The Impact of the Covid-19 Pandemic on Primary Care Referrals and New Diagnoses of Inflammatory Arthritis

Background/Aims The COVID-19 pandemic abruptly changed healthcare delivery. This study describes the impact the pandemic had on time to referral and diagnosis of inflammatory arthropathies (IA), including rheumatoid arthritis (RA) and juvenile inflammatory arthritis (JIA), in patients presenting in primary care with musculoskeletal problems. Methods Data from the Clinical Practice Research Datalink (CPRD) Aurum were analysed from 01/04/17 to 01/10/2021 to describe episodes of care for patients with musculoskeletal conditions for pre-COVID-19 (01/04/ 2017-31/03/2020), peri-COVID-19 (01/04/2020-31/07/2021), and post- COVID-19 lockdown (01/08/2020-31/10/2021) periods. Prevalent and incident musculoskeletal consultations were determined. Referrals were matched to these consultations. Trends in referrals to musculoskeletal services and further incident diagnoses of IA were described using Joinpoint Regression and comparisons made between timeperiods. Negative binomial regression was used to compare incident rates between time-periods of: RA/JIA/IA diagnosis and referral from first musculoskeletal consultation;and RA/JIA/IA diagnosis from first referral. The number of consultations between first musculoskeletal consultation and referral/diagnosis were described. Results were adjusted for age and sex and further stratified by geographical region and deprivation. Results The incidence rate of RA and JIA reduced by average -13.32% (from 31.98 per 1,000,000 to 17.15 per 1,000,000) and -17.43% (from 1.77 per 1,000,000 to 0.97 per 1,000,000) per month respectively between January 2020 and April 2020, then increased by 1.9% (from 17.15 per 1,000,000 to 25.22 per 1,000,000) and 3.7% (from 0.97 per 1,000,000 to 1.28 per 1,000,000) per month respectively between April 2020 and October 2021. Referral incidence decreased between February 2020 and May 2020 by -16.8% per month in patients presenting with a musculoskeletal condition. After May 2020, referrals increased significantly (16.8% per month) July 2020. Time from first musculoskeletal consultation to RA diagnosis, and referral to RA diagnosis increased in the peri-COVID-19 period (IRR 1.11, 95%CI 1.07-1.15;IRR 1.23, 95%CI 1.17-1.30) and remained consistent in the post- COVID-19 (IRR 1.13, 95%CI 1.11-1.16;IRR 1.27, 95%CI 1.23-1.32) periods respectively, compared to the pre-COVID-19 period. Similarly, number of consultations between first musculoskeletal consultation and referral/RA diagnosis reduced significantly in the peri-COVID-19 (IRR 0.92, 95%CI 0.88-0.96) and post-COVID-19 (IRR 0.92, 95%CI 0.90-0.95) periods. No change was observed between first musculoskeletal consultation and first referral. Similar results were observed for IA but not for JIA. Conclusion Patients with RA/JIA onset during the pandemic may be yet to present or are currently transitioning through referral and diagnosis. Primary care clinicians should remain alert to possible IA diagnosis and consider fast-track referral pathways where indicated. Patients developing incident episodes of IA may display a prodrome of other musculoskeletal symptoms and conditions, which alone may not warrant referral but in combination require further investigation. Commissioners should be alert to these findings to allow for the appropriate planning and commissioning of services.

Mental health and psychological well-being in rheumatoid arthritis during COVID-19. can physical activity help?

In response to the COVID-19 pandemic, many countries have adopted community containment to manage COVID-19. These measures to reduce human contact, such as social distancing, are deemed necessary to contain the spread of the virus and protect those at increased risk of developing complications following infection with COVID-19. People with rheumatoid arthritis (RA) are advised to adhere to even more stringent restrictions compared to the general population and avoid any social contact with people outside their household. This social isolation, combined with the anxiety and stress associated with the pandemic, is likely to particularly have an impact on mental health and psychological well-being in people with RA. Increasing physical activity and reducing sedentary behavior can improve mental health and psychological well-being in RA. However, COVID-19 restrictions make it more difficult for people with RA to be physically active and facilitate a more sedentary life-style. Therefore, guidance is necessary for people with RA to adopt a healthy life-style within the constraints of COVID-19 restrictions to support their mental health and psychological well-being during and after the COVID-19 pandemic rheumatoid arthritis, COVID-19, mental health, psychological well-being, physical activity, sedentary behavior.

Effect of COVID-19 on severity of signs and symptoms of autoimmune diseases

It is an observational cross-sectional study, the data collected by convenience sampling method from 33 patients in the Ranya General Hospital and private clinics for follow-up patient's autoimmune diseases state in the Ranya city from the 10th November 2020 to the 20th May 2021 and the study included all the patients had autoimmune diseases that recovered from the COVID-19 disease. For the study materials, the data was collected by a questionnaire form that included demographic and autoimmune disease questions also questions about the patient's intensity of their autoimmune disease's signs and symptoms before and after they recovered from COVID-19. Determine patient's autoimmune disease signs and symptoms intensity based on the prescribed drug for a treat the autoimmune diseases which are changed by special doctors. Furthermore, the data were analysed by SPSS software to produce descriptive statistic measures and to find the difference between dependent categorical variables Sign tests were used but the Chi-square test was used for the categorical independent variables with regarding 0.05 as a significant critical value. The result reveals that the range of their age started from 42 to 74 years old with mean..standard deviation (57.3 .. 8.06) and most of the cases 15(45.5%) were between (55-65) years old, followed by less than 55 years old 13(39.4%) and more than 65 years old age 5(3.8%) cases respectively. Rheumatoid arthritis was a major type 16 (48.5%) of the autoimmune disease compared to other types, Ankylosing Spondylitis 8(24.2%) cases, and Ulcerative Colitis 6(18.2%) cases respectively while Crohn's disease was the minimum 3(9.1%) cases and before the got COVID-19 most of the cases 25(75.8%) had moderate intensity signs and symptoms of their autoimmune diseases and 8(24.2%) cases had severe signs and symptoms but after they recovered from the COVID-19 disease the rate of their signs and symptoms changed to mild 19(57.6%) and moderate 14(42.4%) intensity while severe intensity signs and symptoms were zero with highly significant differences (P-value 0.0001). Despite the current study concluded autoimmune disease patients recovered from the COVID-19 their autoimmune diseases signs and symptoms intensity decreased significantly but still further studies are needed with a bigger sample size to determine and explain this association.

