SYSTEMIC SCLEROSIS AND COVID-19 VACCINE-ASSOCIATED DELAYED ADVERSE EVENTS: INSIGHTS FROM THE COVAD-2 STUDY

BackgroundWe have previously reported short term safety of the COVID-19 vaccination in patients with Systemic sclerosis (SSc) but delayed adverse events (ADEs) (occurring >7 days post-vaccination) are poorly characterized in this rare yet vulnerable disease group.ObjectivesWe analyzed delayed COVID-19 vaccine-related ADEs among patients with SSc, other systemic autoimmune and inflammatory disorders (SAIDs) and healthy controls (HC) using data from the ongoing 2nd global COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) study [1].MethodsThe COVAD-2 study was a cross-sectional, patient self-reporting e-survey utilizing an extensively validated, pilot tested questionnaire, translated into 19 languages, circulated by a group of 157 physicians across 106 countries from February to June 2022.We captured data on demographics, SSc/SAID disease characteristics (including skin subset, treatment history and self-reported disease activity), autoimmune and non-autoimmune comorbidities, COVID-19 infection history and course, and vaccination details including delayed ADEs as defined by the CDC.Delayed ADEs were categorized into local injection site pain/soreness;minor and major systemic ADEs, and hospitalizations. We descriptively analyzed the risk factors for overall and specific ADEs in SSc and SAIDs, and further triangulated clinically significant variables in binominal logistic regression analysis with adjustment for age, gender, ethnicity, comorbidity, and immunosuppressive therapy to analyze the survey responses.ResultsFrom among 17 612 respondents, 10 041 patients (median age 51 (18-58) years, 73.4% females, 44.9% Caucasians) vaccinated against COVID-19 at least once (excluding incomplete responses and trial participants) were included for analysis. Of these, 2.6 % (n=258) had SSc, 63.7% other SAIDs, and 33.7% were HCs. BNT162b2 Pfizer (69.4%) was the most administered vaccine, followed by MRNA-1273 Moderna (32.25%) and ChadOx1 nCOV-19 Oxford/AstraZeneca (12.4%) vaccines.Among the patients with SSc, 18.9% reported minor while 8.5% experienced major delayed ADEs, and 4.6% reported hospitalization. These values were comparable to those of the ADEs reported in other SAIDs and HCs. Patients with SSc reported higher frequency of difficulty in breathing than HCs [OR=2.3 (1.0-5.1), p=0.042].Individuals receiving Oxford/AstraZeneca reported more minor ADEs [OR=2.5 (1.0-6.0), p=0.045];whereas patients receiving Moderna were less likely to develop myalgia and body ache [OR=0.1 (0.02-1.0), p=0.047 and OR=0.2 (0.05-1.0), p=0.044 respectively].Patients with diffuse cutaneous SSc experienced minor ADEs and specifically fatigue more frequently [OR=2.1 (1.1-4.4), p=0.036, and OR=3.9 (1.3-11.7), p=0.015] than those with limited cutaneous SSc. Self-reported active disease pre-vaccination did not confer any increased risk of vaccine ADEs in the adjusted analysis. Unlike our previous observations in myositis, autoimmune and non-autoimmune comorbidities did not affect the risk of delayed ADEs in SSc. SSc patients with concomitant myositis reported myalgia [OR=3.4 (1.1-10.7), p=0.035] more frequently, while those with thyroid disorders were more prone to report a higher frequency of joint pain [OR=5.5 (1.5-20.2), p=0.009] and dizziness [OR=5.9 (1.3-27.6), p=0.024] than patients with SSc alone. Patients with SSc-interstitial lung disease did not report increased frequency of ADEs.ConclusionA diagnosis of SSc did not confer a higher risk of delayed post COVID-19 vaccine-related ADEs than other SAIDs and HCs. Diffuse cutaneous phenotype and certain co-existing autoimmune conditions including myositis and thyroid disease can increase the risk of minor ADEs. These patients may benefit from pre-vaccination counselling, close monitoring, and early initiation of appropriate care in the post COVID-19 vaccination period.Reference[1]Fazal ZZ, Sen P, Joshi M, Ravichandran N, Lilleker JB, et al. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int 2022 Dec;42(12):2151-2158AcknowledgementsCOVAD Study Team.Disclosure of InterestsBo dana Doskaliuk: None declared, Parikshit Sen: None declared, Mrudula Joshi: None declared, Naveen Ravichandran: None declared, Ai Lyn Tan Speakers bureau: Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB, Samuel Katsuyuki Shinjo: None declared, Sreoshy Saha: None declared, Nelly Ziade Speakers bureau: Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis,Boehringer Ingelheim, Janssen, and Pierre Fabre, Consultant of: Pfizer, Roche, Abbvie, Eli Lilly,NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre, Grant/research support from: Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and.Pierre Fabre, Tulika Chatterjee: None declared, Masataka Kuwana: None declared, Johannes Knitza: None declared, Oliver Distler Speakers bureau: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Consultant of: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Grant/research support from: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Rohit Aggarwal Consultant of: Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, EMD Serono, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim, Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, Actigraph, Abbvie, Scipher, Horizontal Therapeutics, Teva, Biogen, Beigene, ANI Pharmaceutical, Nuvig, Capella, CabalettaBio, Grant/research support from: Mallinckrodt, Pfizer, Bristol Myers-Squibb, Q32, EMD Serono, Janssen, Boehringer Ingelheim (BI), Ashima Makol: None declared, Latika Gupta: None declared, Vikas Agarwal: None declared.

