key: cord-0332227-d559lgl1 authors: Li, X.; Gao, L.; Tong, X.; Chan, V. K. Y.; Chui, C. S. L.; Lai, F.; Wong, C.; Wan, E. Y. F.; Chan, E. W. Y.; Lau, K. K.; Lau, C. S.; Wong, I. C. K. title: Autoimmune conditions following mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccination: a descriptive cohort study among 1.1 million vaccinated people in Hong Kong date: 2021-10-23 journal: nan DOI: 10.1101/2021.10.21.21265314 sha: 0388abc527926f4750915121c6c710eac40a5dd4 doc_id: 332227 cord_uid: d559lgl1 Background Concerns regarding the autoimmune safety of COVID-19 vaccines may negatively impact vaccine uptake. We aimed to describe the incidence of autoimmune conditions following BNT162b2 and CoronaVac vaccination and compare these with age-standardized incidence rates in non-vaccinated individuals. Methods This is a descriptive cohort study conducted in public healthcare service settings. Territory-wide longitudinal electronic medical records of Hong Kong Hospital Authority users ([≥]16 years) were linked with COVID-19 vaccination records between February 23, 2021 and June 30, 2021. We classified participants into first/second dose BNT162b2 groups, first/second dose CoronaVac groups and non-vaccinated individuals for incidence comparison. The study outcomes include hospitalized autoimmune diseases (16 types of immune-mediated diseases across six body systems) within 28 days after first and second dose of vaccination. Age-standardized incidence rate ratios (IRRs) with exact 95% confidence intervals (CIs) were estimated using Poisson distribution. Results This study included around 3.9 million Hong Kong residents, of which 1,122,793 received at least one dose of vaccine (BNT162b2: 579,998; CoronaVac: 542,795), and 721,588 completed two doses (BNT162b2: 388,881; CoronaVac: 332,707). Within 28 days following vaccination, cumulative incidences for all autoimmune conditions were below 9 per 100,000 persons, for both vaccines and both doses. None of the age-standardized incidence rates were significantly higher than the non-vaccinated individuals, except for an observed increased incidence of hypersomnia following the first dose of BNT162b2 (standardized IRR: 1.47; 95% CI: 1.10-1.94). Conclusions Autoimmune conditions requiring hospital care are rare following mRNA and inactivated virus COVID-19 vaccination with similar incidence to non-vaccinated individuals. The association between first dose BNT162b2 vaccination and immune-related sleeping disorders requires further research. Population-based robust safety surveillance is essential to detect rare and unexpected vaccine safety events. Funding: Research Grant from the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01). There has been a long-standing debate about vaccination and its potential to trigger 63 autoimmune diseases (AID). For example, the influenza vaccine and Guillain-Barré 64 syndrome 1 , the Measles-Mumps-Rubella vaccine and thrombocytopenic purpura 2 . 65 Although causality is not fully established, the fear of new onset or recurrence of AID 66 may contribute to vaccine hesitancy and negatively impact vaccine uptake 3 . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. ; https://doi.org/10.1101/2021.10.21.21265314 doi: medRxiv preprint routine vaccination for infection control, it is of timely importance to assess the 86 autoimmune safety of COVID-19 vaccines in real-world settings. 87 Hong Kong (HK) is among the few jurisdictions in the world that has approved the 88 emergency use of COVID-19 vaccines from two different technology platforms: program for safety monitoring. In this study, we analyzed the territory-wide electronic 96 medical records (EMRs) database and summarized the incidence of AID across the 97 predefined disease spectrum among CoronaVac and BNT162b2 recipients in HK. 98 We assessed the population-level risk of AID following mRNA and inactivated virus 99 COVID-19 vaccination to inform vaccination decisions. EMRs database managed by HA is centralized from the territory-wide clinical 108 management system of 42 public hospitals with high population coverage, representativeness, and coding accuracy [16] [17] [18] [19] is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. ; https://doi.org/10.1101/2021.10.21.21265314 doi: medRxiv preprint dose, in the first dose analysis, we also censored the follow-up one day before the Outcome measures 138 We assessed the incidence of hospital admission related to a spectrum of 16 pre- is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. ; https://doi.org/10.1101/2021.10.21.21265314 doi: medRxiv preprint Main analysis 158 We reported two age-standardized health situation measurements as the main 159 outcome of this study. First, we described the 28-day cumulative incidence (per 160 100,000 persons) of each condition, using 5-year age band weightings (16-19, 20- proportion of person-years in each age strata to calculate age-specific crude 171 incidence rate and aggregated the age-standardized incidence rate. We further 172 estimated the expected cases in each group and calculated the standardized is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. ; https://doi.org/10.1101/2021.10.21.21265314 doi: medRxiv preprint We obtained the EMRs of 3,946,550 HA active patients with affirmed vaccination Table 1 . is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. The incidence of reactive arthritis and narcolepsy-related disorders were relatively 230 higher compared to other AIDs, with cumulative incidence ranging between 4.12 and 231 8.35 per 100,000 persons among first dose vaccine recipients (Table 2) . Similarly, 232 the majority of the autoimmune conditions following the second dose also had a 28-233 day cumulative incidence of less than 1 per 100,000 persons ( Figure 1 ). Reactive 234 arthritis, narcolepsy-related disorders and thrombocytopenia appeared to have a 235 numerically higher incidence than the corresponding incidence reported after the first 236 dose. When considering the follow-up time and measuring the disease occurrence using 238 standardized incidence rate, we did not detect a significantly increased incidence is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. ; https://doi.org/10.1101/2021.10.21.21265314 doi: medRxiv preprint as narcolepsy (ICD-9-CM: 347). Therefore, the increased incidence should not be 328 attributed to narcolepsy, but mainly associated with hypersomnia. To date, no 329 narcolepsy-related disorder case report is related to COVID-19 vaccination. There is 330 a recent proof-of-concept study using wearable devices found an increased sleeping 331 duration up to four days post-BNT162b2 vaccination 37 . The sleeping signal detected 332 in this study encourages further investigation on the immunogenicity, mechanism 333 and association between mRNA vaccine and sleeping disorders. To the best of our knowledge, this is the first population-based study describing a 335 spectrum of AIDs subsequent to exposure to BNT162b2 and CoronaVac vaccination. With the availability of territory-wide longitudinal EMRs, this study systematically is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint confidence intervals, IRs, incidence rates, IRRs, incidence rate ratios. 506 . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint confidence intervals, IRs, incidence rates, IRRs, incidence rate ratios. 511 . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. confidence intervals, IRs, incidence rates, IRRs, incidence rate ratios. 532 . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. Note: The line for CIs without a cap means the upper CI is greater than 5. Abbreviations: CIs, 536 confidence intervals, IRs, incidence rates, IRRs, incidence rate ratios. 537 . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. Note: The line for CIs without a cap means the upper CI is greater than 5. Abbreviations: CIs, 542 confidence intervals, IRs, incidence rates, IRRs, incidence rate ratios. 543 . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. Note: The line for CIs without a cap means the upper CI is greater than 5. Abbreviations: CIs, 548 confidence intervals, IRs, incidence rates, IRRs, incidence rate ratios. 549 . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 23, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Other encephalitis, myelitis, and encephalomyelitis due to infection classified elsewhere 323.5 Encephalitis, myelitis, and encephalomyelitis following immunization procedures 323.6 Postinfectious encephalitis, myelitis, and encephalomyelitis 323.8 Other causes of encephalitis, myelitis, and encephalomyelitis Note: for those diseases without specific ICD-9-CM diagnosis code, series of ICD-9-CM diagnosis 553 codes based on literature were used as approximated diagnosis. 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