Fenofibrate and statins in patients with COVID-19

Statins, which are widely used to treat hypercholesterolemia, have anti-inflammatory and antioxidant effects, upregulate angiotensin-converting enzyme 2 (ACE2) receptors, which happen to be SARS-CoV-2's gateway into cells. This study aims to analyse the effects of Fenofibrate in comparison to Statins and a control group in patients with COVID-19. This is a retrospective open blind observational study of cohort of 300 patients experienced COVID-19 (symptoms' severity varied between patients). The participants were divided into three cohorts;a control group received standard COVID-19 treatment (n=100);a second group (n=100) of patients who were on Statins, in addition they received the standard treatment;and a third cohort for patients who were already taking Fenofibrate (TRICORR) as a medication to treat hyperlipidemia (n=100). Most symptoms (including cough, exertional dyspnoea, SOB, sore throat, sneezing, headache, tiredness, agitation, diarrhoea, joint pain, insomnia, myalgia, and fatigue) were less prevalent for patients who administered antihyperlipidemic drugs compared to the control group. Patients who were already taking Cholesterol-lowering medication presented with symptoms varied between mild to severe. Patients on Statins or Fenofibrate also showed less tachycardia and tachypnoea compared to those who were not on antihyperlipidemic drugs, and also the need for oxygen and ICU admission were less frequent. The length of stay in hospital was shorter in patients who were already on Statins or Fenofibrate. Both Statins and Fenofibrate have improved the outcome and the severity of symptoms for patients with Covid 19 infection.

Ulcerative Colitis: Rapid Evidence Review

Ulcerative colitis is a relapsing and remitting inflammatory bowel disease of the large intestine. Risk factors include recent Salmonella or Campylobacter infection and a family history of ulcerative colitis. Diagnosis is suspected based on symptoms of urgency, tenesmus, and hematochezia and is confirmed with endoscopic findings of continuous inflammation from the rectum to more proximal colon, depending on the extent of disease. Fecal calprotectin may be used to assess disease activity and relapse. Medications available to treat the inflammation include 5-aminosalicylic acid, corticosteroids, tumor necrosis factor-alpha antibodies, anti-integrin antibodies, anti-interleukin-12 and -23 antibodies, and Janus kinase inhibitors. Choice of medication and method of delivery depend on the location and severity of mucosal inflammation. Other treatments such as fecal microbiota transplantation are considered experimental, and complementary therapies such as probiotics and curcumin have mixed data. Surgical treatment may be needed for fulminant or refractory disease. Increased risk of colorectal cancer and use of immunosuppressive therapies affect the preventive care needs for these patients. (Am Fam Physician. 2022;105(4):406-411. Copyright © 2022 American Academy of Family Physicians.)Copyright © 2022 American Academy of Family Physicians. All rights reserved.

COVID-19 course in connective tissue disease-related interstitial lung disease patients

INTRODUCTION: Coronovirus 2019 (Covid-19) infection has been related to increased mortality amongst patients with lung disease. In this study it was aimed to showed the mortality rate and possible prognostic factors related to Covid-19 in connective tissue disease related interstitial lung disease patients (CTD-ILD) METHODS: In a tertiary referral center, patients with previously diagnosed CTD-ILD retrospectively reviewed. Between 1th April 2020 to 1 th April 2021 patients data related to ILD disease, Covid-19 infection and mortality obtained from electronic records retrospectively. The primary outcome was death at day 30 of COVID-19 infection RESULTS: There were 271patients diagnosed with CTD-ILD. 74 patients had Covid-19 infection, which was confirmed by polymerase chain reaction. 29 patients were dead during the followed-up period of whom 13 patients had Covid-19 infection-related mortality (17.5% vs 8.1%, p: 0.045). Covid-19 infection related to mortality was more frequently seen in patients with decreased forced vital capacity, smoking history, extended disease and rheumatoid arthritis. On multivariate regression analysis, only decreased forced vital capacity were related to poor outcomes. DISCUSSION AND CONCLUSION: Covid-19 infection is related to increased risk of mortality in CTD-ILD patients. Decreased forced vital capacity is a poor prognostic risk factor.

Active vaccination campaign to increase seasonal influenza vaccination coverage: a monocenter experience in a cohort of Italian patients with systemic autoimmune diseases.

