An exploratory study of maternal diabetes and offspring use of dental services-Northern Ireland national cohort study.

INTRODUCTION: A small number of literature has posited a link between prenatal exposure to gestational diabetes mellitus and an increased risk of developmental defects in the enamel of offspring. However, the evidence remains inconclusive. AIMS: This study examined the relationship between the diabetes status of mothers and the use of dental services by offspring to that pregnancy. MATERIAL AND METHODS: Anonymised data from a cohort of mothers who carried a child to term in Northern Ireland between 2012 and 2017 and service use by the child were taken from administrative databases from March 2015 to September 2021. Descriptive statistics, differences in means and regression analyses were used to examine the relationship between service use and maternal diabetes status, controlling for covariates. RESULTS: In multivariate analyses that controlled inter alia for age and deprivation, diabetes status was negatively related to restoration, extraction, prevention, and total service use. In the analysis of the COVID period, pre-COVID prevention was negatively related to extractions, restorations, prevention and services in general. CONCLUSION: The relationship between maternal diabetic status and aspects of offspring use of dental services was contrary to that suggested in previous studies and warrants more detailed investigation using this valuable data resource.

Potentially Zoonotic Viruses in Wild Rodents, United Arab Emirates, 2019-A Pilot Study.

The majority of emerging viral infectious diseases in humans originate from wildlife reservoirs, such as rodents and bats. We investigated a possible reservoir, namely wild gerbils and mice trapped in a desert reserve within the emirate of Dubai, United Arab Emirates (UAE). In total, 52 gerbils and 1 jird (Gerbillinae), 10 house mice (Mus musculus), and 1 Arabian spiny mouse (Acomys dimidiatus) were sampled. Oro-pharyngeal swabs, fecal samples, attached ticks, and organ samples (where available) were screened by (RT-q)PCR for the following viruses: Middle East respiratory syndrome-related coronavirus, Crimean-Congo hemorrhagic fever orthonairovirus, Alkhumra hemorrhagic fever virus, hantaviruses, Lymphocytic choriomeningitis mammarenavirus, Rustrela virus, poxviruses, flaviviruses, and herpesviruses. All of the samples were negative for all investigated viruses, except for herpesviruses: 19 gerbils (35.8%) and seven house mice (70.0%) were positive. The resulting sequences were only partly identical to sequences in GenBank. Phylogenetic analysis revealed three novel betaherpesviruses and four novel gammaherpesviruses. Interestingly, species identification of the positive gerbils resulted in eight individuals clustering in a separate clade, most closely related to Dipodillus campestris, the North African gerbil, indicating either the expansion of the geographic range of this species, or the existence of a closely related, yet undiscovered species in the UAE. In conclusion, we could not find evidence of persistence or shedding of potentially zoonotic viruses in the investigated rodent cohorts of limited sample size.

Global Matrix 4.0 Physical Activity Report Card Grades for Children and Adolescents: Results and Analyses From 57 Countries.

BACKGROUND: The Global Matrix 4.0 on physical activity (PA) for children and adolescents was developed to achieve a comprehensive understanding of the global variation in children's and adolescents' (5-17 y) PA, related measures, and key sources of influence. The objectives of this article were (1) to summarize the findings from the Global Matrix 4.0 Report Cards, (2) to compare indicators across countries, and (3) to explore trends related to the Human Development Index and geo-cultural regions. METHODS: A total of 57 Report Card teams followed a harmonized process to grade the 10 common PA indicators. An online survey was conducted to collect Report Card Leaders' top 3 priorities for each PA indicator and their opinions on how the COVID-19 pandemic impacted child and adolescent PA indicators in their country. RESULTS: Overall Physical Activity was the indicator with the lowest global average grade (D), while School and Community and Environment were the indicators with the highest global average grade (C+). An overview of the global situation in terms of surveillance and prevalence is provided for all 10 common PA indicators, followed by priorities and examples to support the development of strategies and policies internationally. CONCLUSIONS: The Global Matrix 4.0 represents the largest compilation of children's and adolescents' PA indicators to date. While variation in data sources informing the grades across countries was observed, this initiative highlighted low PA levels in children and adolescents globally. Measures to contain the COVID-19 pandemic, local/international conflicts, climate change, and economic change threaten to worsen this situation.

