroon. HTLV-1 infection was first screened by ELISA, then tested by western blot and envelope gene targeted polymerase chain reaction. Risk factors associated with HTLV-1 infection were identified by logistic regression in univariable and multivariable analyses. RESULTS: Among 3400 participants, HTLV-1 prevalence was 1.1% (95% confidence interval [CI], .7-1.5). Factors independently associated with HTLV-1 infection were Pygmy ethnicity (adjusted odd ratio [aOR], 2.9; 95% CI, 1.3-6.2), history of surgery (aOR, 6.3; 95% CI, 2.2-17.8), and NHP bite (aOR, 6.6; 95% CI, 2.2-19.8). CONCLUSIONS: These results suggest both iatrogenic and zoonotic transmission of HTLV-1 in Cameroon. Further studies are needed to assess the risk of nosocomial transmission of HTLV-1, to guide public health authorities in implementing preventive measures to control HTLV-1 transmission.

Intensified screening for SARS-CoV-2 in 18 emergency departments in the Paris metropolitan area, France (DEPIST-COVID): A cluster-randomized, two-period, crossover trial.

BACKGROUND: Asymptomatic and paucisymptomatic infections account for a substantial portion of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions. The value of intensified screening strategies, especially in emergency departments (EDs), in reaching asymptomatic and paucisymptomatic patients and helping to improve detection and reduce transmission has not been documented. The objective of this study was to evaluate in EDs whether an intensified SARS-CoV-2 screening strategy combining nurse-driven screening for asymptomatic/paucisymptomatic patients with routine practice (intervention) could contribute to higher detection of SARS-CoV-2 infections compared to routine practice alone, including screening for symptomatic or hospitalized patients (control). METHODS AND FINDINGS: We conducted a cluster-randomized, two-period, crossover trial from February 2021 to May 2021 in 18 EDs in the Paris metropolitan area, France. All adults visiting the EDs were eligible. At the start of the first period, 18 EDs were randomized to the intervention or control strategy by balanced block randomization with stratification, with the alternative condition being applied in the second period. During the control period, routine screening for SARS-CoV-2 included screening for symptomatic or hospitalized patients. During the intervention period, in addition to routine screening practice, a questionnaire about risk exposure and symptoms and a SARS-CoV-2 screening test were offered by nurses to all remaining asymptomatic/paucisymptomatic patients. The primary outcome was the proportion of newly diagnosed SARS-CoV-2-positive patients among all adults visiting the 18 EDs. Primary analysis was by intention-to-treat. The primary outcome was analyzed using a generalized linear mixed model (Poisson distribution) with the center and center by period as random effects and the strategy (intervention versus control) and period (modeled as a weekly categorical variable) as fixed effects with additional adjustment for community incidence. During the intervention and control periods, 69,248 patients and 69,104 patients, respectively, were included for a total of 138,352 patients. Patients had a median age of 45.0 years [31.0, 63.0], and women represented 45.7% of the patients. During the intervention period, 6,332 asymptomatic/paucisymptomatic patients completed the questionnaire; 4,283 were screened for SARS-CoV-2 by nurses, leading to 224 new SARS-CoV-2 diagnoses. A total of 1,859 patients versus 2,084 patients were newly diagnosed during the intervention and control periods, respectively (adjusted analysis: 26.7/1,000 versus 26.2/1,000, adjusted relative risk: 1.02 (95% confidence interval (CI) [0.94, 1.11]; p = 0.634)). The main limitation of this study is that it was conducted in a rapidly evolving epidemiological context. CONCLUSIONS: The results of this study showed that intensified screening for SARS-CoV-2 in EDs was unlikely to identify a higher proportion of newly diagnosed patients. TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov NCT04756609.

Reduction of SARS-CoV-2 intra-household child-to-parent transmission associated with ventilation: results from a case-control study.

