Rheumatoid factor is associated with severe COVID-19.

AIM: Coronavirus disease 2019 (COVID-19) has been proposed as triggering autoimmunity. The aim of this study was to evaluate the presence and clinical significance of autoantibodies in patients with COVID-19. METHODS: We retrospectively collected data from 245 patients who were hospitalized for COVID-19. All patients were tested for the presence of antinuclear antibody (ANA), rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA), and anti-cytoplasmic neutrophil antibody (ANCA). Risk factors for death and critical COVID-19, defined as the need for invasive mechanical ventilation or extracorporeal membrane oxygenation, were analyzed. RESULTS: Ninety (36.7%) patients tested positive for ANA, and 51 (20.8%) patients tested positive for RF. Three patients each (1.2%) tested positive for ACPA and ANCA. RF-positive patients had higher rates of invasive mechanical ventilation and death than RF-negative patients (70.6% vs 28.4%, P < 0.001 and 45.1% vs 18.6%, P < 0.001, respectively). Underlying lung disease, kidney disease, heart disease, quick COVID severity index (qCSI), and lactate dehydrogenase (LDH) were associated with in-hospital death. RF (odds ratio [OR] 7.31, 95% CI 2.50-21.37, P < 0.001), qCSI (OR 1.42, 95% CI 1.19-1.69, P < 0.001), and LDH (OR 1.004, 95% CI 1.002-1.005, P < 0.001) were associated with critical COVID-19. Combination of RF, qCSI, and LDH showed good prognostic value (area under the curve = 0.903, P < 0.001) for critical COVID-19. CONCLUSIONS: ANA and RF were frequently detected in COVID-19 patients. RF could be a risk factor for critical COVID-19. The results of this study suggest immune dysfunction contributes to the complications of COVID-19.

BNT162b2 coronavirus disease-2019 vaccination accelerated rheumatoid arthritis disease activity in chronic eosinophilic pneumonia: A case report.

RATIONALE: The relationship between rheumatoid arthritis (RA) and eosinophilic inflammation is unclear. According to recent studies, it has been suggested that T helper 2 cell responses play a role in the inhibition of RA. It is unclear how the immunological response after coronavirus disease-2019 (COVID-19) vaccination affects T cell immune reactions. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of an 88-year-old woman diagnosed with RA and chronic eosinophilic pneumonia (CEP). She was diagnosed with CEP about 20 years ago, and, through steroid treatment, she improved and had no relapse for 16 years. At the time of diagnosis of CEP, the rheumatoid factor (RF) was increased; however, there were no joint symptoms. After receiving the COVID-19 vaccine, joint and respiratory symptoms gradually worsened. Laboratory examinations showed increased RF, anti-cyclin citrullinated peptide antibody, and peripheral absolute eosinophil count. Musculoskeletal ultrasonography showed synovitis. INTERVENTION AND OUTCOME: Methylprednisolone pulse therapy improved respiratory and joint symptoms immediately; RA and CEP stabilized with no relapses. LESSONS: Eosinophilic and rheumatoid reactions following COVID-19 vaccination were an-reported adverse events. Eosinophilic inflammation might be reflected on an anti-inflammatory reaction in initial phase of RA.

New-onset Seropositive Rheumatoid Arthritis Following COVID-19 Vaccination in a Patient with Seronegative Status.

Coronavirus disease 2019 (COVID-19) has spread worldwide since 2019, and mRNA vaccines for the disease have been rapidly delivered to limit the severity of infection. However, while these vaccines are effective in reducing the morbidity and severity of the disease, some patients develop severe adverse drug reactions and new-onset autoimmune phenomena, such as myocarditis, thrombosis with thrombocytopenia, and vasculitis. In addition, some patients develop arthritis following vaccination, including rheumatoid arthritis (RA). We herein report a case of new-onset seropositive RA following COVID-19 mRNA vaccination. Although tests for rheumatoid factor and anti-cyclic citrullinated peptide antibody had been negative three years before vaccination, the patient developed seropositive RA following COVID-19 mRNA vaccination.

Immunogenicity of Inactivated SARS-CoV-2 Vaccines in Patients With Rheumatoid Arthritis: A Case Series.

