The Impact of COVID-19 on the Thyroid Gland: Unraveling the Connection to Autoimmune Thyroid Diseases


As of January 31, 2023, the world has been grappling with the ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

With more than 750 million infections and over 6 million reported deaths worldwide, the COVID-19 pandemic has taken a staggering toll on public health [1].

The manifestations of this viral respiratory disease, which range from mild upper respiratory tract symptoms to life-threatening acute respiratory distress syndrome (ARDS), have left the medical community in a constant state of discovery and adaptation [2,3].

The Clinical Spectrum of COVID-19

COVID-19 presents with a diverse array of symptoms. Among hospitalized patients, cough (70-80%), shortness of breath (50-60%), myalgia or fatigue (40-50%), and fever (90-98%) are the most frequent presenting complaints [4].

Approximately 20-30% of patients develop gastrointestinal symptoms, such as nausea, vomiting, and diarrhea, while other less common symptoms include sputum production, headache (8%), and hemoptysis [5].

Notably, the lag time from symptom onset to dyspnea is around 5.0 days, with hospitalization occurring at approximately 7.0 days, and the development of ARDS taking place around day 8.0 [4,5].

Severe Cases and ICU Admission

Around 20-30% of COVID-19 patients require admission to intensive care units (ICUs) for ventilatory support. Patients in the ICU tend to be older (median age, 66 years vs. 51 years) and often have comorbidities, including cardiovascular diseases (10-15%), hypertension (15-25%), obesity, diabetes (20-25%), or chronic obstructive pulmonary disease (COPD) [5].

Blood tests frequently reveal leukopenia (20-40%) with lymphopenia (20-45%) and elevated levels of aspartate aminotransferase (AST) [6]. Furthermore, chest computed tomographic (CT) scans commonly show bilateral patchy shadows or ground glass opacities in the lungs, which are characteristic features of COVID-19 [6].

Interestingly, a Chinese study has demonstrated that chest CT scans can be more sensitive and faster than polymerase chain reaction (PCR) testing for diagnosing SARS-CoV-2 infection [7].

Evolution of Therapies and Vaccination Efforts

During the initial stages of the pandemic, treatment options were primarily focused on alleviating symptoms and providing supportive care. However, over time, new antiviral drugs and, most importantly, vaccines have revolutionized the approach to COVID-19 [8]. The advent of mRNA-based technology vaccines, such as Pfizer-Biontech’s BNT162b2 and Moderna’s mRNA-1273, marked a significant milestone in the fight against the virus [9,10].

These vaccines have demonstrated their ability to induce robust humoral responses and have proven to be generally safe in the majority of immunized individuals [11,12]. As of the end of January 2023, the European Union alone has administered more than 970 million doses of COVID-19 vaccines [13].

The Thyroid Gland’s Vulnerability to SARS-CoV-2

Beyond the well-documented respiratory and systemic effects of SARS-CoV-2, emerging evidence suggests a potential impact on the endocrine system, specifically the thyroid gland. This impact can occur through direct viral involvement, resembling other post-viral subacute thyroiditis, or indirectly via the systemic immune response and the infamous “cytokine storm.”

The pro-inflammatory cytokines released during this immune storm can have detrimental consequences on thyroid function, creating a complex interplay between the virus and the endocrine system.

Autoimmune Thyroid Diseases (AITD) and COVID-19

Furthermore, COVID-19 has been associated with both the onset and recurrence of autoimmune thyroid diseases (AITD), particularly Graves’ disease (GD) and Hashimoto’s thyroiditis (HT).

This raises significant concerns about the virus’s potential role in triggering or exacerbating autoimmune responses within the thyroid gland. The intricate relationship between SARS-CoV-2 infection and AITD is a topic of growing interest and investigation within the medical community.

Potential Pathogenetic Mechanisms of SARS-CoV-2 Thyroid Autoimmunity Induction

As the COVID-19 pandemic continues to unfold, researchers are delving deeper into understanding the potential mechanisms by which SARS-CoV-2, the virus responsible for the disease, can impact the thyroid gland and lead to autoimmune thyroid diseases (AITD). Several intriguing pathways and mechanisms have been proposed to elucidate this complex relationship.

Hyper-Stimulation of the Immune System by SARS-CoV-2

One of the key features of COVID-19 is the hyper-stimulation of the immune system that the virus triggers [45]. Studies analyzing sera collected from COVID-19 patients, ranging from mild to severe cases, have revealed significant changes in peripheral leukocyte subpopulations and a surge in pro-inflammatory cytokine levels, particularly Interleukin-6 (IL-6), Interleukin-1β (IL-1β), Interleukin-10 (IL-10), Interleukin-17 (IL-17), Tumor Necrosis Factor (TNF), and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) [79].

