Phenome-wide association study to explore the long-term symptoms after infection with novel coronavirus in the UK Biobank

Background Observational research studies have shown that even after the acute phase, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect patients, and increase the risk of cardiovascular, mental, metabolic, and other disorders. However, the spectrum of diseases for individuals with a genetic predisposition to COVID-19 remains unclear. Methods We leveraged individual-level data from UK Biobank to implement a phenome-wide association study to explore the relationships between COVID-19 and 1061 diseases. Then, the inverse-variance weighted (IVW) method was adopted with summary-level data from global consortiums as sensitivity analyses combined with other MR methods with different model assumptions to identify robust associations. Findings The PheWAS found severe respiratory, hospitalized, and susceptibility COVID-19 had detrimental effects on 36, 37, and 51 kinds of diseases, separately. The IVW test found severe respiratory COVID-19 had detrimental effects on breast cancer [OR 95% CI: 1.065 (1.000-1.133)], pan-cancer [OR 95% CI: 1.002 (1.000-1.004)], and Alzheimer’s disease [OR 95% CI: 1.042 (1.005-1.081)], etc. Hospitalized COVID-19 had detrimental effects on ischemic stroke (IS) [OR 95%CI: 1.049 (1.001-1.100)], breast cancer [OR 95%CI: 1.139 (1.011-1.283)], and pan-cancer [OR 95%CI: 1.003 (1.000-1.006)], etc. Susceptibility COVID-19 had detrimental effects on deep vein thrombosis (DVT) of lower extremities [OR 95%CI: 2.392 (1.167-4.902)], venous thromboembolism [OR 95%CI: 1.962 (1.115-3.453)], pulmonary heart disease/diseases of pulmonary circulation [OR 95%CI: 1.767 (1.142-2.733)], IS (large artery atherosclerosis) [OR 95%CI: 1.405 (1.025-1.927)], myocardial infarction [OR 95%CI: 1.235 (1.012-1.509)], heart failure [OR 95%CI: 1.140 (1.009-1.287)], etc. Interpretation This study describes the extensive link between genetically determined COVID-19 and a broad range of diseases, especially those of the circulatory system, neuropsychiatric system, neoplasms, immune system, and digestive systems. Early detection and management of post-COVID-19 conditions could be tremendously beneficial to public health. Funding This work was supported by the National Natural Science Foundation of China (81773547 and 82173625) and the National Key Research and Development Program (2020YFC2003500).