High‐resolution HLA genotyping identifies alleles associated with severe COVID‐19: A preliminary study from India

Vishnubhotla, Ravikanth; Sasikala, M.; Ketavarapu, Vijayasarathy; Reddy, Duvvur Nageshwar

doi:10.1002/iid3.481

Cited by 14 publications

(16 citation statements)

References 12 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our finding on the association between HLA-C*04:01 genomic quantity and COVID-19 severity is consistent with some previous reports of cross-sectional studies, involving Indian ( 32 ), German ( 21 ) and USA (multiethnic) ( 21 , 22 ) cohorts. Consistently to our results, Warren and Birol ( 22 ) also report that the high prevalence of HLA-C*04:01 allele may predispose to severe COVID-19 in patients with a white ethnic background, female gender and advanced age (≥65 years old).…”

Section: Discussionsupporting

confidence: 93%

“…The threshold of the plot was calculated from the optimal sensitivity and specificity in the AUC, which revealed a significant difference between hospitalized and non-hospitalized cases (P=6,54E-21; Figure 3D). The model was able to discriminate higher OR Our finding on the association between HLA-C*04:01 genomic quantity and COVID-19 severity is consistent with some previous reports of cross-sectional studies, involving Indian (32), German (21) and USA (multiethnic) (21,22) cohorts. Consistently to our results, Warren and Birol (22) also report that the high prevalence of HLA-C*04:01 allele may predispose to severe COVID-19 in patients with a white ethnic background, female gender and advanced age (≥65 years old).…”

Section: Predictors Of Hospitalization and Icu Admission Of Armenian ...supporting

confidence: 91%

“…Another study indicates HLA-C*04:01 association with susceptibility but not COVID-19 severity in the Sardinian/Italian population ( 34 ). Despite this allelic variability conferring COVID‐19 or its clinical heterogeneity across ethnicities, the inability of the identified alleles to effectively bind the SARS‐CoV‐2 viral peptides and to trigger an adequate immune response among others may be one of the main causative mechanisms for severe disease ( 20 , 26 , 31 , 32 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity

Հովհաննիսյան

Madelian²,

Avagyan³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

The novel SARS-CoV-2 coronavirus infection has become a global health concern, causing the COVID-19 pandemic. The disease symptoms and outcomes depend on the host immunity, in which the human leukocyte antigen (HLA) molecules play a distinct role. The HLA alleles have an inter-population variability, and understanding their link to the COVID-19 in an ethnically distinct population may contribute to personalized medicine. The present study aimed at detecting associations between common HLA alleles and COVID-19 susceptibility and severity in Armenians. In 299 COVID-19 patients (75 asymptomatic, 102 mild/moderate, 122 severe), the association between disease severity and classic HLA-I and II loci was examined. We found that the advanced age, male sex of patients, and sex and age interaction significantly contributed to the severity of the disease. We observed that an age-dependent effect of HLA-B*51:01 carriage [odds ratio (OR)=0.48 (0.28-0.80), Pbonf <0.036] is protective against severe COVID-19. Contrary, the HLA-C*04:01 allele, in a dose-dependent manner, was associated with a significant increase in the disease severity [OR (95% CI) =1.73 (1.20-2.49), Pbonf <0.021] and an advancing age (P<0.013). The link between HLA-C*04:01 and age was secondary to a stronger association between HLA-C*04:01 and disease severity. However, HLA-C*04:01 exerted a sex-dependent differential distribution between clinical subgroups [females: P<0.0012; males: P=0.48]. The comparison of HLA-C*04:01 frequency between subgroups and 2,781 Armenian controls revealed a significant incidence of HLA-C*04:01 deficiency in asymptomatic COVID-19. HLA-C*04:01 homozygous genotype in patients blueprinted a decrease in heterozygosity of HLA-B and HLA class-I loci. In HLA-C*04:01 carriers, these changes translated to the SARS-CoV-2 peptide presentation predicted inefficacy by HLA-C and HLA class-I molecules, simultaneously enhancing the appropriate HLA-B potency. In patients with clinical manifestation, due to the high prevalence of HLA-C*04:01, these effects provided a decrease of the HLA class-I heterozygosity and an ability to recognize SARS-CoV-2 peptides. Based on our observations, we developed a prediction model involving demographic variables and HLA-C*04:01 allele for the identification of potential cases with the risk of hospitalization (the area under the curve (AUC) = 86.2%) or severe COVID-19 (AUC =71%).