SYSTEMIC SCLEROSIS at the TIME of COVID-19 PANDEMIC: A BIBLIOMETRIC STUDY

Background: The Coronavirus disease 2019 (COVID-19) affects different organs and systems of the human organism. However, the main target remains the respiratory system and lungs in particular. Systemic sclerosis (SSc) is one of the systemic autoimmune diseases that can cause severe lung impairment. Considering the existence of common points of influence on the human organism, the overlapping of these two pathologies can signifcantly increase the negative impact on the patient's health. Objectives: This study was aimed to analyze the common features of articles covering the link between COVID-19 and systemic sclerosis. Methods: We retrieved the literature items in the Scientific bibliometric database Scopus conducting our search on the 26th of January. We didn't set any time limits and did use the following keywords: 'systemic sclerosis' OR 'scleroderma' AND 'Covid-19' OR 'COVID-19' OR 'coronavirus'. The exclusion criteria were: absence of an , literature items in form of conference papers, and articles dedicated to the rheumatological pathology in general with scarce mention of SSc. All selected papers were analyzed in view of the following characteristics: documents' type, authorship, journal, citations score, the origin of an article, language, and keywords. For data visualization, we have used software tool VOSviewer version 1.6.15 which make possible to build authors' and keywords' network (Figure 1 A and B) (the minimum keywords' threshold was 3 and the minimum author occurrence was 5). Results: In the result of our comprehensive literature search only 206 items were obtained. After screening of title, and keywords we omitted 166 articles as they met our exclusion criteria and were irrelevant for our study. The most (87.5%) of remained 40 articles were open access publications, which improves the articles' visibility and simplifes data sharing. The top journals covering this topic were: Annals Of The Rheumatic Diseases (n=7), Journal of Psychosomatic Research (n=4), Journal Of Scleroderma And Related Disorders (n=4), Clinical Rheumatology (n=3), Lancet Rheumatology (n=3) and Scandinavian Journal Of Rheumatology (n=3). The post productive authors originated from Italy (n of articles = 20);other countries with highest number of publications were: UK-10;USA-7;France-7 and Netherlands-6). The majority of papers were written in English and just one was in Chinese. The most prevalent research type among analyzed articles was Letter (47.5%), about a third of the articles were designed as Original Articles (35%), 7.5% were Notes, the number of Reviews and Editorials was 5% for each type. Based on the citations score, the most relevant article was dedicated to COVID-19 course in patients with SSc associated interstitial lung disease (SSC-ILD) using tocilizumab. The second highly cited paper highlighted a disease course of COVID-19 pneumonia in SSc patients treated with rituxi-mab and the third actively cited article was World Scleroderma Foundation preliminary advice for patient management. It should also be noted that a lot of articles (n=7, 17.5%) were dedicated to the emotional wellbeing of SSc patients in time of COVID-19 pandemic. Conclusion: Based on our literature analysis, it is the frst attempt to overview comprehensively the papers focusing on SSc and COVID-19 overlap. The biblio-metric studies offer an essential opportunity to emphasize the main features and trends in the particular topic and could be used by scientists as a guidance for forthcoming research.