Maternal Early-Life Risk Factors and Later Gestational Diabetes Mellitus: A Cross-Sectional Analysis of the UAE Healthy Future Study (UAEHFS).

Limited studies have focused on maternal early-life risk factors and the later development of gestational diabetes mellitus (GDM). We aimed to estimate the GDM prevalence and examine the associations of maternal early-life risk factors, namely: maternal birthweight, parental smoking at birth, childhood urbanicity, ever-breastfed, parental education attainment, parental history of diabetes, childhood overall health, childhood body size, and childhood height, with later GDM. This was a retrospective cross-sectional study using the UAE Healthy Future Study (UAEHFS) baseline data (February 2016 to April 2022) on 702 ever-married women aged 18 to 67 years. We fitted a Poisson regression to estimate the risk ratio (RR) for later GDM and its 95% confidence interval (CI). The GDM prevalence was 5.1%. In the fully adjusted model, females with low birthweight were four times more likely (RR 4.04, 95% CI 1.36-12.0) and females with a parental history of diabetes were nearly three times more likely (RR 2.86, 95% CI 1.10-7.43) to report later GDM. In conclusion, maternal birthweight and parental history of diabetes were significantly associated with later GDM. Close glucose monitoring during pregnancy among females with either a low birth weight and/or parental history of diabetes might help to prevent GDM among this high-risk group.

Deep Learning-Based Automatic Assessment of Lung Impairment in COVID-19 Pneumonia: Predicting Markers of Hypoxia With Computer Vision.

Background: Hypoxia is a potentially life-threatening condition that can be seen in pneumonia patients. Objective: We aimed to develop and test an automatic assessment of lung impairment in COVID-19 associated pneumonia with machine learning regression models that predict markers of respiratory and cardiovascular functioning from radiograms and lung CT. Materials and Methods: We enrolled a total of 605 COVID-19 cases admitted to Al Ain Hospital from 24 February to 1 July 2020 into the study. The inclusion criteria were as follows: age ≥ 18 years; inpatient admission; PCR positive for SARS-CoV-2; lung CT available at PACS. We designed a CNN-based regression model to predict systemic oxygenation markers from lung CT and 2D diagnostic images of the chest. The 2D images generated by averaging CT scans were analogous to the frontal and lateral view radiograms. The functional (heart and breath rate, blood pressure) and biochemical findings (SpO2, H C O 3 - , K +, Na +, anion gap, C-reactive protein) served as ground truth. Results: Radiologic findings in the lungs of COVID-19 patients provide reliable assessments of functional status with clinical utility. If fed to ML models, the sagittal view radiograms reflect dyspnea more accurately than the coronal view radiograms due to the smaller size and the lower model complexity. Mean absolute error of the models trained on single-projection radiograms was approximately 11÷12% and it dropped by 0.5÷1% if both projections were used (11.97 ± 9.23 vs. 11.43 ± 7.51%; p = 0.70). Thus, the ML regression models based on 2D images acquired in multiple planes had slightly better performance. The data blending approach was as efficient as the voting regression technique: 10.90 ± 6.72 vs. 11.96 ± 8.30%, p = 0.94. The models trained on 3D images were more accurate than those on 2D: 8.27 ± 4.13 and 11.75 ± 8.26%, p = 0.14 before lung extraction; 10.66 ± 5.83 and 7.94 ± 4.13%, p = 0.18 after the extraction. The lung extraction boosts 3D model performance unsubstantially (from 8.27 ± 4.13 to 7.94 ± 4.13%; p = 0.82). However, none of the differences between 3D and 2D were statistically significant. Conclusion: The constructed ML algorithms can serve as models of structure-function association and pathophysiologic changes in COVID-19. The algorithms can improve risk evaluation and disease management especially after oxygen therapy that changes functional findings. Thus, the structural assessment of acute lung injury speaks of disease severity.

