Pilar Brito-Zerón1, Nihan Acar-Denizli2, Vasco C Romão3, Berkan Armagan4, Raphaèle Seror5, Francesco Carubbi6, Sheila Melchor7, Roberta Priori8, Valeria Valim9, Soledad Retamozo10, Sandra G Pasoto11, Virginia Fernandes Moça Trevisani12, Benedikt Hofauer13, Antonia Szántó14, Nevsun Inanc15, Gabriela Hernández-Molina16, Agata Sebastian17, Elena Bartoloni18, Valerie Devauchelle-Pensec19, Miriam Akasbi20, Federico Giardina21, Matilde Bandeira3, Antoni Sisó-Almirall22, Manuel Ramos-Casals23. 1. Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA- Sanitas, Barcelona, Spain. 2. Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Barcelona, Spain. 3. Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte and Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon Academic Medical Centre, Lisbon, Portugal. 4. Department of Internal Medicine, Hacettepe University, Faculty of Medicine, Ankara, Turkey. 5. Department of Rheumatology, National Reference Centre for Sjögren's Syndrome and Rare Autoimmune Diseases, Université Paris-Saclay; Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, AP-HP, Le Kremlin Bicêtre, France. 6. COVID-19 Medical Unit, San Salvatore Hospital, Department of Medicine, ASL1 Avezzano-Sulmona-L'Aquila, Italy. 7. Servicio de Reumatologia, Hospital Universitario 12 de Octubre, Madrid, Spain. 8. Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, and Saint Camillus International University of Health Science, UniCamillus, Rome, Italy. 9. Department of Medicine, Federal University of Espírito Santo, Vitória, Brazil. 10. Instituto Modelo de Cardiología Privado SRL, Córdoba, and Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Argentina, and Rheumatology Department, Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain. 11. Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Brazil. 12. Federal University of São Paulo, Brazil. 13. Otorhinolaryngology, Head and Neck Surgery, Technical University Munich, Germany. 14. Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Hungary. 15. Division of Rheumatology, Marmara University, School of Medicine, Istanbul, Turkey. 16. Immunology and Rheumatology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico. 17. Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland. 18. Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, Italy. 19. Rheumatology Department, Brest University, INSERM 1227, Brest, France. 20. Department of Internal Medicine, Hospital Infanta Leonor, Madrid, Spain. 21. Department of Internal Medicine and Medical Specialties, Rheumatology Clinic, Sapienza University of Rome, Italy. 22. Primary Care Centre Les Corts, Consorci d'Atenció Primària de Salut Barcelona Esquerra (CAPSBE), Barcelona; Primary Healthcare Transversal Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, and Department of Medicine, Universitat de Barcelona, Spain. 23. Department of Medicine, Universitat de Barcelona, and Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain. mramos@clinic.cat.
Abstract
OBJECTIVES: To analyse the frequency and characteristics of post-COVID-19 syndrome in patients with primary Sjögren's syndrome (pSS) affected by acute SARS-CoV-2 infection. METHODS: By the first week of April 2021, all centres included in the Big Data Sjögren Consortium were contacted asking for patients included in the Registry diagnosed with SARSCoV-2 infection according to the ECDC guidelines. According to the NICE definitions, symptoms related to COVID-19 were classified as acute COVID-19 (signs and symptoms for up to 4 weeks), ongoing symptomatic COVID-19 (presence of signs and symptoms from 4 to 12 weeks) and post-COVID-19 syndrome (signs and symptoms that continue for > 12 weeks not explained by an alternative diagnosis after a protocolized study). RESULTS: We identified 132 patients who were followed a mean follow-up of 137.8 days (ranging from 5 days to 388 days) after being diagnosed with COVID-19. In the last visit, 75 (57%) patients remained symptomatic: 68 (52%) remained symptomatic for more than 4 weeks fulfilling the NICE definition for ongoing symptomatic post-COVID-19, and 38 (29%) remained