Comorbidities Pose Higher Risk of Severe COVID-19 Outcomes Than IMIDs


An IMID diagnosis or use of immunomodulatory medications were not shown to be a significant risk factor of severe COVID-19 outcomes.

Comorbidities Pose Higher Risk of Severe COVID-19 Outcomes Than IMIDs

Qi Wei, PhD

Credit: LinkedIn

A retrospective cohort study demonstrated chronic comorbidities, not being fully vaccinated, and age may be greater risk factors for severe COVID-19 outcomes among patients with immune-mediated inflammatory diseases (IMIDs) than the IMIDs themselves or the use of immunomodulatory medications (IMMs), according to research published in The Lancet Digital Health.1

IMIDs, including autoimmune diseases psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease, are defined by immune dysregulation, chronic inflammation, and even organ damage.

“Given established and potential COVID-19 risk factors, individuals with IMIDs are of particular interest for risk analysis due to the complexity of the diseases,” wrote a team of investigators led by Qi Wei, PhD, a data scientist at the Institute for Systems Biology in Seattle. “This patient population has an increased rate of severe COVID-19 outcomes; however, reasons why remain unclear.”

Possible reasons for the increased rate of severe outcomes could include immune dysregulation and the use of IMMs, which could theoretically promote viral replication. Additionally, heart disease and diabetes—comorbidities linked to severe COVID-19 outcomes—are more prevalent among patients with IMIDs compared with the general population.2

The retrospective cohort study analyzed clinical data from electronic health records of a US-based integrated healthcare system (Providence St. Joseph Health) to determine the risk of severe COVID-19 outcomes among individual IMIDs, classes of IMMs, chronic comorbidities, and COVID-19 vaccination status. The database contained information from 51 hospitals and 1085 clinics located in 7 states.

Patients with ≥ 1 IMID and unmatched controls were included in the analysis. A positive SARS-CoV-2 test was used to identify COVID-19 cases. Investigators divided the study period into pre-omicron (March 1, 2020-December 25, 2021) and omicron-predominant (December 26, 2021-August 30, 2022) cohorts.

The primary endpoints were hospitalization, mortality, and mechanical ventilation in patients with COVID-19 infection. Multivariable logistic regression and extreme gradient boosting were used to evaluate the factors that could impact severe COVID-19 outcomes.

In total, 2,167,656 patients were tested for COVID-19 infection, of which 290,855 (13.4%) had a confirmed diagnosis. Of these patients, 15,397 (5.3%) had ≥ 1 IMIDs and 275,458 (94.7%) did not.

In the early stage of the pandemic, 169,993 (11.2%) of 1,517,295 people tested positive for COVID-19. Among these patients, 13.7% were hospitalized, .6% received mechanical ventilation, and 3.1% died. When compared with controls, those with IMIDs and concurrent COVID-19 exhibited higher rates of hospitalization (14.6% vs 13.7%, respectively) and mortality (3.9% vs 3.1%, respectively).

In the omicron-predominant period, 120,862 (18.6%) of 650,361 people tested positive for COVID-19. In this cohort, 12.0% were hospitalized, .5% received mechanical ventilation, and 1.7% died. Similar to the previous period, patients with IMIDs had higher rates of hospitalization (14.8% vs 11.8%, respectively) and mortality (2.6% vs 1.6%, respectively) compared with controls.

Despite these results, an IMID diagnosis or use of IMMs were not shown to be a significant risk factor of severe COVID-19 outcomes; however, findings were limited by a relatively small sample size.

Significant risk factors for all 3 outcomes were observed in 7 chronic comorbidities: heart failure, coronary artery disease, atrial fibrillation, chronic liver disease, chronic kidney disease, chronic obstructive pulmonary disease, and cancer.

While age was a risk factor for worse outcomes (adjusted odds ratio [aOR] 2.1—3.0, P <.0001), both COVID-19 vaccination and booster vaccination were linked to better outcomes. Asthma (aOR .33—.49, P <.0001) and psoriasis (.52—.80, P <.0001) were also associated with a reduced risk of severe COVID-19 outcomes.

Investigators noted the lack of information on IMID disease activity and severity, as well as the severity of non-IMID comorbidities as limitations of the study. However, the study was strengthened by the large sample size and the use of multivariable analysis. The comparison of 2 different time periods throughout the pandemic also helped to determine if risk factors have changed post-omicron.

“Overall, there is a need to take age and comorbidities into consideration when developing COVID-19 guidelines for patients with IMIDs,” investigators concluded. “Further research is needed for specific IMIDs (including IMID severity at the time of SARS-CoV-2 infection) and IMMs (considering dosage and timing before a patient's first COVID-19 infection).”


  1. Wei Q, Mease PJ, Chiorean M, et al. Machine learning to understand risks for severe COVID-19 outcomes: a retrospective cohort study of immune-mediated inflammatory diseases, immunomodulatory medications, and comorbidities in a large US health-care system. Lancet Digit Health. 2024;6(5):e309-e322. doi:10.1016/S2589-7500(24)00021-9
  2. Schieir O, Tosevski C, Glazier RH, Hogg-Johnson S, Badley EM. Incident myocardial infarction associated with major types of arthritis in the general population: a systematic review and meta-analysis. Ann Rheum Dis. 2017; 76: 1396-1404
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