Abstract Acute respiratory viral infections (ARVI) are the most frequently occurring global illnesses causing significant morbidity and mortality. Adults with rheumatoid arthritis (RA) have increased risk of infection and clinical complications, although the underlying molecular and cellular immune responses remain poorly understood. To address this, we performed a prospective study of patients with rheumatoid arthritis (n = 88) and healthy controls (n = 28) to study mucosal responses to ARVI. Nasal swab samples were collected while participants were asymptomatic (baseline), and then during symptom onset (Days 1-3, Days 4-6, Days 8-11), 30 days post-symptom onset, and one-year post-baseline (total samples = 499). We used the validated Wisconsin Upper Respiratory Symptom Survey (WURSS) questionnaire to evaluate the severity of ARVI. Gene expression from nasal mucosal swabs was assessed using bulk RNA-sequencing and viral detection using PathSeq. The majority of participants were infected with SARS-CoV-2 or seasonal coronavirus (n = 49). We found that patients with rheumatoid arthritis had a higher rate of asymptomatic viral carriage in the nares at asymptomatic timepoints (28/187) compared to healthy controls (5/74, p = 0.06). Asymptomatic viral carriage was associated with a local chemokine response (CCL8, CXCL11, CXCL10, nominal p = 6.7x10-6). During ARVI, patients with rheumatoid arthritis had prolonged symptom burden by WURSS score compared to healthy controls. We also found that symptom burden correlated with RA severity by Routine Assessment of Patient Index Data 3 (RAPID3) score (r = 0.35, p = 0.001). Using gene modules created with Weighted Gene Co-expression Network Analysis (WGCNA), we found decreased expression of modules enriched in cilium associated pathways in patients with RA compared to healthy controls at baseline and during ARVI. This decreased cilial gene module expression correlated with an increased signature of neutrophilic inflammation (r=-0.63, p = 2.2x10-16). Our novel longitudinal study suggests that RA patients have impaired ciliated epithelial cell responses compared to healthy controls and that this is associated with increased inflammation and symptom burden during and following ARVI. This abstract is funded by: NIH
Smith-Rockne et al. (Fri,) studied this question.