Seasonal influenza is a frequent cause of hospitalization and mortality among patients with systemic autoimmune diseases. Despite this evidence, vaccination coverage is generally much lower than the minimum 75% target proposed by the WHO. Therefore, an active campaign was implemented in the years 2019/2020 and 2020/2021 within the Rheumatology Department of the Niguarda Hospital (Milan, Italy) to improve the vaccination coverage in patients with inflammatory arthritis. This study aims to evaluate the vaccination coverage in the 2019/2020 and 2020/2021 (active campaigns) seasons and to compare these results with the 2018/2019 season. A monocenter observational study was conducted among adult patients with rheumatoid arthritis, spondylarthritis, or psoriatic arthropathy, who were referred to the Rheumatology Department of the Niguarda Hospital. Patients were given a questionnaire to investigate previous years' vaccination coverage and to propose an influenza vaccine for the 2020/2021 season. Compared with 2018/2019, a trend for increase in vaccination coverage was reported in 2019/2020 season (+ 10.7%, p = 0.055; 45.5% of coverage) and a statistically significant increase was reported in 2020/2021 (+ 31.2%, p < 0.001; 65.9% of coverage). The increase was also significant when comparing the 2020/2021 and 2019/2020 seasons (+ 20.5%, p < 0.001). The greatest increase in vaccination coverage was observed among under-65-year-old patients. Obtained results support the implementation of active vaccination campaigns to increase vaccination coverage among patients with systemic autoimmune diseases and highlight the importance of external factors (such as the COVID-19 pandemic) in directing the patient to adopt preventive measures to avoid infections and related complications.

Nail ridging in rheumatoid arthritis patients and relation to disease activity: An integrated rheumatology-dermatology multi-centre study

Aim of the work: To evaluate the frequency of nail ridging (NR) in patients with rheumatoid arthritis (RA) and to study its relation to disease activity. Patients and methods: 230 RA patients and 97 matched controls from Helwan, Ain Shams and Mansoura university hospitals were studied. Disease activity score (DAS28) was assessed. NR has been searched for in all patients. The number of affected fingers was recorded. NR was determined by a magnifying lens, seen by naked eye or seen and felt. Dermoscopic photography of the NR using Dermalite DL4 3Gen dermatoscope has been recorded. Results: The median age of patients was 49 years (42–58 years);they were 221 females and 19 males (F:M 11.1:1) with a disease duration 9 years (5–11 years). Their DAS28 was 3.6 (2.9–4.6). NR was significantly increased in RA cases vs. control;73% vs 20%;p < 0.001. In patients, NR was detected by a magnifying lens in 32.6%, seen in 27% and seen and felt in 13.5%. Joint deformities were significantly higher in those with NR. DAS28 was a significant independent predictor of NR;for every one-point increase in DAS28, there was a 153 times higher odds to exhibit NR at a sensitivity of 93.5%, specificity 80.3% and at a diagnostic accuracy of 90%. Conclusion: NR is a frequent finding in RA. An integrated rheumatological- dermatological clinical evaluation may be helpful and further studies are required to prove the importance of this sign for follow up of RA patients.

The Persistence of Anti-Spike Antibodies Following Two Sars-Cov-2 Vaccines in Patients with Inflammatory Bowel- and Joint Diseases on Immunosuppressive Therapy Compared to Healthy Controls - a Prospective Cohort Study

Introduction: Limited data is available regarding long-term effectiveness of SARS-CoV-2 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy. Whether the persistence of vaccine-induced humoral immunity differs between IMID patients and the general public is currently unknown. Aims & Methods: IMID patients on immunosuppressive medication and healthy controls were enrolled in the prospective, observational Nor-vaC study. Serum samples were collected at two time points following two dose SARS-CoV-2 vaccination (first assessment within 6-48 days and second within 49-123 days). Sera were analysed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Anti-RBD <200 BAU /ml were defined as low levels. The estimated percent reduction in anti-RBD standardised to 30 days was calculated and factors associated with reduction were identified in multivariable regression models. The aims of the study were to compare the persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses between IMID patients and healthy controls, and to identify predictors of antibody decline. Result(s): A total of 1097 patients (190 Crohn's disease, 129 ulcerative colitis, 400 rheumatoid arthritis, 189 psoriatic arthritis, 189 spondyloarthritis) (median age 54 years [IQR 43-64];56% women) and 133 controls (age 45 years [35-56];83% women) provided blood samples within the defined intervals (median 19 days [IQR 15-24] and 97 days [86-105] after second vaccine dose). Of the patients, 464 used tumor necrosis factor inhibitor (TNFi) monotherapy, 259 TNFi + metabolite inhibitor(s), 212 methotrexate monotherapy, 42 interleukin inhibitors, 34 vedolizumab, 29 rituximab, and 23 janus kinase inhibitors. Antibody levels were significantly lower in patients compared to controls at both assessments, with median anti-RBD 1468 BAU/ml [IQR 500-5062] in patients and 5514 BAU/ml [2528-9580] in controls (p<0.0001) and 298 BAU/ml [IQR 79-500] in patients and 715 BAU/ ml [28-2870] in controls (p<0.0001), at first and second assessment respectively. At the second assessment, anti-RBD antibody levels decreased below 200 BAU/ml in 452 (41%) patients and in 1 (0.8%) control (p<0.0001) (Table). The percentage change in anti-RBD levels were -86 % in patients and -77 % in controls (p<0.0001). In the multivariable regression analyses, patients had a greater decline in anti-RBD levels compared to controls beta -3.7 (95% CI -6.0, -1.4) (p<0.001). Use of TNFi in mono- or combination therapy was associated with the greatest decline compared to controls, beta -6.1 (95% CI -8.1, -4.1) and beta -6.4 (-8.4, -4.2) respectively (p<0.001). Conclusion(s): Within four months after the second vaccine dose, anti-Spike antibody levels declined considerably in both IMID patients and controls. Patients had lower antibody levels at the first assessment and a more pronounced decline compared to controls, and were consequently more likely to have low antibody levels four months after the second vaccine dose. Our results support that IMID patients lose humoral protection and need additional vaccine doses sooner than healthy individuals. (Table Presented).

