EFFECTS OF DMARD TREATMENT ON SARS-CoV-2 mRNA VACCINATION IN PATIENTS WITH SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASE: A MATCHED, PROSPECTIVE COHORT STUDY

BackgroundPatients suffering from systemic autoimmune rheumatic disease (SARD) display poor antibody development after two doses of mRNA vaccinations leaving these patients with only limited humoral protection against severe SARS-CoV-2 disease courses. Of key interest is the effect of conventional synthetic (csDMARD) and biological/ targeted drugs (b/tsDMARDs) disease modifying antirheumatic drugs on the time of protection.ObjectivesTo compare antibody titer development in patients with vasculitis and connective tissue disease (CTD) with healthy controls 6 months after two mRNA vaccinations and after third immunization. To analyze factors, that affect the velocity of titer decline, well as qualitative humoral response.MethodsPatients with SARD were enrolled and matched for gender and age with healthy control subjects (HC) and the humoral response after 6 months to two doses of mRNA vaccine BNT162b2 in terms of SARS-COV-2 antibody titer was assessed. In addition to binding antibody units (BAU) we also analyzed neutralizing antibodies. Patients receiving B-cell depleting therapy and those with prior SARS-CoV-2 infection (via detection of nucleocapsid antibodies) were excluded. Differences between two groups were calculated with Wilcoxon signed-rank test.ResultsA total of 53 patients with SARD (42 patients suffering from connective tissue disease and 11 with vasculitis respectively) and 73 HC were analysed. Interestingly only patients receiving a combination therapy of different csDMARDs/ b/tsDMARDs demonstrated diminished antibody titers 6 months after two doses of mRNA vaccine (p-value p-value<0,001), whereas patients receiving only csDMARD as monotherapy displayed comparable antibody levels to healthy controls. This effect was equalized after a third booster vaccination (p-value=0,13). Concerning disease entities, patients with vasculitis seemed to have lower BAU than HC (p-value<0,05) and patients suffering from CTD. After third vaccination both patient groups had lower antibody levels than HC (vasculitis: p-value <0,0001;CTD: p-value p-value<0,01). Lower antibody levels before third vaccination correlated with lower antibodies after third immunization.ConclusionPatients with autoimmune rheumatic diseases undergoing combination therapy may be more vulnerable to SARS-CoV-2 infection, due to reduced antibody levels 6 months following two doses of mRNA vaccine. Our data strongly recommends antibody measurements in patients receiving combination therapy and individualized earlier booster vaccination.Figure 1.Anti-SARS-Cov-2 S antibody titers. A: Antibody titers measured 6 months after two doses of mRNA vaccination in patients with connective tissue disease, vasculitis and healthy controls. B, Antibody levels according to disease entity. AB: antibody;BAU: binding antibody unit;CTD: connective tissue disease;HC: healthy control;mono: disease modifying anti-rheumatic drug monotherapy;combination: combination therapy of disease modifying anti-rheumatic drugs;RBD: receptor binding domain;[Figure omitted. See PDF]Table 1.Demographic parameters and therapy of study participants.SARD (n=53)HC (n=73)Age, mean (standard deviation)53.55 (±14.04)51.27 (±14.07)Female45 (84.9%)47 (64.4%)Connective tissue disease42 (79%)Vasculitis11 (21%)csDMARD or b/tsDMARD monotherapy22 (41%)csDMARD and/or b/tsDMARD combination therapy13 (25%)No therapy18 (34%)Methotrexate8 (15%)Mycophenolate mofetil10 (19%)Hydroxychloroquine17 (32%)Azathioprine8 (15%)Belimumab3 (6%)Tocilizumab3 (6%)Glucocorticoid dose 1. vaccination, mean (standard deviation)2.8 (±10.8)Glucocorticoid dose 2. vaccination, mean (standard deviation)2.6 (±10.7)SARD: Systemic autoimmune rheumatic disease, HC: Healthy controls, csDMARD: conventional synthetic disease modifying antirheumatic drugs and b/tsDMARD: biological/ targeted drugs disease modifying antirheumatic drugsREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsElisabeth Simader Speakers bureau: Lilly, Thomas Deimel: None declared, Felix Kartnig: None declared, Selma Tobudic: None declared, Helmuth Hasla her Grant/research support from: Glock Health, BlueSky Immunotherapies and Neutrolis, Thomas Maria Karonitsch: None declared, Daniel Mrak: None declared, Thomas Nothnagl: None declared, Thomas Perkmann: None declared, Helga Lechner-Radner: None declared, Judith Sautner: None declared, Florian Winkler: None declared, Heinz Burgmann Speakers bureau: speaker fees from Shionogi, Pfizer, MSD, Paid instructor for: advisory boards for Valneva, MSD, Gilead, Consultant of: consulting fees from MSD, Pfizer, Takeda, Gilead, Daniel Aletaha Speakers bureau: other from Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: grants from Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Stefan Winkler: None declared, Stephan Blüml Speakers bureau: personal fees from Abbvie, personal fees from Novartis, Peter Mandl Speakers bureau: reports speaker fees from AbbVie, Janssen and Novartis, Grant/research support from: research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB.

