HLA-B*15 predicts survival in Egyptian patients with COVID-19

Abdelhafiz, Ahmed Samir; Ali, Asmaa; Fouda, Merhan A.; Sayed, Douaa; Kamel, Mahmoud M.; Kamal, Lamyaa Mohamed; Khalil, Mahmoud A F; Bakry, Rania

doi:10.1016/j.humimm.2021.09.007

Cited by 14 publications

(27 citation statements)

References 45 publications

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“…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%

“… 62 A study conducted in Egypt reported on the protective role of HLA‐B*15 against COVID‐19 related mortality, but we detected various discordances in the presentation of their results. 50 …”

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%

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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

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

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“…individuals from our cohort, we did not find statistical significance in the comparison between groups (S2 Fig) . In order to determine whether the amino acid exchanges at positions 9, 11, 24, 77, 80, 90, 94, and 95, which are characteristic of groups C1 and C2, may differentially influence the bindingpocket structure in HLA-C alleles, we used the 3D structure of HLA-C � 07:02 [53] as a template to perform mutagenesis in silico in these positions (marked as grey residues in Fig 1A and 1B). These positions were changed to Tyr 9 , Ser 11 , Ala 24 , Ser 77 , Asn 80 , Ala 90 , Thr 94 , and Leu 95 , as are in HLA-C � 08:02 allele, which belongs to group C1 and its frequency was significantly higher in individuals with mild COVID-19 (Fig 1A, left image), as well as to Asp 9 , Ala 11 , Ser 24 , Asn 77 , Lys 80 , Asp 90 , Ile 94 , and Ile 95 , as are in HLA-C � 07:01 allele, which belongs to group C2 and its frequency was significantly higher in individuals with severe COVID-19 (Fig 1A, right graph). We observed that these amino acid exchanges induced a conformational modification in the binding pocket structure due to changes in the number and/or position of hydrogen-type bonds (red lines), which could affect both residue-residue and residue-antigenic amino acids interactions in the pocket (green residues) (Fig 1B), as well as the molecule stability.…”

Section: Plos Onementioning

confidence: 99%

“…Therefore, HLA-B is traditionally subdivided into -Bw6 (Ser 77 and Asn 80 ) and -Bw4 epitopes [28] that are characterized by at least seven different patterns of amino acid exchanges in these positions, whereas HLA-C alleles are subdivided into groups C1 and C2, which are mutually exclusive. Alleles from group C1 contain Ser 77 and Asn 80 and are ligands for the inhibitory KIR2DL2 and -2DL3, as well as for the activating KIR2DS2, whereas alleles from group C2 contain Asn 77 and Lys 80 [29] and are ligands for the inhibitory KIR2DL1 and activating KIR2DS1 [30]. As a major characteristic, HLA-C molecules show a distinctly lower expression on the cell surface in comparison with HLA-A and -B molecules, most likely due to low mRNA expression, poor assembly with β2M, or restricted peptide binding that leads to the accumulation of misfolded intermediates in the endoplasmic reticulum [31].…”

Section: Introductionmentioning

confidence: 99%

Association between HLA-C alleles and COVID-19 severity in a pilot study with a Spanish Mediterranean Caucasian cohort

Vigón

Galán²,

Torres³

et al. 2022

PLoS ONE

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The clinical presentations of COVID-19 may range from an asymptomatic or mild infection to a critical or fatal disease. Several host factors such as elderly age, male gender, and previous comorbidities seem to be involved in the most severe outcomes, but also an impaired immune response that causes a hyperinflammatory state but is unable to clear the infection. In order to get further understanding about this impaired immune response, we aimed to determine the association of specific HLA alleles with different clinical presentations of COVID-19. Therefore, we analyzed HLA Class I and II, as well as KIR gene sequences, in 72 individuals with Spanish Mediterranean Caucasian ethnicity who presented mild, severe, or critical COVID-19, according to their clinical characteristics and management. This cohort was recruited in Madrid (Spain) during the first and second pandemic waves between April and October 2020. There were no significant differences in HLA-A or HLA-B alleles among groups. However, despite the small sample size, we found that HLA-C alleles from group C1 HLA-C*08:02, -C*12:03, or -C*16:01 were more frequently associated in individuals with mild COVID-19 (43.8%) than in individuals with severe (8.3%; p = 0.0030; pc = 0.033) and critical (16.1%; p = 0.0014; pc = 0.0154) disease. C1 alleles are supposed to be highly efficient to present peptides to T cells, and HLA-C*12:03 may present a high number of verified epitopes from abundant SARS-CoV-2 proteins M, N, and S, thereby being allegedly able to trigger an efficient antiviral response. On the contrary, C2 alleles are usually poorly expressed on the cell surface due to low association with β2-microglobulin (β2M) and peptides, which may impede the adequate formation of stable HLA-C/β2M/peptide heterotrimers. Consequently, this pilot study described significant differences in the presence of specific HLA-C1 alleles in individuals with different clinical presentations of COVID-19, thereby suggesting that HLA haplotyping could be valuable to get further understanding in the underlying mechanisms of the impaired immune response during critical COVID-19.

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The role of HLA genetic variants in COVID‐19 susceptibility, severity, and mortality: A global review

Hoseinnezhad,

Soltani,

Ziarati

et al. 2024

Clinical Laboratory Analysis

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BackgroundThe COVID‐19 pandemic has had a profound global impact, with variations in susceptibility, severity, and mortality rates across different regions. While many factors can contribute to the spread and impact of the disease, specifically human leukocyte antigen (HLA) genetic variants have emerged as potential contributors to COVID‐19 outcomes.MethodsIn this comprehensive narrative review, we conducted a thorough literature search to identify relevant studies investigating the association between HLA genetic variants and COVID‐19 outcomes. Additionally, we analyzed allelic frequency data from diverse populations to assess differences in COVID‐19 incidence and severity.ResultsOur review provides insights into the immunological mechanisms involving HLA‐mediated responses to COVID‐19 and highlights potential research directions and therapeutic interventions. We found evidence suggesting that certain HLA alleles, such as HLA‐A02, may confer a lower risk of COVID‐19, while others, like HLA‐C04, may increase the risk of severe symptoms and mortality. Furthermore, our analysis of allele frequency distributions revealed significant variations among different populations.ConclusionConsidering host genetic variations, particularly HLA genetic variants, is crucial for understanding COVID‐19 susceptibility and severity. These findings have implications for personalized treatment and interventions based on an individual's genetic profile. However, further research is needed to unravel the precise mechanisms underlying the observed associations and explore the potential for targeted therapies or preventive measures based on HLA genetic variants.

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HLA-B*15 predicts survival in Egyptian patients with COVID-19

Cited by 14 publications

References 45 publications

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

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

Association between HLA-C alleles and COVID-19 severity in a pilot study with a Spanish Mediterranean Caucasian cohort

The role of HLA genetic variants in COVID‐19 susceptibility, severity, and mortality: A global review

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