Comparing the Long-Term Health Effects After COVID-19, Influenza, and Sepsis Hospitalization

People who survive COVID-19 infection, and especially those who were hospitalized with a severe infection, have an increased risk of developing new cardiovascular, neurological, mental health, and inflammatory autoimmune conditions.

Post-acute sequalae of COVID-19, commonly called “long COVID,” can range in severity from inconvenient to debilitating. The infamy of long COVID begs the question: is the risk of developing medical and mental health conditions after COVID-19 greater than after other serious infectious illnesses?

A new study, published in JAMA Internal Medicine, sought to the compare risk of cardiovascular, neurological, and mental health conditions and rheumatoid arthritis in the year following COVID-19 hospitalization against 3 comparator groups: prepandemic hospitalization for influenza and hospitalization for sepsis before and during the COVID-19 pandemic.

The investigators conducted a population-based cohort study in Ontario, Canada, utilizing clinical and health administrative databases. Ontario is the most populous province in Canada, with more than 13 million adult residents and 1.4 million confirmed COVID-19 infections, making it a good case study.

The cohort included all Ontario adults, aged 18 years and older, who were hospitalized with COVID-19 between April 1, 2020-October 31, 2021. Investigators followed up for 1 year after hospitalization, accounting for death or loss to follow-up.

Historical comparator cohorts included people hospitalized with influenza or sepsis between January 1, 2014-March 25, 2019. A contemporary comparator cohort consisted of individuals hospitalized for non-COVID-19 sepsis between April 1, 2020-October 31, 2021. The study authors noted there were insufficient influenza cases during the pandemic to form a comparator cohort.

The primary outcomes were a set of individual cardiovascular, neurological, and mental health conditions, as well as rheumatoid arthritis. Patients could experience more than 1 outcome, though the risk of developing each was assessed separately. Death following hospital discharge was a secondary outcome.

Specifically, the study authors wrote, the new conditions for which they evaluated were “cardiovascular conditions and procedures (including acute myocardial infarction, stroke, heart failure, hypertension, percutaneous coronary intervention, and coronary artery bypass grafting), venous thromboembolic disease (deep vein thrombosis and pulmonary embolism), neurological disorders (seizure, Parkinson disease, and dementia), rheumatoid arthritis, and mental health conditions (depression, anxiety, and substance use disorders).” These conditions were evaluated because they are known adverse outcomes of COVID-19 infection, influenza, sepsis, or a general critical illness.

The final cohort included 26499 people hospitalized for COVID-19, as well as 2 comparator cohorts of 17516 people hospitalized with influenza and 282473 people hospitalized with sepsis. While median age varied across the groups, the COVID-19 patients averaged younger, at 61 years. Additionally, a lower proportion of female patients were hospitalized with COVID-19 than with sepsis or influenza.

During index hospitalization, mortalities occurred in 18% of the COVID-19 group, 5% of the historical influenza group, 11% of the historical sepsis group, and 1.6% of the contemporary sepsis group. The investigators noted that 7% of the COVID-19 patients were partially or fully vaccinated with an approved COVID-19 vaccine.

Venous thromboembolic disease was more common after COVID-19 hospitalization than after hospitalization with sepsis or influenza. “The risks of all other outcomes were similar or lower after hospitalization for COVID-19 compared with hospitalization for sepsis, before or during the pandemic, or influenza,” the study authors wrote. “Within 1 year of discharge from hospital, mortality ranged between 6% and 23% across the study cohort.”

In the first 30 days after hospital discharge, COVID-19 was correlated with a higher risk of 3 outcomes than the other comparator cohorts, including venous thromboembolic disease, stroke, and anxiety and depression. After 30 days, however, COVID-19 hospitalization was not associated with an increased risk of any prespecified outcomes compared to the sepsis and influenza cohorts. The one exception was the risk of venous thromboembolism, which was increased within the first year after COVID-19 hospitalization.

However, the study authors wrote, “It is important to note that a higher proportion of people hospitalized for COVID-19 died during hospitalization compared with influenza or sepsis, which influences the risk profile of survivors and may explain why the risks of many outcomes were lower among survivors of COVID-19 hospitalization compared with influenza or sepsis.”