(138) The risks of immune- and inflammatory related post-acute sequelae of COVID-19: a network study in 6 European countries, the US, and Korea

Background: Post-acute sequelae of COVID-19 (PASC) have started to emerge from the pandemic

Objectives: To assess the risks of immune- and inflammatory PASC

Methods: We performed a network cohort study using electronic health records from British (CPRD GOLD, CPRD Aurum) and Dutch primary care (IPCI), Norwegian primary and secondary care, hospital records of specialist centres in Spain (IMASIS), France (CHUM), and Korea (AUSOM), and from health care claims from Estonia (CORIVA) and the US (PharMetrics® Plus for Academics). We followed individuals between September 2020 and the latest available data from the day they fulfilled at least 365 days of observation (general population), additionally from the day of a SARS-Cov-2 negative test result (comparator) or COVID-19 (exposed patients). As outcomes, we assessed postural orthostatic tachycardia syndrome (POTS) diagnoses, POTS symptoms, myalgic encephalomyelitis / chronic fatigues syndrome (ME/CFS) diagnoses, ME/CFS symptoms, multi-inflammatory syndrome (MIS), and several autoimmune diseases. As a control outcome, we assessed any diabetes mellitus (DM). Incidence rate ratios (IRR) of outcomes measures among COVID-19 versus test negative patients yield the ratio of absolute risks of individual outcomes associated with COVID-19. Incidence rate (IR) in the general database population describe the overall disease burden.

Results: We included 34’549’575 individuals of whom 2’521’812 had COVID-19, and 4’233’145 a negative test. Among 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. For autoimmune diseases, we observed IRRs of 0.88 (0.82-0.94) and 0.90 (0.84-0.97) for inflammatory bowel disease and rheumatoid arthritis, respectively. Systemic lupus erythematosus yielded a null result, others had too few counts for analyses. The control outcome DM yielded an IRR of 0.81 (0.72-0.89). In the general population, POTS and ME/CFS symptoms had highest IRs with >821/100’000 person-years (pys) and >636/100’000 pys, respectively. IRs of POTS and ME/CFS diagnoses were >58/100’000 pys and >14/100’000 pys, respectively. Disease burden of MIS was lowest with IRs < 16/100’000 pys. Crude IRs of DM as a benchmark yielded < 86/100’000 pys.

Conclusions: Following COVID-19, POTS symptoms and ME/CFS yielded 1.12 and 1.24 times the rates than those in test negative patients. POTS and ME/CFS being similarly frequent as DM implies a significant strain on the healthcare system. Lower rates among COVID-19 patients of autoimmune diseases and DM may be due to delayed diagnoses following COVID-19.