Effectiveness of BNT162b2 COVID-19 Vaccination in Children Aged 5-17 Years in the United States (preprint)

Importance: COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. Objective: To estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children. Design: A cohort study of children aged 5--17 years vaccinated with BNT162b2 matched with unvaccinated children. Setting: Participants identified in Optum and CVS Health insurance administrative claims databases were linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Participants: Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Exposure: BNT162b2 vaccinations were identified using IIS vaccination records and insurance claims. Main Outcomes and Measures: Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. Results: There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person- years; CVS Health, 44.1 per 10,000 person- years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36%-40%]) and hospital/ED-diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56%-65%]). VE estimates were lowest among children 5--11 years and during the omicron variant era. Conclusions and Relevance: Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED-diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era.

Profiling post-COVID syndrome across different variants of SARS-CoV-2 (preprint)

Background: Self-reported symptom studies rapidly increased our understanding of SARS-CoV-2 during the pandemic and enabled the monitoring of long-term effects of COVID-19 outside the hospital setting. It is now evident that post-COVID syndrome presents with heterogeneous profiles, which need characterisation to enable personalised care among the most affected survivors. This study describes post-COVID profiles, and how they relate to different viral variants and vaccination status. Methods: In this prospective longitudinal cohort study, we analysed data from 336,652 subjects, with regular health reports through the Covid Symptom Study (CSS) smartphone application. These subjects had reported feeling physically normal for at least 30 days before testing positive for SARS-CoV-2. 9,323 individuals subsequently developed Long-COVID, defined as symptoms lasting longer than 28 days. 1,459 had post-COVID syndrome, defined as more than 12 weeks of symptoms. Clustering analysis of the time-series data was performed to identify distinct symptom profiles for post-COVID patients, across variants of SARS-CoV-2 and vaccination status at the time of infection. Clusters were then characterised based on symptom prevalence, duration, demography, and prior conditions (comorbidities). Using an independent testing sample with additional data (n=140), we investigated the impact of post-COVID symptom clusters on the lives of affected individuals. Findings: We identified distinct profiles of symptoms for post-COVID syndrome within and across variants: four endotypes were identified for infections due to the wild-type variant; seven for the alpha variant; and five for delta. Across all variants, a cardiorespiratory cluster of symptoms was identified. A second cluster related to central neurological, and a third to cases with the most severe and debilitating multi-organ symptoms. Gastrointestinal symptoms clustered in no more than two specific phenotypes per viral variant. The three main clusters were confirmed in an independent testing sample, and their functional impact was assessed. Interpretation: Unsupervised analysis identified different post-COVID profiles, characterised by differing symptom combinations, durations, and functional outcomes. Phenotypes were at least partially concordant with individuals reported experiences. Our classification may be useful to understand distinct mechanisms of the post-COVID syndrome, as well as subgroups of individuals at risk of prolonged debilitation. Funding: UK Government Department of Health and Social Care, Chronic Disease Research Foundation, The Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value-Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation and Alzheimers Society, and ZOE Limited, UK.

Vaccination against SARS-CoV-2 in UK school-aged children and young people decreases infection rates and reduces COVID-19 symptoms (preprint)

Background We aim to explore the effectiveness of one-dose BNT162b2 vaccination upon SARS-CoV-2 infection rates in children and young people (CYP) during Delta and Omicron variant predominance in the UK, and study its effect on COVID-19 presentation and post-vaccination symptoms. Methods In this prospective longitudinal cohort study, we analysed data from 115,775 CYP aged 12-17 years, proxy-reported through the Covid Symptom Study (CSS) smartphone application. We calculated post-vaccination infection risk after one dose of BNT162b2. We described the illness profile of CYP with post-vaccination SARS-CoV-2 infection, compared to unvaccinated CYP. Findings Between August 5, 2021 and February 14, 2022, 25,971 UK CYP aged 12-17 years received one dose of BNT162b2 vaccine. Vaccination reduced infection (reporting) risk (-80.4% and -53.7% at 14-30 days with Delta and Omicron variants respectively, and -61.5% and -63.7% after 61-90 days). The probability of remaining infection-free diverged after vaccination, and was more robust with prior infection. Vaccinated CYP who contracted SARS-CoV-2 during the Delta period had milder disease than unvaccinated CYP; however, during the Omicron period this was only evident in children aged 12-15 years, and overall disease profile was similar in both vaccinated and unvaccinated CYP. Post-vaccination local side-effects were common, systemic side-effects were uncommon, and both resolved quickly. Interpretation One dose of BNT162b2 vaccine reduced risk of SARS-CoV-2 infection for at least 90 days in CYP aged 12-17 years. Vaccine protection was modulated by SARS-CoV-2 variant type (lower for Omicron than Delta variant), and was enhanced by pre-vaccination SARS-CoV-2 infection. Severity of COVID-19 presentation after vaccination is generally milder, although unvaccinated CYP also have an uncomplicated course. Overall, vaccination was well-tolerated.

COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: two prospective observational cohort studies (preprint)

Background The Delta (B.1.617.2) variant became the predominant UK circulating SARS-CoV-2 strain in May 2021. How Delta infection compares with previous variants is unknown. Methods This prospective observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period. Findings 3,581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta vs. Alpha infection (including fever, sore throat and headache) and vice versa (dyspnoea). Symptom burden in the first week was higher with Delta vs. Alpha infection; however, the odds of any given symptom lasting [≥]7 days was either lower or unchanged. Illness duration [≥]28 days was lower with Delta vs. Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1.47) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly (69-84%) reduced risk of Delta infection. Interpretation COVID-19 from Delta or Alpha infections is clinically similar. The Delta variant is more transmissible than Alpha; however, current vaccines show good efficacy against disease. Funding UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, Alzheimer's Society, and ZOE Limited.

Illness characteristics of COVID-19 in children infected with the SARS-CoV-2 Delta variant (preprint)

Background The Delta (B.1.617.2) SARSCoV2 variant became the predominant UK circulating strain in May 2021. Whether COVID19 from Delta infection differs to infection with other variants in children is unknown. Methods Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between December 28, 2020 and July 8, 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the main UK circulating variant); and May 26 to July 8, 2021 (Delta the main UK circulating variant). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (>28 day) illness; and calculated odds ratios for symptoms presenting within the first 28 days of illness. Findings 694 (276 younger [5 11 years], 418 older [12 17 years]) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2 9.75) with Alpha, 5 days (IQR 2 9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2 5) with Alpha, 4 (IQR 2 7) with Delta; in older children 5 (IQR 3 8) with Alpha and 6 (IQR 3 9) with Delta infection in older children). The odds of several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. Interpretation COVID-19 in UK school-aged children due to SARSCoV2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden.

Incidence and Outcomes of COVID-19 in People With CKD: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: Coronavirus disease 2019 (COVID-19) disproportionately affects people with chronic diseases such as chronic kidney disease (CKD). We assessed the incidence and outcomes of COVID-19 in people with CKD. STUDY DESIGN: Systematic review and meta-analysis by searching MEDLINE, EMBASE, and PubMed through February 2021. SETTING & STUDY POPULATIONS: People with CKD with or without COVID-19. SELECTION CRITERIA FOR STUDIES: Cohort and case-control studies. DATA EXTRACTION: Incidences of COVID-19, death, respiratory failure, dyspnea, recovery, intensive care admission, hospital admission, need for supplemental oxygen, hospital discharge, sepsis, short-term dialysis, acute kidney injury, and fatigue. ANALYTICAL APPROACH: Random-effects meta-analysis and evidence certainty adjudicated using an adapted version of GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: 348 studies (382,407 participants with COVID-19 and CKD; 1,139,979 total participants with CKD) were included. Based on low-certainty evidence, the incidence of COVID-19 was higher in people with CKD treated with dialysis (105 per 10,000 person-weeks; 95% CI, 91-120; 95% prediction interval [PrI], 25-235; 59 studies; 468,233 participants) than in those with CKD not requiring kidney replacement therapy (16 per 10,000 person-weeks; 95% CI, 4-33; 95% PrI, 0-92; 5 studies; 70,683 participants) or in kidney or pancreas/kidney transplant recipients (23 per 10,000 person-weeks; 95% CI, 18-30; 95% PrI, 2-67; 29 studies; 120,281 participants). Based on low-certainty evidence, the incidence of death in people with CKD and COVID-19 was 32 per 1,000 person-weeks (95% CI, 30-35; 95% PrI, 4-81; 229 studies; 70,922 participants), which may be higher than in people with CKD without COVID-19 (incidence rate ratio, 10.26; 95% CI, 6.78-15.53; 95% PrI, 2.62-40.15; 4 studies; 18,347 participants). LIMITATIONS: Analyses were generally based on low-certainty evidence. Few studies reported outcomes in people with CKD without COVID-19 to calculate the excess risk attributable to COVID-19, and potential confounders were not adjusted for in most studies. CONCLUSIONS: The incidence of COVID-19 may be higher in people receiving maintenance dialysis than in those with CKD not requiring kidney replacement therapy or those who are kidney or pancreas/kidney transplant recipients. People with CKD and COVID-19 may have a higher incidence of death than people with CKD without COVID-19.