Immunogenicity and Safety of a Three-Dose Sars-Cov-2 Vaccination Strategy in Patients with Immune-Mediated Inflammatory Diseases on Immunosuppressive Therapy

Introduction: Humoral vaccine responses to SARS-Cov-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID). Concerns have been raised regarding their protection against severe COVID-19 disease. Knowledge regarding efficacy and safety of repeated vaccination in this large patient group is currently lacking. Aims & Methods: The prospective observational Nor-vaC study (NCT04798625) enrolled adult patients on immunosuppressive therapy for inflammatory bowel-and joint diseases. Healthy controls were health care workers from participating hospitals. All participants received standard vaccines according to the national vaccination program with three doses in patients and two doses in controls. The third dose was offered to IMID patients >4 weeks after the second dose. Anti-Spike antibodies were assessed 2-4 weeks, and 12 weeks following each dose. The main outcome was anti-Spike antibody levels 2-4 weeks following three-and two-dose vaccination in patients and controls, respectively. Levels were compared across groups by Mann-Whitney U test. Factors associated with anti-Spike antibody level following the third dose were assessed by uni-and multivariable linear regression adjusted for time between vaccine and sampling. The aim of the study was to evaluate humoral immune responses and safety of repeated vaccination in IMID patients. Result(s): Overall, 1100 patients (156 ulcerative colitis, 217 Crohn's disease, 366 rheumatoid arthritis, 177 spondyloarthritis, and 184 psoriatic arthritis;median age 54 [IQR 42-64];602 women [55%]) and 303 controls (median age 43 [IQR 33-55];226 women [75 %]) were included. Immunosuppressants were tumor necrosis factor inhibitor (TNFi) monotherapy (n=461), TNFi with concomitant immunomodulator (n=254), methotrexate (n=220), vedolizumab (n=46), janus kinase inhibitors (n=33), and other (n=86). Vaccine series were Pfizer BNT162b2 (54% patients, 54% controls), Moderna mRNA-1273 (17% patients, 23% controls), or combination of vaccines (29% patients, 23% controls)). Patients received the third vaccine dose a median of 126 (IQR 105-154) days after the second dose. Following three-dose vaccination, patients achieved median (IQR) antibody levels of 5720 BAU/ml (2138-8732) compared to 4495 (1591-6639) in controls receiving two doses, p=0.27. In patients, anti-Spike antibody levels increased by a median of 1932 BAU/ ml (IQR 150-4978) from the second to the third dose, p<0.001. Factors associated with response were a greater interval between the second and third vaccine dose (>5 months) (p=0.03), vaccination with mRNA-1273 (p<0.001), and a combination of vaccines (p<0.001). Antibody levels had a slower decline-rate following the third vaccine dose, as compared to after the second dose, with a significant difference (p<0.001). Adverse events were reported by 488 (53%) and 464 (47%) patients after second and third dose, respectively, and by 196 (68%) controls. Disease flares were reported by 50 (5%) and 70 (7%) patients following the second and third dose. Conclusion(s): This large observational study shows that additional vaccine doses to IMID patients contributes to strong and sustained immune-responses comparable to healthy persons vaccinated twice. This study highlights the importance of repeated vaccination of IMID patients to ensure a stronger and more durable protection from severe COVID-19.

Proceedings of the 28th European Paediatric Rheumatology Congress, PReS 2022

The proceedings contain 520 papers. The topics discussed include: Modeling HLH MAS susceptibility identifies the characteristics of hyperinflammatory CD8 T-cells;characteristics and disease course of patients with systemic juvenile idiopathic arthritis without arthritis in the German AID-NET cohort;impact of interferon signaling on response to canakinumab treatment in systemic juvenile idiopathic arthritis as revealed by whole blood RNA sequencing;systemic juvenile idiopathic arthritis associated lung disease in Europe;analysis of pyrin inflammasome activation defines surf patients from FMF and other recurrent fevers;MIS-C phenotypes vary between SARS-COV-2 variants;development of the oncoreum score for differential diagnosis between childhood cancer with arthropathy and juvenile idiopathic arthritis;NLRP3 splicing variants as a regulatory mechanism of inflammasome priming in auto-inflammation;and candidate gene sequencing in systemic juvenile idiopathic arthritis implicates rare variation in hereditary periodic fever and familial hemophagocytic lymphohistiocytosis genes.

A CASE OF COMMON VARIABLE IMMUNODEFICIENCY (CVID) COMPLICATED BY GRANULOMATOUS LYMPHOCYTIC INTERSTITIAL LUNG DISEASE (GLILD) TRIGGERED BY RECENT COVID-19 INFECTION

SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by low serum IgG, IgA and/or IgM, and poor specific antibody production. CVID is estimated to affect as many as 1 in 25,000 individuals. Chronic lung disease is a common problem in patients with CVID. About 10-20% of patients have lymphocytic infiltrates and/or sarcoid-like granulomas, with several histological findings, termed granulomatous and lymphocytic interstitial lung disease (GLILD). CASE PRESENTATION: Patient is a 61-year-old Caucasian woman with a history significant for CVID in remission who presented to the Pulmonary Clinic with a chief compliant of dyspnea of exertion (DOE). Patient was not suffering from any respiratory complaints until the diagnosis of severe COVID-19 pneumonia 4 months prior. For the following months, patient was slowly improving but was still suffering from severe DOE that has negatively impacted her quality of life. Patient has a remote history of smoking, having quit 10 years ago. Patient denied any joint pain, stiffness, swelling, skin rash, muscle ache, or weakness. No known history of SLE, Rheumatoid Arthritis, or other collagen vascular disorders had been reported. Patient denied any exposure to birds. Physical exam was significant only for bilateral basal rales with no wheezing or crackles. No skin rash, joints deformities, or clubbing was noticed. Laboratory studies revealed ESR was 17 with a CRP of 10.6. Negative ANA, SM, RNP, and SSA/SSB antibodies. Her Immunoglobulins levels were low with IgG 382 (nl > 610) and IgA < 2 (nl > 85). Her PFT revealed severe restrictive process with TLC 46% of predicted and severe reduction in DLCO at 35%. CT chest revealed diffuse central groundglass opacities, and interstitial thickening with traction bronchiectasis. Lung biopsy via VATS revealed lung parenchymal with focal, noncaseating granulomas, foci of focal interstitial lymphocytic infiltration and fibrosis;features consistent with Granulomatosis-Lymphocytic Interstitial Lung Disease (GLILD). Systemic steroid initiated and for the following weeks patient reports significant improvement in DOE. Her PFT at 3 month follow up showed significant improvement in FVC (5% increase), TLC (11% increase), and DLCO (5% increase). DISCUSSION: The respiratory manifestations of CVID follow two main mechanisms: injury due to acute or recurrent infections and damage due to poorly understood immune-mediated processes. Severe COVID-19 results in dysregulated immune and inflammatory response that can worsen an underlying lung disease. Previous cases have been reported about CVID with GLILD complicated with COVID-19 infection but not vice versa. CONCLUSIONS: To our knowledge, this is a rare case of CVID complicated by GLILD triggered by recent COVID-19 infection. However, little is known about the association between COVID-19 infection and GLILD and further investigation is needed. Reference #1: Ho HE, Mathew S, Peluso MJ, Cunningham-Rundles C. Clinical outcomes and features of COVID-19 in patients with primary immunodeficiencies in New York City. J Allergy Clin Immunol Pract. 2020;S2213–2198(20):31102–8. Reference #2: Prasse A, Kayser G, Warnatz K. Common variable immunodeficiency-associated granulomatous and interstitial lung disease. Curr Opin Pulm Med. 2013;19:503–9. Reference #3: Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48. DISCLOSURES: No relevant relationships by husam nayef No relevant relationships by Arshia Vahabzadeh No relevant relationships by Zaid Yaqoob No relevant relationships by Mohammad Zalt

Patterns of Viral Arthropathy and Myalgia Following COVID-19: A Cross-Sectional National Survey.

Introduction: Viral arthropathy is an increasingly recognized sequela of several viral pathogens including alphaviruses, hepatitis, and potentially coronaviruses. Case reports of viral arthropathy and myalgia associated with SARS-CoV-2 infection (COVID-19) both during active disease and following resolution of acute COVID-19 symptoms are becoming more prevalent. We sought to describe the prevalence of viral arthropathy and myalgia associated with COVID-19, as well as to identify factors that may predict these symptoms. Methods: A national, cross-sectional survey was conducted using a questionnaire administered online. Subjects self-reporting previous confirmed COVID-19 were recruited using the Amazon Mechanical Turk crowdsourcing platform. Questionnaire items included demographics, frequency and severity of common COVID-19 symptoms, requirement for hospitalization or mechanical ventilation, subject recall of arthropathy or myalgia onset, duration, and severity, as well as WOMAC score. Binary logistic regression was used to identify potential predictive co-variates for the development of either arthropathy or myalgia. Results: A total of 3222 participants completed the arthropathy/myalgia questionnaire with 1065 responses remaining for analysis following application of exclusion criteria, data integrity review, and omission of respondents with confounding conditions. Of the 1065 cases, 282 (26.5%) reported arthralgia and 566 (53.2%) reported myalgia at some point during or after COVID-19 with 9.9% and 6.0% reporting onset of arthralgia or myalgia, respectively, after resolution of acute COVID-19 symptoms. The presence of several commonly reported COVID symptoms or indicators of disease severity was predictive of arthralgia including hospitalization (OR 3.7; 95% CI 2.4 to 5.8), sore throat (OR 2.3; 95% CI 1.5 to 3.5), fatigue (OR 2.9; 95% CI 1.7 to 4.9), and ageusia/anosmia (OR 1.7; 95% CI 1.1 to 2.7). Discussion: Based on these results, new-onset arthropathy and myalgia following COVID-19 resolution may be an increasingly encountered etiology for pain.

Correlation between stress, anxiety and depression of patients with rheumatoid arthritis during COVID-19 pandemic and their non-compliance to treatment: a cross-sectional study

Background: The prevalence of anxiety and depression is high in rheumatoid arthritis (RA) patients. As RA patients tend to be immunodeficient, they are at greater risk of coronavirus disease 2019 (COVID-19) infection due to their scheduled hospital appointments. Therefore, they have become more anxious and worried during COVID-19 pandemic, and some patients recently have canceled or postponed their treatment. Objectives: This study aimed to assess the effect of stress, anxiety, and depression due to COVID-19 outbreak on non-compliance to treatment among RA patients.

