A Comprehensive Exploration of the Relationships between Structural Vulnerability Factors and Gestational Weight Gain Pre-COVID-19: A Scoping Review (preprint)

Background:Insufficient and excessive gestational weight gain (GWG) have emerged as rising public health concerns affecting the majority of pregnant women in high-income countries, and are associated with a multitude of adverse maternal and infant health outcomes. The goal of this scoping review was to identify key structural vulnerability factors related to GWG and to examine the extent, range, and nature of research examining associations between those factors and GWG before the advent of the COVID-19 pandemic. Methods: Electronic searches were performed in October 2018, and updated in August 2019 in the databases MEDLINE(R) ALL, EMBASE, PsycINFO, CINAHL, and Sociological Abstracts. Studies included needed to be set in high-income countries, have pregnant participants and an observational methodological design with inferential statistics performed between one or more structural vulnerability factors and GWG. Results: Of the 11,382 citations identified through database searches, 157 articles were included in the review. The structural vulnerability factors most commonly studied in association with GWG were race and ethnicity (n=91 articles), age (n=87), parity (n=48), education (n=44), income (n=39), marital status (n=28), immigration (n=19) and abuse (n=12). Moststudies were conducted in the USA (77%), a majority reported significant associations between these factors and GWG and 34% were specific to a population where all individuals were affected by one of more structural vulnerability factors. Race and ethnicity stood out as the most extensively studied factor; i.e., for the longest period (since 1976), with the highest number of published articles, the largest sample size (n=7,966,573) and the second highest (79%) proportion of studies reporting a significant relationship with GWG, with immigration status having the highest proportion (95%). Conclusions: To advance knowledge on the causes and consequences of excessive and insufficient GWG, research should extend beyond the USA and adopt an intersectional approach to unravel the complex interplay between social context, interacting structural vulnerability factors and specific measures of GWG. Such knowledge is required for the prevention of detrimental impacts on both maternal and offspring health.

Factors Associated with Anxiety During COVID-19 Pandemic and Its Association with Hypertension in Saudi Arabia.

Objective: Patients with chronic diseases such as hypertension (HTN) are considered a vulnerable group, and they are prone to anxiety and other psychological conditions during pandemics. Very few reports discussed factors related to anxiety and how it is associated with HTN during COVID-19 pandemic. In this project, we aimed to identify the prevalence of anxiety among hypertensive patients in Saudi Arabia during the COVID-19 pandemic. Methods: A cross-sectional study was conducted, and data were collected using an electronic self-administered pretested questionnaire distributed via trained data collectors. Data were analyzed using t-test and chi-test. Results: A total of 2135 participants were enrolled in this study. Anxiety was reported in 5% of all participants and 8% of the hypertensive participants. Older age, marital status, higher body mass index (BMI), smoking, and Khat chewing were strongly associated with anxiety among the general population. In addition, less adherence to medication made participants with HTN significantly more anxious. Conclusion: The prevalence of anxiety among hypertensive individuals is higher compared to the general population. Moreover, anxiety is significantly associated with some sociodemographic in the general population, and with less adherence to medications in hypertensive patients. Further studies with data from medical record including more variables are needed to highlight this association.

The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity (preprint)

The SARS-CoV-2 genome encodes a multitude of accessory proteins. Using comparative genomic approaches, an additional accessory protein, ORF3c, has been predicted to be encoded within the ORF3a sgmRNA. Expression of ORF3c during infection has been confirmed independently by ribosome profiling. Despite ORF3c also being present in the 2002-2003 SARS-CoV, its function has remained unexplored. Here we show that ORF3c localises to mitochondria during infection, where it inhibits innate immunity by restricting IFN-β production, but not NF-κB activation or JAK-STAT signalling downstream of type I IFN stimulation. We find that ORF3c acts after stimulation with cytoplasmic RNA helicases RIG-I or MDA5 or adaptor protein MAVS, but not after TRIF, TBK1 or phospho-IRF3 stimulation. ORF3c co-immunoprecipitates with the antiviral proteins MAVS and PGAM5 and induces MAVS cleavage by caspase-3. Together, these data provide insight into an uncharacterised mechanism of innate immune evasion by this important human pathogen.

