Correlation Between HLA Type and Covid-19 Severity Among the Palestinian Population رسالة ماجستير

Abstract

Background: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020. In the West Bank and Gaza Strip, the deaths are 5,708, with over 703,228 infection cases. (University, 2020). The progression of associated symptoms varies considerably, ranging from asymptomatic cases to severe, critical, and fatal ones. (F. Wang et al., 2020a)'(WHO, 2020) This variability has prompted global research to understand the underlying factor. One major focus has been the Human Leukocyte Antigen (HLA) system and its role in shaping the immune response and influencing disease severity. Purpose: The study aimed to explore the statistical correlation between HLA class I alleles and COVID-19 severity among a Palestinian cohort of 18 ICU patients in the West Bank with severe and critical illness during the period from February 2021 to September 2021. It also aimed to suggest a potential immunological mechanism involving T cell epitope interaction. Methods: DNA extracted from blood samples of ICU patients was subjected to whole-exome sequencing using Next Generation Sequencing technologies. Genotyping was conducted using HISAT, with comparisons across HLA-LA, HISAT genotyping, and Seq2HLA tools. Statistical associations between HLA-I alleles and disease severity were assessed using Fisher’s Exact and Yates χ² tests via Prism software. The Benjamini-Hochberg method was used for P-value correction. Additionally, Python scripts were developed to visualize T cell epitopes on the SARS-CoV-2 Spike and Nucleocapsid proteins using the Immune Epitope Database (IEDB). Results: The analysis identified several HLA-I alleles A*01:03, B*15:10, B*57:03, C*03:04, C*07:01, C*07:02, and C*14:02. as significantly associated with critical COVID-19 cases (P < 0.05). HLA-C*07:01 and HLA-C*07:02 may play a role in disease severity through their interaction with key viral epitopes, potentially facilitating viral entry or immune. Conclusion: These findings suggest a possible role for these HLA-I alleles in modulating the immune response and influencing the severity of COVID-19.