tetano
Editor, Senior Moderator
PLoS One
. 2025 Nov 24;20(11):e0333704.
doi: 10.1371/journal.pone.0333704. eCollection 2025. Risk of neurologic or immune-mediated adverse events after COVID-19 diagnosis in the United States
Shelby S Fisher[SUP] 1 [/SUP], Arnstein Lindaas[SUP] 2 [/SUP], Stella G Muthuri[SUP] 3 [/SUP], Patricia C Lloyd[SUP] 4 [/SUP], Joann F Gruber[SUP] 4 [/SUP], Morgan M Richey[SUP] 5 [/SUP], Hai Lyu[SUP] 2 [/SUP], Angela S Cheng[SUP] 2 [/SUP], Lisa S Kowarski[SUP] 3 [/SUP], Mollie M McKillop[SUP] 3 [/SUP], Christine Bui[SUP] 5 [/SUP], Tainya C Clarke[SUP] 4 [/SUP], Jeffrey Beers[SUP] 3 [/SUP], Timothy Burrell[SUP] 3 [/SUP], Pablo Freyria Duenas[SUP] 2 [/SUP], Yangping Chen[SUP] 2 [/SUP], Minya Sheng[SUP] 3 [/SUP], Richard A Forshee[SUP] 4 [/SUP], Steven A Anderson[SUP] 4 [/SUP], Yoganand Chillarige[SUP] 2 [/SUP], Mary S Anthony[SUP] 5 [/SUP], Azadeh Shoaibi[SUP] 4 [/SUP], J Bradley Layton[SUP] 5 [/SUP]
Affiliations
Introduction: 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 association of AEs with COVID-19 diagnoses among US adults 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. The cohort (study period, 1 April 2020-10 December 2020) included adults with COVID-19 diagnoses and matched comparators. 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) identified the AEs in risk windows after COVID-19 diagnosis and pre- and postexposure reference windows. Relative incidences (RIs) and 95% CIs were estimated with seasonality-adjusted conditional Poisson regression models accounting for outcome-dependent observation windows.
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 not consistent evidence of an association with COVID-19, with estimates that were generally modest, imprecise, 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. Increased risks of other neurologic/immune-mediated AEs cannot be ruled out.
. 2025 Nov 24;20(11):e0333704.
doi: 10.1371/journal.pone.0333704. eCollection 2025. Risk of neurologic or immune-mediated adverse events after COVID-19 diagnosis in the United States
Shelby S Fisher[SUP] 1 [/SUP], Arnstein Lindaas[SUP] 2 [/SUP], Stella G Muthuri[SUP] 3 [/SUP], Patricia C Lloyd[SUP] 4 [/SUP], Joann F Gruber[SUP] 4 [/SUP], Morgan M Richey[SUP] 5 [/SUP], Hai Lyu[SUP] 2 [/SUP], Angela S Cheng[SUP] 2 [/SUP], Lisa S Kowarski[SUP] 3 [/SUP], Mollie M McKillop[SUP] 3 [/SUP], Christine Bui[SUP] 5 [/SUP], Tainya C Clarke[SUP] 4 [/SUP], Jeffrey Beers[SUP] 3 [/SUP], Timothy Burrell[SUP] 3 [/SUP], Pablo Freyria Duenas[SUP] 2 [/SUP], Yangping Chen[SUP] 2 [/SUP], Minya Sheng[SUP] 3 [/SUP], Richard A Forshee[SUP] 4 [/SUP], Steven A Anderson[SUP] 4 [/SUP], Yoganand Chillarige[SUP] 2 [/SUP], Mary S Anthony[SUP] 5 [/SUP], Azadeh Shoaibi[SUP] 4 [/SUP], J Bradley Layton[SUP] 5 [/SUP]
Affiliations
- PMID: 41284649
- DOI: 10.1371/journal.pone.0333704
Introduction: 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 association of AEs with COVID-19 diagnoses among US adults 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. The cohort (study period, 1 April 2020-10 December 2020) included adults with COVID-19 diagnoses and matched comparators. 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) identified the AEs in risk windows after COVID-19 diagnosis and pre- and postexposure reference windows. Relative incidences (RIs) and 95% CIs were estimated with seasonality-adjusted conditional Poisson regression models accounting for outcome-dependent observation windows.
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 not consistent evidence of an association with COVID-19, with estimates that were generally modest, imprecise, 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. Increased risks of other neurologic/immune-mediated AEs cannot be ruled out.