Appraising SARS-CoV-2 infections after full mRNA COVID-19 vaccination in patients with systemic lupus erythematosus (SLE)

The 2019 Coronavirus disease (COVID-19) vaccine is a major weapon in the fight against the severe acute respiratory syndrome brought about by coronavirus 2 (SARS-CoV-2). The vaccine significantly reduces the risk and severity of infection by SARS-CoV-2. Patients with systemic lupus erythematosus (SLE) need protection from vaccine-preventable diseases including COVID-19. SLE patients have higher rates of severe infections due to immunosuppressive therapies and multiple immunologic defects - both of which are capable of blunting the immune responses after vaccination. In the management of COVID-19, recommendations have been developed to guide adjustments and/or continuation of immunosuppressive therapies for an effective immune response following vaccination with mRNA-based or viral vector-delivered vaccines. Monoclonal antibodies have also become available since December 2021. Here we present three cases of SLE patients who contracted COVID-19 after vaccination. One was managed in ambulatory settings and two required inpatient hospital admission.Copyright © 2022

SAFETY PROFILE of SARS COV-2 VACCINES in PATIENTS with CONNECTIVE TISSUE DISEASE, VASCULITIS and POLYMYALGIA RHEUMATICA. BI-CENTRIC STUDY

Background: In recent times, safety and potential adverse effects (AEs) of Sars-CoV-2 vaccines have gained great relevance and have been a central topic in Scientific discussion. Objectives: The aim of this study was to evaluate the incidence of AEs after Sars-CoV-2 vaccine administration in patients affected by Connective Tissue Disease, Vasculitis or Polymyalgia Rheumatica. Moreover, we assessed patients' adherence to the American College of Rheumatology (ACR)1 or Italian Rheumatology Society (SIR)2 recommendations. Methods: 139 patients affected by Connective Tissue Disease, Vasculitis or Polymyalgia Rheumatica were enrolled at the Rheumatology Units of University Hospitals of Bari and Foggia. All patients were given a questionnaire to evaluate vaccine type and dose number, AEs, potential pre-vaccine prophylaxis, immuno-suppressive therapy and its possible suspension according to the clinical guidance summary proposed by ACR or SIR. Results: Among the 139 enrolled patients (120 females and 19 males, mean age 54 ± 14,7 year, mean disease duration 8,6 ± 7, 4 years), 31 subjects (19%) received anti Sars-CoV-2 vaccination. 5 patients received the Astra-Zeneca COVID-19 vaccine, 23 the BioNTech-Pfzer COVID-19 vaccine and 3 the Moderna vaccine. Only 48% of subjects received two doses. 42% of patients reported non-severe AEs after the frst dose of vaccine, specifcally 45% of patients who received the BioNTech-Pfzer COVID-19 vaccine, 40% of those who were administered the AstraZeneca vaccine and 33% of those who received the Moderna vaccine. Most frequent AEs were site injection pain (19%), fatigue (13%), headache (13%), myalgia (6%), fever (6%), nausea (3%), rheumatic disease fare (3%) (the latest was reported only among the Polymyalgia Rheumatica patients). Considering the different diseases, the highest trend of AEs was observed in Polymialgya Rheumatica (66%), Systemic Sclerosis (57%), Sjogren Syndrome (40%) and undifferentiated connective tissue disease (23%) patients. 30% of patients who received the second vaccine dose reported AEs. All of them were administered the BioNTech-Pfzer COVID-19 vaccine. Most reported AEs after the second vaccine dose were site injection pain (6%), headache (3%), myalgia (6%), fever (6%). The highest trend of AEs was observed in undifferentiated connective tissue disease (60%) and Sjogren Syndrome (33%) patients. Only 13 % of subjects who reported AEs after the frst vaccine administration, reported AEs also after the second dose. Only 9,7% of patients did not comply with the COVID-19 vaccine clinical guidance prosed by ACR or SIR regarding immunosuppressive treatment management before and after immunization. Conclusion: Patients enrolled in this study developed mild AEs. Only among Polymyalgia Rheumatica patients were described disease fares and higher trend of AEs. Although patients affected by Systemic Lupus Erythematosus, Antiphospholipid Syndrome and Vasculitis were enrolled, none of them reported severe AEs, included the extensively discussed post-vaccine thrombosis. We found no signifcant dissimilarity of AEs relating to different types of vaccine and good patient compliance to physician recommendations about treatment management.

