We present the results of an association study involving hospitalized coronavirus disease 2019 (COVID-19) patients with a clinical background during the 3rd pandemic wave of COVID-19 in Slovakia. Seventeen single nucleotide variants (SNVs) in the eleven most relevant genes, according to the COVID-19 Host Genetics Initiative, were investigated. Our study confirms the validity of the influence of LZTFL1 and 2'-5'-oligoadenylate synthetase (OAS)1/OAS3 genetic variants on the severity of COVID-19. For two LZTFL1 SNVs in complete linkage disequilibrium, rs17713054 and rs73064425, the odds ratios of baseline allelic associations and logistic regressions (LR) adjusted for age and sex ranged in the four tested designs from 2.04 to 2.41 and from 2.05 to 3.98, respectively. The OAS1/OAS3 haplotype 'gttg' carrying a functional allele G of splice-acceptor variant rs10774671 manifested its protective function in the Delta pandemic wave. Significant baseline allelic associations of two DPP9 variants in all tested designs and two IFNAR2 variants in the Omicron pandemic wave were not confirmed by adjusted LR. Nevertheless, adjusted LR showed significant associations of NOTCH4 rs3131294 and TYK2 rs2304256 variants with severity of COVID-19. Hospitalized patients' reported comorbidities were not correlated with genetic variants, except for obesity, smoking (IFNAR2), and hypertension (NOTCH4). The results of our study suggest that host genetic variations have an impact on the severity and duration of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the differences in allelic associations between pandemic waves, they support the hypothesis that every new SARS-CoV-2 variant may modify the host immune response by reconfiguring involved pathways.

1st Department of Internal Medicine Faculty of Medicine Comenius University and University Hospital Bratislava Slovakia

2nd Department of Internal Medicine Faculty of Medicine Masaryk University and St Anne'S University Hospital Brno Czech Republic; International Clinical Research Centre St Anne's University Hospital and Masaryk University Brno Czech Republic

Biomedical Centre Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Clinic of Infectology and Travel Medicine University Hospital in Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Clinic of Internal Medicine Gastroenterology University Hospital in Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Clinic of Pneumology and Phthisiology University Hospital in Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Clinic of Stomatology and Maxillofacial Surgery University Hospital in Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Department of Medical Biochemistry Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Department of Microbiology and Immunology Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Department of Molecular Biology and Genomics Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Department of Pathological Anatomy Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Martin Slovakia

Faculty of Health Care and Social Work University of Trnava in Trnava Slovakia

Faculty of Health Sciences University of Ss Cyril and Methodius in Trnava Trnava Slovakia

Faculty of Medicine University of Oviedo and Central University Hospital of Asturias Oviedo Spain

Faculty of Medicine University of Oviedo and Central University Hospital of Asturias Oviedo Spain; Research and Development Services Olomouc Czech Republic

National Medical Research Centre for Cardiology Moscow Russia

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