COVID-19-Related Mortality amongst Physicians in Italy: Trend Pre- and Post-SARS-CoV-2 Vaccination Campaign.

Globally, there has been a high burden of COVID-19-related mortality amongst physicians and other healthcare workers during the ongoing SARS-CoV-2 pandemic. Fortunately, anti-COVID-19 vaccination campaigns have helped to protect frontline workers and reduce COVID-19-related mortality amongst this occupational group. We analyzed COVID-19-related mortality data for doctors in Italy and compared the crude mortality rate between March-May 2020 (i.e., the beginning of the pandemic in Italy, with the highest rates of COVID-19-related deaths) and the same time period in March-May 2021 (high vaccination coverage amongst Italian physicians). The mortality rate was 12 times higher in March-May 2020 compared to the same time period after the start of the Italian vaccination campaign. Moreover, there was a strong inverse correlation between the number of deaths and the cumulative number of vaccine doses administered in the Italian population. Although non-pharmaceutical interventions, virus evolution and environmental factors probably had an effect, our analysis clearly supports the hypothesis that the vaccination campaign helped to protect Italian physicians and reduce COVID-19-related mortality. The latest available death trends from September to October 2021 for both physicians and the general population are also in favor of the need for the third vaccine dose, currently underway for the majority of the population at risk.

Genetic and Clinical Characteristics of Patients in the Middle East With Multisystem Inflammatory Syndrome in Children.

Importance: Clinical, genetic, and laboratory characteristics of Middle Eastern patients with multisystem inflammatory syndrome in children (MIS-C) have not yet been documented. Objective: To assess the genetic and clinical characteristics of patients with MIS-C of primarily Arab and Asian origin. Design, Setting, and Participants: A prospective, multicenter cohort study was conducted from September 1, 2020, to August 31, 2021, in the United Arab Emirates and Jordan. Forty-five patients with MIS-C and a matched control group of 25 healthy children with a confirmed SARS-CoV-2 infection status were recruited. Whole exome sequencing in all 70 participants was performed to identify rare, likely deleterious variants in patients with MIS-C and to correlate genetic findings with the clinical course of illness. Exposures: SARS-CoV-2. Main Outcomes and Measures: Fever, organ system complications, laboratory biomarkers, whole exome sequencing findings, treatments, and clinical outcomes were measured. The Mann-Whitney U test was used to assess the association between genetic variants and MIS-C attributes. The Fisher exact test was used to compute the genetic burden in MIS-C relative to controls. Results: A total of 45 patients with MIS-C (23 [51.1%] male; 30 [66.7%] of Middle Eastern origin; mean [SD] age, 6.7 [3.6] years) and 25 controls (17 [68.0%] male; 24 [96.0%] of Middle Eastern origin; mean [SD] age 7.4 [4.0] years) participated in the study. Key inflammatory markers were significantly dysregulated in all patients with MIS-C. Mucocutaneous and gastrointestinal manifestations were each reported in 36 patients (80.0%; 95% CI, 66.1%-89.1%), cardiac findings were reported in 22 (48.9%; 95% CI, 35.0%-63.0%), and neurologic findings were reported in 14 (31.1%; 95% CI, 19.5%-45.6%). Rare, likely deleterious heterozygous variants in immune-related genes, including TLR3, TLR6, IL22RA2, IFNB1, and IFNA6, were identified in 19 patients (42.2%; 95% CI, 29.0%-56.7%), of whom 7 had multiple variants. There was higher enrichment of genetic variants in patients relative to controls (29 vs 3, P < .001). Patients with those variants tended to have earlier disease onset (7 patients [36.8%; 95% CI, 19.1%-58.9%] with genetic findings vs 2 [7.7%; 95% CI, 2.1%-24.1%] without genetic findings were younger than 3 years at onset) and resistance to treatment (8 patients [42.1%; 95% CI, 23.1%-63.7%] with genetic findings vs 3 patients [11.5%; 95% CI, 4.0%-29.0%] without genetic findings received 2 doses of intravenous immunoglobulin). Conclusions and Relevance: The results of this cohort study suggest that rare, likely deleterious genetic variants may contribute to MIS-C disease. This finding paves the way for additional studies with larger, diverse populations to fully characterize the genetic contribution to this new disease entity.