EXCELLENT PROGNOSIS of RHEUMATIC MANIFESTATIONS FOLLOWING COVID-19 VACCINATION: 7 MONTHS FOLLOW-UP DATA

Background: It is well established that severe forms of SARS-CoV2 infection can induce a massive cytokine storm, which may disrupt the immune system stability and conceivably stimulate the development of reactive manifestations through a molecular mimicry process. Likewise, anti-COVID-19 vaccines, which have so far proved an excellent tolerability and safety profile, are able boost the immune response via different biologic technologies and adjuvant combinations possibly facilitating, in predisposed subjects, the onset of infammatory or even autoimmune manifestations. Objectives: We report a case series of suspected rheumatic adverse events following immunization (AEFI) associated with anti-COVID-19 vaccine. We focused our attention on the prognosis of these patients by analysing their available follow-up data. Methods: We included patients evaluated at frst-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padua University Hospital between May and September 2021 presenting with new-onset rheumatic manifestation or a fare of an underlying rheumatic disease within 30 days after receiving an anti-COVID-19 vaccine dose. Inclusion and exclusion criteria were in accordance with the World Health Organization guidelines for AEFI surveillance. All patients were re-evaluated in January 2022: telemedicine or face-to-face visit. Response to therapy was classifed as complete, good or absent according to the clinician's judgment based on clinical examination, patient's reporting and analysis of laboratory data. Results: We identifed 30 cases of suspected rheumatic AEFI reported in Table 1. Comprehensively the most common manifestations were infammatory arthritis (40.0%), rheumatic polymyalgia (26.7%) and adult-onset Still disease (13.3%). Among patients with an underlying rheumatic disease we recorded an AOSD fare, a rheumatoid arthritis fare with involvement of hands proximal inter-phalangeal joints, one case of wrist arthritis in a patient with psoriatic arthritis, one of aortitis in a patient with large vessels vasculitis, one case of polyarthritis in undifferentiated connective tissue disease and a nephritis fare in a patient with systemic lupus erythematosus. Treatment for the suspected AEFI was based on systemic glucocorticoids (GC) alone (63.3%), systemic GC plus IL-1R antagonists (13.3%), non-steroidal autoinfammatory drugs (13.3%), intra-articular GC (6.6%), colchicine (3.3%) and non-steroidal anti-infammatory drugs (13.3%). At last follow-up contact (7.8±1.5 months) 26 patients (89.6%) were classified as complete responders. Eleven of them (42.3%) withdrew therapy without experiencing recurrence of disease manifestation. One patient with lupus nephritis had a proteinuric flare after the first BNT162b dose;he showed an initial good response to increased glucocorticoid therapy but had a new 24h proteinuria increase at second follow-up visit three months later requiring implementation of immunosuppressive therapy. Another patient with AOSD was in remission at last FU visit in December 2021 but required hospitalization in January 2022 for disease relapse due to a suspected gastrointestinal infection. Finally, one patient hospitalized for a seronegative polyarthritis after the first BNT162b dose achieved complete remission at last available contact (one month after hospital discharge) but was then lost in follow-up. Conclusion: After a mean follow-up of 7.8±1.5 months nearly all of patients showed a complete/good response to standard therapy and about half of them withdrew the treatment without losing the remission status.