Notably, IL-6 plays a central role in initiating a rapid and intense inflammatory response, commonly referred to as the “cytokine storm” or “cytokine release syndrome,” which can have detrimental effects on the host. Severe respiratory distress syndrome (ARDS) and hemophagocytic lympho-histiocytosis (HLH) observed in severely ill COVID-19 patients are believed to be manifestations of this hyper-stimulated immune response [80].

ARDS itself, along with ensuing respiratory failure, is a leading cause of mortality in 70% of critically ill COVID-19 patients [81]. The cytokine storm has also been linked to the development of non-thyroidal illness syndrome (NTIS) in critically ill patients, as supported by both in vitro and in vivo studies [82].

Molecular Mimicry between SARS-CoV-2 and Humans

Historically, molecular mimicry has been recognized as a potential mechanism by which infections can influence the development of autoimmune diseases, including AITD. Recent findings have identified homologous peptide sequences between human proteins and SARS-CoV-2 proteins [83,84].

Importantly, this homology has not been observed in non-SARS-CoV-2 affected mammals, suggesting that the adaptive immune system may generate antibodies against viral components that cross-react with self-antigens. This cross-reactivity can lead to tissue damage and potentially trigger the onset or exacerbation of AITD.

Studies have shown that key SARS-CoV-2 proteins, including the spike protein, nucleoprotein, and membrane protein, share peptide sequences with thyroid peroxidase (TPO), potentially contributing to autoimmunity [84].

Neutrophil Extracellular Traps and SARS-CoV-2 Infection

Neutrophils are central players in the innate immune response, and they release extracellular traps called Neutrophil Extracellular Traps (NETs) to combat pathogens.

While NETs are essential for pathogen clearance, they can also contribute to autoimmune conditions by releasing self-antigens. Excessive NET production has been associated with autoimmune disorders like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), myositis, and multiple sclerosis (MS) [85,86,87].

SARS-CoV-2 infection has been linked to increased NET formation and neutrophil-related cytokine responses [88]. Additionally, clinical reports have shown that non-survivors of COVID-19 exhibit a progressive increase in NETs compared to survivors [89,90]. These excessive NETs can damage lung tissue, contributing to the respiratory complications of COVID-19. Moreover, the virus’s ability to induce coagulation dysfunction and widespread thromboses, similar to those observed in lupus patients, further underscores the potential link between NETs and autoimmune responses [91,92,93,94,95].

Transcriptional Changes of Immune Genes

The development of AITD in COVID-19 patients may involve not only the direct presence of the virus within the thyroid gland but also transcriptional changes in immune genes. Recent studies have detected SARS-CoV-2 RNA and proteins in the thyroid tissue of deceased COVID-19 patients, suggesting a potential thyroid tropism of the virus [21,22].

The transcriptional changes observed in the immune genes of the thyroid cells with evidence of SARS-CoV-2 include the activation of both type I (IFN-alpha) and type II (IFN-gamma) interferon pathways. IFN-gamma, in particular, plays a crucial role in connecting innate and adaptive immune responses and promoting nitric oxide release via macrophages. However, prolonged and intense cytokine stimulation may have damaging effects, potentially leading to the development of autoimmune thyroiditis [101,105]. These findings suggest that COVID-19 could trigger or exacerbate thyroid autoimmunity in individuals predisposed to such conditions.


The COVID-19 pandemic has posed unprecedented challenges to healthcare systems worldwide. As we continue to battle this global health crisis, it is crucial to recognize the virus’s multifaceted effects on the human body. The thyroid gland, a critical component of the endocrine system, has not been spared from potential repercussions of SARS-CoV-2 infection. Whether through direct viral involvement or the indirect consequences of the immune response, the thyroid gland’s vulnerability is an intriguing area of study.

Understanding the relationship between COVID-19 and autoimmune thyroid diseases, such as Graves’ disease and Hashimoto’s thyroiditis, is essential for both clinicians and researchers. As we navigate the complexities of this virus, ongoing investigation into its impact on various bodily systems, including the endocrine system, will undoubtedly contribute to our evolving understanding of COVID-19 and guide future therapeutic strategies.

In the face of adversity, the medical community’s dedication to unraveling the mysteries of this pandemic remains unwavering, offering hope for better management and prevention of the consequences of SARS-CoV-2 infection on thyroid health.

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