Modelling the impact of JNJ-1802, a first-in-class dengue inhibitor blocking the NS3-NS4B interaction, on in-vitro DENV-2 dynamics.

Dengue virus (DENV) is a public health challenge across the tropics and subtropics. Currently, there is no licensed prophylactic or antiviral treatment for dengue. The novel DENV inhibitor JNJ-1802 can significantly reduce viral load in mice and non-human primates. Here, using a mechanistic viral kinetic model calibrated against viral RNA data from experimental in-vitro infection studies, we assess the in-vitro inhibitory effect of JNJ-1802 by characterising infection dynamics of two DENV-2 strains in the absence and presence of different JNJ-1802 concentrations. Viral RNA suppression to below the limit of detection was achieved at concentrations of >1.6 nM, with a median concentration exhibiting 50% of maximal inhibitory effect (IC50) of 1.23x10-02 nM and 1.28x10-02 nM for the DENV-2/RL and DENV-2/16681 strains, respectively. This work provides important insight into the in-vitro inhibitory effect of JNJ-1802 and presents a first step towards a modelling framework to support characterization of viral kinetics and drug effect across different host systems.

A simulation-based method to inform serosurvey design for estimating the force of infection using existing blood samples.

The extent to which dengue virus has been circulating globally and especially in Africa is largely unknown. Testing available blood samples from previous cross-sectional serological surveys offers a convenient strategy to investigate past dengue infections, as such serosurveys provide the ideal data to reconstruct the age-dependent immunity profile of the population and to estimate the average per-capita annual risk of infection: the force of infection (FOI), which is a fundamental measure of transmission intensity. In this study, we present a novel methodological approach to inform the size and age distribution of blood samples to test when samples are acquired from previous surveys. The method was used to inform SERODEN, a dengue seroprevalence survey which is currently being conducted in Ghana among other countries utilizing samples previously collected for a SARS-CoV-2 serosurvey. The method described in this paper can be employed to determine sample sizes and testing strategies for different diseases and transmission settings.

A systematic review of the data, methods and environmental covariates used to map Aedes-borne arbovirus transmission risk.

BACKGROUND: Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. METHODS: We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.). RESULTS: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002-2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. CONCLUSIONS: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping.

Is There an Inflammatory Profile of Perinatal Depression?

PURPOSE OF REVIEW: To synthesize and critically examine recent evidence regarding associations between immune system activity and perinatal depression. RECENT FINDINGS: Despite a significant number of studies assessing potential immunological markers of perinatal depression, it does not appear that levels of any individual pro- or anti-inflammatory marker is a useful predictor of perinatal depression. Some recent studies have observed differences in overall immune system functioning and adaptation across this period, taking into account multiple pro- and anti- inflammatory markers. Furthermore, there is evidence for interactions between depression and maternal psychosocial factors. Immune system functioning may be a mechanism through which social determinants of health contribute to risk for perinatal depression. There is substantial evidence implicating dysregulated immune activity in perinatal depression, yet little clarity regarding a consistent immune profile, especially based on analysis of circulating peripheral cytokines.

Pregnant women with bipolar disorder who have a history of childhood maltreatment: Intergenerational effects of trauma on fetal neurodevelopment and birth outcomes.

OBJECTIVES: Intergenerational transmission of trauma occurs when the effects of childhood maltreatment (CM) influence the next generation's development and health; prenatal programming via maternal mood symptoms is a potential pathway. CM is a risk factor for bipolar disorder which is present in 1.8% of pregnant women. Mood symptoms are likely to increase during pregnancy, particularly for those with a history of CM. We examined whether there was evidence for intergenerational transmission of trauma in utero in this population, and whether maternal mood was a transmission pathway. METHODS: CM and maternal mood were self-reported by N = 82 pregnant women in treatment for bipolar disorder. Fetal heart rate variability (FHRV) was measured at 24, 30, and 36 weeks' gestation. Gestational age at birth and birth weight were obtained from medical charts. RESULTS: A cluster analysis yielded two groups, Symptom+ (18.29%) and Euthymic (81.71%), who differed on severe mood symptoms (p < 0.001) but not on medication use. The Symptom+ group had more CM exposures (p < 0.001), a trend of lower FHRV (p = 0.077), and greater birth complications (33.3% vs. 6.07% born preterm p < 0.01). Maternal prenatal mood mediated the association between maternal CM and birth weight in both sexes and at trend level for gestational age at birth in females. CONCLUSIONS: This is the first study to identify intergenerational effects of maternal CM prior to postnatal influences in a sample of pregnant women with bipolar disorder. These findings underscore the potential enduring impact of CM for women with severe psychiatric illness and their children.

