The risks of autoimmune- and inflammatory post-acute COVID-19 conditions: a network cohort study in six European countries, the US, and Korea

ObjectivesWe 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 34549575 individuals of whom 2521812 had COVID-19, and 4233145 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 17-1477/100000 person-years (pys) and 2-473/100000 pys, respectively. IRs of MIS were lowest with IRs 0.4-16/100000 pys, those of DM as a benchmark 8-86/100000 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 TOPICO_LIObservational research suggested positive associations between COVID-19 and so called post-acute COVID-19 conditions, whose spectrum is yet to be established C_LIO_LIBasic 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 diseases C_LI WHAT THIS STUDY ADDSO_LIAfter COVID-19, the rates of POTS symptoms and ME/CFS symptoms/diagnoses was higher than those after negative testing C_LIO_LIAfter 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 elderly C_LIO_LIDisease 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 C_LI