SARS-CoV-2 detection and inactivation in water and wastewater: review on analytical methods, limitations and future research recommendations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in wastewater. Wastewater-based epidemiology (WBE) is a practical and cost-effective tool for the assessment and controlling of pandemics and probably for examining SARS-CoV-2 presence. Implementation of WBE during the outbreaks is not without limitations. Temperature, suspended solids, pH, and disinfectants affect the stability of viruses in wastewater. Due to these limitations, instruments and techniques have been utilized to detect SARS-CoV-2. SARS-CoV-2 has been detected in sewage using various concentration methods and computer-aided analyzes. RT-qPCR, ddRT-PCR, multiplex PCR, RT-LAMP, and electrochemical immunosensors have been employed to detect low levels of viral contamination. Inactivation of SARS-CoV-2 is a crucial preventive measure against coronavirus disease 2019 (COVID-19). To better assess the role of wastewater as a transmission route, detection, and quantification methods need to be refined. In this paper, the latest improvements in quantification, detection, and inactivation of SARS-CoV-2 in wastewater are explained. Finally, limitations and future research recommendations are thoroughly described.

Corrigendum: Evolution, ecology, and zoonotic transmission of betacoronaviruses: a review.

[This corrects the article DOI: 10.3389/fvets.2021.644414.].

Long-term study on wastewater SARS-CoV-2 surveillance across United Arab Emirates.

Wastewater-based epidemiology (WBE) demonstrates an efficient tool to monitor and predict SARS-CoV-2 community distribution. Many countries across the world have adopted the technique, however, most of these studies were conducted for a short duration with a limited sampling size. In this study, long-term reliability and quantification of wastewater SARS-CoV-2 surveillance is reported via analyzing 16,858 samples collected from 453 different locations across the United Arab Emirates (UAE) from May 2020 to June 2022. The collected composite samples were first incubated at 60 °C followed by filtration, concentration, and then RNA extraction using commercially available kits. The extracted RNA was then analyzed by one-step RT-qPCR and RT-ddPCR, and the data was compared to the reported clinical cases. The average positivity rate in the wastewater samples was found to be 60.61 % (8.41-96.77 %), however, the positivity rate obtained from the RT-ddPCR was significantly higher than the RT-qPCR suggesting higher sensitivity of RT-ddPCR. Time-lagged correlation analysis indicated an increase in positive cases in the wastewater samples when the clinical positive cases declined suggesting that wastewater data are highly affected by the unreported asymptomatic, pre-symptomatic and recovering individuals. The weekly SARS-CoV-2 viral count in the wastewater samples are positively correlated with the diagnosed new clinical cases throughout the studied period and the studied locations. Viral count in wastewater peaked approximately one to two weeks prior to the peaks appearing in active clinical cases indicating that wastewater viral concentrations are effective in predicting clinical cases. Overall, this study further confirms the long-term sensitivity and robust approach of WBE to detect trends in SARS-CoV-2 spread and helps contribute to pandemic management.

Risk of hospitalization and vaccine effectiveness among COVID-19 patients in the UAE during the Delta and Omicron outbreaks

Introduction A rapid increase in COVID-19 cases due to the spread of the Delta and Omicron variants in vaccinated populations has raised concerns about the hospitalization risk associated with, and the effectiveness of, COVID-19 vaccines. Method This case–control study aims to determine the hospitalization risk associated with the inactivated BBIBP-CorV (Sinopharm) and mRNA BNT162b2 (Pfizer–BionTech) vaccines, and their effectiveness reducing the rate of hospital admission between 28 May 2021 and 13 January 2022, during the Delta and Omicron outbreaks. The estimation of vaccine effectiveness of 4,618 samples was based on the number of patients hospitalized at different vaccination statuses, adjusted for confounding variables. Results Hospitalization risk increases in patients affected with the Omicron variant if patients are aged ≤ 18 years (OR 6.41, 95% CI 2.90 to 14.17;p < 0.001), and in patients affected with the Delta variant if they are aged > 45 years (OR 3.41, 95% CI 2.21 to 5.50;p < 0.001). Vaccine effectiveness reducing the rate of hospital admission for fully vaccinated participants infected with the Delta and Omicron variants was similar for both the BBIBP-CorV (94%, 95% CI 90% to 97%;90%, 95% CI 74% to 96%) and BNT162b2 vaccines (95%, 95% CI 61% to 99.3%;94%, 95% CI 53% to 99%), respectively. Discussion The BBIBP-CorV and BNT162b2 vaccines utilized in the UAE vaccination program were highly effective in reducing the rate of COVID-19-related hospitalization during the Delta and Omicron outbreaks, and further effort must be taken to achieve high vaccine coverage rates in children and adolescents in the global context to reduce the hospitalization risk associated with COVID-19 on an international scale.

