The risks of autoimmune- and inflammatory post-acute COVID-19 conditions: a network cohort study in six European countries, the US, and Korea
Authors: Burkard Theresa , López-Güell Kim , Català Martí , Burn Edward , Delmestri Antonella , Khalid Sara , Joedicke Annika M , Dedman Daniel , Oyinlola Jessie O , Abellan Alicia , Pérez-Crespo Laura , Mercadé-Besora Núria , Duarte-Salles Talita , Prieto-Alhambra Daniel , Arinze Johnmary T , Mosseveld Mees , Kolde Raivo , Meléndez-Cardiel Jaime , López-Blasco Raúl , Martínez Álvaro , Valdivieso Bernardo , Delseny Dominique , Mercier Gregoire , Kim Chungsoo , Kim Ji-woo , Kostka Kristin , Ramírez-Anguita Juan Manuel , Mayer Miguel A , Trinh Nhung TH , Nordeng Hedvig ME , Paredes Roger , Uusküla Anneli , Nishimura Akihiko , Loste Cora , Mateu Lourdes , Xie Junqing 
Published: May 2024

ABSTRACTObjectivesWe aimed to assess the risk of autoimmune- and inflammatory post-acute COVID-19 conditions.DesignDescriptive network cohort study.SettingElectronic health records from UK and Dutch primary care, Norwegian linked health registry, hospital records of specialist centres in Spain, France, and Korea, and healthcare claims from Estonia and the US.ParticipantsWe followed individuals between September 2020 and the latest available data from the day they fulfilled at least 365 days of prior observation (general population), additionally from day 91 after a SARS-Cov-2 negative test (comparator) or a COVID-19 record (exposed patients).Main outcome measuresWe assessed postural orthostatic tachycardia syndrome (POTS) diagnoses/symptoms, myalgic encephalomyelitis / chronic fatigues syndrome (ME/CFS) diagnoses/symptoms, multi-inflammatory syndrome (MIS), and several autoimmune diseases. For contextualisation, we assessed any diabetes mellitus (DM).Meta-analysed crude incidence rate ratios (IRR) of outcomes measures after COVID-19 versus negative testing yield the ratios of absolute risks. Furthermore, incidence rates (IR) of the outcomes in the general population describe the total disease burden.ResultsWe included 34’549’575 individuals of whom 2’521’812 had COVID-19, and 4’233’145 a first negative test. After COVID-19 compared to test negative patients, we observed IRRs of 1.24 (1.23-1.25), 1.22 (1.21-1.23), and 1.12 (1.04-1.21) for POTS symptoms, ME/CFS symptoms and diagnoses, respectively. In contrast, autoimmune diseases and DM did not yield higher rates after COVID-19. In individual general database populations, IRs of POTS and ME/CFS diagnoses were 17-1’477/100’000 person-years (pys) and 2-473/100’000 pys, respectively. IRs of MIS were lowest with IRs 0.4-16/100’000 pys, those of DM as a benchmark 8-86/100’000 pys. IRs largely depended on the care setting.ConclusionIn our unmatched comparison, we observed that, following COVID-19, POTS and ME/CFS yielded higher rates than after negative testing. In absolute terms, we observed POTS and ME/CFS diagnoses to have a similar disease burden as DM.WHAT IS ALREADY KNOWN ON THIS TOPICObservational research suggested positive associations between COVID-19 and so called post-acute COVID-19 conditions, whose spectrum is yet to be establishedBasic research suggested pathways that link COVID-19 with autoimmune- and inflammatory diseases such as postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis / chronic fatigues syndrome (ME/CFS), multiple inflammatory syndrome (MIS), and autoimmune diseasesWHAT THIS STUDY ADDSAfter COVID-19, the rates of POTS symptoms and ME/CFS symptoms/diagnoses was higher than those after negative testingAfter COVID-19 versus negative testing, rates of ME/CFS diagnoses were increased in the working age group and rates of symptoms of POTS and ME/CFS were increased in children and elderlyDisease burdens of POTS and ME/CFS diagnoses in the general population were higher among women than among men and overall similar to that of diabetes mellitus