The impact of the COVID-19 pandemic on the mental health of healthcare workers: study protocol for the COVID-19 HEalth caRe wOrkErS (HEROES) study.

BACKGROUND: Preliminary country-specific reports suggest that the COVID-19 pandemic has a negative impact on the mental health of the healthcare workforce. In this paper, we summarize the protocol of the COVID-19 HEalth caRe wOrkErS (HEROES) study, an ongoing, global initiative, aimed to describe and track longitudinal trajectories of mental health symptoms and disorders among health care workers at different phases of the pandemic across a wide range of countries in Latin America, Europe, Africa, Middle-East, and Asia. METHODS: Participants from various settings, including primary care clinics, hospitals, nursing homes, and mental health facilities, are being enrolled. In 26 countries, we are using a similar study design with harmonized measures to capture data on COVID-19 related exposures and variables of interest during two years of follow-up. Exposures include potential stressors related to working in healthcare during the COVID-19 pandemic, as well as sociodemographic and clinical factors. Primary outcomes of interest include mental health variables such as psychological distress, depressive symptoms, and posttraumatic stress disorders. Other domains of interest include potentially mediating or moderating influences such as workplace conditions, trust in the government, and the country's income level. RESULTS: As of August 2021, ~ 34,000 health workers have been recruited. A general characterization of the recruited samples by sociodemographic and workplace variables is presented. Most participating countries have identified several health facilities where they can identify denominators and attain acceptable response rates. Of the 26 countries, 22 are collecting data and 2 plan to start shortly. CONCLUSIONS: This is one of the most extensive global studies on the mental health of healthcare workers during the COVID-19 pandemic, including a variety of countries with diverse economic realities and different levels of severity of pandemic and management. Moreover, unlike most previous studies, we included workers (clinical and non-clinical staff) in a wide range of settings.

Evidence for cognitive plasticity during pregnancy via enhanced learning and memory.

Human and animal neuroscience studies support the view that plastic shifts occur in the brain during pregnancy that support the emergence of new maternal behaviours. The idea of adaptive plasticity in pregnancy is at odds with the notion of "baby brain", in which pregnant women describe the onset of forgetfulness. While inconsistent evidence for memory deficits during pregnancy has been reported, few studies have investigated spatial associative memory (which is consistently enhanced in studies of pregnant rodents). Moreover, most studies assess domain-general stimuli, which might miss adaptations specific to parent-relevant stimuli. In the present study, we examined the retention of spatial associative memory for parenting-relevant and non-parenting-relevant stimuli across 4-weeks in a sample of women in their third trimester of pregnancy, and compared their performance to a sample of never pregnant women. We demonstrated that relative to never pregnant women, pregnant women exhibited enhanced long-term retention of object-scene-location associations (spatial associative memory), as well as better initial learning about parenting-relevant, relative to non-parenting-relevant, stimuli. Thus, similar to studies in rodents, cognitive improvements were seen during pregnancy in humans, and those improvements were specific to the domain of spatial associative retention, and in the recognition of stimuli relevant to parenting.

Maternal prenatal stress phenotypes associate with fetal neurodevelopment and birth outcomes.

