Risk of Neurologic or Immune-Mediated Adverse Events After COVID-19 Diagnosis in the United States

Background Many neurologic or immune-mediated conditions have been evaluated as potential adverse events (AEs) in coronavirus disease 2019 (COVID-19) vaccine safety surveillance. To contextualize United States (US) surveillance findings, it is important to quantify the risk of neurologic or immune-mediated AEs associated with COVID-19 diagnosis among adults in the US before the introduction of COVID-19 vaccines. Methods Cohort and self-controlled risk interval (SCRI) designs were used in 2 US administrative claims data sources—Merative™ MarketScan® Commercial Database (ages 18–64 years) and Medicare fee-for-service data (ages ≥ 65 years). AEs included Guillain-Barré syndrome (GBS), Bell’s palsy, encephalitis/encephalomyelitis, narcolepsy, immune thrombocytopenia (ITP), and transverse myelitis; each was analyzed separately with AE-specific exclusion criteria. The cohort (study period, 1 April 2020-10 December 2020) included adults with a COVID-19 diagnosis and a matched comparator group. Inverse probability of treatment-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. The SCRI (study period, 1 June 2020-10 December 2020) used a risk window after COVID-19 diagnosis and pre- and postexposure reference windows within individuals with a COVID-19 diagnosis and the AE. Relative incidences (RIs) and 95% CIs were estimated with seasonality-adjusted conditional Poisson regression models accounting for outcome-dependent observation windows. SCRI analyses were not performed for encephalitis/encephalomyelitis because of high case fatality rates. Results The study observed a consistent association between COVID-19 diagnosis and GBS: MarketScan HR = 9.57 (95% CI, 1.23–74.74), RI = 8.53 (95% CI, 2.45–29.7); Medicare HR = 1.97 (95% CI, 1.04–3.74), RI = 4.63 (95% CI, 1.78–12.01). For ITP, the association was weaker, but still consistently elevated: MarketScan HR = 2.06 (95% CI, 1.20–3.53), RI = 1.74 (95% CI, 1.01-3.00); Medicare HR = 1.36 (95% CI, 1.18–1.57), RI = 1.91 (95% CI, 1.60–2.28). For all remaining AEs, there was no consistent evidence of an association with COVID-19, with estimates that were generally modest, imprecise, and/or varying by study design. Conclusions COVID-19 diagnoses were associated with an increased risk of GBS and ITP in both data sources and study designs. Although increased risks of other neurologic/immune-mediated AEs cannot be ruled out, no consistent associations with COVID-19 were observed.