Objectives: Attenuated humoral response to mRNA SARS-CoV-2 vaccines has been reported in some patients with autoimmune disease, e.g., rheumatoid arthritis (RA). However, data of immune responses to inactivated SARS-CoV-2 vaccine in the RA population are still unknown. Herein, the safety and immunogenicity of inactivated SARS-CoV-2 vaccines in RA patients were analyzed. Methods: Seventy five RA patients and 26 healthy controls (HC) were respectively recruited from Yunnan Provincial Hospital of Traditional Chinese Medicine and the community in Kunming city. Neutralizing Antibody (NAb) Test ELISA kit was used to measure the percentage of inhibition. AKA (anti-keratin antibody) positivity was detected using indirect immunofluorescence. Rheumatoid factor (RF)-IgA was detected by ELISA. RF-IgG, RF-IgM, and anti-cyclic citrullinated peptide (CCP) antibodies were measured by chemiluminescence. ESR (erythrocyte sedimentation rate) was detected by ESR analyzer. C-RP (c-reactive protein) was detected by immunoturbidimetry. NEUT% (percentage of neutrophils) and LYMPH% (percentage of percentage) were calculated by a calculation method. Results: Compared with the HC group, the percentage of inhibition was significantly lower in RA patients receiving two doses of vaccines. Vaccines-induced percentage of inhibition was the lowest in RA patients who had not been vaccinated. In total 80.77% of the HC group had a percentage of inhibition ≧20%, compared with 45.24% of vaccinated RA patients and 6.06% of unvaccinated RA patients. Spearman correlation analysis revealed that antibody responses to SARS-CoV-2 did not differ between RA patients according to their age and disease duration. Furthermore, the results showed that no correlation was found between the percentage of inhibition and indices for RA, including RF-IgA, IgG, IgM; anti-CCP antibody; ESR; C-RP; NEUT% and LYMPH%. Conclusion: Our study showed inactivated vaccine-induced SARS-COV-2 antibody responses differ in RA patients and healthy subjects, emphasizing the importance of a third or fourth vaccination in RA patients.

Impact of Perceived Stress During the SARS-CoV-2 Pandemic on Rheumatoid Arthritis Patients' Disease Activity: An Online Survey.

INTRODUCTION/OBJECTIVES: Psychological stress worsens rheumatoid arthritis (RA) disease activity, and the COVID-19 pandemic has increased stress/anxiety in rheumatic patients. The purpose of this study was to determine if stress during the COVID-19 pandemic specifically impacts RA disease activity as reported by the patient. METHOD: This was a cross-sectional COVID-19 RA survey study. University of California, Los Angeles rheumatology clinic patients were emailed a link to a survey in July and November 2020. The 30-question survey pertained to COVID-19-related stress, RA disease activity, and demographics. For the survey responders, anti-cyclic citrullinated antibody, rheumatoid factor, and age were extracted from the electronic health record. Analyses were performed to examine the association between the 4-item Perceived Stress Scale (PSS-4) and other COVID-19-related stress measures with the Routine Assessment of Patient Index Data 3 (RAPID3). RESULTS: A total of 1138/5037 subjects completed the emailed survey (22.6% response rate). When examining responses across RAPID3 categories (near remission, low, moderate, and high disease severity), there were significant increases in PSS-4 and other stress variables. Multiple linear regression models showed that PSS-4, financial stress, age, seropositivity, disease duration, and Black race were independently associated with worsened RAPID3 scores, when controlling for other confounding factors. CONCLUSIONS: This study suggests that stress overall negatively impacts RAPID3, and Black RA patients had a higher RAPID3 scores during the COVID-19 pandemic. Despite colossal efforts to combat the pandemic, RA patients currently suffer from stress/anxiety, and methods to mitigate these psychological effects are needed.

Lack of cross-reactivity between rheumatoid factor IgM and anti-S1 receptor binding domain of SARS-CoV-2 IgM: a case-control study.