PURPOSE: Our objective was to describe circumstances of SARS-CoV-2 household transmission and to identify factors associated with a lower risk of transmission in a nationwide case-control study in France. METHODS: In a descriptive analysis, we analysed cases reporting transmission from someone in the household (source case). Index cases could invite a non-infected household member to participate as a related control. In such situations, we compared the exposures of the index case and related control to the source case by conditional logistic regression matched for household, restricted to households in which the source case was a child, and the index case and related control were the infected child's parents. RESULTS: From October 27, 2020 to May 16, 2022, we included 104 373 cases for the descriptive analysis with a documented infection from another household member. The source case was mostly the index case's child (46.9%) or partner (45.7%). In total, 1026 index cases invited a related control to participate in the study. In the case-control analysis, we included 611 parental pairs of cases and controls exposed to the same infected child. COVID-19 vaccination with 3 + doses versus no vaccination (OR 0.1, 95%CI: 0.04-0.4), isolation from the source case (OR 0.6, 95%CI: 0.4-0.97) and the ventilation of indoor areas (OR 0.6, 95%CI: 0.4-0.9) were associated with lower risk of infection. CONCLUSION: Household transmission was common during the SARS-CoV-2 pandemic in France. Mitigation strategies, including isolation and ventilation, decreased the risk of secondary transmission within the household. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT04607941.

SARS-CoV-2 self-test uptake and factors associated with self-testing during Omicron BA.1 and BA.2 waves in France, January to May 2022.

BackgroundFollowing the SARS-CoV-2 Omicron variant spread, the use of unsupervised antigenic rapid diagnostic tests (self-tests) increased.AimThis study aimed to measure self-test uptake and factors associated with self-testing.MethodsIn this cross-sectional study from 20 January to 2 May 2022, the case series from a case-control study on factors associated with SARS-CoV-2 infection were used to analyse self-testing habits in France. A multivariable quasi-Poisson regression was used to explore the variables associated with self-testing among symptomatic cases who were not contacts of another infected individual. The control series from the same study was used as a proxy for the self-test background rate in the non-infected population of France.ResultsDuring the study period, 179,165 cases who tested positive through supervised tests were recruited. Of these, 64.7% had performed a self-test in the 3 days preceding this supervised test, of which 79,038 (68.2%) were positive. The most frequently reported reason for self-testing was the presence of symptoms (64.6%). Among symptomatic cases who were not aware of being contacts of another case, self-testing was positively associated with being female, higher education, household size, being a teacher and negatively associated with older age, not French by birth, healthcare-related work and immunosuppression. Among the control series, 12% self-tested during the 8 days preceding questionnaire filling, with temporal heterogeneity.ConclusionThe analysis showed high self-test uptake in France with some inequalities which must be addressed through education and facilitated access (cost and availability) for making it a more efficient epidemic control tool.

Estimated protection against COVID-19 based on predicted neutralisation titres from multiple antibody measurements in a longitudinal cohort, France, April 2020 to November 2021.

BackgroundThe risk of SARS-CoV-2 (re-)infection remains present given waning of vaccine-induced and infection-acquired immunity, and ongoing circulation of new variants.AimTo develop a method that predicts virus neutralisation and disease protection based on variant-specific antibody measurements to SARS-CoV-2 antigens.MethodsTo correlate antibody and neutralisation titres, we collected 304 serum samples from individuals with either vaccine-induced or infection-acquired SARS-CoV-2 immunity. Using the association between antibody and neutralisation titres, we developed a prediction model for SARS-CoV-2-specific neutralisation titres. From predicted neutralising titres, we inferred protection estimates to symptomatic and severe COVID-19 using previously described relationships between neutralisation titres and protection estimates. We estimated population immunity in a French longitudinal cohort of 905 individuals followed from April 2020 to November 2021.ResultsWe demonstrated a strong correlation between anti-SARS-CoV-2 antibodies measured using a low cost high-throughput assay and antibody response capacity to neutralise live virus. Participants with a single vaccination or immunity caused by infection were especially vulnerable to symptomatic or severe COVID-19. While the median reduced risk of COVID-19 from Delta variant infection in participants with three vaccinations was 96% (IQR: 94-98), median reduced risk among participants with infection-acquired immunity was only 42% (IQR: 22-66).ConclusionOur results are consistent with data from vaccine effectiveness studies, indicating the robustness of our approach. Our multiplex serological assay can be readily adapted to study new variants and provides a framework for development of an assay that would include protection estimates.