Disentangling post-vaccination symptoms from early COVID-19 (preprint)

Background Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app. Design We conducted a prospective observational study in UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (other than local symptoms at injection site) and were tested for SARS-CoV-2, aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were also recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models including UK testing criteria. Findings Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. A majority of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue). Interpretation Post-vaccination side-effects per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2, to prevent community spread. Funding Zoe Limited, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK National Institute for Health Research, UK Medical Research Council and British Heart Foundation, Alzheimer’s Society, Chronic Disease Research Foundation, Massachusetts Consortium on Pathogen Readiness (MassCPR). Research in context Evidence before this study There are now multiple surveillance platforms internationally interrogating COVID-19 and/or post-vaccination side-effects. We designed a study to examine for differences between vaccination side-effects and early symptoms of COVID-19. We searched PubMed for peer-reviewed articles published between 1 January 2020 and 21 June 2021, using keywords: “COVID-19” AND “Vaccination” AND (“mobile application” OR “web tool” OR “digital survey” OR “early detection” OR “Self-reported symptoms” OR “side-effects”). Of 185 results, 25 studies attempted to differentiate symptoms of COVID-19 vs. post-vaccination side-effects; however, none used artificial intelligence (AI) technologies (“machine learning”) coupled with real-time data collection that also included comprehensive and systematic symptom assessment. Additionally, none of these studies attempt to discriminate the early signs of infection from side-effects of vaccination (specifically here: Pfizer-BioNTech mRNA vaccine (BNT162b2) and Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19)). Further, none of these studies sought to provide comparisons with current testing criteria used by healthcare services. Added value of this study This study, in a uniquely large community-based cohort, uses prospective data capture in a novel effort to identify individuals with COVID-19 in the immediate post-vaccination period. Our results show that early symptoms of SARS-CoV-2 cannot be differentiated from vaccination side-effects robustly. Thus, post-vaccination systemic symptoms should not be ignored, and testing should be considered to prevent COVID-19 dissemination by vaccinated individuals. Implications of all the available evidence Our study demonstrates the critical importance of testing symptomatic individuals - even if vaccinated – to ensure early detection of SARS-CoV-2 infection, helping to prevent future pandemic waves in the UK and elsewhere.

Anxiety and depression symptoms after COVID-19 infection: results from the COVID Symptom Study app (preprint)

Background: Mental health issues have been reported after SARS-CoV-2 infection. However, comparison to prevalence in uninfected individuals and contribution from common risk factors (e.g., obesity, comorbidities) have not been examined. We identified how COVID-19 relates to mental health in the large community-based COVID Symptom Study. Methods: We assessed anxiety and depression symptoms using two validated questionnaires in 413,148 individuals between February and April 2021; 26,998 had tested positive for SARS-CoV-2. We adjusted for physical and mental pre-pandemic comorbidities, BMI, age, and sex. Findings: Overall, 26.4% of participants met screening criteria for general anxiety and depression. Anxiety and depression were slightly more prevalent in previously SARS-CoV-2 positive (30.4%) vs. negative (26.1%) individuals. This association was small compared to the effect of an unhealthy BMI and the presence of other comorbidities, and not evident in younger participants ([≤]40 years). Findings were robust to multiple sensitivity analyses. Association between SARS-CoV-2 infection and anxiety and depression was stronger in individuals with recent (<30 days) vs. more distant (>120 days) infection, suggesting a short-term effect. Interpretation: A small association was identified between SARS-CoV-2 infection and anxiety and depression symptoms. The proportion meeting criteria for self-reported anxiety and depression disorders is only slightly higher than pre-pandemic.

Illness duration and symptom profile in a large cohort of symptomatic UK school-aged children tested for SARS-CoV-2 (preprint)

Background In children, SARS-CoV-2 is usually asymptomatic or causes a mild illness of short duration. Persistent illness has been reported; however, its prevalence and characteristics are unclear. We aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, the largest citizen participatory epidemiological study to date. Methods Data from 258,790 children aged 5-17 years were reported by an adult proxy between 24 March 2020 and 22 February 2021. Illness duration and symptom profiles were analysed for all children testing positive for SARS-CoV-2 for whom illness duration could be determined, considered overall and within younger (5-11 years) and older (12-17 years) age groups. Data from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessed. Findings 1,734 children (588 younger children, 1,146 older children) had a positive SARS-CoV-2 test result and calculable duration of illness with the study time frame. The commonest symptoms were headache (62.2%) and fatigue (55.0%). Median illness duration was six days (vs. three days in children testing negative); and was positively associated with age (rs 0.19, p<1.e-4) with median duration seven days in older vs. five days in younger children. Seventy-seven (4.4%) children had illness duration =>28 days (LC28); LC28 was more common in older compared with younger children (59 (5.1%) vs. 18 (3.1%), p=0.046). The commonest symptoms experienced by children with LC28 were fatigue (84.4%), headache and anosmia (both 77.9%); however, by day 28 the median symptom burden was two. Only 25 (1.8%) of 1,379 children experienced symptoms for [≥]56 days. Few children (15 children, 0.9%) in the negatively-tested cohort experienced prolonged symptom duration; however, these children experienced greater symptom burden (both throughout their illness and at day 28) than children positive for SARS-CoV-2. Interpretation Some children with COVID-19 experience prolonged illness duration; reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. Thus, a holistic approach for all children with persistent illness during the pandemic is required.