PERFORMANCE of AN EARLY TRIAGE SYSTEM for IDENTIFICATION of PATIENTS with INFLAMMATORY RHEUMATIC DISEASES

Background: The preselection of patients with suspicion of an infammatory rheumatic disease is not easy for general practitioners and orthopedists. In countries with a limited number of practicing rheumatologists waiting lists are often long, since a full rheumatologic examination often needs a long consultation time. Objectives: To test the performance of an early triage strategy for early identif-cation of patients with infammatory rheumatic diseases. Methods: Prior to the SARS-CoV 2 pandemic, physicians caring for patients contacting a tertiary rheumatologic cente were frst contacted by a health-care professional (HPR) who offered an appointment the timing of which was based on the symptoms reported (Step 1). Patients were then seen by a rheumatolo-gist who, within a 10-minute consultation (Step 2), shortly examined the patient to determine the urgency of a planned full work up. The main outcome of the study was the comparison between the initial assessment and the fnal expert diagnosis (Step 3). Results: Within 9 months, physicians caring for 1.180 patients contacted the hospital, 972 of whom kept their appointment (82.4%). Most patients were transferred by GPs (73.1%) and orthopedists (22.1%). The mean time between Step 1 and Step 2 was 10.4 days, while 6.2% of patients were seen within 4 days, 24.4% within 7 days and 69.3% within 12 weeks. Only 36 patients (3.7%) of patients had an already established rheumatic disease. Complaints lasting between 0-4 weeks were reported by 69 (7.1%), of > 4-12 weeks by 100 (10.3%), and of > 12 weeks by 973 (82.6%) patients. Almost 90% of patients reported a pain intensity >4/10 (NRS) for < 2 weeks. An elevated CRP was found in 207 patients (24.5%). Prior treatment with glucocorticoids was reported in 163 (16.8%) and with NSAIDs in 730 (75.1% of) patients. The confirmed diagnosis at Step 3 was rheumatoid arthritis in 127 (13.1%), spondyloarthritis including pso-riatic arthritis in 72 (7.4%), systemic diseases including connective tissue diseases in 112 (11.5%), vasculitides in 41 (4.2%), and crystal arthropathy in 38 (3.9%) patients, while 38 (3.9%) had an infection, a malignancy or a differential diagnosis such as Raynaud's phenomenon or sicca syndrome. Degenerative joint diseases (n=254;26.1%) and non-inflammatory soft tissue syndromes such as fibromyalgia (n=369;38%) accounted for more than half of the patients. Conclusion: This study describes the performance of a standardized triage system hereby confrming the need for an early identifcation and preselection of patients with rheumatic musculoskeletal symptoms, including involvement of HPRs in the initial phase of contact. Based on the results, three patients with musculoskeletal complaints had to be examined in order to identify one patient with an infammatory rheumatic disease.

INCIDENT CASES of COVID-19 and VACCINATION ADHERENCE in A MULTICENTRIC COHORT of INFLAMMATORY ARTHRITIS in BRAZIL

Background: The SARS-CoV-2 virus has caused a worldwide health crisis. Patients with infammatory arthritis are at higher risk of hospitalization and death by COVID-19 due to comorbidities or immunosuppressive treatments. Vaccination is one the most important strategies to control the pandemic. Objectives: To evaluate the incident cases of SARS-CoV-2 infection in a multi-centric cohort of infammatory arthritis in Brazil. Methods: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their frst bDMARD or tsDMARD (1). The present analysis is a retrospective evaluation of adult patients with infam-matory arthritis (rheumatoid arthritis-RA, spondylarthritis-SpA and psoriatic arthritis-PsA) that were alive since the beginning of the COVID-19 pandemics in Brazil in February 2020. We evaluated the incidence and severity of COVID-19 infection and the adherence to anti-SARS-CoV-2 vaccines schedules, up to January 2022. Results: A total of 300 patients were interviewed and 69 (23.0%) reported con-frmed anti-SARS-CoV infection and 5 (1.7%) had a second infection. Among known infected patients, 18.8% need hospitalization and oxygen support, 7.2% were admitted at ICU, and 5.8% died. After COVID-19 infection, 31.8% reported worsening of disease activity but only 6.1% had modifcation in medication due to disease activity. Distribution of cases followed the pattern of waves observed in Brazil (Figure 1). Regarding vaccination, 285 (95%) reported to have received at least one dose of any anti-SARS-CoV-2 vaccine: 43% received the frst with the adenovirus ChAdOx1 nCoV-19 (AstraZeneca) adenovirus vaccine, 32% received the Sinovac-CoronaVac inactivated vaccine, 22% received the BNT162b2 (Pfzer-BioNtech) mRNA vaccine and 3% received the BNT162b2 (Pfzer-BioNtech) adenovirus vaccine. Almost all (98.1%) of these patients had already received the second dose of vaccine and after the frst and second vaccine doses, 6% and 4% of patients, respectively, reported worsening of articular disease activity, while, after the third dose, no patient reported disease activity worsening. Conclusion: During the pandemics, patients with infammatory arthritis had a pattern of distribution of cases very similar to general population. Adherence to vaccination is high and well tolerated.

