Graves' Disease Before and After the SARS-CoV-2 Pandemic

A Clinical Center's Experience

The Silent Shift: How the Pandemic Changed an Autoimmune Landscape

What Is Graves' Disease?

Graves' disease, an autoimmune disorder that causes the thyroid gland to produce excessive hormones, has long been a familiar condition to endocrinologists. Yet, since the emergence of the SARS-CoV-2 pandemic, clinicians worldwide began noticing something unusual: more patients were being diagnosed with this autoimmune condition, particularly among younger populations 1 .

To understand why these changes matter, we must first grasp what Graves' disease is. Graves' disease is an autoimmune disorder in which the immune system mistakenly attacks the thyroid gland, causing it to produce too much thyroid hormone—a condition known as hyperthyroidism 4 8 .

The disease stems from a complex interaction between genetic predisposition and environmental factors 8 . Before the pandemic, its incidence remained relatively stable across populations.

80%

Of all hyperthyroidism cases are caused by Graves' disease

7:1

Female to male ratio in Graves' disease incidence

30-50

Typical age of onset (years) before pandemic changes

Symptoms of Graves' Disease

This condition accelerates your body's metabolism, leading to symptoms that can include 4 8 :

  • Weight loss despite increased appetite
  • Rapid or irregular heartbeat and palpitations
  • Anxiety, irritability, and sleep disturbances
  • Fine tremors in hands or fingers
  • Heat sensitivity and increased sweating
  • Fatigue and muscle weakness
  • Bulging eyes (in a condition called Graves' ophthalmopathy)
  • Enlarged thyroid gland (goiter)

Clinical Insight: During the pandemic, clinicians observed that patients often presented with more severe biochemical profiles at diagnosis, suggesting either more aggressive disease onset or possibly delayed healthcare access during pandemic restrictions 3 .

The Pandemic Effect: Clinical Observations

Multiple clinical studies from around the world began reporting an unexpected increase in new Graves' disease diagnoses during the COVID-19 pandemic. Rather than a subtle shift, some centers documented dramatic changes.

Study Population Time Period Analyzed Key Findings Proposed Triggers
Children & Adolescents, New York 3 Sept 2017 - Aug 2022 Incidence significantly higher during pandemic: 0.90% vs 0.56% pre-pandemic; rise followed COVID-19 case spikes SARS-CoV-2 infection
Adult Population, Spain 6 2017-2021 Cases doubled in 2021 compared to 2020; 2.44 times higher than 2017-2019 average SARS-CoV-2 infection and vaccination
International Case Reviews 9 2020-2022 48 new diagnoses and 12 recurrences of Graves' disease post-vaccination reported SARS-CoV-2 vaccination
Graves' Disease Incidence Before and During Pandemic
Pre-Pandemic
0.56%
Pandemic Period
0.90%
Post-Vaccination Cases
48+12

A Closer Look: The New York Pediatric Study

One particularly revealing investigation came from pediatric endocrinologists in New York, who conducted a retrospective analysis of Graves' disease diagnoses at their center 3 .

Methodology: Tracking the Trend

The researchers employed a straightforward but powerful approach:

  • Patient Selection: They reviewed records of 156 children and adolescents (mean age 12.5 years) diagnosed with new-onset Graves' disease between September 2017 and August 2022.
  • Time Comparison: Patients were categorized into two groups: those diagnosed before COVID-19 (September 2017-February 2020) and during COVID-19 (March 2020-August 2022).
  • Incidence Calculation: The team calculated incidence rates based on new Graves' disease cases relative to total new patient referrals to their endocrine clinic.
  • Temporal Analysis: They compared the timing of Graves' diagnoses with community COVID-19 case rates.
Results and Analysis: Revealing Numbers

The findings were striking:

  • The incidence of Graves' disease was significantly higher during the pandemic—0.90% compared to 0.56% in the pre-COVID era 3 .
  • The monthly diagnosis rate increased from 2-2.5 cases per month before the pandemic to 3.3-3.5 cases per month during it.
  • Perhaps most notably, the rise in Graves' disease cases closely followed spikes in local COVID-19 infections, suggesting a possible triggering relationship 3 .
Characteristic Pre-COVID Era (n=63) COVID Era (n=93) P-value
Female 81% 73.1% 0.34
Median Age 12.5 ± 3.3 years 12.4 ± 4.4 years 0.48
Race Distribution 28.6% White, 27% Asian, 14.3% African American, 17.4% Hispanic/Latino 37.6% White, 34.4% Asian, 9.7% African American, 17.2% Hispanic/Latino 0.026

Study Timeline & Key Findings

Sept 2017 - Feb 2020

Pre-Pandemic Baseline: Established baseline incidence of 0.56% with 2-2.5 cases per month

March 2020

Pandemic Declaration: Beginning of "COVID era" in study parameters

2020-2022

Increased Incidence: Rise to 0.90% incidence with 3.3-3.5 cases per month

Throughout Study

Temporal Correlation: Graves' disease cases followed COVID-19 infection spikes in the community

Beyond Infection: The Vaccination Question

As COVID-19 vaccines became widely available, reports began emerging of Graves' disease occurring shortly after vaccination 5 9 . Case studies documented individuals developing symptoms of hyperthyroidism within days to weeks of receiving their shots 5 .

