SUN-375 - Thyroid Adverse Events Following mRNA COVID-19 Vaccination: A Dose-Specific Disproportionality Analysis Using VAERS, 2021-2024

Background Case reports link mRNA COVID-19 vaccines to thyroid dysfunction, including subacute thyroiditis and Graves' disease; proposed mechanisms include molecular mimicry between spike protein and thyroid antigens. Whether signals are dose- or brand-specific at population scale, and whether they persist with bivalent boosters, remains uncharacterized.

Methods Retrospective disproportionality analysis of VAERS reports Jan 2021–Dec 2024, deduplicated on VAERS_ID (domestic + foreign; 18.9% non-U.S.). Thyroid AEs defined a priori by 7 MedDRA PTs (Thyroiditis, Thyroiditis subacute, Autoimmune thyroiditis, Hyperthyroidism, Hypothyroidism, Basedow's, Graves'). Exposure: BNT162b2 or mRNA-1273 monovalent/bivalent (XBB.1.5 not separately identifiable in VAX_NAME). Primary comparator: non-mRNA-COVID reports. Sensitivity comparators: (a) non-COVID vaccines; (b) Janssen Ad26.COV2.S as active adenoviral-vector comparator. PRR with 95% Wald CI and Evans χ² computed; EMA signal = PRR ≥2, χ² ≥4, a ≥3. Strata: dose, brand, formulation, PT, age, sex.

Results Of 1,158,341 reports, 936,939 named mRNA vaccines; 1,137 named ≥1 thyroid PT (median age 52; F:M 4.0:1; 21.9% hospitalized; 14 deaths, consistent with VAERS co-coding on reports with unrelated fatal events). Overall mRNA PRR sub-threshold: 1.69 (1.43–2.00), χ² 39.3. Pfizer signaled (2.04 [1.72–2.43], χ² 69.1); Moderna did not (1.33 [1.11–1.59]). Peak at Dose 2 (2.52 [2.11–3.02]), driven by Pfizer Dose 2 (2.88 [2.38–3.48], χ² 131); Dose 3 also signaled (2.20 [1.77–2.73]). PT signals: Thyroiditis subacute (3.51 [1.53–8.01]), Thyroiditis (2.46 [1.28–4.70]), Hyperthyroidism (2.58 [1.74–3.83]); no signal for Hypothyroidism (1.40 [1.09–1.81]), Autoimmune thyroiditis (1.27 [0.89–1.82]), or Graves'/Basedow's combined (1.84 [1.29–2.64]). Female-predominant (F 2.07 [1.75–2.46]; M 1.04 [0.85–1.28]). Monovalent and bivalent PRRs comparable (1.69 vs. 1.67), though bivalent cohort ~20-fold smaller and older. Sensitivity: vs. non-COVID only, signal crossed EMA threshold (2.27 [1.80–2.86]); vs. Janssen, attenuated to null (1.12 [0.89–1.41], χ² 1.0).

Conclusion mRNA COVID-19 vaccination shows a dose-dependent, brand-asymmetric, female-predominant thyroid signal peaking at Pfizer Dose 2 and concentrating in subacute thyroiditis, thyroiditis, and hyperthyroidism; hypothyroidism does not signal. Attenuation to null against Janssen suggests a substantial portion reflects differential reporting intensity rather than mRNA-specific excess. As a hypothesis-generating signal-detection study, these findings cannot establish causation; confirmation requires cohort studies with denominators and adjudicated outcomes.

AI Use: ChatGPT was used only for language editing to improve clarity and grammar. All scientific content, data interpretation, and conclusions were generated and verified by the authors.

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