Assessing the quality of evidence in studies estimating prevalence of exposure to occupational risk factors: The QoE-SPEO approach applied in the systematic reviews from the WHO/ILO Joint Estimates of the Work-related burden of disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) have produced the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury (WHO/ILO Joint Estimates). For these, systematic reviews of studies estimating the prevalence of exposure to selected occupational risk factors have been conducted to provide input data for estimations of the number of exposed workers. A critical part of systematic review methodology is to assess the quality of evidence across studies. In this article, we present the approach applied in these WHO/ILO systematic reviews for performing such assessments on studies of prevalence of exposure. It is called the Quality of Evidence in Studies estimating Prevalence of Exposure to Occupational risk factors (QoE-SPEO) approach. We describe QoE-SPEO's development to date, demonstrate its feasibility reporting results from pilot testing and case studies, note its strengths and limitations, and suggest how QoE-SPEO should be tested and developed further. METHODS: Following a comprehensive literature review, and using expert opinion, selected existing quality of evidence assessment approaches used in environmental and occupational health were reviewed and analysed for their relevance to prevalence studies. Relevant steps and components from the existing approaches were adopted or adapted for QoE-SPEO. New steps and components were developed. We elicited feedback from other systematic review methodologists and exposure scientists and reached consensus on the QoE-SPEO approach. Ten individual experts pilot-tested QoE-SPEO. To assess inter-rater agreement, we counted ratings of expected (actual and non-spurious) heterogeneity and quality of evidence and calculated a raw measure of agreement (Pi) between individual raters and rater teams for the downgrade domains. Pi ranged between 0.00 (no two pilot testers selected the same rating) and 1.00 (all pilot testers selected the same rating). Case studies were conducted of experiences of QoE-SPEO's use in two WHO/ILO systematic reviews. RESULTS: We found no existing quality of evidence assessment approach for occupational exposure prevalence studies. We identified three relevant, existing approaches for environmental and occupational health studies of the effect of exposures. Assessments using QoE-SPEO comprise three steps: (1) judge the level of expected heterogeneity (defined as non-spurious variability that can be expected in exposure prevalence, within or between individual persons, because exposure may change over space and/or time), (2) assess downgrade domains, and (3) reach a final rating on the quality of evidence. Assessments are conducted using the same five downgrade domains as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach: (a) risk of bias, (b) indirectness, (c) inconsistency, (d) imprecision, and (e) publication bias. For downgrade domains (c) and (d), the assessment varies depending on the level of expected heterogeneity. There are no upgrade domains. The QoE-SPEO's ratings are "very low", "low", "moderate", and "high". To arrive at a final decision on the overall quality of evidence, the assessor starts at "high" quality of evidence and for each domain downgrades by one or two levels for serious concerns or very serious concerns, respectively. In pilot tests, there was reasonable agreement in ratings for expected heterogeneity; 70% of raters selected the same rating. Inter-rater agreement ranged considerably between downgrade domains, both for individual rater pairs (range Pi: 0.36-1.00) and rater teams (0.20-1.00). Sparse data prevented rigorous assessment of inter-rater agreement in quality of evidence ratings. CONCLUSIONS: We present QoE-SPEO as an approach for assessing quality of evidence in prevalence studies of exposure to occupational risk factors. It has been developed to its current version (as presented here), has undergone pilot testing, and was applied in the systematic reviews for the WHO/ILO Joint Estimates. While the approach requires further testing and development, it makes steps towards filling an identified gap, and progress made so far can be used to inform future work in this area.