COVID-19 across rheumatology: A bibliometric study

Background: The Coronavirus disease 2019 (COVID-19) outbreak spread rapidly among the whole world, becoming the greatest pandemic for the decades. It triggered the enormous challenges for the global health system, forcing doctors and patients to adapt to new realities and the field of rheumatology was not an exclusion. Objectives: The aim of this study was to analyze articles covering interconnection between COVID-19 and rheumatic diseases;to investigate the common features of papers in this category and indicate the most influential among them;to determine which rheumatic nosologies were most represented. Methods: For retrieving of literature data, we applied the bibliometric database Scopus and conducted our search on 12th of January using following keywords: “rheumatoid arthritis” OR “systemic lupus erythematosus” OR “systemic sclerosis” OR “vasculitis” OR “myositis” OR “rheumatology” AND “COVID-19”. All selected articles were analyzed according to various aspects: type of document, authorship, journal, citations score, rheumatology field, country of origin, language, and keywords. We have built the visualizing keywords network (Figure 1) with the help of software tool VOSviewer version 1.6.15 (the minimum keyword occurrence threshold was set at 5). Results: A total of 844 literature items were obtained. After screening of title, abstract and keywords we excluded 106 records as they were not emphasized the rheumatological perspective on COVID-19 and as a result were inapplicable for this study. The 738 retrieved articles were mostly (86.8%) open access publications. The top five journals that contributed most to the coverage of this topic were: Annals Of The Rheumatic Diseases (n=59), Clinical Rheumatology (n=41), Lancet Rheumatology (n=24), Arthritis And Rheumatology (n=20) and Rheumatology International (n=19). The origin of most studies was not surprisingly from those countries, which belong to the top ten according to the total cases of COVID-19 [1] (USA -167;Italy -148;UK -76;India -60 and Spain -58). Most items were written in English but articles in German (n=12), Spanish (n=11), Russian (n=5) and Chinese (n=2) could also be found. Analyzed studies were designed in the form of Original Articles (41.2%), Reviews (23.7%), Letters (21.8), Notes (6.9%), Editorials (5.1%). According to the citations scores, articles of highest interest were dedicated to clinical course of COVID-19 in patients with autoimmune pathologies. The other highly cited studies were about cytokine storm and perspective usage of biological drugs for severe cases of COVID-19. Our analysis of keywords showed that the most widely discussed rheumatic disease in the view of COVID-19 was systemic lupus erythematosus (n=188), followed by vasculitis (n=132), rheumatoid arthritis (n=90), systemic sclerosis (n=32) and psoriatic arthritis (24). The liveliest discussion about disease-modifying antirheumatic drugs in COVID-19 revolved around hydroxychloroquine (n=305), corticosteroids (n=161), tocilizumab (n=83), methotrexate (n=46) and anakinra (n=34). Conclusion: As far as we know, it is the first bibliometric overview of studies dedicated to interrelation between COVID-19 and rheumatic pathology. The high number of open access items contributes to the increase of research visibility in this emergently developing research field and facilitates the process of scientific data sharing. The conducting of bibliographic studies may provide a valuable guide through this area of knowledge.