INCIDENCE and OUTCOMES of SARS-COV-2 INFECTION in PATIENTS with SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES: A POPULATION-BASED STUDY of MORE THAN FOUR MILLION INHABITANTS in the LAZIO ITALIAN REGION

Background: The impact of the severe acute respiratory syndrome Coronavirus 2 disease (COVID-19) pandemic on people with systemic autoimmune rheumatic diseases (SARDs) remains to be fully established. It is unclear whether SARDs are an independent risk factor for COVID-19 infection and poor outcome. Objectives: The aim of our study is to assess the incidence and prognosis of test-proven SARS-CoV-2 infection during the frst COVID-19 wave in a large population of SARD patients of the Lazio Italian region. Methods: We retrospectively evaluated in a cohort of 4.716.119 subjects aged over 18 years and affiliated to the health system of the Lazio Italian Region, the incidence and 30-day outcomes of COVID-19 infection in 40.490 SARD pts and compared to the affiliated population as incidence rate ratio adjusted for demographics and comorbidities (adjIRR). SARD diagnosis and comorbidities were derived from medical administrative records using the Chronic Related Group classifcation system. Data on COVID-19 infection were derived from a dedicated regional digital network. Results: The risk of COVID-19 infection was increased in patients with Psoriatic Arthritis (adjIRR=1.21, 95% CI 1.10-1.33) and Undifferentiated Connective Tissue Disease (adjIRR=1.26, 95% CI 1.03-1.54). The risk of hospitalisation was higher in patients with Axial Spondylarthritis (adjIRR=2.16, 95% CI 1.45-3.22), and Systemic Vasculitis (adjIRR=1.81, 95% CI 1.07-3.06) while the risk of Intensive care unit admission was higher in Systemic Erythematous Lupus (adjIRR=3.67, 95% CI 1.52-8.83) and primary Sjögren Syndrome (adjIRR=4.13, 95% CI 1.71-9.96) patients. An increased COVID-19 mortality was reported in patients with Rheumatoid Arthritis (adjIRR=1.50, 95% CI 1.04-2.17), Systemic Erythematous Lupus (adjIRR=2.67, 95% CI 1.10-6.44), primary Sjögren Syndrome (adjIRR=2.51, 95% CI 1.12-5.62), and Scleroderma (adjIRR=4.60, 95% CI 2.06-10.29). Conclusion: The incidence of severe COVID-19 is not increased in the same percentage in SARDs. Each SARD presents a peculiar pattern in terms of increased risk of COVID-19 incidence, hospitalisation, intensive care unit admission and death, that is not linked to the immunosuppressive behaviour of the disease.

LONG-TERM OUTCOMES of COVID-19 VACCINATION in PATIENTS with RARE and COMPLEX CONNECTIVE TISSUE DISEASES: AN AD-INTERIM ANALYSIS of ERN-RECONNET VACCINATE STUDY

Background: Since the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefts of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group). Objectives: To evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://bright-oncollaboration.us/wp-content/uploads/2021/01/SO2-D2.1.2-V1.2-COVID-19- AESI-update-23Dec2020-review-fnal.pdf) Methods: The frst ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defned as at least one of the following: new manifestations attributable to disease activity, hospital-ization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants. Results: A cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren's syndrome (SS,12%), idiopathic infammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Dan-los's syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the frst and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%). Conclusion: This preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the frst month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.

