BACKGROUND: Many neurological or immune-mediated conditions have been evaluated as potential adverse events (AEs) in coronavirus 2019 (COVID-19) vaccine surveillance activities. To contextualize United States (US) surveillance findings, data are needed to quantify the risk of AEs associated with COVID-19 diagnoses.
OBJECTIVES: To estimate the association of 7 neurological or immune-mediated AEs with a COVID-19 diagnosis in adults in the US.
METHODS: This study used cohort and self-controlled risk interval (SCRI) designs 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 (Guillain-Barré syndrome [GBS], Bell’s palsy, encephalitis/encephalomyelitis, narcolepsy, appendicitis, immune thrombocytopenia [ITP], and transverse myelitis) were analyzed separately with AE-specific exclusion criteria. The cohort (study period: 1 April 2020 through 10 December 2020, before availability of COVID-19 vaccines) included adults with a COVID-19 diagnosis and a comparator group matched on calendar date and personal characteristics. Follow-up began the day after COVID-19 diagnosis or matched index date. Inverse probability of treatment-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. The SCRI (study period: 1 June 2020 through 10 December 2020) used a risk window after COVID-19 diagnosis and 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 AE-dependent observation windows. Encephalitis/encephalomyelitis SCRI analyses were not performed due to 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). Smaller but consistent associations were also seen for ITP. For Bell’s palsy, the results were less consistent: MarketScan HR = 1.13 (95% CI, 0.85-1.50), RI = 1.95 (95% CI, 1.39-2.74); Medicare HR = 1.11 (95% CI, 1.00-1.24), RI = 1.05 (95% CI, 0.91-1.22). For encephalitis/encephalomyelitis, narcolepsy, appendicitis, and transverse myelitis, results were inconsistent across data sources and/or designs, had small effect sizes, or were imprecise.
CONCLUSIONS: COVID-19 diagnoses were associated with increased risks of GBS and ITP. While increased risks of other neurological/immune-mediated AEs cannot be ruled out, the observed associations were generally modest and variable. These results may apply only to the time period before the introduction of COVID-19 vaccines.