ATTITUDES and HESITANCY in PATIENTS with INFLAMMATORY RHEUMATIC DISEASES TOWARDS SARS-COV-2 VACCINATION: A SINGLE-CENTER STUDY from BULGARIA

Background: Bulgaria is among the countries with the lowest vaccination rate of adult population in Europe. The presence of autoimmune rheumatic disease could further contribute to vaccine hesitancy and skepticism and influence patients' attitudes towards vaccination [1, 2]. However, little is still known about the willingness and particular causes of hesitancy in patients with infammatory joint diseases in the skeptical part of adult population across Europe. Objectives: Our goal was to assess the rate of SARS-CoV-2 vaccination among patients with immune-mediated rheumatic joint diseases receiving biological and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) and to determine the modifable predictors of vaccination hesitancy. Methods: Patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis undergoing biological or targeted synthetic DMARDs therapy were consecutively selected and included in this single-center cross-sectional study. Excluding criteria in patients were psychiatric or neurological disease preventing understanding or responding to the questions, being illiterate, or not willing to participate in the study. Various demographic, anthropometric, and clinical data were collected. Disease activity was determined using DAS28-CRP for rheumatoid arthritis and peripheral psoriatic arthritis and ASDAS for ankylosing spondy-litis and psoriatic spondylitis. All patients were given a questionnaire assessing their vaccination status, hesitancy, and attitude towards vaccination. Binary logistic regression analysis was used to analyze the relationship between self-reported modifable parameters and vaccination status for SARS-CoV-2. Results: Two hundred and one participants were eligible for participating in the study with mean age and BMI of 54.6 years and 28.2, respectively. Of these, 40.3% were women;30.3% had rheumatoid arthritis, 17.9%-psoriatic arthritis, and 51.7%-ankylosing spondylitis. 29.4 % of all participants had already survived a COVID-19 infection with a mean time of 8.4 months since the COVID-19 onset. Only slightly above 1/3 (35.8%) of the study group was fully vaccinated and the majority of them were vaccinated with BNT162b2 (68.1%). Among the modifable factors, we identifed preceding discussion with a rheumatologist, hesitancy due to autoimmune disease presence and (un)awareness of vaccine safety and efficacy as signifcant predictors of vaccination status Conclusion: Our data suggest that there are still possibilities to influence rheumatic patients on their decision to vaccinate against SARS-CoV-2 in Bulgaria. Raising the awareness of the safety and efficacy of the SARS-CoV-2 vaccines and spending more time on the education of patients with rheumatic diseases may positively affect their attitude towards vaccination.

ANALYSIS of the ACCEPTANCE and USEFULNESS of A NON-PRESENTIAL CONSULTATION, in PATIENTS with CHRONIC INFLAMMATORY JOINT DISEASES USING A DIGITAL PLATFORM

Background: The Covid-19 pandemic has meant a modifcation of the patterns of the doctor-patient relationship, favoring online visits and reducing face-to-face visits. Likewise, the implementation of Patient-Reported Outcomes (PROs) that do not require the intervention of the doctor in our clinical practice and that given their close relationship with the clinical activity of chronic infammatory joint diseases (CIJD) has favored an empowerment of patients and can allow the development of the online visit. Objectives: Know the use and acceptance of patients with CIJD: rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthropathies (SpA) of a non-face-to-face online visit, through a digital environment. Methods: Patients were included in a platform called Rheumanet for access by username and passwords (https://www.laconsultacercadetI.com/). At the time of inclusion, demographic variables were collected: date of birth, sex, level of education (primary education, secondary education, vocational training, further education and higher education), distance from the hospital to the patient's home, and clinical variables such as diagnosis: RA, PsA or SpA, as well as the duration of the disease. Prior to the appointment, patients were encouraged to complete a PRO survey to assess their clinical situation: Routine Assessment of Patient Index Data 3 (RAPID3) for RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for SpA and RAPID3 and/or BASDAI for the PsA. Both the RAPID3 and BASDAI were scored for the patient's knowledge and assigned to a color scale based on disease activity in green (remission or low activity), orange (moderate activity) or red (severe activity). Likewise, they were ordered to express through a free text what they would tell us as if they were in a face-to-face consultation. Complementary tests (analytical, radiological studies and others) are obtained simultaneously from the medical records and a joint assessment of the visit is carried out. Results: Between September 1, 2020 and January 31, 2022, a total of 248 patients (113 RA, 53 SpA and 82 PsA) were included in the platform. 172 (69.3%) patients used the digital platform and made at least one non-face-to-face visit during follow-up. The number of online visits made by each patient ranged from 1 to a maximum of 13 visits. 80 patients (70.7%) suffered from RA, 40 (75.4%) from SpA and 52 (63.4%) from PsA. The number of patients who made non-face-to-face visits was 38 (72.3%) for a disease duration of <5 years and 137 (64.5%) for >5 years. When the ages of the patients were analyzed, the number of patients who made visits was 75 (73.5%) between 18 and 30 years old, 50 (67.7%) between 30 and 50 and 47 (66.4 %) from 50 years. According to the degree of activity of the disease, 75 patients were in remission or low activity at some point during the visits, 63 patients with moderate activity and 34 with severe activity. The distribution according to level of education was: 11 (6.3%) primary education, 21 (12.2%) secondary education, 37 (21.5%) vocational training, 63 (36.6%) further education and 40 (23.2%)higher education. The number of online visits was higher in patients who lived at a distance of 50 km or more from the hospital, reaching 100% of the visits in this subgroup of patients. Conclusion: The online visit through a digital platform through PROs is well accepted by our population with CIJD, especially in the young population, with a higher cultural level and whose home is far from the hospital. The online visit was made by patients regardless of the severity of their disease activity. Speed and ease of use using PROs already known to the patient and clinician is an important consideration for rheumatolo-gists working in healthcare systems where patient contact time is limited. It would be interesting to obtain this information in non-pandemic situations such as COVID-19, which would make it possible to assess actual acceptance and its use in this type of patient in circumstances in which fear of contagion is not a variabl to consider.