Information seeking, mental health and loneliness: Longitudinal analyses of adults in the UK COVID-19 Mental Health & Wellbeing study

Information-seeking has generally been seen as an adaptive response to the COVID-19 pandemic. However, it may also result in negative outcomes on mental health. The present study tests whether reporting COVID-related information-seeking throughout the pandemic is associated with subsequently poorer mental health outcomes. A quota-based, non-probability-sampling methodology was used to recruit a nationally representative sample. COVID-related information-seeking was assessed at six waves along with symptoms of depression, anxiety, mental wellbeing and loneliness (N = 1945). Hierarchical linear modelling was used to assess the relationship between COVID-related information-seeking and mental health outcomes. Information-seeking was found to reduce over time. Overall, women, older and higher socioeconomic group individuals reported higher levels of information-seeking. At waves 1-4 (March-June 2020) the majority of participants reported that they sought information on Covid 1-5 times per day, this decreased to less than once per day in waves 5 and 6 (July-November 2020). Higher levels of information-seeking were associated with poorer mental health outcomes, particularly clinically significant levels of anxiety. Use of a non-probability sampling method may have been a study limitation, nevertheless, reducing or managing information-seeking behaviour may be one method to reduce anxiety during pandemics and other public health crises.

Parental mental health and associations between living in temporary accommodation and socio-political determinants during the COVID-19 pandemic

576 Figure 1Is the adjusted odds ratio (OR) plot showing the odds of an increased rank of depression severity with living in Temporary Accommodation as the main exposure and each predictior variable given all the other variables were held constant in the model[Figure omitted. See PDF] 576 Figure 2Is the adjusted odds ratio (OR) plot showing the odds of an increased rank of anxiety severity with living in temporary accommodation as the main exposure and each predictior variable given all the other variables were held constant in the model[Figure omitted. See PDF]22.9% and 20.0% of TA parents/caregivers had severe anxiety and moderate anxiety compared to 4.0% and 25.0% of non-TA parents/caregivers, respectively. For parents/caregivers living in TA, the odds of a more severe anxiety rank were 2.46 times higher (95%CI:1.27–4.75). Other significant factors for anxiety were: Very Low Food Security (OR 4.45, 95%CI:3.26–6.08);families ‘finding it very difficult’ financially (OR 1.62, 95%CI:0.96–2.73). [Figure 2]ConclusionFamilies living in TA had a greater odds of poor parental mental health outcomes, which was further compounded by factors including NRPF status, financial insecurity, food insecurity and poor housing environments. Poor parental mental health is an adverse childhood experience (ACE) directly impacting both the health and wellbeing of the parent and child throughout the life course. Targeted policies and tailored community-based mental health strategies, including the co-location of mental health and housing support within settings already accessed by TA families with under 5s, are vitally needed, since this vulnerable group is at higher risk of poorer parental mental health and a higher ACE count, which is exacerbated by the unsuit ble and unsafe TA environment.

Socio-political determinants of health inequalities during the COVID-19 pandemic: Under 5s and their families living in temporary accommodation in a socially diverse and deprived population—Newham, East London

605 Figure 1Comparisons Between TA and Non-TA Families: Socio-political Determinants[Figure omitted. See PDF] 605 Table 1Health care access: comparison of non-TA and TA families n (%)ConclusionTA children were increasingly disadvantaged among multiple domains: socio-demographics, food insecurity, inadequate/poor housing, health service access. Therefore, the need is urgent to minimise the potential lifelong health impacts of these socio-political determinants of health experienced by this vulnerable group in addition to tackling the immediate risks arising from issues such as digital exclusion and poor housing conditions, which were likely exacerbated during the pandemic. The future of the pandemic is uncertain and future lockdowns are possible, so all families must have digital access now that many vital health services and schooling are online, even some exclusively. The time families spend in TA must be reduced, and the co-production of interim solutions and future policies to ensure a minimum set of housing standards for TA should be made a priority to address these inequalities and inequities.

