COVID-19 Impact on Patients with Immune-Mediated Rheumatic Disease: A Comparative Study of Disease Activity and Psychological Well-Being Over Six Months

Objectives To compare the impact of COVID-19 on clinical status and psychological condition in patients with immune-mediated rheumatic diseases (IMRD) infected by SARS-CoV-2 with IMRD controls not infected, during a 6-month follow-up. Methods The ReumaCoV Brasil is a longitudinal study designed to follow-up IMRD patients for 6 months after COVID-19 (cases) compared with IMRD patients no COVID-19 (controls). Clinical data, disease activity measurements and current treatment regarding IMRD, and COVID-19 outcomes were evaluated in all patients. Disease activity was assessed through validated tools at inclusion and at 3 and 6 months post-COVID-19. The FACIT-F (Functional Assessment of Chronic Illness Therapy) and DASS 21 (Depression, Anxiety and Stress Scale – 21 Items) questionnaires were also applied at 6 months after COVID-19 in both groups before large-scale vaccination. The significance level was set as p<0.05, with a 95% confidence interval. Results A total of 601 patients were evaluated, being 321 cases (IMRD COVID-19+) and 280 controls (IMRD COVID-19 –), predominantly female with similar median age. No significant differences were noted in demographic data between the groups, including comorbidities, disease duration, and IMRD. Disease activity assessment over a 6-month follow-up showed no significant difference between cases and controls. While mean activity scores did not differ significantly, some patients reported worsened disease activity post-COVID-19, particularly in rheumatoid arthritis (RA) (32.2%) and systemic lupus erythematosus (SLE) (23.3%). Post-COVID-19 worsening in RA patients correlated with medical global assessment (MGA) and CDAI scores, with a moderate to large effect size. Diabetes mellitus showed a positive association (OR=7.15), while TNF inhibitors showed a protective effect (OR=0.51). Comparing SLEDAI pre– and post-COVID-19, a minority showed increased scores, with few requiring treatment changes. Fatigue, depression, anxiety, and stress were significantly higher in cases compared to controls. Worsening disease activity post-COVID correlated with worsened FACIT-F and DASS-21 stress scale in RA patients. No significant associations were found between COVID-19 outcomes and post-COVID-19 disease activity or psychological assessments. Conclusions Post-COVID-19 IMRD patients show significant psychological well-being deterioration despite similar disease activity scores. The variability in reports on IMRD flares and the potential trigger of SARS-CoV-2 for autoimmune manifestations underline the need for detailed clinical assessment and a comprehensive approach to managing them. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by National Council for Scientific and Technological Development (CNPq) and Brazilian Society of Rheumatology ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Hospital das Clinicas of Universidade Federal de Pernambuco and Brazilian National Committee of Ethics in Research (CONEP/CNS/MS) gave ethical approval for this work. Technical advice number: 3.955.206 CAAE number: 30186820.2.1001.8807 Confirm information using CAAE number: I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors