0795: Post-Acute COVID-19 Sequalae (PACS) with New-onset Rheumatological Complications

Neel Thanavala¹, Kiho Son², Nardien Sedhom², Snehal Somalwar³, Zil Patel¹, Rameen Jamil², Carmen Venegas², Ashutosh Thakar², Agnes Yuen⁴, Melanie Kjarsgaard², Susan Waserman², Mylinh Duong², Parameswaran Nair², Christopher Carlsten⁴, Maggie Larche², Terence Ho², Sarah Svenningsen², KONSTANTINOS TSELIOS⁵ and Manali Mukherjee², ¹The Research Institute of St. Joe's Hamilton, Hamilton, ON, Canada, ²McMaster University, Hamilton, ON, Canada, ³The Research Institute of St Joe's Hamilton, Hamilton, ON, Canada, ⁴University of British Columbia, Vancouver, BC, Canada, ⁵McMaster University, Population Health Research Institute, Hamilton, ON, Canada

Background/Purpose: Post-Acute Sequalae of COVID-19 (PASC), prevalent in ~20-30% of convalescent COVID-19 patients is characterized by new/persistent symptoms after the initial recovery. Certain autoantibodies have been described in acute COVID-19 but their clinical significance is unknown. The purpose of this study was the assessment of such antibodies in PASC, their association with symptom persistence as well as the potential for the development of future rheumatic and/or autoimmune diseases.

Methods: In a multi-center, observational study (Post-COVID), we enrolled n=58 PCR⁺ COVID-19 patients between August'20-September'21 +/- symptoms, at 12 months post-recovery. In a subsequent, observational study (Autoimmunity in Post-Acute COVID Sequelae, AIPACS), between September'21-April'22, we recruited n=58 PASC patients (persistent symptoms for >12 weeks, PCR-confirmed) at 3-6 months (n=11), 6-9 months (n=9), 9-12 months (n=18), and >12 months (n=20) post-infection. All patients were ≥18 years, without history of autoimmune disease. Rapid assessment line immunoassays (HUMAN Diagnostics, Germany) were used to detect circulating autoantibodies.

Results: In the Post-COVID study, 43% (25/58) of patients reported symptoms (fatigue, dyspnea, or cough) at 12 months post-infection. Anti-U1-snRNP (30%) and anti-SS-B/La (21%) were the most prevalent autoantibodies (Fig. 1A) that positively correlated with and predicted persisting symptoms of fatigue and dyspnea at 12-month post-infection (simple logistic regression, P< 0.05) (Fig. 1B, C). In the AIPACS study, patients at >12 months post-infection had significantly higher numbers of positive autoreactivities compared to patients 6-12 months post-infection (p=0.03) (Fig. 1D). Finally, six patients (10%, 2 males/4 females, median age 42 years) were newly diagnosed with an autoimmune and/or rheumatic disease; systemic lupus erythematosus (n=1), postural orthostatic tachycardia syndrome (n=3), psoriasis (n=1) and polymyalgia rheumatica (n=1) (Table 1). Anti-SS-B/La and/or anti-U1-snRNP were detectable in 5/6 patients.

Conclusion: Autoantibodies to certain nuclear antigens were detected in PASC patients beyond 12 months post-infection. A subset of PASC patients without prior history of autoimmunity may be susceptible to new-onset rheumatological complications.
Figure 1. Prevalence of circulating anti-nuclear/extractable nuclear antibodies: Histograms visualizing the most prevalent ANAs at 12 months post-infection time point of 58 convalescent covid-19 patients with a representative line immunoassay strip showing positive band intensities (A). Regression analysis showing the ODDs ratio for predicting fatigue and dyspnea persistent at 12 months (B,C) in Post-COVID study. Scatter plot showing the number of ANA reactivities per patient in AIPAC study (n=58) as a cross-sectional dataset- over the different recovery time frames, compared to an age-sex matched healthy never-COVID pre-vaccinated healthy control (n=22). Red symbols indicate the seven patients diagnosed with an autoimmune disease during AIPAC study visit (rheumatology consult). Kruskal Wallis with multiple comparison test.

N.B. BMI - Body mass index; MQV is mean quantitative value of the band intensity on the ANA Line immunoassay; Sx - symptoms; mMRC - modified Medical Research Council; SGRQ - St George's Respiratory Questionnaire; ANA - antinuclear/extractable nuclear antibodies; SLE - systemic lupus erythematosus; POTS - postural orthostatic tachycardia syndrome; PMR - polymyalgia rheumatica;
Disclosures: N. Thanavala, None; K. Son, None; N. Sedhom, None; S. Somalwar, None; Z. Patel, None; R. Jamil, None; C. Venegas, None; A. Thakar, None; A. Yuen, None; M. Kjarsgaard, None; S. Waserman, Alk Abello, CAAIF, Aimmune, Takeda, Siolta, GlaxoSmithKlein(GSK), AstraZeneca, Novartis, CSL Behring, Pfizer, Sanofi, Medexus, Miravo Health, AbbVie, Bausch Lomb; M. Duong, None; P. Nair, AstraZeneca, Teva, Sanofi, Equillium, Foresee, Arrowhead Pharma, Cyclomedica, GlaxoSmithKlein(GSK); C. Carlsten, None; M. Larche, None; T. Ho, Fisher and Paykel, Sanofi, Valeo, AstraZeneca; S. Svenningsen, Cyclomedica, Arrowhead Pharmaceuticals, AstraZeneca, Novartis, Polarean; K. TSELIOS, AstraZeneca, GlaxoSmithKlein(GSK); M. Mukherjee, COVID-19 Immunity Task Force (CIHR), Methapharm Specialty Pharmaceuticals, Canadian Asthma Allergy Immunology Foundation, Canadian Institutes of Health Research, Novartis, GlaxoSmithKline, AstraZeneca.