Postacute Effects of COVID on par With Those of Sepsis, Flu

Gwendolyn Rak

July 05, 2023

Posthospitalization risks associated with COVID-19 are similar to those associated with other infectious diseases, new research finds.

A large observational study examined population-wide data for 13 postacute conditions in patients who had been hospitalized with a COVID-19 infection and found that all but one of these conditions, venous thromboembolism, occurred at comparable rates in those hospitalized for sepsis and influenza.

Dr Kieran Quinn

"For us, the main takeaway was that patients hospitalized for severe illness in general really require ongoing treatment and support after they’re discharged. That type of care is often very challenging to coordinate for people in a sometimes siloed and fragmented healthcare system," study author Kieran Quinn, MD, PhD, a clinician at Sinai Health in Toronto, and assistant professor at the University of Toronto, Toronto, Ontario, Canada, told Medscape Medical News.

The study was published June 20 in JAMA Internal Medicine.

Postacute Effects

The investigators compared clinical and health administrative data from 26,499 Ontarians hospitalized with COVID-19 with data from three additional cohorts who had been hospitalized with influenza (17,516 patients) and sepsis. The sepsis cohort was divided into two groups, those hospitalized during the COVID-19 pandemic (52,878 patients) and a historical control population (282,473 patients).

These comparators allowed the researchers to compare COVID-19 with other severe infectious illnesses and control for any changes in healthcare delivery that may have occurred during the pandemic. The addition of sepsis cohorts was needed for the latter purpose, since influenza rates dropped significantly after the onset of the pandemic.

The study outcomes (including cardiovascular, neurological, and mental health conditions and rheumatoid arthritis) were selected based on previous associations with COVID-19 infections, as well as their availability in the data, according to Quinn. The investigators used diagnostic codes recorded in Ontario’s Institute for Clinical Evaluative Sciences (ICES) database. The investigators observed some of the studied conditions in their own patients. "Many of us on the research team are practicing clinicians who care for people living with long COVID," said Quinn.

Compared with cohorts with other serious infections, those hospitalized with COVID-19 were not at increased risk for selected cardiovascular or neurological disorders, rheumatoid arthritis, or mental health conditions within 1 year following hospitalization. Incident venous thromboembolic disease, however, was more common after hospitalization for COVID-19 than after hospitalization for influenza (adjusted hazard ratio, 1.77).

The study results corroborate previous findings that influenza and sepsis can have serious long-term health effects, such as heart failure, dementia, and depression, and found that the same was true for COVID-19 infections. For all three infections, patients at high risk require additional support after their initial discharge.

Defining Long COVID

Although there was no increased risk with COVID-19 for most conditions, these results do not mean that the postacute effects of the infection, often called "long COVID," are not significant, Quinn emphasized. The researcher believes that it’s important to listen to the many patients reporting symptoms and validate their experiences.

There needs to be greater consensus among the global health community on what constitutes long COVID. While the research led by Quinn focuses on postacute health conditions, some definitions of long COVID, such as that of the World Health Organization, refer only to ongoing symptoms of the original infection.

While there is now a diagnostic code for treating long COVID in Ontario, the data available to the researchers did not include information on some common symptoms of post-COVID condition, like chronic fatigue. In the data used, there was not an accurate way to identify patients who had developed conditions like myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome, said Quinn.

In addition to creating clear definitions and determining the best treatments, prevention is essential, said Quinn. Prior studies have shown that vaccination helps prevent ICU admission for COVID-19.

'Important Questions Remain'

Commenting on the findings for Medscape, Aravind Ganesh, MD, DPhil, a neurologist at the University of Calgary, Calgary, Alberta, Canada, said that by including control populations, the study addressed an important limitation of previous research. Ganesh, who was not involved in the study, said that the controls help to determine the cause of associations found in other studies, including his own research on long-term symptoms following outpatient care for COVID-19.

Dr Aravind Ganesh

"I think what this tells us is that maybe a lot of the issues that we’ve been seeing as complications attributable to COVID are, in fact, complications attributable to serious illness," said Ganesh. He also found the association with venous thromboembolism interesting because the condition is recognized as a key risk factor for COVID-19 outcomes.

Compared to smaller randomized control trials, the population-level data provided a much larger sample size for the study. However, this design comes with limitations as well, Ganesh noted. The study relies on the administrative data of diagnostic codes and misses symptoms that aren’t associated with a diagnosis. In addition, because the cohorts were not assigned randomly, it may not account for preexisting risk factors.

While the study demonstrates associations with physical and mental health conditions, the cause of postacute effects from COVID-19, influenza, and sepsis is still unclear. "Important questions remain," said Ganesh. "Why is it that these patients are experiencing these symptoms?"

The study was supported by ICES and the Canadian Institutes of Health Research. Quinn reported part-time employment at Public Health Ontario and stock in Pfizer and BioNTech. Ganesh reported no relevant financial relationships.

JAMA Intern Med. Published June 20, 2023. Full text.

Gwendolyn Rak is a health reporter for Medscape and Univadis based in Brooklyn, New York.

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