Maternal Age at First Childbirth and Geographical Variation in Hepatitis B Virus Prevalence in Cameroon: Important Role of Mother-to-Child Transmission.

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection varies geographically around the world. Yet, its underlying mechanisms are unknown. Using a nationally representative population-based sample from all 58 administrative divisions in Cameroon, we examined the association between median maternal age at first childbirth in a preceding generation, a proxy for the frequency of mother-to-child transmission (MTCT) of HBV in a region, and the risk of chronic HBV infection, defined as positive surface antigen (HBsAg), in the index generation. METHODS: We estimated a division-specific median maternal age at first childbirth using Demographic Health Surveys (DHSs) conducted in 1991, 1998, 2004, and 2011. We tested HBsAg in 2011 DHS participants. We used maps to display spatial variation. RESULTS: In 14 150 participants (median age, 27 years; 51% females), the overall weighted prevalence of HBsAg was 11.9% (95% confidence interval [CI], 11.0 to 12.8), with a wide geographical variation across the divisions (range, 6.3%-23.7%). After adjusting for confounders and spatial dependency, lower maternal age at first childbirth was significantly associated with positive HBsAg at the division level (ß, 1.89; 95% CI, 1.26 to 2.52) and at the individual level (odds ratio, 1.20; 95% CI, 1.04 to 1.39). A similar ecological correlation was observed across other African countries. CONCLUSIONS: The significant association between the maternal age at first childbirth and HBsAg positivity suggests a crucial role of MTCT in maintaining high HBV endemicity in some areas in Cameroon. This underlines an urgent need to effectively prevent MTCT in sub-Saharan Africa.

Nocardia Infections in Hematopoietic Cell Transplant Recipients: A Multicenter International Retrospective Study of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.

BACKGROUND: Nocardiosis is rare after hematopoietic cell transplantation (HCT). Little is known regarding its presentation, management, and outcome in this population. METHODS: This retrospective international study reviewed nocardiosis episodes in HCT recipients (1/1/2000-31/12/2018; 135 transplant centers; 33 countries) and described their clinical, microbiological, radiological, and outcome characteristics. RESULTS: We identified 81 nocardiosis episodes in 74 allo- and 7 auto-HCT recipients. Nocardiosis occurred a median of 8 (IQR: 4-18) months post-HCT. The most frequently involved organs were lungs (70/81; 86%) and brain (30/81; 37%); 29 (36%) patients were afebrile; 46/81 (57%) had disseminated infections. The most common lung imaging findings were consolidations (33/68; 49%) or nodules (32/68; 47%); brain imaging findings were multiple brain abscesses (19/30; 63%). Ten of 30 (33%) patients with brain involvement lacked neurological symptoms. Fourteen of 48 (29%) patients were bacteremic. Nocardia farcinica was the most common among molecularly identified species (27%; 12/44). Highest susceptibility rates were reported to linezolid (45/45; 100%), amikacin (56/57; 98%), trimethoprim-sulfamethoxazole (57/63; 90%), and imipenem (49/57; 86%). One-year and last follow-up (IQR: 4-42.5 months) all-cause mortality were 40% (32/81) and 52% (42/81), respectively. In the multivariable analysis, underlying disease not in complete remission (HR: 2.81; 95% CI: 1.32-5.95) and prior bacterial infection (HR: 3.42; 95% CI: 1.62-7.22) were associated with higher 1-year all-cause mortality. CONCLUSIONS: Nocardiosis is a late post-HCT infection usually manifesting as a pulmonary disease with frequent dissemination, brain infection, and bacteremia. Brain imaging should be performed in HCT recipients with nocardiosis regardless of neurological symptoms. Overall mortality is high.

National Monkeypox Surveillance, Central African Republic, 2001-2021.