OBJECTIVES: Since the onset of the COVID-19 outbreak, concern has been raised about reliability of SARS-CoV-2 serological tests in people with serum positivity for rheumatoid factor (RF), due to its ability to interfere during tests carried out with immunoassay techniques, leading to false positive results. The aim of this study was to analyse, on sera from RF seropositive rheumatoid arthritis (RA) patients, the interference between RF IgM and anti-S1 RBD IgM. METHODS: The study was conducted on consecutive patients affected by RF seropositive RA and, as control group, COVID-19 patients with SARS-CoV-2 pneumonia hospitalised at Sapienza University of Rome from April 2020 and April 2021. Serum samples from COVID-19 patients during their hospitalisation were collected, while RA subjects' samples were harvested prior to the onset of the COVID-19 pandemic. All samples were tested for RF IgM using nephelometry and ELIA, and for anti-S1 RBD IgM by ELISA. RESULTS: Forty RF seropositive RA and 42 COVID-19 patients were enrolled. In all RA patients, both nephelometric assay and ELIA showed RF IgM positivity, while only one patient of the control group tested positive for RF IgM by nephelometric assay and ELIA. IgM directed to S1 RBD were not detected in sera of RA patients, while all COVID-19 patients presented anti-S1 RBD IgM (median anti-S1 RBD IgM COVID-19 vs. RA: 368.5 IU/mL, IQR 654 IU/mL vs. 18.45 IU/mL, IQR 20 IU/mL; p<0.0001). CONCLUSIONS: This study confirmed the lack of cross-reactivity between RF and anti-S1 RBD IgM, offering to clinicians a valuable tool for a better management of RA patients undergoing SARSCoV-2 serological tests.

Post-COVID-19 arthritis: is it hyperinflammation or autoimmunity?

BACKGROUND:  Various musculoskeletal and autoimmune manifestations have been described in patients with coronavirus disease 2019 (COVID-19). Objectives: This study aims to investigate the prevalence and etiology of arthritis in post-COVID Egyptian patients. Methods: We included 100 post-COVID Egyptian patients who recovered 6 months ago and assessed several inflammatory and autoimmune markers. Results: The prevalence of post-COVID arthritis was 37%. Ankle, knee, and wrist were the most commonly affected joints. Old age (P = 0.010), smoking (P = 0.001), and arthralgia (P = 0.049) were all linked with post-COVID arthritis. Levels of pretreatment (baseline) interleukin (IL)-6 (46.41 ± 3.67 vs. 24.03 ± 2.46; P = 0.001), as well as 6-month post-COVID C-reactive protein (CRP; 98.49 ± 67.55 vs. 54.32 ± 65.73; P = 0.002), and erythrocyte sedimentation rate (ESR; 109.08 ± 174.91 vs. 58.35 ± 37.87; P = 0.029) were significantly higher in patients with arthritis compared to those without. On the other hand, complement C3 (P = 0.558) and C4 (P = 0.192), anti-nuclear antibodies (P = 0.709), and anti-cyclic citrullinated peptides (anti-CCP; P = 0.855) did not show significant differences. Only pretreatment IL-6 level was the significant single predictor of post-COVID arthritis with an odds ratio (95% confidence interval) of 3.988 (1.460-10.892) and a P-value of 0.007. CONCLUSION:  The strong association observed with inflammatory markers (ESR and CRP) and the insignificant association with serologic markers of autoimmunity (ANA and anti-CCP) in our study support the notion that the underlying mechanism of post-COVID-19 arthritis is primarily due to the hyperinflammatory process associated with COVID-19 infection, and not the result of an autoimmune reaction. IL-6 levels before therapy can predict post-COVID arthritis allowing for early management.

False Positive Results in SARS-CoV-2 Serological Tests for Samples From Patients With Chronic Inflammatory Diseases.

Patients with chronic inflammatory diseases are often treated with immunosuppressants and therefore are of particular concern during the SARS-CoV-2 pandemic. Serological tests will improve our understanding of the infection and immunity in this population, unless they tests give false positive results. The aim of this study was to evaluate the specificity of SARS-Cov-2 serological assays using samples from patients with chronic inflammatory diseases collected prior to April 2019, thus defined as negative. Samples from patients with multiple sclerosis (MS, n=10), rheumatoid arthritis (RA, n=47) with or without rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti-CCP2) and systemic lupus erythematosus (SLE, n=10) with or without RF, were analyzed for SARS-CoV-2 antibodies using 17 commercially available lateral flow assays (LFA), two ELISA kits and one in-house developed IgG multiplex bead-based assay. Six LFA and the in-house validated IgG assay correctly produced negative results for all samples. However, the majority of assays (n=13), gave false positive signal for samples from patients with RA and SLE. This was most notable in samples from RF positive RA patients. No false positive samples were detected in any assay using samples from patients with MS. Poor specificity of commercial serological assays could possibly be, at least partly, due to interfering antibodies in samples from patients with chronic inflammatory diseases. For these patients, the risk of false positivity should be considered when interpreting results of the SARS-CoV-2 serological assays.