2249: Impact of Interstitial Lung Disease on COVID-19 Severity Among Patients with Rheumatoid Arthritis: A Multicenter Comparative Study

Gabriel Figueroa Parra¹, Emily Gilbert², Maria Valenzuela Almada¹, Sebastian Vallejo¹, Matthew Neville³, Naomi Patel⁴, Claire Cook⁵, Xiaoqing Fu⁵, Ramla Hagi⁵, Gregory McDermott⁶, Michael Dilorio⁶, Lucy Masto⁶, Kathleen Vanni⁶, Emily Kowalski⁶, Grace Qian⁶, Zachary Wallace⁵, Ali Duarte-Garcia¹ and Jeffrey Sparks⁷, ¹Mayo Clinic, Rochester, MN, ²Mayo Clinic, Jacksonville, FL, ³Mayo Clinic, Phoenix, AZ, ⁴Massachusetts General Hospital, Sale Creek, TN, ⁵Massachusetts General Hospital, Boston, MA, ⁶Brigham and Women's Hospital, Boston, MA, ⁷Brigham and Women's Hospital and Harvard Medical School, Boston, MA

Background/Purpose: Rheumatoid arthritis (RA) has been associated with severe COVID-19, but few studies have investigated outcomes in RA phenotypes such as interstitial lung disease (RA-ILD), seropositivity, and bone erosions. We aimed to assess COVID-19 outcomes in patients with RA overall, and those with and without RA-ILD, compared to general population comparators.

Methods: A multicenter, retrospective comparative cohort study was conducted at two healthcare systems with hospitals and outpatient centers in 6 states across the US. Consecutive patients with RA meeting 2010 ACR/EULAR criteria and a positive COVID-19 test (index date) from March 1, 2020, through June 6, 2021, were matched 1:5 on age, sex, race, and calendar date to general population comparators without RA. We examined subgroups of RA by phenotypic features: RA-ILD per Bongartz criteria (Bongartz, T. Arthritis Rheum. 2010), serostatus (either rheumatoid factor or cyclic citrullinated peptide antibody), and bone erosions. Severe COVID-19 was a composite of hospitalization or death within 14 days of COVID-19 diagnosis. We used multivariable Cox regression to investigate the association of RA and RA phenotypes with COVID-19 outcomes compared to matched comparators.

Results: We identified 582 patients with RA and 2,875 matched comparators, all with COVID-19. The mean age was 62 years, 72% were female, and 79% were White. Among patients with RA, median RA duration was 8 years, 9% had RA-ILD, 68% were seropositive, 27% had bone erosions. 28% were using glucocorticoids, and 79% were on DMARDs at the time of COVID-19 diagnosis. During a follow-up of 41,411 person-days, there were 126 (22%) severe outcomes observed in the RA patients and 363 (13%) in the comparators (follow-up 226,550 person-days). The corresponding rate was higher among RA patients than comparators (3.0 per 1,000 days [95% CI 2.5-3.6] vs. 1.6 per 1,000 days [95% CI 1.4-1.8], respectively). Overall, RA patients had a 75% higher risk of severe COVID-19 than comparators after adjustment (HR 1.75, 95% CI 1.45-2.10). Among those with RA-ILD, the severe COVID-19 rate was significantly higher than their comparators (10.9 [95% CI 6.7-15.2] vs. 2.5 per 1,000 days [1.8-3.2], respectively). RA-ILD was associated with 2.5-fold higher risk for severe COVID-19 than comparators (multivariable HR 2.50 [95% CI 1.66-3.77], Table). There was a significant interaction between RA/comparator status and presence/absence of ILD for risk of severe COVID-19 (p< 0.046, Figure). The elevated risk for severe COVID-19 was similarly higher for seropositive and erosive RA compared to the general population but these were not effect modifiers of the association of RA with severe outcomes.

Conclusion: RA patients have a higher risk of severe COVID-19, especially those with ILD. Our findings suggest that ILD or its treatment may be a significant contributor to severe COVID-19 outcomes in RA.
Table. Frequencies, proportions, and hazard ratios for COVID-19 outcomes, comparing all RA patients, and subgroups with or without RA-ILD, to matched comparators.

Figure. Multivariable hazard ratios for severe COVID-19, comparing all RA and subgroups by serostatus, bone erosions, and RA-ILD to matched comparators without RA. Cox model adjusted for age, sex, race and smoking status.
Disclosures: G. Figueroa Parra, None; E. Gilbert, None; M. Valenzuela Almada, None; S. Vallejo, None; M. Neville, None; N. Patel, FVC Health; C. Cook, None; X. Fu, None; R. Hagi, None; G. McDermott, None; M. Dilorio, None; L. Masto, None; K. Vanni, None; E. Kowalski, None; G. Qian, None; Z. Wallace, Sanofi, Bristol-Myers Squibb(BMS), Zenas Biopharma, Shionogi, Horizon; A. Duarte-Garcia, None; J. Sparks, Bristol Myers Squibb, AbbVie/Abbott, Amgen, Boehringer Ingelheim, Gilead, Inova Diagnostics, Janssen, Optum, Pfizer.