Risk of hospitalization and vaccine effectiveness among COVID-19 patients in the UAE during the Delta and Omicron outbreaks.

Introduction: A rapid increase in COVID-19 cases due to the spread of the Delta and Omicron variants in vaccinated populations has raised concerns about the hospitalization risk associated with, and the effectiveness of, COVID-19 vaccines. Method: This case-control study aims to determine the hospitalization risk associated with the inactivated BBIBP-CorV (Sinopharm) and mRNA BNT162b2 (Pfizer-BionTech) vaccines, and their effectiveness reducing the rate of hospital admission between 28 May 2021 and 13 January 2022, during the Delta and Omicron outbreaks. The estimation of vaccine effectiveness of 4,618 samples was based on the number of patients hospitalized at different vaccination statuses, adjusted for confounding variables. Results: Hospitalization risk increases in patients affected with the Omicron variant if patients are aged ≤ 18 years (OR 6.41, 95% CI 2.90 to 14.17; p < 0.001), and in patients affected with the Delta variant if they are aged > 45 years (OR 3.41, 95% CI 2.21 to 5.50; p < 0.001). Vaccine effectiveness reducing the rate of hospital admission for fully vaccinated participants infected with the Delta and Omicron variants was similar for both the BBIBP-CorV (94%, 95% CI 90% to 97%; 90%, 95% CI 74% to 96%) and BNT162b2 vaccines (95%, 95% CI 61% to 99.3%; 94%, 95% CI 53% to 99%), respectively. Discussion: The BBIBP-CorV and BNT162b2 vaccines utilized in the UAE vaccination program were highly effective in reducing the rate of COVID-19-related hospitalization during the Delta and Omicron outbreaks, and further effort must be taken to achieve high vaccine coverage rates in children and adolescents in the global context to reduce the hospitalization risk associated with COVID-19 on an international scale.

Corrigendum: Evolution, ecology, and zoonotic transmission of betacoronaviruses: A review.

[This corrects the article DOI: 10.3389/fvets.2021.644414.].

Genetic variants and serum profiles of cytokines in COVID-19 severity.

BACKGROUND: Patients with severe COVID-19 are at an increased risk of Acute Respiratory Distress Syndrome (ARDS) and mortality. This is due to the increased levels of pro-inflammatory cytokines that amplify downstream pathways that are controlled by immune regulators. OBJECTIVE: This study aimed to investigate the association between cytokine genetic variants, cytokine serum levels/profiles, and disease severity in critically and non-critically ill COVID-19 patients. METHODS: This cross-sectional study recruited 646 participants that tested positive for SARS-CoV-2 from 6 collection sites across the United Arab Emirates. Medical files were accessed to retrieve clinical data. Blood samples were collected from all participants. Patients were divided into two clinical groups; non-critical (n = 453) and critical (n = 193); according to WHO classification guidelines for COVID-19 patients. Cytokine analyses were conducted on serum of a subset of the cohort. specifically on 426 participants (non-critical = 264; critical = 162). Candidate gene analyses of 33 cytokine-related genes (2,836 variants) were extracted from a Genome-Wide Association Study (GWAS) to identify genetic variants with pleiotropic effects on a specific cytokine and the severity of COVID-19 disease. RESULTS: Age, Body Mass Index (BMI), and pre-existing medical conditions were found to be significant risk factors that contribute to COVID-19 disease severity. After correcting for age, gender and BMI, IP-10 (p < 0.001), IFN (p = 0.001), IL-6 (p < 0.001), and CXCL-16 (p < 0.001) serum levels were significantly higher among critical COVID-19 cases, when compared to non-critically ill patients. To investigate if the genetic variants involved in the serum cytokine levels are associated with COVID-19 severity, we studied several genes. Single Nucleotide Polymorphisms (SNPs) in IL6 (rs1554606; ORG = 0.67 (0.66, 0.68); p = 0.017), IFNG (rs2069718; ORG = 0.63 (0.62, 0.64); p = 0.001), MIP (rs799187; ORA = 1.69 (1.66, 1.72); p = 0.034), and CXCL16 (rs8071286; ORA = 1.42 (1.41, 1.44); p = 0.018) were found to be associated with critically ill patients. Polymorphisms in the CXCL10, CCL2, IL1, CCL7 and TNF genes were not associated with the COVID-19 critical phenotype. The genotypes of IL-6 (Gene: IL6 (7p15.3)) and CXCL-16 (Gene: CXCL16 (17p13.2)) were significantly associated with the serum levels of the respective cytokine in critical cases of COVID-19. CONCLUSION: Data obtained from measuring cytokine levels and genetic variant analyses suggest that IL-6 and CXCL-16 could potentially be used as potential biomarkers for monitoring disease progression of COVID-19 patients. The findings in this study suggest that specific cytokine gene variants correlate with serum levels of the specific cytokine. These genetic variants could be of assistance in the early identification of high-risk patients on admission to the clinic to improve the management of COVID-19 patients, and other infectious diseases.

