key: cord-0764394-vekguz48
authors: Arroyo, Anna Chen; Robinson, Lacey B.; Cash, Rebecca E.; Blumenthal, Kimberly G.; Camargo, Carlos A.
title: Emergency department visits for vaccine-related severe allergic reactions among US adults: 2006-2018
date: 2021-12-01
journal: Ann Allergy Asthma Immunol
DOI: 10.1016/j.anai.2021.11.017
sha: f639063b995718673a3843241720ec4ac7e34587
doc_id: 764394
cord_uid: vekguz48

nan

Vaccine-related severe allergic reactions are of growing public concern given reports of anaphylaxis after COVID-19 mRNA vaccination 1 and may contribute to vaccine hesitancy and incomplete vaccination. 2 Little is known about prior trends in healthcare utilization for vaccinerelated severe allergic reactions among the United States (US) adult population. 3 Understanding these trends over time, especially prior to the COVID-19 pandemic, may be helpful to contextualize COVID-19 vaccine-related allergic reactions and inform public understanding of the overall risk of vaccine-related severe allergic reactions.

Our objective was to characterize trends in rates of emergency department (ED) visits for vaccine-related severe allergic reactions among the US adult population from 2006-2018 and to examine factors associated with these severe allergic reactions (including anaphylaxis). We performed cross-sectional analyses of 1) ED visits for vaccine-related severe allergic reactions among US adults (>18 years) using a nationally representative sample of US ED visits, the Nationwide Emergency Department Sample (NEDS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality 4 and 2) severe allergic events requiring ED care from a national passive reporting system, the Vaccine Adverse Event Reporting System (VAERS). 5 NEDS is the largest all-payer US ED database which provides nationally-representative data from approximately 145 million ED visits each year using discharge data from 990 hospitals For identification of severe allergic events in VAERS, 5,6 cases occurring within 0-1 days of vaccination were included if the following MedDRA terms were documented: anaphylactic reaction, anaphylactic shock, and anaphylactoid reaction. Additionally, cases occurring within 0-1 days of vaccination were included if major or minor skin, respiratory, or cardiovascular symptoms or minor gastrointestinal symptoms were documented in combination based on Brighton Collaboration criteria (levels 1 through 3 of diagnostic certainty). 7 We used US Census population estimates for the respective years to determine population rates. 8 Chronic conditions were identified using the HCUP Chronic Condition Indicator (CCI). Roughly one third of these ED visits (weighted n=1364; 34%) were considered severe, defined as resulting in hospitalization (weighted n= 1335; 34%), cardiac arrest or intubation (weighted n=271; 7%), or death (n<10, 1%). After controlling for age, sex, primary payer, geographical region, urban/rural hospital, and presence of chronic conditions, factors associated with vaccine-related severe allergic reactions included increasing age (OR, 2.24; 95% CI, 1.04-4.86 for ≥65 years compared to age 18-24 years), male sex (OR, 1.56; 95% CI, 1.08-2.24 compared to female sex), public insurance (OR, 1.84; 95% CI, 1.18-2.82 compared to private insurance), or having any chronic condition (OR, 14.36; 95% CI, 8.88-23.21).

Using nationally representative data, we report that vaccine-related severe allergic reactions resulting in ED visits among adults were rare and significantly decreased from 2006 to 2018, prior to the COVID-19 pandemic. Vaccine-related anaphylaxis had previously been estimated to be 1.3 cases per million vaccine doses given from 2009-2011. 3 Slightly higher rates of anaphylaxis have been reported after administration of mRNA COVID-19 vaccinations, with recent estimates of 7.9 cases per million vaccinations. 1 Previous reports of vaccine-related anaphylaxis may not be comparable to our findings given that we report population-based rates.

Similar to studies on mRNA COVID-19 vaccines, we found that passive reporting of vaccinerelated events through VAERS underestimated rates. 9 Reassuringly, death from vaccine-related severe allergic reactions were exceedingly rare.

Older adults, especially ≥65 years, were more likely to experience vaccine-related severe allergic reactions compared to younger adults, which may be secondary to preexisting co-morbidities.

Older adults have been noted to have increased risk of fatal anaphylaxis, especially secondary to drug-related anaphylaxis. 10 Documented epinephrine use was noted to be low perhaps secondary to pre-hospital use or inadequate documentation.

Limitations include potential coding errors and minimal clinical information, including lack of allergist-performed diagnostic testing to confirm vaccine-related severe allergic reactions including anaphylaxis. However, we have used national data from two different sources to capture healthcare utilization for vaccine-related severe allergic reactions: 1) voluntarily reported data (VAERS) and 2) a population-based sample of ED discharges based on physician diagnosis (NEDS). Together these data may provide a more comprehensive picture of trends in vaccinerelated severe allergic reactions.

Vaccine-related severe allergic reactions are rare and healthcare utilization for these severe allergic reactions decreased from 2006 to 2018 (before the COVID-19 pandemic).

Reassuringly fatal vaccine-related allergic reactions were exceedingly rare. Recognition, diagnosis, and appropriate treatment of vaccine-related severe allergic reactions should be considered important components of public health vaccination efforts.

The risk of allergic reaction to SARS-CoV-2 vaccines and recommended evaluation and management: A systematic review, metaanalysis, GRADE assessment, and international consensus approach

Allergic symptoms after mRNA COVID-19 vaccination and risk of incomplete vaccination

Risk of anaphylaxis after vaccination in children and adults

Healthcare Cost and Utilization Project (HCUP)

Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS)

Anaphylaxis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data

Annual Estimates of the Resident Population for Selected Age Groups by Sex for the United States

Available at

Acute allergic reactions to mRNA COVID-19 vaccines

Trends in emergency department visits and hospitalizations for acute allergic reactions and anaphylaxis among US older adults: 2006-2014

ED visit rates for vaccine-related severe allergic reactions per million population by age group and data source

Abbreviations: NEDS, National Emergency Department Sample

Vaccine Adverse Event Reporting System

Vaccine-Related Severe Allergic Reactions Rate (per 1,000,000 population) Year NEDS, age ≥18 years NEDS, age 18-64 years NEDS, age ≥65 years VAERS, age ≥18 years VAERS, age 18-64 years VAERS, age ≥65 years ≥18 and 18-64 years, P for trend <0.001, decrease All VAERS, P for trend >0

≥65 years, P for trend 2006-2008 = .22 ≥65 years, P for trend