IL-18 Levels Associated With Long COVID Risk in People With Rheumatic Diseases

New research has found an association with IL-18 levels and risk of long COVID in people with systemic autoimmune rheumatic diseases (SARDs) across vaccination strategies, viral variants, and multivariable analyses, supporting the theory that blunted immune responses may be a mechanism for long COVID in this population.¹

Data from a prospective study of people with SARDs and COVID-19 were presented at the American College of Rheumatology (ACR) Convergence 2024, held November 15-19 in Washington, DC, by Jeffrey Sparks, MD, MMSc, Assistant Professor of Medicine and Associate Physician at Brigham and Women's Hospital and Harvard Medical School.

“This hypothesis has profound clinical implications, suggesting that treatments often used by rheumatologists could potentially have a role in treating or preventing post-infectious consequences of COVID-19, including long COVID,” Leonard H. Calabrese, DO, Professor of Medicine and Vice Chair, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, said in a statement.² “Given that the scientific research in this field changes on a daily basis, it is important for clinicians to be aware of data that might affect treatment for patients with autoimmune disorders.”

Sparks and colleagues analyzed a total of 201 participants with a mean age of 56.3 years, 81% of which were female. Participants had SARDs including inflammatory arthritis (60%), and connective tissue disease (22%). The investigators found that IL-18 levels were lower among those with long COVID (199 units) compared to in those without long COVID (221 units; P = .001). This association was confirmed in multivariable analysis, under which participants with long COVID still had lower IL-18 levels than those without long COVID (β -55 units; standard error [SE], 17, P = .0011).¹

The investigators also found associations of CSF2, IL2, and CCL6 with long COVID. Looking at specific SARDs and SARD characteristics, IL-18 levels were consistently lower in those with long COVID and inflammatory arthritis (P = .021), remission/low disease activity (P = .02), and moderate/high disease activity (P = .015). The association was also preserved across different characteristics of COVID characteristics, including in participants with pre-Omicron variants (P = .004), Omicron variants (P = .06), and long COVID (defined as at least days of persistent symptoms; P = .004), as well as when compared to comparators P = .011).¹

Calabrese will be giving a related talk during the meeting on immune dysfunction’s possible role in causing long COVID. “As of August 2024, the data are far from clear as to whether autoimmunity is a driver of all or even part of the long COVID clinical spectrum,” he said.²

“The establishment of a small animal model of long COVID could potentially be a breakthrough for both understanding the cause of the disorder and testing new therapies… The role of autoimmunity in COVID-19 and long COVID is clearly a work in progress, and the rheumatology community has much to add based on their vast experience with immune mediated inflammatory diseases and autoimmunity,” Calabrese said.²

REFERENCES

1. Sparks J, Wang X, Lee P, et al. Associations of Circulating Inflammatory Cytokines with Long COVID Among Patients with Systemic Autoimmune Rheumatic Diseases. Presented at: ACR Convergence 2024; November 15-19; Washington, DC. Abstract 2616

2. New Theory Suggests that Autoimmunity May be Causing Long COVID in Some People. News release. ACR. November 14, 2024.