Airways tissue expression of type I interferons and their stimulated genes is higher in children than adults.

There is emerging evidence that age-dependent differences in susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlate with stronger innate immune response in the upper respiratory tract in children compared to adults. The efficient induction of interferon (IFN) alpha and beta (α and ß) signaling, and interferon-stimulated genes (ISGs) is fundamental to the host antiviral response. In-silico transcriptomic analyses was conducted to determine the expression levels of IFN α/ß pathway genes as well as 524 human ISGs in upper and lower airways of children and adults at baseline and post respiratory infections including coronavirus disease 2019 (COVID-19). To validate our in-silico analysis, we conducted qRT-PCR to measure ISGs levels in children and adult's nasal epithelial samples. At baseline, children had significantly higher levels of IFN α/ß and ISGs genes compared to adults. More distinction was also seen in bronchial compared to nasal basal levels. Children nasal epithelial cells exhibited superior antiviral IFN α/ß and associated ISGs response following ex-vivo poly (I:C) treatment model, and in clinical samples of SARS-CoV-2 infected patients. This was also confirmed in nasal epithelial samples using qRT-PCR validation. No gender-based difference in type I IFN levels across both age groups were observed. Understanding the biological basis for children resistance against severe COVID-19 is a challenge that has substantial clinical importance. More mechanistic studies are needed to carefully quantify how much of early IFN levels is needed to bypass the viral evasion mechanism and prevent its further replication and dissemination to lower airways and the rest of the body.

Vitamin D enhances type I IFN signaling in COVID-19 patients.

The ability of Vitamin D (VitD) to modulate antiviral responses through induction of antimicrobial peptide is well established. However, the effect of VitD on host responses to SARS-CoV-2 is not well investigated. We here report the ability of VitD to enhance host IFN-alpha/beta (a/ß) signaling both in vitro and among severe COVID-19 patients treated with VitD. Blood and saliva specimens were obtained from severe COVID-19 patients treated (43 patients), or not (37 patients), with vitD, during their stay in intensive care unit. Patients were followed up to 29 days following admission, and patient survival outcomes were collected. Higher activity levels of RIG-1/MDA-5 and JAK-STAT signaling pathways were observed with significantly higher gene and protein levels of antiviral interferon stimulating genes (ISGs) such as MX-1 and ISG-15; both in vitro, following treatment of PBMCs with vitD, and in whole blood and saliva specimens of VitD treated patients. Moreover, VitD treated patients had lower risk of all-cause mortality by day 29 compared to untreated patients (adjusted hazard ratio, 0.37, 95% confidence interval of 0.14-0.94; P = 0.038). The herein uncovered regulatory role of VitD on type I IFNs suggests the importance of insuring a normal level of VitD for the prevention and probably treatment of SARS-CoV-2 infection. Additional mechanistic studies, however, are needed to fully elucidate the antiviral effects of VitD particularly in the setting of COVID-19 infection.

Detection of SARS-CoV-2 in clinical and environmental samples using highly sensitive reduced graphene oxide (rGO)-based biosensor.

