Massachusetts General Hospital Boston, Massachusetts, United States
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Background/Purpose: Individuals with systemic autoimmune rheumatic diseases (SARDs) are at risk for worse acute and post-acute COVID-19 outcomes due to use of immunosuppressive medications and possibly prolonged viral shedding. Whether individuals with SARDs have higher levels of viral antigens and/or longer persistence of viral antigens after COVID-19 has not been studied. Methods: We evaluated differences between an immunocompromised state and prolonged SARS-CoV-2 antigen (spike, S1 [Spike protein that contains the receptor binding domain], and nucleocapsid) positivity after COVID-19 in two prospective cohorts. We studied immunosuppressed individuals with SARDs in the RheumCARD study at a large US healthcare system and immunocompetent individuals in the RECOVER study. SARS-CoV-2 antigens were measured in collected plasma or serum samples using previously validated ultra-sensitive single molecule array, a digital enzyme-linked immunosorbent assay that uses antibody-coated magnetic beads to capture antigen molecules, which are then detected and loaded into microwell arrays through the enzymatic cleavage of a fluorescent substrate. We used logistic regression to evaluate unadjusted and adjusted (for age, sex, calendar year of infection, and vaccination status at the time of infection) odds ratios for SARS-CoV-2 antigen positivity comparing RheumCARD vs. RECOVER at 3 and 6-months following COVID-19. Results: Among 210 immunocompromised individuals with SARDs in RheumCARD and 429 immunocompetent individuals in RECOVER (Table), the mean age was 56.3 vs. 45.0 years, respectively, and 81.0% vs. 66.4% were female in each cohort. COVID-19 occurred in pre-Omicron variants (before 12/16/2021) in 37.6% of RheumCARD vs. 33.8% of RECOVER. Most individuals were vaccinated at the time of infection (73.3% in RheumCARD vs. 89.0% in RECOVER). Among those with SARDs, the most common SARD type was inflammatory arthritis (61.0%) and most (53.8%) had low disease activity. Many patients (31.4%) were receiving conventional synthetic DMARDs only, with 25.2% receiving TNF inhibitors and 8.6% receiving CD20 inhibitors. A minority (15.7%) were receiving glucocorticoids at the time of infection.
At the time of blood draw, any SARS-CoV-2 antigen positivity was more common in those with SARDs (36.7% in RheumCARD vs. 18.9% in RECOVER; p< 0.001) (Figure 1). Those with SARDs had higher odds of nucleocapsid antigen positivity (adjusted OR 3.17, 95%CI 1.21-8.33) or any antigen positivity (adjusted OR 2.68, 95%CI 1.38-5.20) 3 months after COVID-19 (Figure 2). At 6 months following COVID-19 infection, nucleocapsid antigen positivity remained significantly higher among those with SARDs (adjusted OR 6.92, 95%CI 1.21-39.43). Conclusion: Individuals with SARDs were more likely to have SARS-CoV-2 antigen positivity at 3 and 6 months following COVID-19 infection compared with immunocompetent individuals, not explained by demographics, variant, or vaccination. Persistent nucleocapsid antigen positivity, a marker of viral shedding rather than vaccination, was the greatest driver of differences between groups, suggesting that an immunocompromised state may result in prolonged antigenemia.