Maternal prenatal stress influences offspring neurodevelopment and birth outcomes including the ratio of males to females born; however, there is limited understanding of what types of stress matter, and for whom. Using a data-driven approach with 27 variables from questionnaires, ambulatory diaries, and physical assessments collected early in the singleton pregnancies of 187 women, 3 latent profiles of maternal prenatal stress emerged that were differentially associated with sex at birth, birth outcomes, and fetal neurodevelopment. Most women (66.8%) were in the healthy group (HG); 17.1% were in the psychologically stressed group (PSYG), evidencing clinically meaningful elevations in perceived stress, depression, and anxiety; and 16% were in the physically stressed group (PHSG) with relatively higher ambulatory blood pressure and increased caloric intake. The population normative male:female secondary sex ratio (105:100) was lower in the PSYG (2:3) and PHSG (4:9), and higher in the HG (23:18), consistent with research showing diminished male births in maternal stress contexts. PHSG versus HG infants were born 1.5 wk earlier (P < 0.05) with 22% compared to 5% born preterm. PHSG versus HG fetuses had decreased fetal heart rate-movement coupling (P < 0.05), which may indicate slower central nervous system development, and PSYG versus PHSG fetuses had more birth complications, consistent with previous findings among offspring of women with psychiatric illness. Social support most strongly differentiated the HG, PSYG, and PHSG groups, and higher social support was associated with increased odds of male versus female births. Stress phenotypes in pregnant women are associated with male vulnerability and poor fetal outcomes.

Following up internet-delivered cognitive behaviour therapy (CBT): A longitudinal qualitative investigation of clients' usage of CBT skills.

BACKGROUND: While the acquisition and application of Cognitive Behaviour Therapy (CBT) skills is a core component and likely mechanism of effect maintenance in all CBT-based treatments, the extent of post-therapeutic CBT skills usage among internet-delivered CBT (iCBT) clients remains under-researched. METHOD: Nested within a pragmatic randomized controlled trial, 241 participants received an 8-week supported iCBT intervention for anxiety and/or depression and answered open-ended questions about their use and experience of CBT skills at 3-, 6-, 9-, and 12-month follow-up. Recurrent, cross-sectional qualitative analysis following the descriptive and interpretive approach was used to create a taxonomy, through which all qualitative data was coded. RESULTS: In total, 479 qualitative responses across 181 participants were analysed. Participants reported using a wide range of CBT skills and associated helpful and hindering experiences and impacts. The reasons for discontinued CBT skills usage were diverse, ranging from rare adverse effects to healthy adaptation. CONCLUSION: The study shows how clients receiving iCBT in routine care learn CBT skills during treatment and utilize them in productive ways post-treatment. Findings coincide with similar research in face-to-face CBT and may inform future research to drive innovation and iCBT intervention development.

Maternal childhood adversity and inflammation during pregnancy: Interactions with diet quality and depressive symptoms.

Inflammatory processes are a candidate mechanism by which early adversity may be biologically embedded and subsequently lead to poorer health outcomes; in pregnancy, this has been posited as a pathway for intergenerational transmission of adversity. Studies in non-pregnant adults suggest that factors such as mood, diet, BMI, and social support may moderate associations between childhood trauma history and inflammation in adulthood, though few studies have examined these associations among pregnant women. In a sample of healthy pregnant women (N = 187), we analyzed associations between maternal childhood adversity, including maltreatment and non-optimal caregiving experiences, with circulating Interleukin-6 (IL-6) levels during trimesters 2 (T2) and 3 (T3) of pregnancy. We also assessed whether these associations were moderated by psychosocial and lifestyle factors including depressive symptoms, social support, physical activity, and diet quality. History of childhood maltreatment was not associated with IL-6 in either T2 or T3 of pregnancy, either independently or in interaction with depressive symptom severity. However, in there was a significant positive association between childhood maltreatment and IL-6 in Trimester 2 in the context of poorer diet quality (p = 0.01), even after adjusting for BMI. Additionally, the quality of caregiving women received in childhood was associated with levels of IL-6 in Trimester 3, but only via interaction with concurrent depressive symptoms (p = 0.02). These findings provide evidence that for those with a history of childhood adversity, levels of inflammatory cytokines in pregnancy may be more sensitive to depressive symptoms and diet quality.

Added sugar intake during pregnancy: Fetal behavior, birth outcomes, and placental DNA methylation.