Quantitative RT-PCR (qRT-PCR) is the most commonly used diagnostic tool for SARS-CoV-2 detection during the COVID-19 pandemic. Despite its sensitivity and accuracy, qRT-PCR is a time-consuming method that requires expensive laboratories with highly trained personnel. In this work, on-site detection of SARS-CoV-2 in municipal wastewater was investigated for the first time. The wastewater was unprocessed and did not require any prefiltration, prior spiking with virus, or viral concentration in order to be suitable for use with the biosensor. The prototype reported here is a reduced graphene oxide (rGO)-based biosensor for rapid, sensitive and selective detection of SARS-CoV-2. The biosensor achieved a limit of detection (LOD) of 0.5 fg/mL in phosphate-buffered saline (PBS) and exhibited specificity when exposed to various analytes. The response time was measured to be around 240 ms. To further explore the capabilities of the biosensor in real clinical and municipal wastewater samples, three different tests were performed to determine the presence or absence of the virus: (i) qRT-PCR, (ii) a rapid antigen-based commercially available test (COVID-19 Test Strips), and (iii) the biosensor constructed and reported here. Taken together, our results demonstrate that a biosensor that can detect SARS-CoV-2 in clinical samples as well as unfiltered and unprocessed municipal wastewater is feasible.

Analysis of SARS-CoV-2 viral loads in stool samples and nasopharyngeal swabs from COVID-19 patients in the United Arab Emirates.

Coronavirus disease 2019 (COVID-19) was first identified in respiratory samples and was found to commonly cause cough and pneumonia. However, non-respiratory symptoms including gastrointestinal disorders are also present and a big proportion of patients test positive for the virus in stools for a prolonged period. In this cross-sectional study, we investigated viral load trends in stools and nasopharyngeal swabs and their correlation with multiple demographic and clinical factors. The study included 211 laboratory-confirmed cases suffering from a mild form of the disease and completing their isolation period at a non-hospital center in the United Arab Emirates. Demographic and clinical information was collected by standardized questionnaire and from the medical records of the patient. Of the 211 participants, 25% tested negative in both sample types at the time of this study and 53% of the remaining patients had detectable viral RNA in their stools. A positive fecal viral test was associated with male gender, diarrhea as a symptom, and hospitalization during infection. A positive correlation was also observed between a delayed onset of symptoms and a positive stool test. Viral load in stools positively correlated with, being overweight, exercising, taking antibiotics in the last 3 months and blood type O. The viral load in nasopharyngeal swabs, on the other hand, was higher for blood type A, and rhesus positive (Rh factor). Regression analysis showed no correlation between the viral loads measured in stool and nasopharyngeal samples in any given patient. The results of this work highlight the factors associated with a higher viral count in each sample. It also shows the importance of stool sample analysis for the follow-up and diagnosis of recovering COVID-19 patients.

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.

Genomic epidemiology and emergence of SARS-CoV-2 variants of concern in the United Arab Emirates.

Since the declaration of SARS-CoV-2 outbreak as a pandemic, the United Arab Emirates (UAE) public health authorities have adopted strict measures to reduce transmission as early as March 2020. As a result of these measures, flight suspension, nationwide RT-PCR and surveillance of viral sequences were extensively implemented. This study aims to characterize the epidemiology, transmission pattern, and emergence of variants of concerns (VOCs) and variants of interests (VOIs) of SARS-CoV-2 in the UAE, followed by the investigation of mutations associated with hospitalized cases. A total of 1274 samples were collected and sequenced from all seven emirates between the period of 25 April 2020 to 15 February 2021. Phylogenetic analysis demonstrated multiple introductions of SARS-CoV-2 into the UAE in the early pandemic, followed by a local spread of root clades (A, B, B.1 and B.1.1). As the international flight resumed, the frequencies of VOCs surged indicating the January peak of positive cases. We observed that the hospitalized cases were significantly associated with the presence of B.1.1.7 (p < 0.001), B.1.351 (p < 0.001) and A.23.1 (p = 0.009). Deceased cases are more likely to occur in the presence of B.1.351 (p < 0.001) and A.23.1 (p = 0.022). Logistic and ridge regression showed that 51 mutations are significantly associated with hospitalized cases with the highest proportion originated from S and ORF1a genes (31% and 29% respectively). Our study provides an epidemiological insight of the emergence of VOCs and VOIs following the borders reopening and worldwide travels. It provides reassurance that hospitalization is markedly more associated with the presence of VOCs. This study can contribute to understand the global transmission of SARS-CoV-2 variants.