Ethnicity-Specific Features of COVID-19 Among Arabs, Africans, South Asians, East Asians, and Caucasians in the United Arab Emirates.

Background: Dubai (United Arab Emirates; UAE) has a multi-national population which makes it exceptionally interesting study sample because of its unique demographic factors. Objective: To stratify the risk factors for the multinational society of the UAE. Methods: A retrospective chart review of 560 patients sequentially admitted to inpatient care with laboratory confirmed COVID-19 was conducted. We studied patients' demographics, clinical features, laboratory results, disease severity, and outcomes. The parameters were compared across different ethnic groups using tree-based estimators to rank the ethnicity-specific disease features. We trained ML classification algorithms to build a model of ethnic specificity of COVID-19 based on clinical presentation and laboratory findings on admission. Results: Out of 560 patients, 43.6% were South Asians, 26.4% Middle Easterns, 16.8% East Asians, 10.7% Caucasians, and 2.5% are under others. UAE nationals represented half of the Middle Eastern patients, and 13% of the entire cohort. Hypertension was the most common comorbidity in COVID-19 patients. Subjective complaint of fever and cough were the chief presenting symptoms. Two-thirds of the patients had either a mild disease or were asymptomatic. Only 20% of the entire cohort needed oxygen therapy, and 12% needed ICU admission. Forty patients (~7%) needed invasive ventilation and fifteen patients died (2.7%). We observed differences in disease severity among different ethnic groups. Caucasian or East-Asian COVID-19 patients tended to have a more severe disease despite a lower risk profile. In contrast to this, Middle Eastern COVID-19 patients had a higher risk factor profile, but they did not differ markedly in disease severity from the other ethnic groups. There was no noticeable difference between the Middle Eastern subethnicities-Arabs and Africans-in disease severity (p = 0.81). However, there were disparities in the SOFA score, D-dimer (p = 0.015), fibrinogen (p = 0.007), and background diseases (hypertension, p = 0.003; diabetes and smoking, p = 0.045) between the subethnicities. Conclusion: We observed variations in disease severity among different ethnic groups. The high accuracy (average AUC = 0.9586) of the ethnicity classification model based on the laboratory and clinical findings suggests the presence of ethnic-specific disease features. Larger studies are needed to explore the role of ethnicity in COVID-19 disease features.

Impact of Age and Sex on COVID-19 Severity Assessed From Radiologic and Clinical Findings.

Background: Data on the epidemiological characteristics and clinical features of COVID-19 in patients of different ages and sex are limited. Existing studies have mainly focused on the pediatric and elderly population. Objective: Assess whether age and sex interact with other risk factors to influence the severity of SARS-CoV-2 infection. Material and Methods: The study sample included all consecutive patients who satisfied the inclusion criteria and who were treated from 24 February to 1 July 2020 in Dubai Mediclinic Parkview (560 cases) and Al Ain Hospital (605 cases), United Arab Emirates. We compared disease severity estimated from the radiological findings among patients of different age groups and sex. To analyze factors associated with an increased risk of severe disease, we conducted uni- and multivariate regression analyses. Specifically, age, sex, laboratory findings, and personal risk factors were used to predict moderate and severe COVID-19 with conventional machine learning methods. Results: Need for O2 supplementation was positively correlated with age. Intensive care was required more often for men of all ages (p < 0.01). Males were more likely to have at least moderate disease severity (p = 0.0083). These findings were aligned with the results of biochemical findings and suggest a direct correlation between older age and male sex with a severe course of the disease. In young males (18-39 years), the percentage of the lung parenchyma covered with consolidation and the density characteristics of lesions were higher than those of other age groups; however, there was no marked sex difference in middle-aged (40-64 years) and older adults (≥65 years). From the univariate analysis, the risk of the non-mild COVID-19 was significantly higher (p < 0.05) in midlife adults and older adults compared to young adults. The multivariate analysis provided similar findings. Conclusion: Age and sex were important predictors of disease severity in the set of data typically collected on admission. Sexual dissimilarities reduced with age. Age disparities were more pronounced if studied with the clinical markers of disease severity than with the radiological markers. The impact of sex on the clinical markers was more evident than that of age in our study.

