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Genetic determinants of SARS-CoV-2 and the clinical outcome of COVID-19 in Southern Bangladesh.

Md Mahbub Hasan·Chayan Kumar Saha·H M Hamidullah Mehedi·Kallyan Chakma·Asma Salauddin·Md Shakhawat Hossain·Farjana Sharmen·S M Rafiqul Islam·Afroza Akter Tanni·Farhana Yasmin·Al-Shahriar Akash·Mohammad Enayet Hossain·Mojnu Miah·Sanjoy Kanti Biswas·Nahid Sultana·Adnan Mannan
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Abstract

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a severe impact on population health. The genetic determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Bangladesh are not well understood. METHODS: This study aimed to determine the genomic variation in SARS-CoV-2 genomes that have evolved over 2 years of the pandemic in southern Bangladesh and their association with disease outcomes and virulence of this virus. We investigated demographic variables, disease outcomes of COVID-19 patients and genomic features of SARS-CoV-2. RESULTS: We observed that the disease severity was significantly higher in adults (85.3%) than in children (14.7%), because the expression of angiotensin-converting enzyme-2 (ACE-2) diminishes with ageing that causes differences in innate and adaptive immunity. The clade GK (n = 66) was remarkable between June 2021 and January 2022. Because of the mutation burden, another clade, GRA started a newly separated clustering in December 2021. The burden was significantly higher in GRA (1.5-fold) highlighted in mild symptoms of COVID-19 patients than in other clades (GH, GK, and GR). Mutations were accumulated mainly in S (22.15 mutations per segment) and ORF1ab segments. Missense (67.5%) and synonymous (18.31%) mutations were highly noticed in adult patients with mild cases rather than severe cases, especially in ORF1ab segments. Moreover, we observed many unique mutations in S protein in mild cases compared to severe, and homology modeling revealed that those might cause more folding in the protein's alpha helix and beta sheets. CONCLUSION: Our study identifies some risk factors such as age comorbidities (diabetes, hypertension, and renal disease) that are associated with severe COVID-19, providing valuable insight regarding prioritizing vaccination for high-risk individuals and allocating health care and resources. The findings of this work outlined the knowledge and mutational basis of SARS-CoV-2 for the next treatment steps. Further studies are needed to confirm the effects of structural and functional proteins of SARS-CoV-2 in detail for monitoring the emergence of new variants in future.

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AdultChildHumansSARS-CoV-2COVID-19BangladeshAdaptive ImmunityAgingORF1abS protein structurecladeclinical outcomegenetic determinantsmutationsJournal ArticleResearch Support, Non-U.S. Gov't

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Md Mahbub Hasan, Chayan Kumar Saha, H M Hamidullah Mehedi, Kallyan Chakma, Asma Salauddin, Md Shakhawat Hossain, Farjana Sharmen, S M Rafiqul Islam, Afroza Akter Tanni, Farhana Yasmin, Al-Shahriar Akash, Mohammad Enayet Hossain, Mojnu Miah, Sanjoy Kanti Biswas, Nahid Sultana, Adnan Mannan. 2024. Genetic determinants of SARS-CoV-2 and the clinical outcome of COVID-19 in Southern Bangladesh.. https://doi.org/10.1002/iid3.1171

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