Risk of Sequelae Following COVID-19 Infection: A Nationwide Study Focusing on Risk Factors and Long-Term Impacts

<b>Background/Objective</b>: The SARS-CoV-2 pandemic, emerging in late 2019, led to a global health crisis, with many patients developing prolonged symptoms after infection known as sequelae of COVID-19. This condition is theorized to be driven by systemic inflammation and immune dysregulation and presents with diverse symptoms from cardiovascular, pulmonary, and neurological systems. This study investigates the prevalence, risk factors, and long-term impacts of sequelae of COVID-19. <b>Method</b>: Using Denmark's healthcare databases, this population-based cohort study included 1,034,093 individuals over 40 years who tested positive for COVID-19 between 1 March 2020 and 28 February 2022. Participants were divided into two age groups: 40-59 years and 60 years or older. Part A examined the risk of sequelae of COVID-19 diagnoses (ICD-10 code B94.8A) based on the Charlson Comorbidity Index (CCI). Part B assessed two-year outcomes for patients diagnosed with sequelae of COVID-19. <b>Results</b>: Results showed a 0.55% prevalence of sequelae of COVID-19 in both age groups. Higher CCI scores correlated with an increased risk of sequelae of COVID-19. During the two-year follow-up, patients with sequelae of COVID-19 faced significantly elevated risks of thromboembolic events, chronic lung diseases, and infections. Adjusted hazard ratios were notably high: 14.50 (7.54-27.86) and 12.50 (6.95-22.49) for thromboembolic events in adults and older adults, respectively; 33.81 (13.30-85.96) and 9.83 (6.09-15.87) for chronic lung disease; and 8.40 (4.49-15.70) and 15.44 (10.47-22.78) for infections. <b>Conclusions</b>: While the overall prevalence of sequelae of COVID-19 was low among individuals over 40, those with higher comorbidity burdens were at greater risk of severe sequelae and subsequent health complications. These findings underscore the need for clinical monitoring, especially for patients with pre-existing comorbidities, to mitigate long-term health risks associated with COVID-19 sequelae.