Evaluating telehealth lifestyle therapy versus telehealth psychotherapy for reducing depression in adults with COVID-19 related distress: The curbing anxiety and depression using lifestyle medicine (CALM) randomised non-inferiority trial protocol

Background: There is increasing recognition of the substantial burden of mental health disorders at an individual and population level, including consequent demand on mental health services. Lifestyle-based mental healthcare offers an additional approach to existing services with potential to help alleviate system burden. Despite the latest Royal Australian New Zealand College of Psychiatrists guidelines recommending that lifestyle is a 'first-line', 'non-negotiable' treatment for mood disorders, few such programs exist within clinical practice. Additionally, there are limited data to determine whether lifestyle approaches are equivalent to established treatments. Using an individually randomised group treatment design, we aim to address this gap by evaluating an integrated lifestyle program (CALM) compared to an established therapy (psychotherapy), both delivered via telehealth. It is hypothesised that the CALM program will not be inferior to psychotherapy with respect to depressive symptoms at 8 weeks. Methods: The study is being conducted in partnership with Barwon Health's Mental Health, Drugs & Alcohol Service (Geelong, Victoria), from which 184 participants from its service and surrounding regions are being recruited. Eligible participants with elevated psychological distress are being randomised to CALM or psychotherapy. Each takes a trans-diagnostic approach, and comprises four weekly (weeks 1-4) and two fortnightly (weeks 6 and 8) 90-min, group-based sessions delivered via Zoom (digital video conferencing platform). CALM focuses on enhancing knowledge, behavioural skills and support for improving dietary and physical activity behaviours, delivered by an Accredited Exercise Physiologist and Accredited Practising Dietitian. Psychotherapy uses cognitive behavioural therapy (CBT) delivered by a Psychologist or Clinical Psychologist, and Provisional Psychologist. Data collection occurs at baseline and 8 weeks. The primary outcome is depressive symptoms (assessed via the Patient Health Questionnaire-9) at 8 weeks. Societal and healthcare costs will be estimated to determine the cost-effectiveness of the CALM program. A process evaluation will determine its reach, adoption, implementation and maintenance. Discussion: If the CALM program is non-inferior to psychotherapy, this study will provide the first evidence to support lifestyle-based mental healthcare as an additional care model to support individuals experiencing psychological distress. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Reactogenicity, Safety, and Serological and Cellular Immunogenicity of a Booster Dose of SARS-CoV-2 mRNA Prototype, Variant, and Bivalent Vaccines (preprint)

Waning immunity after two SARS-CoV-2 mRNA vaccinations and the emergence of variants precipitated the need for booster doses. We evaluated safety and serological and cellular immunogenicity through 6 months after a third mRNA vaccination in adults who received the mRNA-1273 primary series in the Phase 1 trial approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA-1273.351 that encodes Beta variant spike protein, and bivalent vaccine of 25 mcg each of mRNA-1273 and mRNA-1273.351. A third dose of mRNA vaccine appeared safe with acceptable reactogenicity. Vaccination induced rapid increases in binding and neutralizing antibody titers to D614G, Beta, Delta and Omicron variants that persisted through 6 months post-boost, particularly after administration of Beta-containing vaccines. Spike-specific CD4 + and CD8 + T cells increased to levels similar to those following the second dose. Boost vaccination induced broad and durable humoral and T cell responses. ClinicalTrials.gov numbers NCT04283461 (mRNA-1273 Phase 1) and NCT04785144 (mRNA-1273.351 Phase 1)

A mixed method approach to understanding the impact of COVID-19 on patients with or at risk for aortic dissection.