We analyzed monkeypox disease surveillance in Central African Republic (CAR) during 2001-2021. Surveillance data show 95 suspected outbreaks, 40 of which were confirmed as monkeypox, comprising 99 confirmed and 61 suspected monkeypox cases. After 2018, CAR's annual rate of confirmed outbreaks increased, and 65% of outbreaks occurred in 2 forested regions bordering the Democratic Republic of the Congo. The median patient age for confirmed cases was 15.5 years. The overall case-fatality ratio was 7.5% (12/160) for confirmed and suspected cases, 9.6% (8/83) for children <16 years of age. Decreasing cross-protective immunity from smallpox vaccination and recent ecologic alterations likely contribute to increased monkeypox outbreaks in Central Africa. High fatality rates associated with monkeypox virus clade I also are a local and international concern. Ongoing investigations of zoonotic sources and environmental changes that increase human exposure could inform practices to prevent monkeypox expansion into local communities and beyond endemic areas.

Epidemiology and control of SARS-CoV-2 epidemics in partially vaccinated populations: a modeling study applied to France.

BACKGROUND: Vaccination is expected to change the epidemiology and management of SARS-CoV-2 epidemics. METHODS: We used an age-stratified compartmental model calibrated to French data to anticipate these changes and determine implications for the control of an autumn epidemic. We assumed vaccines reduce the risk of hospitalization, infection, and transmission if infected by 95%, 60%, and 50%, respectively. RESULTS: In our baseline scenario characterized by basic reproduction number R0=5 and a vaccine coverage of 70-80-90% among 12-17, 18-59, and ≥ 60 years old, important stress on healthcare is expected in the absence of measures. Unvaccinated adults ≥60 years old represent 3% of the population but 43% of hospitalizations. Given limited vaccine coverage, children aged 0-17 years old represent a third of infections and are responsible for almost half of transmissions. Unvaccinated individuals have a disproportionate contribution to transmission so that measures targeting them may help maximize epidemic control while minimizing costs for society compared to non-targeted approaches. Of all the interventions considered including repeated testing and non-pharmaceutical measures, vaccination of the unvaccinated is the most effective. CONCLUSIONS: With the Delta variant, vaccinated individuals are well protected against hospitalization but remain at risk of infection and should therefore apply protective behaviors (e.g., mask-wearing). Targeting non-vaccinated individuals may maximize epidemic control while minimizing costs for society. Vaccinating children protects them from the deleterious effects of non-pharmaceutical measures. Control strategies should account for the changing SARS-CoV-2 epidemiology.

Impact of booster vaccination on the control of COVID-19 Delta wave in the context of waning immunity: application to France in the winter 2021/22.

Europe has experienced a large COVID-19 wave caused by the Delta variant in winter 2021/22. Using mathematical models applied to Metropolitan France, we find that boosters administered to ≥ 65, ≥ 50 or ≥ 18 year-olds may reduce the hospitalisation peak by 25%, 36% and 43% respectively, with a delay of 5 months between second and third dose. A 10% reduction in transmission rates might further reduce it by 41%, indicating that even small increases in protective behaviours may be critical to mitigate the wave.

Sex Differences in the Evolution of Neutralizing Antibodies to Severe Acute Respiratory Syndrome Coronavirus 2.

We measured anti-spike (S), nucleoprotein (N), and neutralizing antibodies in sera from 308 healthcare workers with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 and with mild disease, collected at 2 timepoints up to 6 months after symptom onset. At month 1, anti-S and -N antibody levels were higher in male participants aged >50 years and participants with a body mass index (BMI) >25 kg/m2. At months 3-6, anti-S and anti-N antibodies were detected in 99% and 59% of individuals, respectively. Anti-S antibodies and neutralizing antibodies declined faster in men than in women, independent of age and BMI, suggesting an association of sex with evolution of the humoral response.

Kinetics of the Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Response and Serological Estimation of Time Since Infection.