Pregnancy is a critical time for the effects of environmental factors on children's development. The effect of added sugar intake on fetal development and pregnancy outcomes remains understudied despite increasing dietary intake in the United States. This study investigated the effect of added sugar on fetal programming by examining the association between maternal added sugar consumption, fetal movement, birth outcomes, and placental DNA methylation. Further, primary human fibroblasts were cultured under normal or high glucose conditions to assess the effect of high glucose exposure on cells' DNA methylation. We found that higher added sugar intake across pregnancy was associated with reduced 3rd-trimester fetal movement (p < .05) and shorter gestation (p < .01). Our sample size was not powered to detect the alteration of individual placental CpG with genome-wide significance. However, a secondary analysis suggested that added sugar consumption was associated with differential methylation of functionally related gene families across pregnancy. Consistent with this, high glucose exposure in primary cultured human fibroblasts altered the methylation of 17% of all CpGs, providing converging evidence for an effect of sugar on DNA methylation. Our results suggest that diets high in added sugar during pregnancy may have implications for offspring health via prenatal programming effects measurable before birth.

Prenatal alcohol exposure and infant gross motor development: a prospective cohort study.

BACKGROUND: Maternal alcohol consumption in pregnancy may have adverse effects on child gross motor (GM) development. There have been few human studies on this topic, particularly ones examining low exposure. This study examined the association between prenatal alcohol exposure (PAE) and infant GM development at 12-months of age. METHODS: Participants were 1324 women recruited from antenatal clinics in Sydney and Perth, Australia. Maternal and paternal alcohol use was assessed in pregnancy via interview; offspring GM development was measured at 12-months with the Bayley Scales of Infant Development (BSID-III). RESULTS: Any alcohol use in pregnancy was common: 56.1%, of pregnant women drank early in Trimester one (0-6 weeks), however this reduced to 27.9% on average thereafter and at predominantly low levels. However, infant BSID GM scale scores were not found to differ significantly as a function of PAE in the first 6-weeks (low, moderate, binge or heavy PAE), nor with low PAE across pregnancy. CONCLUSIONS: We found no evidence to suggest that low PAE is associated with measurable impairment in infant GM development at 12-months. Further research is needed to examine potential PAE impacts on GM development in heavier exposure groups and through the childhood years when subtle GM deficits may be more detectable.

Correction to: Prenatal alcohol exposure and infant gross motor development: a prospective cohort study.

Following publication of the original article [1], the authors opted to revise the first paragraph of the section "Characteristics associated with maternal drinking in pregnancy". Below is the updated version.

Parental perceptions of prenatal whole exome sequencing (PPPWES) study.

OBJECTIVE: The objective of the study is to investigate the experiences of couples who underwent prenatal whole-exome sequencing (WES) for fetal anomalies and the amount/type of information couples want from prenatal WES. METHOD: Participants in the Fetal Sequencing Study who had genetic testing for fetal anomalies were invited for a semistructured interview about their experience with prenatal WES. A constructivist grounded theory approach with an inductive coding style was used for coding and analysis. RESULTS: We interviewed 29 participants from 17 pregnancies. Two pregnancies had positive prenatal WES results, and 4 were terminated prior to receipt of WES results. The main themes were anxiety and stress around the time of diagnosis, education and consent for WES, coping and support while waiting for results, and receiving genetic testing results. In response to hypothetical scenarios probing the desire for uncertain results, 86% would like to be told about results for which the provider had some degree of uncertainty, and the percent desiring results decreased as the certainty of the results decreased. CONCLUSION: Participants' experience with exome sequence was similar to other prenatal genetic diagnostic tests, except for the longer wait time for results. When probed with hypothetical scenarios, participants desired more results than were provided in the study, including uncertain results that might diagnose the fetal condition. This highlights the need for specialized prenatal genetic counseling to have nuanced discussions of multiple dimensions of uncertainty with implementation of prenatal WES.

Prenatal Alcohol Consumption Between Conception and Recognition of Pregnancy.

