ABSTRACT
Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: ACE rs4646994, ACE2 rs2285666, and LZTFL1 rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases (n = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients (n = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism LZTFL1 rs11385942 as an important risk factor for hospitalization (p < 0.01; OR = 5.73; 95% CI = 1.2-26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79-0.93). These results suggest that LZTFL1 rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.
ABSTRACT
Coronavirus 19 disease (COVID-19) presents a highly variable clinical presentation and course, ranging from asymptomatic patients to rapidly progressive, fatal pneumonia. The known heterogeneous outcomes can affect both previously healthy patients and those with significant comorbidities, who develop clinical courses with possibly more multisystemic compromise. Likewise, the development of thrombotic phenomena during the acute course of the disease is associated with complications that worsen patient prognosis. We present a case report of a 45-year-old multiparous patient with a history of overweight and chronic use of oral hormonal contraception with low doses of levonorgestrel and estradiol as the only risk factors favoring the development of thrombotic events. During her outpatient COVID-19 clinical course, she developed massive pulmonary thromboembolism resulting in secondary obstructive shock, which required pharmacological thrombolysis. At discharge, hormonal contraception was considered contraindicated, and the patient was released from our institution with continued oral anticoagulant therapy. COVID-19 infection, contraceptive hormone therapy, and overweight are known risk factors for the development of thromboembolic events. The impact of their concomitance has not been studied to date. From our experience, we discuss the impact these risk factors have when present together and invite others to report similar cases.