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a complex antibody response that varies by orders of magnitude between individuals and over time. METHODS: We developed a multiplex serological test for measuring antibodies to 5 SARS-CoV-2 antigens and the spike proteins of seasonal coronaviruses. We measured antibody responses in cohorts of hospitalized patients and healthcare workers followed for up to 11 months after symptoms. A mathematical model of antibody kinetics was used to quantify the duration of antibody responses. Antibody response data were used to train algorithms for estimating time since infection. RESULTS: One year after symptoms, we estimate that 36% (95% range, 11%-94%) of anti-Spike immunoglobulin G (IgG) remains, 31% (95% range, 9%-89%) anti-RBD IgG remains, and 7% (1%-31%) of anti-nucleocapsid IgG remains. The multiplex assay classified previous infections into time intervals of 0-3 months, 3-6 months, and 6-12 months. This method was validated using data from a seroprevalence survey in France, demonstrating that historical SARS-CoV-2 transmission can be reconstructed using samples from a single survey. CONCLUSIONS: In addition to diagnosing previous SARS-CoV-2 infection, multiplex serological assays can estimate the time since infection, which can be used to reconstruct past epidemics.

Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas.

BACKGROUND: The risk of congenital neurologic defects related to Zika virus (ZIKV) infection has ranged from 6 to 42% in various reports. The aim of this study was to estimate this risk among pregnant women with symptomatic ZIKV infection in French territories in the Americas. METHODS: From March 2016 through November 2016, we enrolled in this prospective cohort study pregnant women with symptomatic ZIKV infection that was confirmed by polymerase-chain-reaction (PCR) assay. The analysis included all data collected up to April 27, 2017, the date of the last delivery in the cohort. RESULTS: Among the 555 fetuses and infants in the 546 pregnancies included in the analysis, 28 (5.0%) were not carried to term or were stillborn, and 527 were born alive. Neurologic and ocular defects possibly associated with ZIKV infection were seen in 39 fetuses and infants (7.0%; 95% confidence interval, 5.0 to 9.5); of these, 10 were not carried to term because of termination of pregnancy for medical reasons, 1 was stillborn, and 28 were live-born. Microcephaly (defined as head circumference more than 2 SD below the mean for sex and gestational age) was detected in 32 fetuses and infants (5.8%), of whom 9 (1.6%) had severe microcephaly (more than 3 SD below the mean). Neurologic and ocular defects were more common when ZIKV infection occurred during the first trimester (24 of 189 fetuses and infants [12.7%]) than when it occurred during the second trimester (9 of 252 [3.6%]) or third trimester (6 of 114 [5.3%]) (P=0.001). CONCLUSIONS: Among pregnant women with symptomatic, PCR-confirmed ZIKV infection, birth defects possibly associated with ZIKV infection were present in 7% of fetuses and infants. Defects occurred more frequently in fetuses and infants whose mothers had been infected early in pregnancy. Longer-term follow-up of infants is required to assess any manifestations not detected at birth. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT02916732 .).

In utero Zika virus exposure and neurodevelopment at 24 months in toddlers normocephalic at birth: a cohort study.

BACKGROUND: In utero exposure to Zika virus (ZIKV) is known to be associated with birth defects. The impact of in utero ZIKV exposure on neurodevelopmental outcomes in early childhood remains unclear. The objective of this study was to determine the impact of in utero ZIKV exposure on neurodevelopment at 24 months of age among toddlers who were born normocephalic to women who were pregnant during the 2016 ZIKV outbreak in French territories in the Americas. METHODS: We conducted a population-based mother-child cohort study of women whose pregnancies overlapped with the 2016 ZIKV epidemic in Guadeloupe, Martinique, and French Guiana. Infants were included in this analysis if maternal ZIKV infection during pregnancy could be determined, the newborn had a gestational age ≥ 35 weeks, there were no abnormal transfontanelle cerebral ultrasound findings after delivery or no abnormal ultrasound findings on the last ultrasound performed during the third trimester of the mother's pregnancy, there was an absence of microcephaly at birth, and the parent completed the 24-month neurodevelopment assessment of the infant at 24 months (± 1 month) of age. ZIKV exposure of the toddler was determined by evidence of maternal ZIKV infection during pregnancy. Neurodevelopment assessments included the Ages and Stages Questionnaire (ASQ) for five dimensions of general development-communication, gross motor, fine motor, problem solving, and personal-social skills; the Modified Checklist for Autism on Toddlers (M-CHAT) for behavior; and the French MacArthur Inventory Scales (IFDC) for French language acquisition. RESULTS: Between June 2018 and August 2019, 156 toddlers with and 79 toddlers without in utero ZIKV exposure completed neurodevelopment assessments. Twenty-four (15.4%) ZIKV-exposed toddlers and 20 (25.3%) ZIKV-unexposed toddlers had an ASQ result below the reference - 2SD cut-off (P = 0.10) for at least one of the five ASQ dimensions. CONCLUSION: In one of the largest population-based cohorts of in utero ZIKV-exposed, normocephalic newborns to date, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age compared to ZIKV-unexposed toddlers at 24 months of age. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02810210 . Registered 20 June 2016.

