Background: Early evidence that patients with (multiple) pre-existing diseases are at highest risk for severe COVID-19 has been instrumental in the pandemic to allocate critical care resources and later vaccination schemes. However, systematic studies exploring the breadth of medical diagnoses are scarce but may help to understand severe COVID-19 among patients at supposedly low risk.
Methods: We systematically harmonized >12 million primary care and hospitalisation health records from ~500,000 UK Biobank participants into 1448 collated disease terms to systematically identify diseases predisposing to severe COVID-19 (requiring hospitalisation or death) and its post-acute sequalae, Long COVID.
Results: Here we identify 679 diseases associated with an increased risk for severe COVID-19 (n = 672) and/or Long COVID (n = 72) that span almost all clinical specialties and are strongly enriched in clusters of cardio-respiratory and endocrine-renal diseases. For 57 diseases, we establish consistent evidence to predispose to severe COVID-19 based on survival and genetic susceptibility analyses. This includes a possible role of symptoms of malaise and fatigue as a so far largely overlooked risk factor for severe COVID-19. We finally observe partially opposing risk estimates at known risk loci for severe COVID-19 for etiologically related diseases, such as post-inflammatory pulmonary fibrosis or rheumatoid arthritis, possibly indicating a segregation of disease mechanisms.
Conclusions: Our results provide a unique reference that demonstrates how 1) complex co-occurrence of multiple - including non-fatal - conditions predispose to increased COVID-19 severity and 2) how incorporating the whole breadth of medical diagnosis can guide the interpretation of genetic risk loci.
Early in the COVID-19 pandemic it was clear that people with multiple chronic diseases were vulnerable and needed special protection, such as shielding. However, many people without such diseases required hospital care or died from COVID-19. Here, we investigated the importance of underlying diseases, including mild diseases not requiring hospitalization, for COVID-19 outcomes. Using information from electronic health records we find that many severe, but also less severe diseases increase the risk for severe COVID-19 and its impact on health even months after acute infection (Long COVID). This included an almost two-fold higher risk among people that reported poor well-being and fatigue. Our findings show the value of using primary care health records and the need to consider all the medical history of patients to identify those in need of special protection.
© 2024. The Author(s).