Incident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK

As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and food allergy. We used nationwide claims-based cohorts in South Korea (K-CoV-N; n = 836,164; main cohort) and Japan (JMDC; n = 2,541,021; replication cohort A) and the UK Biobank cohort (UKB; n = 325,843; replication cohort B) after 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020−2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13−1.27), notably in asthma (HR, 2.25; 95% CI, 1.80−2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15−1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68−0.96). Similar findings were reported in the replication cohorts A and B. Although the potential for misclassification of pre-existing allergic conditions as incident diseases remains a limitation, ethnic diversity for evidence of incident allergic diseases in post-COVID-19 condition has been validated by utilizing multinational and independent population-based cohorts.


Population characteristics
The dataset was linked and consisted of data on first general health examination results, death records, health insurance data including insurance eligibility data, personal sociodemographic data, inpatient and outpatient healthcare records, and medication records.

Recruitment
The study was a multinational population-based cohort study that included all adults (aged ≥ 20 years) reported to each agency during COVID-19.We used the South Korean population-based cohort (K-CoV-N; N=10,027,506) as a main cohort and the Japanese claims-based cohort (JMDC, replication cohort A; N=12,218,680) and the UK biobank cohort (UKB, replication cohort B; N=468,617).We assessed the risk of incident allergic disorder after COVID-19 diagnosis compared with contemporary controls who were not infected with SARS-CoV-2.The pre-observation period to determine the previous diagnostic history was from 2018 to 2019, and the follow-up period was from 2020 to 2021.Individuals with missing Field-specific reporting Please select the one below that is the best fit for your research.If you are not sure, read the appropriate sections before making your selection.

Life sciences
Behavioural & social sciences Ecological, evolutionary & environmental sciences For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf

Life sciences study design
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Sample size
This study utilized large-scale, population-based, multinational cohorts, including a South Korean claims-based nationwide cohort (K-CoV-N; N=10,027,506) as a main cohort and a Japanese claims-based cohort (JMDC, replication cohort A; N=12,218,680) as well as a UK prospective cohort from the UK Biobank (UKB, replication cohort B; N=468,617) as a replication cohort.They are collected over the observation period from January 1, 2018, to December 31, 2021, among individuals aged 20 and above.
Data exclusions Individuals with missing socioeconomic status data, those who died, or those with a history of allergy disease during the pre-observation period were excluded from the analysis ; and missing indicators (BMI missing indicator [yes or no], blood pressure missing indicator [yes or no], fasting blood glucose missing indicator [yes or no], serum total cholesterol missing indicator [yes or no], glomerular filtration rate missing indicator [yes or no], smoking status missing indicator [yes or no], alcoholic drinks missing indicator [yes or no], and aerobic physical activity missing indicator [yes or no]).-Model (replication cohort A; Japan): adjusted for age (20-39, 40-59, and ≥60 years); sex; Charlson comorbidity index (0, 1, and ≥ 2); BMI (underweight [<18.5 kg/m2], normal [18.5-23.0kg/m2], overweight [23.0-25.0kg/m2], obese [≥25.0 kg/m2], ; and missing indicators (BMI missing indicator [yes or no], blood pressure missing indicator [yes or no], fasting blood glucose missing indicator [yes or no], serum total cholesterol missing indicator [yes or no], glomerular filtration rate missing indicator [yes or no], smoking status missing indicator [yes or no], alcoholic drinks missing indicator [yes or no], and aerobic physical activity missing indicator [yes or no]).
; and missing indicators (household income missing indicator [yes or no], townsend deprivation index missing indicator [yes or no], ethnicity missing indicator [yes or no], education levels [yes or no], obesity missing indicator [yes or no], blood pressure missing indicator [yes or no], fasting blood glucose missing indicator [yes or no], serum total cholesterol missing indicator [yes or no], glomerular filtration rate missing indicator [yes or no], smoking status missing indicator [yes or no], alcoholic drinks missing indicator [yes or no], and aerobic physical activity missing indicator [yes or no]).
unknown); blood pressure (systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, and unknown); fasting blood glucose (<100, ≥100 mg/dL, and unknown); smoking status (non-and current smoker, and unknown); alcohol consumption (every day, sometimes, rarely days per week, and unknown); aerobic physical activity (low, moderate, high, and unknown); previous history of cardiovascular disease, chronic kidney disease, and chronic obstructive pulmonary disease; history of medication use for diabetes mellitus, dyslipidemia, and hypertension; and missing indicators (household income missing indicator [yes or no], townsend deprivation index missing indicator [yes or no], ethnicity missing indicator [yes or no], education levels [yes or no], obesity missing indicator [yes or no], blood pressure missing indicator [yes or no], fasting blood glucose missing indicator [yes or . (K-COV-N excluded n=4,335,150; JMDC excluded n=2,012,073; UKB excluded n=66,974) The final sample size was 5,692,356 for K-CoV-N, 10,206,607 for JMDC, and 401,643 for UKB.The final sample size was 5,692,356 for K-CoV-N, 10,206,607 for JMDC, and 401,643 for UKB.ReplicationSimilar findings were reported in the replication cohorts A and B. A Cox proportional hazards regression model with estimates of HRs and 95% CIs was used to explore incident overall and four subtypes (asthma, allergic rhinitis, atopic dermatitis, and food allergy) of allergic diseases associated with long COVID-19.Models were adjusted for following variables: -Model (main cohort; South Korea): adjusted for age(20-39, 40-59, and ≥60 years); sex; household income (low income, middle income, and high income); region of residence (urban and rural); Charlson comorbidity index (0, 1, and ≥2); BMI (underweight [<18.