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

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

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.

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.

Evolution, Ecology, and Zoonotic Transmission of Betacoronaviruses: A Review.

Coronavirus infections have been a part of the animal kingdom for millennia. The difference emerging in the twenty-first century is that a greater number of novel coronaviruses are being discovered primarily due to more advanced technology and that a greater number can be transmitted to humans, either directly or via an intermediate host. This has a range of effects from annual infections that are mild to full-blown pandemics. This review compares the zoonotic potential and relationship between MERS, SARS-CoV, and SARS-CoV-2. The role of bats as possible host species and possible intermediate hosts including pangolins, civets, mink, birds, and other mammals are discussed with reference to mutations of the viral genome affecting zoonosis. Ecological, social, cultural, and environmental factors that may play a role in zoonotic transmission are considered with reference to SARS-CoV, MERS, and SARS-CoV-2 and possible future zoonotic events.