Physical Exercise and Economic Burden Associated With Anxiety Symptoms in Pregnant Women During the COVID-19 Pandemic (preprint)

Background: COVID-19 with high infectivity and high concealment has been widely spread around the world. This major public health event has caused anxiety among the public, including pregnant women. The aim of this study was to assess the incidence of anxiety symptoms in pregnant women during the COVID-19 pandemic and its influencing factors.Methods: Using an ongoing prospective pregnancy registry, we performed a single center cross-sectional analysis to investigate the overall prevalence of anxiety symptoms among pregnant women during the COVID-19 pandemic. Online questionnaires were used to collect information including sociodemographic data, physical activity and economic situations. The Zung Self-Rating Anxiety Scale (SAS) was used to assess anxiety symptoms. The univariate regression analysis was performed to detect factors potentially influencing anxiety symptoms among pregnant women. The multivariate regression analysis was also conducted to analyze the association of physical exercise and economic burden with anxiety symptoms by adjusting for other variables.Results: A total of 1,517 pregnant women entered the analysis. The study reported that 31.64% of the respondents had anxiety symptoms. Those with bank loans were at higher odds of suffering from anxiety symptoms compared to those without bank loans [(adjusted odds ratio (aOR) 1.494, 95% confidence interval (CI) 1.181~1.889]. Those who took 2,000~5,000 steps/day (aOR 0.825, 95% CI 0.603~0.875) and >5,000 steps/day (aOR 0.924, 95% CI 0.439~0.945) were at lower odds of suffering from anxiety symptoms compared to those who took <500 steps/day. Similarly, the adjusted odds ratios for anxiety symptoms was 0.750 (95% CI 0.663~0.790) and 0.800 (95% CI 0.226~0.889) lower in participants with exercise frequencies of 4-6, and ≥7 times/week, compared to those with a frequency of <2 times/week.Conclusions: Three in ten pregnant women experienced anxiety symptoms during the COVID-19 pandemic, and anxiety symptoms showed association with bank loans and physical exercise. To prevent anxiety of pregnant women, the promotion of healthy lifestyles, improvement of mental health services, and expansion of social support should be implemented during epidemics. In parallel, the integration of psycho-educational interventions with mental health services among public health centers is required to minimize anxiety symptoms in pregnancy women.

Physical exercise and economic burden associated with anxiety symptoms in pregnant women during the COVID-19 pandemic (preprint)

Background: COVID-19 with high infectivity and high concealment has been widely spread around the world. This major public health event has caused anxiety among the public, including pregnant women. The aim of this study was to assess the incidence of anxiety symptoms in pregnant women during the COVID-19 pandemic and its influencing factors. Methods: Using an ongoing prospective pregnancy registry, we performed a single center cross-sectional analysis to investigate the overall prevalence of anxiety symptoms among pregnant women during the COVID-19 pandemic. Online questionnaires were used to collect information including sociodemographic data, physical activity and economic situations. The Zung Self-Rating Anxiety Scale (SAS) was used to assess anxiety symptoms. The univariate regression analysis was performed to detect factors potentially influencing anxiety symptoms among pregnant women. The multivariate regression analysis was also conducted to analyze the association of physical exercise and economic burden with anxiety symptoms by adjusting for other variables. Results: A total of 1,517 pregnant women entered the analysis. The study reported that 31.64% of the respondents had anxiety symptoms. Those with bank loans were at higher odds of suffering from anxiety symptoms compared to those without bank loans [(adjusted odds ratio (aOR) 1.494, 95% confidence interval (CI) 1.181~1.889]. Those who took 2,000~5,000 steps/day (aOR 0.825, 95% CI 0.603~0.875) and >5,000 steps/day (aOR 0.924, 95% CI 0.439~0.945) were at lower odds of suffering from anxiety symptoms compared to those who took <500 steps/day. Similarly, the adjusted odds ratios for anxiety symptoms was 0.750 (95% CI 0.663~0.790) and 0.800 (95% CI 0.226~0.889) lower in participants with exercise frequencies of 4-6, and ≥7 times/week, compared to those with a frequency of <2 times/week. Conclusions: Three in ten pregnant women experienced anxiety symptoms during the COVID-19 pandemic, and anxiety symptoms showed association with bank loans and physical exercise. To prevent anxiety of pregnant women, the promotion of healthy lifestyles, improvement of mental health services, and expansion of social support should be implemented during epidemics. In parallel, the integration of psycho-educational interventions with mental health services among public health centers is required to minimize anxiety symptoms in pregnancy women.