One systematic review published in 2022 identified 27 articles describing such cases, totaling 48 new diagnoses and 12 recurrences of Graves' disease following vaccination 9 . The median time from immunization to symptom onset was approximately 10 days.

However, it's crucial to note that large population-based studies have generally not detected an increased incidence of Graves' disease specifically linked to vaccination 1 . This discrepancy between individual case reports and population-level data highlights the complexity of establishing causation.

Vaccination Timeline
Vaccination Day 0
Symptom Onset ~Day 10
Diagnosis ~Day 20-30

Diagnostic Tools for Graves' Disease

Research Tool Function/Application
TSH Receptor Antibody (TRAb) Test Detects autoantibodies targeting TSH receptors; crucial for confirming Graves' diagnosis 3 9
Thyroid-Stimulating Immunoglobulin (TSI) Measures specific antibodies that stimulate thyroid hormone production 3 8
Radioactive Iodine Uptake (RAIU) Assesses thyroid function by measuring iodine absorption; helps distinguish Graves' from other thyroid conditions 9
Thyroid Ultrasound with Doppler Evaluates gland structure and blood flow; reveals characteristic "thyroid inferno" pattern in Graves' 8
Antithyroid Medications (Methimazole) First-line treatment that blocks thyroid hormone production 5 8

Unraveling the Mystery: Potential Mechanisms

How might SARS-CoV-2 infection or vaccination trigger Graves' disease in susceptible individuals? Researchers have proposed several compelling mechanisms:

Molecular Mimicry

The viral spike protein may contain sequences similar to thyroid proteins, potentially confusing the immune system into attacking the thyroid 2 .

Bystander Activation

The inflammatory response to infection or vaccination may activate pre-existing immune cells that happen to target thyroid antigens 2 .

ACE2 Receptor Involvement

SARS-CoV-2 enters human cells via ACE2 receptors, which are expressed on thyroid cells, providing a direct pathway for thyroid involvement 6 .

Cytokine Storm Effects

The massive inflammatory response seen in some COVID-19 cases may disrupt normal immune regulation, potentially unleashing autoimmune processes .

Despite these plausible mechanisms, a 2025 Mendelian randomization study—a technique that uses genetic variants to assess causality—found no evidence supporting a causal relationship between COVID-19 susceptibility or severity and Graves' disease 7 . This suggests that while SARS-CoV-2 may trigger disease in predisposed individuals, it may not be an independent cause.

Implications and Future Directions

Clinical Implications
  • Clinical Awareness: Healthcare providers should maintain heightened awareness for thyroid symptoms in patients with recent COVID-19 infections or vaccinations 1 .
  • Appropriate Testing: When Graves' disease is suspected, confirmation should include TRAb testing when possible to ensure accurate diagnosis 1 .
Research Directions
  • Vaccination Reassurance: Despite case reports, population-level data doesn't implicate COVID-19 vaccination in significantly increasing Graves' disease risk 1 .
  • Future Research: Long-term studies are needed to determine whether the observed increase represents a temporary "precipitating trigger" in predisposed individuals or a sustained change in disease epidemiology 6 .

Conclusion: A Complex Relationship

The experience of clinical centers documenting Graves' disease before and after the SARS-CoV-2 pandemic reveals a fascinating story of how environmental factors can influence autoimmune disease patterns. While evidence clearly shows increased diagnoses during the pandemic, particularly in pediatric populations, the exact role of SARS-CoV-2—as either a direct trigger or incidental factor—remains complex.

What emerges most importantly is that Graves' disease remains a manageable condition with appropriate treatment, regardless of its trigger 8 . As research continues to unravel the precise relationship between viral infections, immune responses, and thyroid autoimmunity, clinicians are better equipped than ever to recognize, diagnose, and treat this condition in those affected.

For patients and healthcare providers alike, the key takeaways are awareness of symptoms, appropriate evaluation when concerns arise, and reassurance that existing treatments remain effective for Graves' disease, whatever its origin story.

References