EVALUATION of the POTENTIAL INDUCTION of AUTOANTIBODIES after the ANTI-SARS-COV2-VACCINATION in A COHORT of PATIENTS with TRIPLE POSITIVITY for ANTIPHOSPHOLIPID ANTIBODIES

Background: Anti-SARS-CoV2 vaccines showed a good efficacy in prevention of severe COVID-191. Their potential in induction of autoantibodies (abs) has not been well established1. One recent study demonstrated an increase of abs' titre after anti-SARS-CoV2 vaccination only in patients with already pre-existing positivity2. Objectives: To evaluate the potential induction of abs after anti-SARS-CoV2 vaccination in a triple positive antiphospholipid antibodies (aPL) cohort. Methods: 18 subjects were enrolled [M/F= 17/1;median age=52 years;5 Primary Antiphospholipid Syndrome (PAPS), 5 Systemic Lupus Erythematosus (SLE) with associated APS and 8 aPL carriers (1 Behçet Disease, 1 SLE, 4 Undifferentiated Connective Tissue Disease, 2 with no diagnosis of systemic autoimmune disease)]. Serum samples were collected before the first (T0) and at least one month after the second administration (T1) of the anti-SARS-CoV2 vaccine (16 BNT162b2, 1 mRNA-1273, 1 Gam-COVID-Vac). A wide panel of abs were evaluated through routinely methods. Results: None developed any additional sign of autoimmune diseases upon vaccination. Patients majority did not display any new autoantibody posi-tivity (Table 1). Changes were observed in 3 patients: 1) one aPL carrier patient who was antinuclear antibodies (ANA) negative at T0 was found to be ANA positive at T1 [negative anti-double stranded DNA and anti-extractable nuclear antigen (ENA)];this patient was actually ANA positive in her clinical history;2) one aPL carrier patient affected by SLE, who was IgM and IgG aCL and IgG aB2GPI positive at T0, turned positive for IgM and IgA aB2GPI;3) one aPL carrier patient affected by Behçet Disease, who was positive for IgM aCL and for IgM aB2GPI at T0, turned positive for IgA aCL and IgA aB2GPI. All emerging aPL were low titre. None of the patients displayed raising aPL titres from low to medium-high. Conclusion: Anti-SARS-CoV2 vaccination did not induce any clinical signs of autoimmunity in a cohort of patients with triple aPL positivity. Serology for autoantibodies remained stable in the majority of patients. Few patients experienced the emergence of low titre aPL, possibly as an expected inter-assay variation rather than an evolving 'serological fare'.

A SURVEY on ACCEPTANCE of COVID-19 VACCINATION among PATIENTS with RHEUMATIC DISEASES-A SINGLE CENTER EXPERIENCE in MALAYSIA

