The acute clinical manifestations of coronavirus disease 2019 (COVID-19) have been well established. Looking beyond this acute setting, reports have suggested that some people with COVID-19 may experience long-lasting effects after recovering from the disease. However, the post-acute sequalae of COVID-19 have not been comprehensively described, let alone in a large enough sample size to establish a pattern. This lack of characterisation of sequalae is in spite of emerging reports of “long-haulers,” or COVID-19 patients experiencing long-lasting clinical manifestations.
This study aimed to fill the need for the characterisation of long-term effects after COVID-19 infection. More specifically, the goal was to comprehensively identify the six-month incident sequelae – including diagnoses, medication use and laboratory abnormalities – in people who survived the first 30 days after a COVID-19 diagnosis. An electronic health database from the US Department of Veterans Affairs was utilised to systematically characterise the post-acute sequelae using a high dimensional approach. This study features a large patient cohort, with tens of thousands of patients with COVID-19 and millions of non-COVID-19 controls analysed.
The primary outcome of the study was the identification of chronic complications (or incident sequalae) of COVID-19. The study cohort included users of the Veteran Health Administration (VHA) who survived at least the first 30 days after COVID-19 diagnosis and were not hospitalised (n=73,435) and users who did not have COVID-19 and were not hospitalised (n=4,990,835).
In linewith anecdotal reports of long-term effects in the post-acute setting, several incident sequalae were identified in survivors of COVID-19. Respiratory conditions were the most common, as respiratory signs and symptoms were identified in 28.51 per1,000 persons with COVID-19. Other sequalae included diseases of the nervous system, mental health burden, metabolic disorders, cardiovascular conditions, gastrointestinal disorders and poor general wellbeing. COVID-19 survivors had an increased risk of death, with an estimated 8.39 excess deaths per 1,000 people with COVID-19 at six months. People with COVID-19 exhibited greater healthcare utilisation, including a higher risk of outpatient care encounter than those without COVID-19. It was also found that people with COVID-19 had increased risk of incident use of multiple medication categories, including pain medications and antidepressants, compared with non-COVID-19 controls.
While the mechanisms behind the post-acute and chronic clinical manifestations of COVID-19 are still undefined, it is clear from the evidence presented by this study that there is a risk of serious long-term effects from the disease. The results of this study highlight a need for holistic, integrated and multidisciplinary long-term care of COVID-19 survivors.
According to a study in a large patient cohort, thirty-day survivors of COVID-19 have increased risk of death and health resource utilisation, and burden of health loss across multiple organ systems. Several post-acute sequalae were identified after COVID-19 infection. The results of this study inform the global discussion on the long-term effects of COVID-19, as well as health system planning and care strategies for COVID-19 survivors.