Aortic dissection (AD) is a life-threatening rare disease that occurs as a spontaneous tear in the wall of the aorta. Survivors of AD go on to have a chronic disease process that requires lifelong follow-up and management. Although the COVID-19 pandemic has strained health systems and impacted practice in the United States, the effects of these impacts on people living with or at risk for AD is not well understood. This mixed methods project examined the experiences of people in the AD community during the COVID-19 pandemic between March and October 2020. Results reveal that the AD community lacked clear guidance on the role aortic health status plays in COVID-19 risk and experienced significant disruptions in aortic healthcare. At the same time, the new expansion in access to medical care with telehealth conferred unforeseen benefits in the form of reduced barriers for access to specialized aortic health care.

Seeing lockdown through the eyes of children from around the world: Reflecting on a children's artwork project

The COVID-19 pandemic created new challenges for children including access to education and limiting social and emotional connections to extended family, friends, and the community. Globally, opportunities for sharing children's self-reported experiences during lockdown were limited. The primary aim of this project was to create an art-eBook that reflects children's experiences of life during the COVID-19 pandemic that could be shared with other children around the world. Secondly, we wanted to reflect on the consultation undertaken within the International Network of Child and Family Centered Care (INCFCC) using Gibbs (1988) reflective cycle framework. Children from around the world were invited to submit a piece of artwork that reflected their experience during the COVID-19 pandemic via a Qualtrics-survey in May 2020. The children's artwork and written pieces were transcribed verbatim into an eBook and the artwork was further placed into groups based on similarity of meaning. Fifty-five children from 17 countries submitted an artwork piece. Four groups were evident within the children's artwork including infection control measures, positive experiences and emotions (connection to family, fun activities), negative experiences and emotions (social impact, emotional impact), and uniting children globally. The eBook illustrates how children of all ages can provide meaningful insightful commentary and valuable information on their experiences during an unprecedented pandemic.

Safety and Immunogenicity of a Third Dose of SARS-CoV-2 mRNA Vaccine — An Interim Analysis (preprint)

Waning immunity after two SARS-CoV-2 mRNA vaccinations and the emergence of variants precipitated the need for a third dose of vaccine. We evaluated early safety and immunogenicity after a third mRNA vaccination in adults who received the mRNA-1273 primary series in the Phase 1 trial approximately 9 to 10 months earlier. The booster vaccine formulations included 100 mcg of mRNA-1273, 50 mcg of mRNA-1273.351 that encodes Beta variant spike protein, and bivalent vaccine of 25 mcg each of mRNA-1273 and mRNA-1273.351. A third dose of mRNA vaccine appeared safe with acceptable reactogenicity. Vaccination induced rapid increases in binding and neutralizing antibody titers to D614G, Beta, and Delta variants that were similar or greater than peak responses after the second dose. Spike-specific CD4+ and CD8+ T cells increased to similar levels as after the second dose. A third mRNA vaccination was well tolerated and generated robust humoral and T cell responses. ClinicalTrials.gov numbers NCT04283461 (mRNA-1273 Phase 1) and NCT04785144 (mRNA-1273.351 Phase 1)