Characteristics Associated with Olfactory and Taste Disorders in COVID-19.

INTRODUCTION: Olfactory and taste disorders (OTDs) have been reported in COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the mechanisms of which remain unclear. We conducted a detailed analysis of OTDs as part of 2 seroepidemiological investigations of COVID-19 outbreaks. METHODS: Two retrospective cohort studies were conducted in a high school and primary schools of Northern France following a COVID-19 epidemic in February-March 2020. Students, their relatives, and school staff were included. Anti-SARS-CoV-2 antibodies were identified using a flow-cytometry-based assay detecting anti-S IgG. RESULTS: Among 2,004 participants (median [IQR] age: 31 [11-43] years), 303 (15.2%) tested positive for SARS-CoV-2 antibodies. OTDs were present in 91 (30.0%) and 92 (30.3%) of them, respectively, and had 85.1 and 78.0% positive predictive values for SARS-CoV-2 infection, respectively. In seropositive participants, OTDs were independently associated with an age above 18 years, female gender, fatigue, and headache. CONCLUSION: This study confirms the higher frequency of OTDs in females than males and adults than children. Their high predictive value for the diagnosis of COVID-19 suggests that they should be systematically searched for in patients with respiratory symptoms, fever, or headache. The association of OTDs with headache, not previously reported, suggests that they share a common mechanism, which deserves further investigation.

Prevalence of congenital microcephaly and its risk factors in an area at risk of Zika outbreaks.

BACKGROUND: Prevalence of neonatal microcephaly in populations without Zika-epidemics is sparse. The study aimed to report baseline prevalence of congenital microcephaly and its relationship with prenatal factors in an area at risk of Zika outbreak. METHODS: This study included singletons born after 24 gestational weeks in 2017-2018 at four hospitals in Guangzhou, China. Microcephaly was defined as a head circumference at birth >3SD below the mean for sex and gestational age. Prevalence of microcephaly was estimated by binomial exact method. Multivariable logistic regression was used to examine the associations of microcephaly with prenatal factors. The population attributable fraction (PAF) for associated risk factors was calculated. RESULTS: Of 46,610 live births included, 154 (3.3, 95% CI 2.8-3.9 per 1000 live births) microcephalies were identified. Maternal hepatitis B virus carriers (HBV, OR 1.80, 95% CI 1.05-3.10) and primipara (OR 2.68, 95% CI 1.89-3.81) had higher risk of having a microcephalic baby. Higher prevalence of microcephaly was observed in women who had premature labor (OR 1.98, 95% CI 1.17-3.34) and had a baby with fetal growth restriction (OR 16.38, 95% CI 11.81-22.71). Four identified factors (HBV, primiparity, preterm labor, and fetal growth restriction) contributed to 66.4% of the risk of microcephaly. CONCLUSIONS: The prevalence of microcephaly in Guangzhou was higher than expected. This study identified four prenatal risk factors that, together, contributed to two-thirds of the increased risk of microcephaly. This is the first reported association between maternal HBV carrier status and microcephaly.