A deep learning-driven low-power, accurate, and portable platform for rapid detection of COVID-19 using reverse-transcription loop-mediated isothermal amplification.

This paper presents a deep learning-driven portable, accurate, low-cost, and easy-to-use device to perform Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) to facilitate rapid detection of COVID-19. The 3D-printed device-powered using only a 5 Volt AC-DC adapter-can perform 16 simultaneous RT-LAMP reactions and can be used multiple times. Moreover, the experimental protocol is devised to obviate the need for separate, expensive equipment for RNA extraction in addition to eliminating sample evaporation. The entire process from sample preparation to the qualitative assessment of the LAMP amplification takes only 45 min (10 min for pre-heating and 35 min for RT-LAMP reactions). The completion of the amplification reaction yields a fuchsia color for the negative samples and either a yellow or orange color for the positive samples, based on a pH indicator dye. The device is coupled with a novel deep learning system that automatically analyzes the amplification results and pays attention to the pH indicator dye to screen the COVID-19 subjects. The proposed device has been rigorously tested on 250 RT-LAMP clinical samples, where it achieved an overall specificity and sensitivity of 0.9666 and 0.9722, respectively with a recall of 0.9892 for Ct < 30. Also, the proposed system can be widely used as an accurate, sensitive, rapid, and portable tool to detect COVID-19 in settings where access to a lab is difficult, or the results are urgently required.

Identifying Immunological and Clinical Predictors of COVID-19 Severity and Sequelae by Mathematical Modeling.

Since its emergence as a pandemic in March 2020, coronavirus disease (COVID-19) outcome has been explored via several predictive models, using specific clinical or biochemical parameters. In the current study, we developed an integrative non-linear predictive model of COVID-19 outcome, using clinical, biochemical, immunological, and radiological data of patients with different disease severities. Initially, the immunological signature of the disease was investigated through transcriptomics analysis of nasopharyngeal swab samples of patients with different COVID-19 severity versus control subjects (exploratory cohort, n=61), identifying significant differential expression of several cytokines. Accordingly, 24 cytokines were validated using a multiplex assay in the serum of COVID-19 patients and control subjects (validation cohort, n=77). Predictors of severity were Interleukin (IL)-10, Programmed Death-Ligand-1 (PDL-1), Tumor necrosis factors-α, absolute neutrophil count, C-reactive protein, lactate dehydrogenase, blood urea nitrogen, and ferritin; with high predictive efficacy (AUC=0.93 and 0.98 using ROC analysis of the predictive capacity of cytokines and biochemical markers, respectively). Increased IL-6 and granzyme B were found to predict liver injury in COVID-19 patients, whereas interferon-gamma (IFN-γ), IL-1 receptor-a (IL-1Ra) and PD-L1 were predictors of remarkable radiological findings. The model revealed consistent elevation of IL-15 and IL-10 in severe cases. Combining basic biochemical and radiological investigations with a limited number of curated cytokines will likely attain accurate predictive value in COVID-19. The model-derived cytokines highlight critical pathways in the pathophysiology of the COVID-19 with insight towards potential therapeutic targets. Our modeling methodology can be implemented using new datasets to identify key players and predict outcomes in new variants of COVID-19.

Optimization of an rGO-based biosensor for the sensitive detection of bovine serum albumin: Effect of electric field on detection capability.

Despite significant progress in the field of biosensing, the impact of electric field on biosensor detection capability and the feasibility of the biosensor application in wastewater has yet to be investigated. The objective of this study was to develop a low-cost, highly sensitive, and selective reduced graphene oxide (rGO)-based biosensor. The constructed biosensor consists of an in-house prepared GO and a four-terminal Kelvin sensing. Spin-coating was chosen as the deposition technique and results revealed an optimal GO number of layers and concentration of 7 and 2 mg/mL, respectively. Experiments to determine the effects of electric field on the performance of the biosensor showed significant changes in the biosensor surface, also presenting a direct impact on the biosensor functionality, such that the biosensor showed an increase in limit of detection (LOD) from 1 to 106 fg/mL when the applied voltage was increased from 0.0008 to 0.2 V. Furthermore, this study successfully explores a pilot scale setup, mimicking wastewater flow through sewage pipelines. The demonstrated improvements in the detection capability and sensitivity of this biosensor at optimized testing conditions make it a promising candidate for further development and deployment for the detection of protein analytes present at very low concentrations in aqueous solutions. In addition, the application of this biosensor could be extended to the detection of protein analytes of interest (such as the spike protein of SARS-CoV-2) in much more complex solutions, like wastewater.