Changing patterns in paediatric attendances during the COVID-19 pandemic

BackgroundThe WHO declared COVID-19 a pandemic on 11 March 2020. Irish schools closed on 12 March and a nationwide stay-at-home order was issued on 27 March. A 34–76% decrease in paediatric ED presentations has been reported during the pandemic.ObjectivesThis study aims to assess the impact of the pandemic on attendances and admissions to a regional paediatric unit.MethodsA single-centre retrospective review of presentations to the paediatric assessment unit (PAU) and admissions to the paediatric ward from April-July 2019 and 2020 was performed. Data was obtained from the PAU attendance diary and HIPE reporting database. Unscheduled PAU attendances included GP/self-referrals with medical or surgical complaints, excluding injuries. Data was analysed using descriptive statistics.ResultsThere was a 40% decrease in unscheduled PAU presentations in April-July 2020 (n=747) compared with 2019 (n=1244). The most common presenting complaints in 2020 were gastrointestinal symptoms (33.2%), rashes (12.2%), unwell child <1 year including pyrexia (7.4%) and respiratory symptoms (7%).There was a 67.2% decrease in admissions in April-July 2020 (n=170) compared with 2019 (n=519). Discharge diagnoses were categorised for admitted patients in May-July 2019 and 2020. There was a reduction in most categories in 2020 including dermatological (−80.7%), respiratory (−80%), cardiovascular (−75%), neurological (−62.2%), gastrointestinal (−61.3%), surgical (−60%), musculoskeletal (−57.1%), injury & poisoning (−45.2%) and mental health/safeguarding (−33.3%) cases. There was an 11.1% increase in genitourinary cases in 2020.ConclusionsThe COVID-19 pandemic has resulted in a drastic decrease in paediatric clinical activity. Not surprisingly, we have seen a reduction in presentations relating to viral transmission (wheeze, gastroenteritis, rashes) and school-related stress (headaches, abdominal pain). Despite the anticipated negative effects of the pandemic on mental health, psychiatric admissions did not increase. The number of surgical cases, comprised largely of acute appendicitis, was 60% lower during the pandemic, supporting the possibility of a viral trigger. Other factors which may have influenced presentations include greater parental supervision at home, fear of contracting or spreading COVID-19, reduced outdoor/sporting activities and reduced vehicular pollution.Whilst SARS-CoV-2 infections in children have been relatively mild, the pandemic has had a profound impact on paediatric services. Reflecting on these shifts may provide insight into the aetiology of paediatric diseases, the factors influencing a parent’s decision to present to hospital, the factors influencing a clinician’s decision to admit patients and the effect of the pandemic on the health of children in general.

mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates.

B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates received two doses of 30 or 100 µg of Moderna's mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.

A simple mathematical model for the evaluation of the long first wave of the COVID-19 pandemic in Brazil.

We propose herein a mathematical model to predict the COVID-19 evolution and evaluate the impact of governmental decisions on this evolution, attempting to explain the long duration of the pandemic in the 26 Brazilian states and their capitals well as in the Federative Unit. The prediction was performed based on the growth rate of new cases in a stable period, and the graphics plotted with the significant governmental decisions to evaluate the impact on the epidemic curve in each Brazilian state and city. Analysis of the predicted new cases was correlated with the total number of hospitalizations and deaths related to COVID-19. Because Brazil is a vast country, with high heterogeneity and complexity of the regional/local characteristics and governmental authorities among Brazilian states and cities, we individually predicted the epidemic curve based on a specific stable period with reduced or minimal interference on the growth rate of new cases. We found good accuracy, mainly in a short period (weeks). The most critical governmental decisions had a significant temporal impact on pandemic curve growth. A good relationship was found between the predicted number of new cases and the total number of inpatients and deaths related to COVID-19. In summary, we demonstrated that interventional and preventive measures directly and significantly impact the COVID-19 pandemic using a simple mathematical model. This model can easily be applied, helping, and directing health and governmental authorities to make further decisions to combat the pandemic.

Polyp excision rates post-COVID-19: Personal protective equipment does not impairperformance

