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Background: The clinical presentations of coronavirus disease 2019 (COVID-19) exhibit significant variation, ranging from asymptomatic cases to mortality resulting from severe pneumonia. Host genetics can partially explain this variation. Objective: This study evaluated possible associations between severity and outcome of COVID-19 and single nucleotide polymorphism (SNP) rs2285666 in the Methods: The study included a sample of 100 consecutive adult patients admitted to the COVID-19 Isolation and Intensive Care Units of the Zagazig University Hospitals, Zagazig, Egypt from July 2021 to November 2021. For rs2285666, polymerase chain reaction-restriction fragment length polymorphism was carried out. For rs2070788, real-time polymerase chain reaction was performed. Results: For rs2285666, the GA genotype was the most frequent among female patients (39% [16/41]) and the A genotype was more prevalent among male patients (54.2% [32/59]). For rs2070788, the AA genotype was the most frequent among all patients (46% [46/100]). No rs2285666 or rs2070788 genotypes or allele frequencies had significant associations with either severity or outcomes of patients. Conclusion: This study found no significant associations of COVID-19 severity or outcomes of patients with genotypes or allele frequencies of the rs2285666 SNP in the What this study adds: The study reveals that host genetics explain the variation observed in the disease. Specific genetic variants can confer either increased susceptibility or resistance to the disease.