Severe acute infection and chronic pulmonary disease are risk factors for developing post-COVID-19 conditions

Post-COVID-19 conditions, also known as "long COVID", has significantly impacted the lives of many individuals, but the risk factors for this condition are poorly understood. In this study, we performed a retrospective EHR analysis of 89,843 individuals at a multi-state health system in the United States with PCR-confirmed COVID-19, including 1,086 patients diagnosed with long COVID and 1,086 matched controls not diagnosed with long COVID. For these two cohorts, we evaluated a wide range of clinical covariates, including laboratory tests, medication orders, phenotypes recorded in the clinical notes, and outcomes. We found that chronic pulmonary disease (CPD) was significantly more common as a pre-existing condition for the long COVID cohort than the control cohort (odds ratio: 1.9, 95% CI: [1.5, 2.6]). Additionally, long-COVID patients were more likely to have a history of migraine (odds ratio: 2.2, 95% CI: [1.6, 3.1]) and fibromyalgia (odds ratio: 2.3, 95% CI: [1.3, 3.8]). During the acute infection phase, the following lab measurements were abnormal in the long COVID cohort: high triglycerides (mean_longCOVID: 278.5 mg/dL vs. mean_control: 141.4 mg/dL), low HDL cholesterol levels (mean_longCOVID: 38.4 mg/dL vs. mean_control: 52.5 mg/dL), and high neutrophil-lymphocyte ratio (mean_longCOVID: 10.7 vs. mean_control: 7.2). The hospitalization rate during the acute infection phase was also higher in the long COVID cohort compared to the control cohort (rate_longCOVID: 5% vs. rate_control: 1%). Overall, this study suggests that the severity of acute infection and a history of CPD, migraine, CFS, or fibromyalgia may be risk factors for long COVID symptoms. Our findings motivate clinical studies to evaluate whether suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.