1525: Breakthrough Infections in COVID-19 Vaccinated Patients with Systemic Sclerosis: A Survival Analysis from a Multicenter International Patient-Reported Survey

Sakir Ahmed¹, Naveen R², John Pauling³, Darpan Thakare², Chris Wincup⁴, Nicoletta Del Papa⁵, Gianluca Sambataro⁶, Fabiola Atzeni⁷, SIMONE PARISI⁸, Marcello Govoni⁹, Elena Bartoloni Bocci¹⁰, Gian Domenico Sebastiani¹¹, Enrico Fusaro¹², Marco Sebastiani¹³, Luca Quartuccio¹⁴, Franco Franceschini¹⁵, Pier Paolo Sainaghi¹⁶, Giovanni Orsolini¹⁷, Rossella De Angelis¹⁸, Maria Giovanna Danielli¹⁹, Vincenzo Venerito²⁰, Parikshit Sen²¹, Minchul Kim²², Abraham Edgar Gracia-Ramos²³, Akira Yoshida²⁴, James B. Lilleker²⁵, Vishwesh Agarwal²⁶, Sinan Kardes²⁷, Jessica Day²⁸, Mrudula Joshi²⁹, Marcin Milchert³⁰, Tamer A Gheita³¹, Babur Salim³², Ioannis Parodis³³, Albert Selva O’Callaghan³⁴, Elena Nikiphorou³⁵, Tulika Chatterjee²², Ai Lyn Tan³⁶, Arvind Nune³⁷, Lorenzo Cavagna³⁸, Samuel Shinjo³⁹, Nelly Ziade⁴⁰, Johannes Knitza⁴¹, Hector Chinoy⁴², Oliver Distler⁴³, Masataka Kuwana⁴⁴, Rohit Aggarwal⁴⁵, Latika Gupta⁴⁶, Vikas Agarwal² and Ashima Makol⁴⁷, ¹Kalinga Institute of Medical Sciences, Bhubaneswar, India, ²Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, ³North Bristol NHS Trust, Bristol, United Kingdom, ⁴University College London, London, United Kingdom, ⁵Unità operativa complessa (UOC) Day Hospital Reumatologia via Gaetano Pini 9, Centro Specialistico Ortopedico Traumatologico, Gaetano Pini-CTO, Milano, Italy, ⁶Medico Immunologia e reumatologia presso, Artoreuma S.R.L., Cors S, Mascalucia, ⁷Rheumatology Unit, University of Messina, Messina, Italy, ⁸Italian Society for Rheumatology, Turin, Italy, ⁹S. Anna Hospital and University of Ferrara, Ferrara, Italy, ¹⁰Rheumatology Unit. Department of Medicine, Perugia, Perugia, Italy, ¹¹U.O.C. Reumatologia, Ospedale San Camillo-Forlanini,, Roma, ¹²Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy, ¹³Azienda Policlinico di Modena, Modena, Italy, ¹⁴Clinic of Rheumatology, Department of Medicine (DAME), ASUFC, University of Udine, Udine, Italy, ¹⁵Rheumatology and Clinical Immunology Unit, ASST Spedali Civili and University of Brescia, Brescia, Italy, ¹⁶Interdisciplinary Research Center of Autoimmune Diseases, Novara, Italy, ¹⁷Department of Medicine, Rheumatology Unit, University of Verona, Verona, Verona, ¹⁸Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy, ¹⁹Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle, Marche, Italy, ²⁰Department of Emergency and Organ Transplantations-Rheumatology Unit, University of Bari "Aldo Moro", Bari, Italy, ²¹Maulana Azad Medical College, New Delhi, India, ²²University of Illinois College of Medicine Peoria, Peoria, IL, ²³Instituto Mexicano del Seguro Social, Ciudad de México, Mexico, ²⁴Nippon Medical School Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan, ²⁵The University of Manchester, Manchester, United Kingdom, ²⁶Mahatma Gandhi Missions Medical College, Lucknow, India, ²⁷Istanbul University, Istanbul, Turkey, ²⁸Walter and Eliza Hall Institute, Melbourne, Australia, ²⁹Byramjee Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune, India, ³⁰Pomeranian Medical University in Szczecin, Szczecin, Poland, ³¹Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt, ³²Fauji foundation hospital Rawalpindi, Rawalpindi, Pakistan, ³³Karolinska Institutet, Stockholm, Sweden, ³⁴Hospital Universitari Vall d'Hebron, Barcelona, Spain, ³⁵Leiden University Medical Center & King's College London, London, United Kingdom, ³⁶University of Leeds, Leeds, United Kingdom, ³⁷Southport and Ormskirk Hospital NHS Trust, Southport, United Kingdom, ³⁸Università di Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, Pavia, Italy, ³⁹Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil, ⁴⁰Saint-Joseph University, Beirut, Lebanon, ⁴¹Department of Internal Medicine 3 – Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054 Erlangen, Germany; Deutsches Zentrum Immuntherapie, Friedrich-Alexander-UniversityErlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany, ⁴²The University of Manchester, Sale, United Kingdom, ⁴³Department of Rheumatology, University Hospital Zurich, University of Zurich, Zürich, Switzerland, ⁴⁴Nippon Medical School Graduate School of Medicine, Tokyo, Japan, ⁴⁵Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, ⁴⁶Royal Wolverhampton Trust, Wolverhampton/University of Manchester, United Kingdom, ⁴⁷Mayo Clinic, Rochester, MN, Rochester, MN

Background/Purpose: Patients with systemic autoimmune rheumatic diseases (AIRDs) are considered more susceptible to break through infection (BI) following vaccination due to their immunosuppressed status and associated co-morbid conditions. Data on BI in patients with systemic sclerosis (SSc) is scarce. These patients are at higher risks of adverse outcomes from COVID-19 due to high prevalence of interstitial lung disease and cardiovascular co-morbidities.