BACKGROUND: Current estimates of the rates of alcohol-exposed pregnancies may underestimate prenatal alcohol exposure if alcohol consumption in early trimester 1, prior to awareness of pregnancy, is not considered. Extant literature describes predictors of alcohol consumption during pregnancy; however, alcohol consumption prior to awareness of pregnancy is a distinct behavior from consumption after becoming aware of pregnancy and thus may be associated with different predictors. The purpose of this study was therefore to examine prevalence and predictors of alcohol consumption by women prior to awareness of their pregnancy, and trajectories of change to alcohol use following pregnancy recognition. METHODS: Pregnant women (n = 1,403) were prospectively recruited from general antenatal clinics of 4 public hospitals in Australian metropolitan areas between 2008 and 2013. Women completed detailed interviews about alcohol use before and after recognition of pregnancy. RESULTS: Most women (n = 850, 60.6%) drank alcohol between conception and pregnancy recognition. Binge and heavy drinking were more prevalent than low-level drinking. The proportion of women who drank alcohol reduced to 18.3% (n = 257) after recognition of pregnancy. Of women who drank alcohol, 70.5% ceased drinking, 18.3% reduced consumption, and 11.1% made no reduction following awareness of pregnancy. Socioeconomic status (SES) was the strongest predictor of alcohol use, with drinkers more likely to be of high rather than low SES compared with abstainers (OR = 3.30, p < 0.001). Factors associated with different trajectories (either cessation, reduction, or continuation of drinking) included level of alcohol use prior to pregnancy recognition, age, pregnancy planning, and illicit substance use. CONCLUSIONS: In this sample of relatively high SES women, most women ceased or reduced drinking once aware of their pregnancy. However, the rate of alcohol-exposed pregnancies was higher than previous estimates when the period prior to pregnancy recognition was taken into account.

A scoping literature review of global dengue age-stratified seroprevalence data: estimating dengue force of infection in endemic countries.

BACKGROUND: Dengue poses a significant burden worldwide, and a more comprehensive understanding of the heterogeneity in the intensity of dengue transmission within endemic countries is necessary to evaluate the potential impact of public health interventions. METHODS: This scoping literature review aimed to update a previous study of dengue transmission intensity by collating global age-stratified dengue seroprevalence data published in the Medline, Embase and Web of Science databases from 2014 to 2023. These data were then utilised to calibrate catalytic models and estimate the force of infection (FOI), which is the yearly per-capita risk of infection for a typical susceptible individual. FINDINGS: We found a total of 66 new publications containing 219 age-stratified seroprevalence datasets across 30 endemic countries. Together with the previously available average FOI estimates, there are now more than 250 dengue average FOI estimates obtained from seroprevalence studies from across the world. INTERPRETATION: The results show large heterogeneities in average dengue FOI both across and within countries. These new estimates can be used to inform ongoing modelling efforts to improve our understanding of the drivers of the heterogeneity in dengue transmission globally, which in turn can help inform the optimal implementation of public health interventions. FUNDING: UK Medical Research Council, Wellcome Trust, Community Jameel, Drugs for Neglected Disease initiative (DNDi) funded by the French Development Agency, Médecins Sans Frontières International; Swiss Agency for Development and Cooperation and UK aid.

Maternal childhood trauma and observed maternal care behaviors with 4-month-old infants.

OBJECTIVE: To examine the relationship between maternal childhood trauma and early maternal caregiving behaviors (MCB). METHOD: Participants included 74 mother-infant dyads (maternal age 20-45 years; ethnicity 64.9% Latina) from a longitudinal pregnancy cohort study. Maternal childhood trauma was assessed during pregnancy with the childhood trauma questionnaire (CTQ). Observed mother-infant interactions at infant age 4 months were coded utilizing modified Ainsworth's MCB rating scales that assessed a range of behaviors (e.g., acceptance, soothing, and delight) which we analyze grouped together and will summarize using the term "maternal sensitivity." Linear regressions tested the associations between maternal childhood trauma and MCB. Primary analyses examined the relationships of MCB with (a) any maternal childhood trauma (moderate or greater exposure to physical abuse, sexual abuse, emotional abuse, physical neglect, and/or emotional neglect) and (b) cumulative childhood trauma. Secondary analyses examined the relationships between each type of childhood trauma and MCB. RESULTS: Exposure to childhood trauma was not associated with MCB (p = .88). Cumulative childhood trauma score was associated with lower scores on MCB (ß = -1.88, p < .05). Emotional abuse and emotional neglect were individually associated with lower scores on MCB (ß = -1.78, p = .04; ß = -1.55, p = .04, respectively). Physical abuse, sexual abuse, and physical neglect were not associated with MCB. CONCLUSIONS: Many mothers exposed to childhood trauma may be resilient to negative effects on parenting behaviors, while specific experiences of childhood trauma (emotional abuse, emotional neglect, and cumulative childhood trauma) may predict less sensitive early parenting behaviors. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Motherhood and Drinking: The Relative Importance of Mental Health and Psychosocial Factors on Maternal Alcohol Misuse During the Postpartum Period.