Travel ban effects on SARS-CoV-2 transmission lineages in the UAE as inferred by genomic epidemiology.

Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to the later introductions of the G-variant associated with international travel, rather than higher local transmissibility. For clades spanning different emirates, the most recent common ancestors pre-date domestic travel bans. In conclusion, we observe a steep and sustained decline of international transmissions immediately following the introduction of international travel restrictions.

HLA repertoire of 115 UAE nationals infected with SARS-CoV-2.

The class I and class II Human Leucocyte Antigens (HLA) are an integral part of the host adaptive immune system against viral infections. The characterization of HLA allele frequency in the population can play an important role in determining whether HLA antigens contribute to viral susceptibility. In this regard, global efforts are currently underway to study possible correlations between HLA alleles with the occurrence and severity of SARS-CoV-2 infection. Specifically, this study examined the possible association between specific HLA alleles and susceptibility to SARS-CoV-2 in a population from the United Arab Emirates (UAE). The frequencies of HLA class I (HLA-A, -B, and -C) and HLA class II alleles (HLA-DRB1 and -DQB1); defined using Next Generation Sequencing (NGS); from 115 UAE nationals with mild, moderate, and severe SARS-CoV-2 infection are presented here. HLA alleles and supertypes were compared between hospitalized and non-hospitalized subjects. Statistical significance was observed between certain HLA alleles and supertypes and the severity of the infection. Specifically, alleles HLA-B*51:01 and HLA-A*26:01 showed a negative association (suggestive of protection), whilst genotypes HLA-A*03:01, HLA-DRB1*15:01, and supertype B44 showed a positive association (suggestive of predisposition) to COVID-19 severity. The results support the potential use of HLA testing to differentiate between patients who require specific clinical management strategies.

Allelic Variants Within the ABO Blood Group Phenotype Confer Protection Against Critical COVID-19 Hospital Presentation.

Introduction: Coronavirus disease 2019 (COVID-19) disease severity differs widely due to numerous factors including ABO gene-derived susceptibility or resistance. The objective of this study was to investigate the association of the ABO blood group and genetic variations of the ABO gene with COVID-19 severity in a heterogeneous hospital population sample from the United Arab Emirates, with the use of an epidemiological and candidate gene approach from a genome-wide association study (GWAS). Methods: In this cross-sectional study, a total of 646 participants who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited from multiple hospitals and population-based (quarantine camps) recruitment sites from March 2020 to February 2021. The participants were divided into two groups based on the severity of COVID-19: noncritical (n = 453) and critical [intensive care unit (ICU) patients] (n = 193), as per the COVID-19 Reporting and Data System (CO-RADS) classification. The multivariate logistic regression analysis demonstrated the association of ABO blood type as well as circulating anti-A antibodies and anti-B antibodies as well as A and B antigens, in association with critical COVID-19 hospital presentation. A candidate gene analysis approach was conducted from a GWAS where we examined 240 single nucleotide polymorphisms (SNPs) (position in chr9: 136125788-136150617) in the ABO gene, in association with critical COVID-19 hospital presentation. Results: Patients with blood group O [odds ratio (OR): 0.51 (0.33, 0.79); p = 0.003] were less likely to develop critical COVID-19 symptoms. Eight alleles have been identified to be associated with a protective effect of blood group O in ABO 3'untranslated region (UTR): rs199969472 (p = 0.0052), rs34266669 (p = 0.0052), rs76700116 (p = 0.0052), rs7849280 (p = 0.0052), rs34039247 (p = 0.0104), rs10901251 (p = 0.0165), rs9411475 (p = 0.0377), and rs13291798 (p = 0.0377). Conclusion: Our findings suggest that there are novel allelic variants that link genetic variants of the ABO gene and ABO blood groups contributing to the reduced risk of critical COVID-19 disease. This study is the first study to combine genetic and serological evidence of the involvement of the ABO blood groups and the ABO gene allelic associations with COVID-19 severity within the Middle Eastern population.