SARS-CoV-2/COVID-19: Viral Genomics, Epidemiology, Vaccines, and Therapeutic Interventions.

The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 virus that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress, and fatality. To address this global crisis, up-to-date information on viral genomics and transcriptomics is crucial for understanding the origins and global dispersion of the virus, providing insights into viral pathogenicity, transmission, and epidemiology, and enabling strategies for therapeutic interventions, drug discovery, and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.

Occupational Health of Frontline Healthcare Workers in the United Arab Emirates during the COVID-19 Pandemic: A Snapshot of Summer 2020.

The study aim was to understand the availability of personal protective equipment (PPE) and the levels of anxiety, depression, and burnout of healthcare workers (HCWs) in the United Arab Emirates (UAE). This study was an online-based, cross-sectional survey during July and August 2020. Participants were eligible from the entire country, and 1290 agreed to participate. The majority of HCWs were females aged 30-39 years old, working as nurses, and 80% considered PPE to be available. Twelve percent of respondents tested positive for SARS-CoV-2. Half of HCWs considered themselves physically tired (52.2%), reported musculoskeletal pain or discomfort (54.2%), and perceived moderate-to-high levels of burnout on at least one of three burnout domains (52.8%). A quarter of HCWs reported anxiety (26.3%) or depression (28.1%). HCWs reporting not having musculoskeletal pain, having performed physical activity, and higher scores of available PPE reported lower scores of anxiety, depression, and burnout. UAE HCWs experienced more access to PPE and less anxiety, depression, and burnout compared with HCWs in other countries. Study findings can be used by healthcare organizations and policymakers to ensure adequate measures are implemented to maximize the health and wellbeing of HCWs during the current COVID-19 and future pandemics.

Maintenance of neutralizing antibodies over ten months in convalescent SARS-CoV-2 afflicted patients.

Knowledge of the level and duration of protective immunity against SARS-CoV-2 after primary infection is of crucial importance for preventive approaches. Currently, there is a lack of evidence on the persistence of specific antibodies. We investigated the generation and maintenance of neutralizing antibodies of convalescent SARS-CoV-2-afflicted patients over a ten-month period post-primary infection using an immunofluorescence assay, a commercial chemiluminescent immunoassay and an in-house enzyme-linked neutralization assay. We present the successful application of an improved version of the plaque-reduction neutralization assay which can be analysed optometrically to simplify data interpretation. Based on the results of the enzyme-linked neutralization assay, neutralizing antibodies were maintained in 77.4% of convalescent individuals without relevant decay over ten months. Furthermore, a positive correlation between severity of infection and antibody titre was observed. In conclusion, SARS-CoV-2-afflicted individuals have been proven to be able to develop and maintain neutralizing antibodies over a period of ten months after primary infection. Findings suggest long-lasting presumably protective humoral immune responses after wild-type infection.

MERS-CoV in sheep, goats, and cattle, United Arab Emirates, 2019: Virological and serological investigations reveal an accidental spillover from dromedaries.

