| Summary: | Abstract Background COVID-19 has an important component of organ damage which is COVID-19-associated coagulopathy. It is necessary to assess the risk in patients to develop a thrombophylaxis plan. The higher prevalence of key thrombophilic genetic variants, such as mutation of the C677T-methylenetetrahydrofolate reductase (MTHFR) gene in Eastern Mediterranean countries, makes it challenging to use the same criteria in other world countries with differing thrombophilic panels. Objective To find the incidence of MTHFR gene polymorphism in a cohort of Egyptian patients with COVID-19, and its association with thromboembolic events. Subjects and methods This was a prospective observational cohort study, done at Ain-Shams University isolation Hospitals, Cairo, Egypt. It included 33 patients with COVID-19 and 13 healthy controls. The patients underwent lab investigations: HRCT chest in which the extent of radiological affection was described in terms of severe form (> 50% of lungs are affected) and non-severe form (< 50% of lungs are affected) and assessment of MTHFR-C677T genotypes. Then follow-up for 28 days for vascular thrombotic manifestations. Results Out of 33 patients, MTHFR-gene mutation was found in 10 (incidence rate 30.3%). Severe form of affection in the HRCT chest was significantly related to mutation of the MTHFR gene (P value = 0.009). Patient cure and discharge were significantly related to the absence of mutation of MTHFR-gene (P value = 0.025), whereas death and radiological evidence of thrombosis were significantly related to the presence of MTHFR-gene mutation (P value = 0.027 and 0.022 respectively). Age > 55 years (60% sensitivity, 100% specificity, PPV 100%), albumin ≤ 3.2 gm/dl (50% sensitivity, 95.65% specificity, PPV83.3%), and ferritin > 453 ng/L (70% sensitivity, 82.61% specificity, PPV 63.6%) were predictors of mutation of MTHFR-gene. Conclusion Incidence of mutation of MTHFR-gene was 30.3% in COVID-19 patients. Results suggest a potential association between inherited MTHFR gene mutation and severe form of COVID-19, thromboembolic events, and mortality. Trial registration ClinicalTrials.gov ID: NCT05679414. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CU2V&selectaction=Edit&uid=U00056R5&ts=2&cx=lrrb7q . Retrospectively registered. 9th Jan 2023.
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