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Abstract Number: 2616

Associations of Circulating Inflammatory Cytokines with Long COVID Among Patients with Systemic Autoimmune Rheumatic Diseases

Jeffrey Sparks1, Xiaosong Wang2, Pui Lee3, Kailey Brodeur4, Miao Lin5, Naomi Patel5, Yumeko Kawano6, Abigail Schiff7, Andrew King5, Jennifer Hanberg6, Shruthi Srivatsan5, Emily Kowalski6, Colebrook Johnson5, Kathleen Vanni6, Zachary Williams5, Grace Qian2, Caleb Bolden5, Kevin Mueller6, Katarina Bade6, Alene Saavedra6, Rathnam Venkat8 and Zachary Wallace9, 1Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Boston, MA, 2Brigham and Women’s Hospital, Boston, MA, 3Boston Children's Hospital, Newton, MA, 4Boston Children's Hospital, Cumberland, RI, 5Massachusetts General Hospital, Boston, MA, 6Brigham and Women's Hospital, Boston, MA, 7Brigham and Women's Hospital, Cambridge, MA, 8Tufts University School of Medicine, Boston, MA, 9Massachusetts General Hospital, Newton, MA

Meeting: ACR Convergence 2024

Keywords: COVID-19, cytokines, Infection, Inflammation, Interleukins

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Session Information

Date: Monday, November 18, 2024

Title: Abstracts: Infection-related Rheumatic Disease

Session Type: Abstract Session

Session Time: 3:00PM-4:30PM

Background/Purpose: While the incidence of severe acute COVID-19 has decreased, post-acute sequelae of COVID-19 characterized by prolonged symptoms, or ‘long COVID,’ is common and associated with lower quality of life and morbidity. Long COVID may be in part driven by systemic inflammation and immune dysregulation. Patients with systemic autoimmune rheumatic diseases (SARDs) may be at risk for long COVID due to underlying altered immunity, immunosuppressive drug use, and propensity for systemic inflammation. Thus, identifying inflammatory biomarkers for long COVID may be helpful to identify biologic pathways and develop diagnostic tests.

Methods: We investigated biomarkers of inflammation and long COVID using RheumCARD, a prospective study of people with prevalent SARDs with COVID-19 from a large healthcare system. Participants are recruited ≥28 days following onset of acute COVID-19 to answer surveys and provide blood samples (March 2021 to July 2023). Circulating cytokines were measured in serum using the Olink Target 48 cytokine panel. If patients were on a DMARD targeted to a cytokine (e.g., TNF), that result was excluded.  In the primary analysis, long COVID was defined as symptoms persisting for ≥28 days, comparing those with vs. without long COVID. We performed subgroup analyses among those with inflammatory arthritis, pre-Omicron variants, Omicron variants, remission/low disease activity, moderate/high disease activity as well as a more stringent definition of long COVID (≥90 days of persistent symptoms). We compared cytokine levels between those with vs. without long COVID using linear regression.

Results: We analyzed a total of 201 participants (mean age 56.3 years, 81% female). The most common SARD type among cases was inflammatory arthritis (60%), followed by connective tissue disease (22%, Table 1). IL-18 levels were lower among those with long COVID (199 units) vs. without long COVID (221 units; p=0.001). In the multivariable analysis, long COVID cases had lower IL-18 levels than those without long COVID (β -55 units, SE 17, p=0.0011, Table 2). There were also associations of CSF2, IL2, and CCL6 with long COVID. IL-18 levels were consistently lower among those with long COVID in all additional analyses (Table 3): inflammatory arthritis (p=0.021), remission/low disease activity (p=0.02), moderate/high disease activity (p=0.015), pre-Omicron variants (0.004), Omicron variants (p=0.06), long COVID defined as ≥90 days of persistent symptoms (p=0.004), and vs. comparators (p=0.011).

Conclusion: In this prospective study performed among SARDs after COVID-19, lower IL-18 levels were associated with higher risk of long COVID. This finding was robust across all analyses examined and not explained by vaccination or viral variants. IL-18 induces cell-mediated immunity following infection, implicating a blunted immune response, rather than exuberant hyperinflammation, as a potential mechanism for long COVID among patients with SARDs.

Supporting image 1

Table 1. Baseline characteristics at time of blood draw for post-COVID_19 cases with systemic autoimmune rheumatic diseases (n=201).

Supporting image 2

Table 2. Associations of long COVID status (with vs. without) and circulating cytokine levels using multivariable* linear regression.

Supporting image 3

Table 3. Secondary analyses of the association of lower IL_18 levels with long COVID presence.


Disclosures: J. Sparks: Boehringer-Ingelheim, 2, 5, Bristol-Myers Squibb(BMS), 2, 5, Gilead, 2, Janssen, 2, Pfizer, 2, UCB, 2; X. Wang: None; P. Lee: None; K. Brodeur: None; M. Lin: None; N. Patel: Amgen, 5, Arrivo Bio, 2, Chronius Health, 2, FVC Health, 2; Y. Kawano: None; A. Schiff: None; A. King: None; J. Hanberg: None; S. Srivatsan: None; E. Kowalski: None; C. Johnson: None; K. Vanni: None; Z. Williams: None; G. Qian: None; C. Bolden: None; K. Mueller: None; K. Bade: None; A. Saavedra: None; R. Venkat: None; Z. Wallace: Amgen Inc., 2, 12, MITIGATE Committee Member.

To cite this abstract in AMA style:

Sparks J, Wang X, Lee P, Brodeur K, Lin M, Patel N, Kawano Y, Schiff A, King A, Hanberg J, Srivatsan S, Kowalski E, Johnson C, Vanni K, Williams Z, Qian G, Bolden C, Mueller K, Bade K, Saavedra A, Venkat R, Wallace Z. Associations of Circulating Inflammatory Cytokines with Long COVID Among Patients with Systemic Autoimmune Rheumatic Diseases [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/associations-of-circulating-inflammatory-cytokines-with-long-covid-among-patients-with-systemic-autoimmune-rheumatic-diseases/. Accessed .
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