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Predictors Of Hospitalization and Icu Admission Of Armenian ...supporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity

Հովհաննիսյան

Madelian²,

Avagyan³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…In the first two years of extensive research in the area of molecular genetics of COVID‐19, a significant number of association studies related to the disease severity, clinical course and the outcome of SARS‐CoV‐2 infection focused on host polymorphisms in HLA loci. 13 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 These studies were driven by previous results suggesting the involvement of HLA system in the regulation of the immune response to other viruses, as well as by the fine regulation of peptide‐binding properties by the extreme polymorphic feature of HLA loci. 61 , 62 …”

Section: Discussionmentioning

confidence: 99%

“…Based on this hypothesis, a relatively large number of studies investigated the role of HLA class I and class II alleles as predictors of COVID‐19 clinical course and the disease outcome. 13 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 However, their results varied significantly, possibly due to the differences in the study designs, severity‐based classification criteria, ethnicity of participants, or other factors with potential confounding effects. The observed heterogeneity between these studies makes it difficult to comprehensively assess the impact of allelic variants on disease severity.…”

Section: Introductionmentioning

confidence: 99%

The association of human leucocyte antigen (HLA) alleles with COVID‐19 severity: A systematic review and meta‐analysis

Dobrijević

Gligorijević

Šunderić

et al. 2022

Reviews in Medical Virology

View full text Add to dashboard Cite

Due to their pivotal role in orchestrating the immune response, HLA loci were recognized as candidates for genetic association studies related to the severity of COVID‐19. Since the findings on the effects of HLA alleles on the outcome of SARS‐CoV‐2 infection remain inconclusive, we aimed to elucidate the potential involvement of genetic variability within HLA loci in the molecular genetics of COVID‐19 by classifying the articles according to different disease severity/outcomes and by conducting a systematic review with meta‐analysis. Potentially eligible studies were identified by searching PubMed, Scopus and Web of Science literature databases. A total of 28 studies with 13,073 participants were included in qualitative synthesis, while the results of 19 studies with 10,551 SARS‐CoV‐2‐positive participants were pooled in the meta‐analysis. According to the results of quantitative data synthesis, association with COVID‐19 severity or with the lethal outcome was determined for the following alleles and allele families: HLA‐A*01, HLA‐A*03, HLA‐A*11, HLA‐A*23, HLA‐A*31, HLA‐A*68, HLA‐A*68:02, HLA‐B*07:02, HLA‐B*14, HLA‐B*15, HLA‐B*40:02, HLA‐B*51:01, HLA‐B*53, HLA‐B*54, HLA‐B*54:01, HLA‐C*04, HLA‐C*04:01, HLA‐C*06, HLA‐C*07:02, HLA‐DRB1*11, HLA‐DRB1*15, HLA‐DQB1*03 and HLA‐DQB1*06 (assuming either allelic or dominant genetic model). We conclude that alleles of HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 loci may represent potential biomarkers of COVID‐19 severity and/or mortality, which needs to be confirmed in a larger set of studies.

show abstract

Genetics of COVID‐19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review

Tziastoudi

Cholevas

Stefanidis

et al. 2022

Ann Clin Transl Neurol

View full text Add to dashboard Cite

COVID‐19 and ME/CFS present with some similar symptoms, especially physical and mental fatigue. In order to understand the basis of these similarities and the possibility of underlying common genetic components, we performed a systematic review of all published genetic association and cohort studies regarding COVID‐19 and ME/CFS and extracted the genes along with the genetic variants investigated. We then performed gene ontology and pathway analysis of those genes that gave significant results in the individual studies to yield functional annotations of the studied genes using protein analysis through evolutionary relationships (PANTHER) VERSION 17.0 software. Finally, we identified the common genetic components of these two conditions. Seventy‐one studies for COVID‐19 and 26 studies for ME/CFS were included in the systematic review in which the expression of 97 genes for COVID‐19 and 429 genes for ME/CFS were significantly affected. We found that ACE, HLA‐A, HLA‐C, HLA‐DQA1, HLA‐DRB1, and TYK2 are the common genes that gave significant results. The findings of the pathway analysis highlight the contribution of inflammation mediated by chemokine and cytokine signaling pathways, and the T cell activation and Toll receptor signaling pathways. Protein class analysis revealed the contribution of defense/immunity proteins, as well as protein‐modifying enzymes. Our results suggest that the pathogenesis of both syndromes could involve some immune dysfunction.

show abstract

High‐resolution HLA genotyping identifies alleles associated with severe COVID‐19: A preliminary study from India

Cited by 14 publications

References 12 publications

HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity

HLA-C*04:01 Affects HLA Class I Heterozygosity and Predicted Affinity to SARS-CoV-2 Peptides, and in Combination With Age and Sex of Armenian Patients Contributes to COVID-19 Severity

The association of human leucocyte antigen (HLA) alleles with COVID‐19 severity: A systematic review and meta‐analysis

Genetics of COVID‐19 and myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review

Contact Info

Product

Resources

About