Risk for Severe COVID-19 Outcomes With Immune-Mediated Inflammatory Diseases

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virus infected patient in quarantine room with quarantine at hospital,concept coronavirus covid 19
Researchers assessed the risk for severe COVID-19 in adults with immune-mediated inflammatory diseases and those on immune-modifying therapies.

Among individuals with immune-mediated inflammatory diseases, the risk for death and hospitalization associated with COVID-19 infection are higher than in the general population, according to study results published in The Lancet Rheumatology. However, no increased risk for adverse outcomes has been reported in patients on most targeted immune-modifying agents (ie, biologics) compared with those receiving standard systemic treatment (ie, methotrexate).

Researchers sought to evaluate the risk for severe COVID-19 in adult patients with immune-mediated inflammatory diseases and in those receiving immune-modifying therapies. A cohort study was conducted that used OpenSAFELY, a new secure analytics platform for electronic health records, along with TPP, a software provider for general practitioners in England. The study was designed to analyze routinely collected primary care data that were linked to hospitalization, death, and previously unavailable hospital prescription data.

Individuals who were aged at least 18 years on March 1, 2020, and were registered with TPP practices with at least 12 months of primary care records prior to March 2020 were included in the study. A total of 17,672,065 adult participants were included in the study. Of these participants, 1,163,438 had been diagnosed with an immune-meditated inflammatory disease (640,164 [55%] women and 523,274 [45%] men; 827,457 [71%] White), and 16,508,627 did not have a diagnosis of an immune-mediated inflammatory disease (8,215,020 [49.8%] women and 8,293,607 [50.2%] men; 10,614,096 [64%] White).

Among the 1,163,438 patients with an immune-meditated inflammatory disease, 19,119 (1.6%) were treated with targeted immune-mediated therapy and 181,694 (16%) were treated with standard systemic therapy. Results of the study showed that compared with the general population, patients with immune-mediated inflammatory diseases had an increased risk for COVID-19-associated death after adjustments for such confounders as sex, age, smoking status, and deprivation (hazard ratio [HR], 1,23; 95% CI, 1.20-1.27), and further adjustments for such mediators as body mass index (BMI), current glucocorticoid use, cardiovascular disease (CVD), and diabetes (HR, 1.15; 95% CI, 1,11-1.18).

Adults with immune-mediated inflammatory diseases had an increased risk for COVID-19-related critical care admission or death (confounder-adjusted HR, 1.24; 95% CI, 1.12-1.28; mediator-adjusted HR, 1.16; 95% CI, 1.12-1.19) and hospitalization (confounder-adjusted HR, 1.32; 95% CI, 1.29-1.35; mediator-adjusted HR, 1.20; 95% CI, 1.17-1.23).

Per post hoc analyses, the risk for severe COVID-19-associated outcomes among individuals with immune-mediated inflammatory diseases was higher in non-White participants than in White participants, which was also observed in the general population. Further, no evidence of increased COVID-19-related deaths was reported in those receiving targeted immune-mediated treatment vs those who received standard systemic therapy after adjustments for such confounders as sex, age, BMI, deprivation, immune-mediated inflammatory diseases (ie, joint, bowel, and skin), CVD, cancer (excluding nonmelanoma skin cancer), stroke, and diabetes (HR, 1.03; 95% CI, 0.80-1.33), as well as after adjustment for current glucocorticoid use (HR, 1.01; 95% CI, 0.78-1.30).

No evidence of increased COVID-19-associated deaths was reported in adults who were prescribed tumor necrosis factor inhibitors, interleukin (IL)-12/IL-23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors vs those who received standard therapy. Rituximab use was linked to increased COVID-19-associated deaths (HR, 1.68; 95% CI, 1.11-2.56), with some attenuation after individuals with hematologic malignancies or organ transplants were excluded (HR, 1.54; 95% CI, 0.95-2.49).

A limitation of the study included the fact that information on high-cost drug prescriptions was not available after March 2020. Thus, the investigators were unable to evaluate whether individuals continued their treatments throughout the study period.

The study authors concluded, “[T]he increased risk [for] adverse COVID-19 outcomes in people with immune-mediated inflammatory diseases and those treated with rituximab merits further study.” The current findings provide an evidence base to inform policy on booster vaccination prioritization and risk-mitigating behavior advice, but “must be interpreted in the context of UK public health policy on shielding.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


MacKenna B, Kennedy NA, Mehrkar A, et al. Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform. Lancet Rheumatol. 2022;4(7):e490-e506. doi:10.1016/S2665-9913(22)00098-4