Aims The UK JAG on GI Endoscopy's minimum standard for polyp detection rates (PDR) in colonoscopy is 15 %. TheCOVID-19 pandemic precipitated the use of restrictive personal protective equipment (PPE) which might reduce dexterityand decrease PDRs. We audited our polyp excision rates both prior to and post the COVID-19 pandemic in order to assesswhether restrictive PPE led to a diminution therein. Methods Our endoscopy database was queried for all colonoscopies performed between 01/01/2014 and 29/02/2020 (Pre-COVID-19, n = 18,231) and between 01/03/2020 and 02/09/2020 (Post-COVID-19, n = 825) and subsequently irrevocablyanonymised. A polyp excision rate (PER) was calculated for each period as a proxy for PDR. A comparative odds ratio was calculated. An ordinary least squares (OLS) regression, using number of polyps excised as the dependent variable and procedure in thepost-COVID-19 period as a primary explanatory variable, was performed. The regression was controlled for age, malegender and procedure coded as therapeutic (as opposed to diagnostic). Results 4,346 and 209 patients had at least one polyp excised in the pre-COVID-19 (PER 23.8 %) and post-COVID-19 (PER25.3 %) periods respectively. Odds ratio 1.08 (95 %CIs: 0.92, 1.27). OLS regression established positive relationships between number of polyps excised and age (0.004, 95 %CIs: 0.003,0.005), male gender (0.10, 95 %CIs: 0.07, 0.13) and procedure coded as therapeutic (1.75, 95 %CIs: 1.71, 1.78). Itdemonstrated no significant relationship between procedure in the post-COVID-19 period (-0.003, 95 %CIs:-0.07, 0.07)and number of polyps excised. Conclusions Odds ratios comparing PERs and an OLS regression analysing number of polyps excised failed to demonstrateany significant difference between the pre-COVID-19 and post-COVID-19 eras.

Children and young adults hospitalized for severe COVID-19 exhibit thrombotic coagulopathy (preprint)

We report the clinical and laboratory coagulation characteristics of 27 pediatric and young adult patients (2 months to 21 years) treated for symptomatic COVID-19 at a children’s hospital in the Bronx, New York between March 1 and May 31, 2020. D-Dimer was > 0.5 ug/mL (upper limit of normal) in 25 (93%) patients at admission; 11 (41%) developed peak D-Dimer > 5 ug/mL during admission. Seven (26%) patients developed venous thromboembolism: three with deep vein thrombosis and four with pulmonary embolism. Requirement of increased ventilatory support was a risk factor for thrombosis (p=0.006). Three of eight (38%) patients on prophylactic anticoagulation developed thrombosis, however no patients developed VTE on low molecular weight heparin prophylaxis titrated to anti-Xa level. Manifestation of COVID-19 disease was severe or critical in 16 (59%) patients. Four (15%) patients died of COVID-19 complications: all had comorbidities. Elevated D-dimer and increased VTE rate were observed in this young cohort, particularly in those with severe respiratory complications suggesting thrombotic coagulopathy. More data is needed to guide thromboprophylaxis in this age group.

Fever, Diarrhea, and Severe Disease Correlate with High Persistent Antibody Levels against SARS-CoV-2 (preprint)

ABSTRACT Lasting immunity will be critical for overcoming the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, factors that drive the development of high titers of anti-SARS-CoV-2 antibodies and how long those antibodies persist remain unclear. Our objective was to comprehensively evaluate anti-SARS-CoV-2 antibodies in a clinically diverse COVID-19 convalescent cohort at defined time points to determine if anti-SARS-CoV-2 antibodies persist and to identify clinical and demographic factors that correlate with high titers. Using a novel multiplex assay to quantify IgG against four SARS-CoV-2 antigens, a receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralization assay, we found that 98% of COVID-19 convalescent subjects had anti-SARS-CoV-2 antibodies five weeks after symptom resolution (n=113). Further, antibody levels did not decline three months after symptom resolution (n=79). As expected, greater disease severity, older age, male sex, obesity, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 antibody levels. We demonstrated for the first time that COVID-19 symptoms, namely fever, abdominal pain, diarrhea and low appetite, correlated consistently with higher anti-SARS-CoV-2 antibody levels. Our results provide new insights into the development and persistence of anti-SARS-CoV-2 antibodies.

