Identifying factors contributing to increased susceptibility to COVID-19 risk: a systematic review of Mendelian randomization studies

Abstract

Background To summarize modifiable factors for coronavirus disease 2019 (COVID-19) suggested by Mendelian randomization studies. Methods In this systematic review, we searched PubMed, EMBASE and MEDLINE, from inception to 15 November 2021, for Mendelian randomization studies in English. We selected studies that assessed associations of genetically predicted exposures with COVID-19-related outcomes (severity, hospitalization and susceptibility). Risk of bias of the included studies was evaluated based on the consideration of the three main assumptions for instrumental variable analyses. Results We identified 700 studies through systematic search, of which 50 Mendelian randomization studies were included. Included studies have explored a wide range of socio-demographic factors, lifestyle attributes, anthropometrics and biomarkers, predisposition to diseases and druggable targets in COVID-19 risk. Mendelian randomization studies suggested that increases in smoking, obesity and inflammatory factors were associated with higher risk of COVID-19. Predisposition to ischaemic stroke, combined bipolar disorder and schizophrenia, attention-deficit and hyperactivity disorder, chronic kidney disease and idiopathic pulmonary fibrosis was potentially associated with higher COVID-19 risk. Druggable targets, such as higher protein expression of histo-blood group ABO system transferase (ABO), interleukin (IL)-6 and lower protein expression of 2′-5′ oligoadenylate synthetase 1 (OAS1) were associated with higher risk of COVID-19. There was no strong genetic evidence supporting the role of vitamin D, glycaemic traits and predisposition to cardiometabolic diseases in COVID-19 risk. Conclusion This review summarizes modifiable factors for intervention (e.g. smoking, obesity and inflammatory factors) and proteomic signatures (e.g. OAS1 and IL-6) that could help identify drugs for treating COVID-19.

Causal associations between body fat accumulation and COVID-19 severity: A Mendelian randomization study

“…This was supported by multiple MR studies and our analysis, which included BMI as the supplementary exposure. Other studies also assessed multiple anthropometric traits, including waist circumference, hip circumference, waist-to-hip ratio, and trunk fat ratio as well as BMI to evaluate the effect of adiposity on the risk of COVID-19 (7,8,13,14,(25)(26)(27)(28)(29)(30)(31). These MR studies consistently estimated that increases in BMI, waist circumference, and hip circumference are causal for COVID-19 severity (7,13,14,26,28).…”

COVID-19 Reinfection without Vaccination Vs. with Vaccine: They are not Differentiated by Biological Factors, but by Psycho-Social Variables

“…Family support and a herd mentality can help improve vaccination among the undecided [11]. Other family characteristics, such as living alone, without a partner or children, and being single, were negatively associated with the desire to be vaccinated [34][35][36]. People living alone with limited care may have less access, irregular preventive health visits, and less support from family members [37].…”

“…Comorbidities: No strong evidence has been found, and studies showing conflicting results, whether certain diseases (including diseases of the circulatory, digestive, nervous, respiratory, genitourinary, musculoskeletal, and connective tissue systems, metabolic diseases, and mental disorders) increase the risk of COVID-19 [36]. Like all infectious processes, the clinical severity depends on the virulence of the microorganism and the susceptibility of the host.…”

Commentary: Smoking, nicotine and COVID-19 outcomes: unprecedented challenges to epidemiologists

“… 5 Moreover, a meta-analysis found six Mendelian randomization studies which consistently demonstrated ‘strong associations of smoking traits, including smoking initiation, smoking heaviness and lifetime smoking index (which combined smoking initiation, duration, heaviness and cessation), in the risk of COVID-19 severity, hospitalzation and mortality’, and the authors suggested that the mechanism may be ‘an increased expression of ACE2, a receptor for SARS-CoV-2 in the airway epithelium’ in smokers. 6 …”