Background: According to Statista, 78.5% of the population in Malaysia have completed their vaccination as of 6th january 2022 [1].The acceptance of patients with rheumatic diseases on Covid-19 vaccination is crucial in the long term protection against Covid-19 infection. We conducted a survey to determine the acceptance of Covid-19 vaccination amongst patients with underlying rheumatic disease. Objectives: To fnd out the reasons of vaccination refusal amongst rheumatology patients. Methods: This was an interview survey. All rheumatology patients who were follow up in rheumatology clinic Hospital Sultan Ismail, Malaysia from 26th April 2021 to 25th July 2021 (total 3 months) were interviewed. Demographic and diagnosis of the patients were collected. Results: A total of 952 patients were identified. 83.7% of them were female patients (797/952) and majority of them were Malay (46.4%). This was followed by Chinese (36.1%), Indian (16.3%) and others (1.2%). The mean age group was 48 (range from 13-85). 97.6% of the respondents were categorized as having inactive disease during the interview sessions. 36.6% of the patients were diagnosed to have rheumatoid arthritis and 29.1% of them were having systemic lupus erythematosus. These were followed by psoriatic arthritis (10.9%), mixed connective tissue disease (5.5%), systemic sclerosis (2.9%), gout (2.6%), Sjogren syndrome (1.9%), ankylosing spondylitis (1.6%), myositis (1.5%), vascu-litis (1.3%), osteoarthritis (1.2%), antiphospholipid syndrome (0.9%), non-specific arthralgia (0.8%), juvenile idiopathic arthritis (0.8%), seronegative spondyloarthropathy (0.8%), undifferentiated connective tissue disease (0.7%), adult onset still's disease 0.5%) and others (< 0.5% each for Ig G 4 related disease, soft tissue rheumatism and fibro-myalgia). 87.3% of them were keen or have already received Covid-19 vaccination. 12.7% of them were not keen for the vaccination with various reasons. 48.8% of them were worrying about worsening clinical condition, 12.4% of them were not keen as they concerned about side effects (3 worry about fever, 1 worry about hepatitis, 1 for nausea, 1 for dizziness, 1 for breathlessness, and 7 for non-specific reasons). 10.7% of them were not keen due to pregnancy, 5.79% of them were not keen as worried about allergic reactions, 4.9% of them were worrying about sudden cardiac death, 4% were not keen as on chemotherapy treatment, 3 % of them doubted the efficacy of vaccination, 2.5% were not keen as they worried about heart disease, 2.5% worried about increase risks of infection and others (2 for old age, 2 for thrombotic event, 2 for drug interaction and 1 patient due to hemodialysis). Conclusion: The overall acceptance rate of Covid-19 vaccination amongst patients with rheumatic diseases is very encouraging with the percentage of >85% despite of lacking knowledge about vaccine Covid-19. This result can assist our Ministry of Health to plan for future battle to improve vaccine uptake that hopefully can lead to herd immunity against COVID-19 infection. More counseling sessions are required to clear up the doubts of vaccination and increase the vaccination rate amongst rheumatic patients.

Systemic Autoimmune Diseases in Patients Hospitalized with COVID-19 in Spain: A Nation-Wide Registry Study.

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren's Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet's Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78-1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04-1.07), heart failure (OR = 1.67, 95% CI 1.10-2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05-1.59) and liver disease (OR = 1.97, 95% CI 1.13-3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis.

TRACKING DOWN AUTOANTIBODIES

Background/Aims Vaccine-associated autoimmunity is not infrequent, pertaining to either the cross-reaction between antigens or the action of adjuvant. This issue is more inexplicable to the COVID-19 vaccine, because of nucleic acid formulation and the hastened development process inflicted by the urgent pandemic condition. Here we are presenting a young patient who developed a significant abnormal autoimmune profile immediately post covid vaccination. Methods A 31-year-old IT engineer was referred to Rheumatology with postvaccine arthralgia. He had a history of recent aortic root aneurysm repair after having chest pain on exertion. Echocardiography showed dilated aortic root with significant aortic regurgitation, CT aortogram confirmed spiral type A dissection. He underwent an emergency cardiothoracic surgery in October 2020, followed by an uneventful recovery. He received the first dose of Pfizer COVID-19 vaccine on 2nd February, the very next day he developed painful ankles, knees, left hip, and right shoulder. Blood tests showed elevated CRP of 45, ESR 34, rheumatoid factor positive at 92, anti-CCP >340, ANA 13, ds-DNA 202, U1RNP positive, anti-SM antibody positive, Ro and La antibodies positive, antiJo1 antibody positive, with normal complements. He denied any swelling of the joints. No history of hair loss, photosensitive skin rashes, Raynaud's, sicca symptoms, oro-genital ulceration, or cracking of the skin. There were no constitutional symptoms, chest pain, or bowel issues. He was previously labeled as asthmatic, which is stable after surgery. He doesn't smoke or drinks alcohol. There was no family history of autoimmune conditions. On examination, he has tenderness across both hands and wrists with palmar erythema but no synovitis. He has painful right shoulder abduction with left hip pain on flexion and extension. Cardiovascular and GI examination was unremarkable apart from sternotomy scar and metallic valvular heart sounds. His dipstick urinalysis was negative for blood and protein. In recent x-rays hands and feet were normal. We agreed on a trial a tapering course of prednisolone started with 20mg daily. Three weeks later in follow-up, he reported partial response to steroids. His inflammatory markers were coming down. We have started azathioprine as a steroid-sparing agent. Results This gentleman with negative autoimmune screening prior to cardiothoracic surgery expressed florid newly detected autoantibodies straightaway after the COVID-19 vaccine. This is suggestive of undifferentiated connective tissue disease with the likelihood of overlap syndrome between rheumatoid arthritis and SLE. Conclusion COVID-19 vaccination showed a beacon of light to end the pandemic by achieving herd immunity. There is an excusable socioeconomic rush towards mass vaccination without long-term safety analysis, however, it is also crucial that any vaccine licensing process should entail meticulous scrutiny of the human proteome against vaccine peptide sequences. This will minimize the risks of acute autoimmune reactions to inoculation and future chronic autoimmune pathology.

