Influence of COVID-19 Vaccines on the Endocrine System

Introduction

The COVID-19 pandemic shook the world with suffering and death; its worldwide spread has provided a tremendous challenge to the global healthcare system, resulting in an unprecedented medical, economic, and societal crisis. The first mass vaccination drive against the novel coronavirus began in December, 2020. The initial skepticism about vaccination was slowly overcome with education and awareness of the protection it affords and with mandates over travel and at workplaces which resulted in an average of 65 out of every 100 persons being fully vaccinated in the world. After studies and trials on populations and weighing risks against benefits, some vaccines were approved by the World Health Organization (WHO) through the emergency use listing process. However, the long term effects of the vaccines is a subject that we still do not have sufficient knowledge of, and studies to monitor them are still under way.

What Are the Types of Vaccines Against Coronavirus Disease?

There are different types of vaccines which employ different methods of preparing our immune system to fight in case of an encounter with the pathogen. The composition of these vaccines also vary. Some use inactivated whole viruses to induce immunity while others use mRNA vaccine. mRNA-based vaccines are coated with lipid nanoparticles that are used to transport nucleoside-modified mRNA encoding viral proteins to the host cell membrane; genetically engineered RNA is used to generate a protein in the host that safely produces an immune response. Viral vector vaccines use a safe virus that is incapable of causing disease but acts as a platform to produce coronavirus proteins to invoke an immune response. Protein-based vaccines use harmless fragments of proteins or protein shells that mimic the COVID-19 virus. The final common goal of any vaccine is to produce an immune response in the host such that the body is ready to fight the actual germ in the event of an infection.

What Are the Side Effects of COVID-19 Vaccines?

Some of the common symptoms one may face after getting a vaccine shot include fever with chills, headache, pain at the site of injection, fatigue, diarrhea, nausea or vomiting, etc. All individuals experience varying symptoms depending on their health and the type of vaccine administered. These symptoms die down within a few days and the severity of these symptoms does not reflect the body’s response to actual infection. More long lasting effects of vaccination are possible though rare.

How Does It Affect the Endocrine System?

Reported evidence of endocrine dysfunction following SARS-CoV-2 vaccination involves primarily the thyroid gland, adrenal glands, pituitary gland, the reproductive system and diabetic states. Symptoms may manifest anytime between four and twenty one days post vaccination.

1. Effects on the Thyroid Gland:

   1. The most common finding was that of subacute thyroiditis. It is a self-limiting condition due to an immune reaction of the thyroid gland following an upper respiratory tract infection. Possible symptoms include neck pain, fatigue, palpitations, weight loss, etc. It was more commonly reported in middle aged women. Some of the reported cases already had thyroid diseases such as primary hypothyroidism, multinodular goiter, Grave’s disease, papillary carcinoma of thyroid or subacute thyroiditis itself. It was observed that it occurred more frequently with mRNA vaccines.

   2. Grave’s disease, which is an autoimmune disease characterized by an overactive thyroid gland producing excess thyroid hormone, was reported in some individuals. Reported instances included first-onset Graves’ disease as well as previously known quiescent Graves’ disease. Majority of the reported cases were in association with mRNA vaccines either following the first or second dose. Symptoms experienced were insomnia, irritability, hand tremors, palpitations, weight loss, tachycardia, etc. In most cases thyroid function returned to normal with remission of symptoms.

   3. Other thyroid disturbances reported were hypothyroidism and painless thyroiditis.

2. Effects on the Adrenal Gland:

   1. Adrenal insufficiency (impaired function of the adrenal gland causing insufficient production of the hormone cortisol) and bilateral adrenal hemorrhage were reported in association with viral-vector vaccines. In addition to adrenal hemorrhage, systemic thromboembolic and hemorrhagic complications also occurred. Vaccine induced thrombotic thrombocytopenia (VITT) was diagnosed in a few individuals. Anti-platelet factor 4 antibodies (PF-4) were detected in some cases.

3. Effects on the Pituitary Gland: Hypopituitarism was reported with a secondary adrenal insufficiency, central hypothyroidism and hypogonadism. MRI scan showed an enlarged pituitary gland. Hormone replacement therapy was found beneficial. After one month the size and function of the pituitary gland was restored with optimal hormone levels.

4. COVID-19 Vaccines and Diabetes: Worsening hyperglycemic conditions were reported one week after vaccination in individuals with both type I and II diabetes with increased blood glucose levels. This is resolved over the next few days either with increased dosage of anti-diabetic medication or without any intervention. However, emergency states such as diabetic ketoacidosis, hyperosmolar hyperglycemic

5. Impact on Reproductive Health: The common effect of vaccination observed in female reproductive health is a disturbance in the menstrual cycle. Prolonged menstruation and an early or delayed period were self reported by at least 66 % of the women who were vaccinated. The menstrual cycle was reported to normalize after two to three months. There has been no significant effect on male reproductive organs, sperm quality, etc.

The proposed mechanisms by which these effects occur are:

• Autoimmune/inflammatory syndrome induced by vaccine adjuvants (ASIA) - Adjuvants used in manufacturing vaccines may disrupt the immunological balance by triggering immune cells and mechanisms.

• A systemic inflammatory response and cytokine storm may be responsible for transient hyperglycemia by disturbing insulin receptor signaling and damaging islet cells in the pancreas.

• Because of molecular simulation, the cross-recognition between the modified SARS-CoV-2 proteins in vaccines and the thyroid target protein can cause autoimmune thyroiditis.

Conclusion

COVID-19 vaccines played an important role in bringing down the mortality and morbidity associated with the coronavirus disease. Various types of vaccines were given an emergency use listing by the WHO after careful studies and analysis. Side effects of the vaccines involving the endocrine system appear to be rare and temporary with normal function restored shortly. Prolonged or serious side effects should be reported to the doctor at once and treated accordingly. With only two years elapsed since the first vaccination drive, much is left to be studied and understood regarding the long term effects of COVID-19 vaccines.