Elevated Interleukin-13 (IL-13) may play an important role in the pathophysiology of COVID-19, yet, the attenuated response did not notice across all severe cases. Susceptibility to asthma in specific populations is associated with several SNPs of multifunctional cytokines, such as IL-13, IL-31 and IL-33. This prospective case-control study is designed to investigate the extent of genetic susceptibility in subsets of Iraqi patients with COVID-19 by targeting the variants of interleukin IL-13rs20541 polymorphism in relation to disease susceptibility and severity of clinical presentation. One hundred samples were obtained from the throat, nasopharyngeal and nasal swabs enrolled in this study. Eighty samples of the throat, nasopharyngeal and nasal localization swabs were obtained from patients with acute respiratory distress syndrome (ARDS) (both COVID-19 and non-COVID19 patients), while other 20 nasopharyngeal swabs were included as a healthy control group (AHC). Detection of IL-13rs20541 polymorphism was done by ARMS technique. The frequencies of GG- genotype in ARDS- patients with COVID-19, non-COVID19-, and AHC groups were respectively 14%, 12% and 3%, where, and as compared to the control group, showed a significant increase in COVID-19 patients. The AA- genotype in patients with COVID-19 group, non- COVID-19 group and healthy control group documented the frequency of 9%, 7%, and 14%, respectively, where the frequency decreased in the patient's groups as compared to the AHC group. Finally, and among the studied groups, an increase of AG- genotype (as rate OR=1.89) was documented compared to genotype GG and A-. Genetic polymorphisms in the IL-13rs20541 gene might influence its functions in patients with SARS-associated respiratory tract infection and thus might involve the pathogenicity of patients with COVID-19.