symptomatic for more than 12 weeks fulfilling the definition of post-COVID-19 syndrome. More than 40% of pSS patients reported the persistence of four symptoms or more, including anxiety/depression (59%), arthralgias (56%), sleep disorder (44%), fatigue (40%), anosmia (34%) and myalgias (32%). Age-sex adjusted multivariate analysis identified raised LDH levels (OR 10.36), raised CRP levels (OR 7.33), use of hydroxychloroquine (OR 3.51) and antiviral agents (OR 3.38), hospital admission (OR 8.29), mean length of hospital admission (OR 1.1) and requirement of supplemental oxygen (OR 6.94) as factors associated with a higher risk of developing post-COVID-19 syndrome. A sensitivity analysis including hospital admission in the adjusted model confirmed raised CRP levels (OR 8.6, 95% CI 1.33-104.44) and use of hydroxychloroquine (OR 2.52, 95% CI 1.00-6.47) as the key independent factors associated with an enhanced risk of developing post-COVID-19 syndrome. CONCLUSIONS: This is the first study that analyses the frequency and characteristics of post-COVID-19 syndrome in patients affected by a systemic autoimmune disease. We found that 57% of patients with pSS affected by COVID-19 remain symptomatic after a mean follow-up of 5 months. The risk of developing post-COVID-19 syndrome in patients who required hospitalisation was 8-times higher than in non-hospitalised patients, with baseline raised CRP levels and the use of hydroxychloroquine being independent risk factors for post-COVID-19.
OBJECTIVES: To analyse the frequency and characteristics of post-COVID-19 syndrome in patients with primary Sjögren's syndrome (pSS) affected by acute SARS-CoV-2 infection. METHODS: By the first week of April 2021, all centres included in the Big Data Sjögren Consortium were contacted asking for patients included in the Registry diagnosed with SARSCoV-2 infection according to the ECDC guidelines. According to the NICE definitions, symptoms related to COVID-19 were classified as acute COVID-19 (signs and symptoms for up to 4 weeks), ongoing symptomatic COVID-19 (presence of signs and symptoms from 4 to 12 weeks) and post-COVID-19 syndrome (signs and symptoms that continue for > 12 weeks not explained by an alternative diagnosis after a protocolized study). RESULTS: We identified 132 patients who were followed a mean follow-up of 137.8 days (ranging from 5 days to 388 days) after being diagnosed with COVID-19. In the last visit, 75 (57%) patients remained symptomatic: 68 (52%) remained symptomatic for more than 4 weeks fulfilling the NICE definition for ongoing symptomatic post-COVID-19, and 38 (29%) remained symptomatic for more than 12 weeks fulfilling the definition of post-COVID-19 syndrome. More than 40% of pSS patients reported the persistence of four symptoms or more, including anxiety/depression (59%), arthralgias (56%), sleep disorder (44%), fatigue (40%), anosmia (34%) and myalgias (32%). Age-sex adjusted multivariate analysis identified raised LDH levels (OR 10.36), raised CRP levels (OR 7.33), use of hydroxychloroquine (OR 3.51) and antiviral agents (OR 3.38), hospital admission (OR 8.29), mean length of hospital admission (OR 1.1) and requirement of supplemental oxygen (OR 6.94) as factors associated with a higher risk of developing post-COVID-19 syndrome. A sensitivity analysis including hospital admission in the adjusted model confirmed raised CRP levels (OR 8.6, 95% CI 1.33-104.44) and use of hydroxychloroquine (OR 2.52, 95% CI 1.00-6.47) as the key independent factors associated with an enhanced risk of developing post-COVID-19 syndrome. CONCLUSIONS: This is the first study that analyses the frequency and characteristics of post-COVID-19 syndrome in patients affected by a systemic autoimmune disease. We found that 57% of patients with pSS affected by COVID-19 remain symptomatic after a mean follow-up of 5 months. The risk of developing post-COVID-19 syndrome in patients who required hospitalisation was 8-times higher than in non-hospitalised patients, with baseline raised CRP levels and the use of hydroxychloroquine being independent risk factors for post-COVID-19.