The recent COVID-19 pandemic has demonstrated again the global threat posed by emerging zoonotic coronaviruses. During the past two decades alone, humans have experienced the emergence of several coronaviruses, such as SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in 2019. To date, MERS-CoV has been detected in 27 countries, with a case fatality ratio of approximately 34.5%. Similar to other coronaviruses, MERS-CoV presumably originated from bats; however, the main reservoir and primary source of human infections are dromedary camels. Other species within the Camelidae family, such as Bactrian camels, alpacas, and llamas, seem to be susceptible to the infection as well, although to a lesser extent. In contrast, susceptibility studies on sheep, goats, cattle, pigs, chickens, and horses obtained divergent results. In the present study, we tested nasal swabs and/or sera from 55 sheep, 45 goats, and 52 cattle, collected at the largest livestock market in the United Arab Emirates, where dromedaries are also traded, for the presence of MERS-CoV nucleic acid by RT-qPCR, and for specific antibodies by immunofluorescence assay. All sera were negative for MERS-CoV-reactive antibodies, but the nasal swab of one sheep (1.8%) repeatedly tested positive for MERS-CoV nucleic acid. Next generation sequencing (NGS) of the complete N gene of the sheep-derived MERS-CoV revealed >99% nucleotide identity to MERS-CoV sequences of five dromedaries in nearby pens and to three reference sequences. The NGS sequence of the sheep-derived MERS-CoV was confirmed by conventional RT-PCR of a part of the N gene and subsequent Sanger sequencing. All MERS-CoV sequences clustered within clade B, lineage 5. In conclusion, our study shows that noncamelid livestock, such as sheep, goats, and cattle do not play a major role in MERS-CoV epidemiology. The one sheep that tested positive most likely reflects an accidental viral spillover event from infected dromedaries in nearby pens.

Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19.

Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis, as well as a potential therapeutic target.

Innate and Adaptive Immune Genes Associated with MERS-CoV Infection in Dromedaries.

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.

Saliva for molecular detection of SARS-CoV-2 in school-age children.

OBJECTIVES: The high diagnostic accuracy indices for saliva severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase PCR (RT-PCR) reported in adults has not been demonstrated in children, and adequately powered studies focused on the paediatric population are lacking. This study was carried out to determine the diagnostic accuracy of saliva for SARS-CoV-2 RT-PCR in ambulatory children. METHODS: During 1 to 23 October 2020, we recruited a population-based sample of children presenting for coronavirus disease 2019 (COVID-19) screening in Dubai, United Arab Emirates. Each child provided paired nasopharyngeal (NP) swab and saliva for SARS-CoV-2 RT-PCR N, E and RdRp gene detection. RESULTS: Paired NP swab and saliva samples were obtained from 476 children with mean ± standard deviation age of 10.8 ± 3.9 years, and 58.2% were male (277/476). Nine participants were sampled twice, so 485 pairs of NP swab/saliva were tested. Virus detection in at least one specimen type was reported in 17.9% (87/485), with similar detection in NP swab (16.7%, 81/485) and saliva (15.9%, 77/485). Sensitivity and specificity of saliva RT-PCR was 87.7% (95% confidence interval (CI) 78.5-93.9) and 98.5% (95% CI 96.8-99.5). The positive and negative predictive values were 92.2% (95% CI 84.2-96.3) and 97.6% (95% CI 95.7-98.6), with a kappa coefficient of 0.879 (95% CI 0.821-0.937). Concordance of findings between NP swab and saliva did not differ by age (p 0.67) or gender (p 0.29). Cycle threshold (Ct) values were significantly higher in NP swab/saliva pairs with discordant findings compared to those with both specimens positive. CONCLUSIONS: In light of these findings, we recommend saliva as a diagnostic specimen for COVID-19 screening in children.

SEAHIR: A Specialized Compartmental Model for COVID-19.