CHARACTERISTICS and OUTCOMES of SARS-COV-2 BREAKTHROUGH INFECTIONS among DOUBLE and TRIPLE VACCINATED PATIENTS with INFLAMMATORY RHEUMATIC DISEASES

Background: SARS-CoV-2 vaccines offer the most effective way to reduce the risk of severe COVID-19. Recent data indicate sufficient immune response after vaccination in most patients with infammatory rheumatic diseases (IRD) on immunomodulatory treatments. Objectives: To investigate the clinical profile of SARS-CoV-2 breakthrough infections among double and triple vaccinated patients with IRD. Methods: Data from the German COVID-19-IRD registry, collected by treating rheumatologists between February 2021 and January 2022 were analysed. Patients double or triple vaccinated against COVID-19 ≥14 days prior to proven SARS-CoV-2 infection were identifed, and type of IRD, vaccine, immunomodulation, comorbidities and outcome of the infection were compared with 737 unvac-cinated IRD-patients with COVID-19. Results: In total, 271 cases of breakthrough infections were reported, 250 patients (91%) had received two doses of vaccines, 21 (9%) patients three. More than 70% of the patients received Pfzer/Biontech vaccine for the frst, second and third vaccination. The median time from second/third vaccine dose to infection was 148 days (range 14-302) days. Most of the patients were diagnosed with infamma-tory joint diseases (Table 1). Most of the patients were treated with methotrexate (Table 1). The use of Januskinase inhibitors(i) was more frequently reported in double vaccinated patients (10.4% vs 4.8%), whereas tumor necrosis (TNF)i were reported more often in triple vaccinated patients (33.3% vs. 22.8). Hospitalisation rate was higher in unvaccinated IRD-patients than in vaccinated ones, while fatality rate was similar in unvaccinated and double vaccinated patients. Although the rate of comorbidities and median age were higher in triple-vaccinated patients, infected patients showed a lower rate of hospitalisation, neither COVID-19 related complications, nor the need of oxygen treatment or death. Conclusion: In this cohort of triple-vaccinated IRD patients no fatal courses and no COVID-19 related complications were reported, although median age and rate of comorbidities were higher compared to double-vaccinated and unvacci-nated patients. These results support the general recommendations to reduce the risk of severe COVID-19 disease by administering three doses of vaccine, especially in patients with older age, presence of comorbidities, and on immuno-modulatory treatment.

REVERSAL of DECLINE in HUMORAL RESPONSE to BNT162B2 MRNA COVID-19 VACCINE after BOOSTER ADMINISTRATION in AUTOIMMUNE INFLAMMATORY RHEUMATOID DISEASES (AIRD) PATIENTS

Background: Previous studies proved that mRNA vaccinations against SARS CoV2 induced signifcant humoral responses in AIRD patients (pts). However, the humoral response was blunted in pts treated with CD20 depleting antibodies. There are limited data regarding the long-term outcome of the humoral response and the contribution of the booster vaccine, in immunosuppressed AIRD pts. Objectives: To assess the long-term outcome of the humoral response to mRNA vaccine against SARS CoV2, in AIRD pts treated with immunomodulating drugs, and the contribution of the booster vaccination. Methods: Consecutive pts treated at the Rheumatology Institute at Rambam Hospital who received their frst SARS-CoV-2 (Pfzer) vaccine were recruited to the study, at their routine visit. The visit included AIRD activity assessment and questioning regarding vaccine side effects. We performed serology test 4-6 weeks and 24 weeks after receiving the second dose of vaccine. Pts who received the booster (3rd vaccine) were invited for serology tests 4-8 weeks afterwards. The immunomodulating treatment was not modifed, either before or after the vaccination. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay based on a chemi-luminescent microparticle immunoassay (CMIA) on the ARCHITECT ci8200s-ystem from Abbott. This assay is measuring IgG antibodies against the spike receptor-binding domain (S-RBD) of the virus. The test was considered positive above 50 AU/ml. Results: 262 pts (mean age(SD) 57(13), disease duration 11.2(7.4), were recruited. The cohort included 152 pts with infammatory joint disease, 26 pts with systemic lupus erythematosus, 62 pts with other connective tissue disease and 22 pts with vasculitis;27 % received csDMARDs only, 35%-b/tsDMARDs only, 30%-combined therapy (csDMARDs+b/tsDMARDs) and 26% received steroids. 225 pts (86%) were seropositive for IgG Ab against SARS CoV2 virus (median 2832.5 AU/ml, IQR 58-29499). 37 (14%) pts had negative tests, 23 (62.2%) of them were rituximab treated. The IgG levels correlated with the medication used to treat the AIRD, the patients' age but not with the type of the AIRD (Figure 1). 24 weeks afterwards, the median IgG level dropped to 282 AU/ml and 15% of the pts with previous seropositive tests became negative. The booster administration (Pfzer) signif-cantly augmented the humoral response (median 8328 AU/ml, IQR 375-40000). De novo serologic response was observed in 10 out of 37 pts (4/23 rituximab treated pts). The reported side effects of the vaccine were minor (muscle sore, headache, low grade fever). The AIRD remained stable in all pts following all three vaccinations. Conclusion: Although the vast majority of AIRD pts developed a substantial humoral response following the administration of the second dose of the Pfzer mRNA vaccine against SARS CoV2 virus, the humoral response signifcantly declined 24 weeks afterwards. An enhanced response was obtained after the third booster vaccination. Only minor side effects were reported and no apparent impact on AIRD activity was noted. Notably, 62% of the non-responders were treated with B cell depleting agents.