Antibody Reactivity Against SARS-CoV-2 in Adults from the Vancouver Metropolitan Area, Canada (preprint)

Background: Quantifying antibody reactivity against multiple SARS-CoV-2 antigens at the population level may help understand individual differences in COVID-19 severity. Pre-existing low antibody cross-reactivity may be particularly prevalent among childcare providers, including pediatric health care workers (HCW) who may be more exposed to circulating coronaviruses.Methods: Cross-sectional study that included adults in the Vancouver area in British Columbia (BC), Canada, between May 17 and June 19, 2020. SARS-CoV-2 seroprevalence was ascertained by measuring total SARS-CoV-2 IgG/M/A antibodies against a recombinant spike (S1) protein and adjusted for bias due to false-positive and false-negative test results. A novel, high sensitivity multiplex assay was also used to profile IgG against four SARS-CoV-2 antigens, SARS-CoV and four circulating coronaviruses.Findings: Among 276 participants (71% HCW), three showed evidence of direct viral exposure, yielding an adjusted seroprevalence of 0.60% [95%CI 0% – 2.71%], with no difference between HCW and non-HCW, or between paediatric and adult HCW. Among the 273 unexposed individuals, 7.3% [95%CI 4.5% – 11.1%], 48.7 [95%CI 42.7% – 54.8%] and 82.4% [95%CI 77.4% – 86.7%] showed antibody reactivity against SARS-CoV-2 RBD, N or Spike proteins, respectively. SARS-CoV-2 reactivity did not significantly correlate with age, sex, did not significantly differ between HCW and non-HCW (prevalence 1.0% vs 1.0%; P =1.00) and between pediatric and adult HCW (0.7% vs 1.6%; P =0.54), and modestly correlated with reactivity to circulating coronaviruses (Spearman rho range: 0.130 to 0.224 for 7 significant (FDR 5%), out of 16 correlations, from 36 correlations tested).Interpretation: A substantial proportion of individuals showed low, but detectable antibody reactivity against SARS-CoV-2 antigens in this population despite low evidence of direct SARS-CoV-2 exposure.Funding Statement: This study was funded by unrestricted funding to PML and an Intramural Research Program of the Vaccine Research Centre (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study was approved by the University of British Columbia Children’s & Women’s Research Ethic Board (H20-01205).

COVID-19 Mortality Risk Assessment among Various Age Groups using Phylogenetic Analysis (preprint)

The age-related mortality and morbidity risk of COVID-19 has been considered speculative without enough scientific evidence. This study aimed to collect more evidence on the association between patient age and risk of severe disease state and/or mortality from SARS-CoV-2 infection. Genomic dataset along with metadata (3608 samples) retrieved from GISAID from different geographical regions were grouped into 10 age groups (0-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, 91-100 years) as well as high-risk or low-risk according to patient clinical status. Genomic sequences were aligned and analyzed using MAFFT and FASTTREE to build a phylogenetic tree in order to identify age-risk associations based on phylogenetic clustering. Case fatality rates (CFR), as well as the Odds ratio (OR) for high-risk outcomes, were calculated for different age groups. Results revealed that individuals aged between 25-50 years have the best immune response to the infection. On the other hand, disease fatality was higher in patients aging above 50 years. We created an application to calculate the OR of being at high risk given a certain age threshold from GISAID datasets. OR values increased between ages 1-10 years (1.271) and 11-20 years (1.313) but reduced at age range 21-30 years (1.290) and increased again for 61-70 years (2.465). CFR calculated for each of the age groups had peak values at 90-100 years (26.8%) and the lowest at 0-10 years (0%). The CFR for ages above 50 years was about twice greater (11.6%-26.8%) than that for ages below (0-6.6%). The phylogenetic analysis revealed that the majority of samples obtained from India showed low-risk among different age groups and were defined as clade GH. Another cluster from Singapore visualization showed unfavorable patient outcome across several age groups and were classified under clade O. To conclude, this study analyses showed a variety of age-risk associations. As scientists from different countries upload more genomes to globally shared databases, more evidence will reinforce mortality risk associations in COVID-19 patients.