The SEIR (Susceptible-Exposed-Infected-Removed) model is widely used in epidemiology to mathematically model the spread of infectious diseases with incubation periods. However, the SEIR model prototype is generic and not able to capture the unique nature of a novel viral pandemic such as SARS-CoV-2. We have developed and tested a specialized version of the SEIR model, called SEAHIR (Susceptible-Exposed-Asymptomatic-Hospitalized-Isolated-Removed) model. This proposed model is able to capture the unique dynamics of the COVID-19 outbreak including further dividing the Infected compartment into: (1) "Asymptomatic", (2) "Isolated" and (3) "Hospitalized" to delineate the transmission specifics of each compartment and forecast healthcare requirements. The model also takes into consideration the impact of non-pharmaceutical interventions such as physical distancing and different testing strategies on the number of confirmed cases. We used a publicly available dataset from the United Arab Emirates (UAE) as a case study to optimize the main parameters of the model and benchmarked it against the historical number of cases. The SEAHIR model was used by decision-makers in Dubai's COVID-19 Command and Control Center to make timely decisions on developing testing strategies, increasing healthcare capacity, and implementing interventions to contain the spread of the virus. The novel six-compartment SEAHIR model could be utilized by decision-makers and researchers in other countries for current or future pandemics.

Genotype-phenotype correlation identified a novel SARS-CoV-2 variant possibly linked to severe disease.

The geographic location and heterogeneous multi-ethnic population of Dubai (United Arab Emirates; UAE) provide a unique setting to explore the global molecular epidemiology of SARS-CoV-2 and relationship between different viral strains and disease severity. We systematically selected (i.e. every 100th individual in the central Dubai COVID-19 database) 256 patients by age, sex, disease severity and month to provide a representative sample of laboratory-confirmed COVID-19 patients (nasopharyngeal swab PCR positive) during the first wave of the UAE outbreak (January to June 2020). Sociodemographic and clinical data were extracted from medical records and full SARS-CoV-2 genome sequences extracted from nasopharyngeal swabs were analysed. Older age was significantly associated with COVID-19-associated hospital admission and mortality. Overweight/obese or diabetic patients were 3-4 times more likely to be admitted to hospital and intensive care unit (ICU). Sequencing data showed multiple independent viral introductions into the UAE from Europe, Iran and Asia (29 January-18 March), and these early strains seeded significant clustering consistent with almost exclusive community-based transmission between April and June 2020. Majority of sequenced strains (N = 60, 52%) were from the European cluster consistent with the higher infectivity rates associated with the D614G mutation carried by most strains in this cluster. A total of 986 mutations were identified in 115 genomes, 272 were unique (majority were missense, n = 134) and 20/272 mutations were novel. A missense (Q271R) and synonymous (R41R) mutation in the S and N proteins, respectively, were identified in 2/27 patients with severe COVID-19 but not in patients with mild or moderate disease (0/86; p = .05, Fisher's Exact Test). Both patients were women (51-64 years) with no significant underlying health conditions. The same two mutations were identified in a healthy 37-year-old Indian man who was hospitalized in India due to COVID-19. Our findings provide evidence for continued community-based transmission of the European strains in the Dubai population and highlight new mutations that might be associated with severe disease in otherwise healthy adults.

Host transcriptomic profiling of COVID-19 patients with mild, moderate, and severe clinical outcomes.

Characterizing key molecular and cellular pathways involved in COVID-19 is essential for disease prognosis and management. We perform shotgun transcriptome sequencing of human RNA obtained from nasopharyngeal swabs of patients with COVID-19, and identify a molecular signature associated with disease severity. Specifically, we identify globally dysregulated immune related pathways, such as cytokine-cytokine receptor signaling, complement and coagulation cascades, JAK-STAT, and TGF- ß signaling pathways in all, though to a higher extent in patients with severe symptoms. The excessive release of cytokines and chemokines such as CCL2, CCL22, CXCL9 and CXCL12 and certain interferons and interleukins related genes like IFIH1, IFI44, IFIT1 and IL10 were significantly higher in patients with severe clinical presentation compared to mild and moderate presentations. Differential gene expression analysis identified a small set of regulatory genes that might act as strong predictors of patient outcome. Our data suggest that rapid transcriptome analysis of nasopharyngeal swabs can be a powerful approach to quantify host molecular response and may provide valuable insights into COVID-19 pathophysiology.