A three-arm, multicenter, open-label randomized controlled trial of hydroxychloroquine and low-dose prednisone to treat recurrent pregnancy loss in women with undifferentiated connective tissue diseases: protocol for the Immunosuppressant regimens for LIving FEtuses (ILIFE) trial.

BACKGROUND: Undifferentiated connective tissue disease (UCTD) is known to induce adverse pregnancy outcomes and even recurrent spontaneous abortion (RSA) by placental vascular damage and inflammation activation. Anticoagulation can prevent pregnancy morbidities. However, it is unknown whether the addition of immune suppressants to anticoagulation can prevent spontaneous pregnancy loss in UCTD patients. The purpose of this study is to evaluate the efficacy of hydroxychloroquine (HCQ) and low-dose prednisone on recurrent pregnancy loss for women with UCTD. METHODS: The Immunosuppressant for Living Fetuses (ILIFE) Trial is a three-arm, multicenter, open-label randomized controlled trial with the primary objective of comparing hydroxychloroquine combined with low-dose prednisone and anticoagulation with anticoagulation alone in treating UCTD women with recurrent spontaneous abortion. The third arm of using hydroxychloroquine combined with anticoagulant for secondary comparison. A total of 426 eligible patients will be randomly assigned to each of the three arms with a 1:1:1 allocation ratio. The primary outcome is the rate of live births. Secondary outcomes include adverse pregnancy outcomes and progression of UCTD. DISCUSSION: This is the first multi-center, open-label, randomized controlled trial which evaluates the efficacy of immunosuppressant regimens on pregnancy outcomes and UCTD progression. It will provide evidence on whether the immunosuppressant ameliorates the pregnancy prognosis in UCTD patients with RSA and the progression into defined connective tissue disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03671174 . Registered on 14 September 2018.

Necessity of brain imaging in COVID-19 infected patients presenting with acute neurological deficits.

BACKGROUND: Patients undergoing cardiopulmonary stabilization in the intensive care unit for novel coronavirus (COVID-19) are often sedated, placing timely assessment of a neurological decline at risk. CASE DESCRIPTION: Here, we present two cases of COVID-19 infected young patients transferred to our facility in a cardio-pulmonary crisis, with a poor neurological exam. While there was significant delay in obtaining brain imaging in the first patient, the second patient had timely recognition of her ischemic infarct, underwent emergent surgery, and is now doing well. CONCLUSIONS: These cases highlight the importance of early head imaging in COVID-19 patients with a poor neurological exam. While lungs remain the primary target of COVID-19, these cases alert the medical community to suspect involvement of the central nervous system, since there may be life-saving surgical interventions available.