Methods: Data on respondents with SSc, non-SSc AIRDs and healthy controls (HCs) was extracted from the COVAD database, an international self-reported SurveyMonkey platform based online survey that captured respondent demographics, comorbidities, AIRD characteristics, COVID-19 infection history, and COVID-19 Vaccination details. Fully vaccinated patients (completed 2 doses of vaccine) who did not report COVID-19 prior to vaccination were included. BI was defined as per the CDC definition. Frequency of BI, symptoms, duration of illness, and severity (hospitalization or supplementary oxygen) were compared between the groups.

The survival analysis included Kaplan Meier curves with log-rank tests. Cox proportionate regression was used to assess the association of age, gender, ethnicity and immunosuppressive drugs at the time of vaccination on BI.

Results: Of 10900 respondents in the COVAD database, 6836 fulfilling inclusion criteria [SSc (n=427), other AIRDs (n=2934) and HCs (n=3475)] were analysed. BI were reported in 27 (6.3%) of SSc, 202 (6.9%) non-SSc AIRD and 560 (16.1%) of HCs during a median follow up of 100 days (IQR: 60-137) since the first dose of vaccination.

The duration and symptomatology of BI is compared between the three groups in Table-1. Hospitalization [SSc:4 (14.8%); HC:37 (6.61%); non SSc AIRD: 32(15.8%)] and the need for oxygenation [SSc:1 (25%); HC:17 (45.9%); non SSc AIRD: 13(40.6%)] were statistically same between the groups.

The incidence of BI in SSc was lower than that of HC, but comparable to non-SSc AIRD [Figure-1]. SSc had lower risk for BI [Hazard ratio (HR): 0.56 (95%CI: 0.46-0.74)]. BIs were associated with age [HR: 0.98 (0.97-0.98)] but not ethnicities or immunosuppressive drugs at the time of vaccination [Figure 2].

Conclusion: Patients with SSc had lower risk for BI as compared to HC, but similar to that in non-SSc AIRD. This may indicate that people with SSc and other AIRDs have continued to take effective precautions against contracting COVID-19. Severity of BI was not different between groups. Advancing age, but not ethnicity or immunosuppressive medication were associated with BIs.





Disclosures: S. Ahmed, DrReddy, Novartis, Pfizer, Janssen, Cipla; N. R, None; J. Pauling, None; D. Thakare, None; C. Wincup, None; N. Del Papa, None; G. Sambataro, None; F. Atzeni, None; S. PARISI, None; M. Govoni, None; E. Bartoloni Bocci, None; G. Sebastiani, None; E. Fusaro, None; M. Sebastiani, None; L. Quartuccio, None; F. Franceschini, None; P. Sainaghi, None; G. Orsolini, None; R. De Angelis, None; M. Giovanna Danielli, None; V. Venerito, None; P. Sen, None; M. Kim, None; A. Gracia-Ramos, None; A. Yoshida, None; J. Lilleker, None; V. Agarwal, None; S. Kardes, None; J. Day, CSL; M. Joshi, None; M. Milchert, None; T. Gheita, None; B. Salim, None; I. Parodis, GlaxoSmithKlein(GSK), Amgen, AstraZeneca, Aurinia Pharmaceuticals, Eli Lilly, Gilead, Janssen, Novartis, Roche; A. O’Callaghan, None; E. Nikiphorou, Pfizer, Celltrion, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Fresenius; T. Chatterjee, None; A. Tan, None; A. Nune, None; L. Cavagna, None; S. Shinjo, None; N. Ziade, Pfizer, Roche, AbbVie/Abbott, Eli Lilly, Boehringer-Ingelheim, Janssen; J. Knitza, AbbVie, Novartis, ThermoFisher, UCB, ABATON, Sanofi, Medac, Lilly, BMS, Gilead, GSK, Werfen, Vila Health, Böhringer Ingelheim, Janssen, Galapagos, Chugai; H. Chinoy, Eli Lilly, UCB; O. Distler, AbbVie/Abbott, Amgen, GlaxoSmithKlein(GSK), Novartis, Roche, UCB, Kymera, Mitsubishi Tanabe, Boehringer Ingelheim, 4P-Pharma, Acceleron, Alcimed, Altavant Sciences, AnaMar, Arxx, AstraZeneca, Blade Therapeutics, Bayer, Corbus Pharmaceuticals, CSL Behring, Galapagos, Glenmark, Horizon, Inventiva, Lupin, Miltenyi Biotec, Merck/MSD, Prometheus Biosciences, Redx Pharma, Roivant, Sanofi, Topadur, Pfizer, Janssen, Medscape, Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143), FOREUM Foundation, ERS/EULAR Guidelines, EUSTAR, SCQM (Swiss Clinical Quality Management in Rheumatic Diseases), Swiss Academy of Medical Sciences (SAMW), Hartmann Müller Foundation; M. Kuwana, Boehringer-Ingelheim, Ono pharmaceuticals, Mochida, AbbVie/Abbott, Astellas, Janssen, Bayer, Corbus, Horizon; R. Aggarwal, Mallinckrodt, Bristol Myers Squibb, EMD Serono, Pfizer, Octapharma, CSL Behring, Q32, Kezar, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim, Corbus, Janssen, Kyverna, Roivant, AbbVie, Jubilant, Orphazyme, Genentech; L. Gupta, None; V. Agarwal, None; A. Makol, Boehringer-Ingelheim.