OBJECTIVE: Being a mother of a young child may be protective against alcohol misuse for some, but not all, women. This is the first study to identify the mental health and psychosocial correlates of alcohol misuse among postpartum mothers. METHOD: Mothers with a child younger than 12 months (n = 319) were recruited via social media to complete a cross-sectional online survey. Two hierarchical logistic regressions examined unique factors associated with heavy episodic drinking and hazardous alcohol use, including sociodemographic, poor mental health, and psychosocial factors. RESULTS: On average, mothers drank alcohol at low levels (4 drinking days, nine standard drinks in the past month). One in 10 (11.6%) reported heavy episodic drinking during this time, and 1 in 12 (8.5%) were drinking at hazardous or greater levels. In the final models, older age and more severe postpartum anxiety were associated with a higher likelihood of hazardous drinking (odds ratio [OR] = 1.37, 1.09, respectively), whereas breastfeeding was associated with lower odds of heavy episodic drinking (OR = 0.29). Greater perceived social support was associated with lower odds of heavy episodic (OR = 0.56) and hazardous (OR = 0.39) drinking, whereas higher coping-with-anxiety and social-drinking motives were associated with greater odds of both forms of alcohol misuse (ORs = 3.51-10.40). Conformity drinking motives (e.g., drinking to avoid social rejection) were negatively associated with heavy episodic drinking (OR = 0.24). CONCLUSIONS: Maternal anxiety, coping-with-anxiety and social-drinking motives, and reduced social support are important factors associated with postpartum alcohol misuse. These modifiable factors are potential targets for screening and intervention for mothers who may need additional support and preventative care.

Inequality on the frontline: A multi-country study on gender differences in mental health among healthcare workers during the COVID-19 pandemic.

Healthcare workers (HCWs) were at increased risk for mental health problems during the COVID-19 pandemic, with prior data suggesting women may be particularly vulnerable. Our global mental health study aimed to examine factors associated with gender differences in psychological distress and depressive symptoms among HCWs during COVID-19. Across 22 countries in South America, Europe, Asia and Africa, 32,410 HCWs participated in the COVID-19 HEalth caRe wOrkErS (HEROES) study between March 2020 and February 2021. They completed the General Health Questionnaire-12, the Patient Health Questionnaire-9 and questions about pandemic-relevant exposures. Consistently across countries, women reported elevated mental health problems compared to men. Women also reported increased COVID-19-relevant stressors, including insufficient personal protective equipment and less support from colleagues, while men reported increased contact with COVID-19 patients. At the country level, HCWs in countries with higher gender inequality reported less mental health problems. Higher COVID-19 mortality rates were associated with increased psychological distress merely among women. Our findings suggest that among HCWs, women may have been disproportionately exposed to COVID-19-relevant stressors at the individual and country level. This highlights the importance of considering gender in emergency response efforts to safeguard women's well-being and ensure healthcare system preparedness during future public health crises.

Modelling the viral dynamics of the SARS-CoV-2 Delta and Omicron variants in different cell types.

We use viral kinetic models fitted to viral load data from in vitro studies to explain why the SARS-CoV-2 Omicron variant replicates faster than the Delta variant in nasal cells, but slower than Delta in lung cells, which could explain Omicron's higher transmission potential and lower severity. We find that in both nasal and lung cells, viral infectivity is higher for Omicron but the virus production rate is higher for Delta, with an estimated approximately 200-fold increase in infectivity and 100-fold decrease in virus production when comparing Omicron with Delta in nasal cells. However, the differences are unequal between cell types, and ultimately lead to the basic reproduction number and growth rate being higher for Omicron in nasal cells, and higher for Delta in lung cells. In nasal cells, Omicron alone can enter via a TMPRSS2-independent pathway, but it is primarily increased efficiency of TMPRSS2-dependent entry which accounts for Omicron's increased activity. This work paves the way for using within-host mathematical models to understand the transmission potential and severity of future variants.