Effect of COVID-19 on the Endocrine System - An Overview

Introduction

Covid-19 infection has affected the whole world by storm and has been the toughest pandemic to manage and control in recent times. Due to the nature of the infection, the contagiousness and the mortality rate of the infection are extremely high. Apart from affecting the various systems and organs of the body that are known and evident, like the lungs and the heart, the COVID-19 infection also affects the endocrine system of the whole body in many ways. The endocrine system is vulnerable to COVID-19 infection, and the effects of the infection can cause mild to severe systemic problems.

What Is the Link Between COVID-19 and Endocrine System?

The COVID-19 virus (SARS CoV 2) gains entry into the cells by binding to the angiotensin-converting enzyme (ACE2 receptors). The angiotensin-converting enzyme is a membrane-bound aminopeptidase that plays a crucial role in the cellular functioning of the body. ACE2 receptors have been identified as the functional receptor for Coronavirus, including the SARS-CoV-2 virus responsible for COVID-19 infection. The COVID-19 infection is triggered by the binding of the ACE2 receptor with the spike protein of the virus. In the body, the ACE2 receptor is expressed in several endocrine glands, including the thyroid gland, pituitary gland, pancreas, and gonads. Therefore, the endocrine system has the ACE2 receptor necessary for SARS CoV 2 virion cellular access. As a result, the endocrine system becomes susceptible to destruction and alteration in its functioning due to the COVID-19 infection.

What Are the Effects of COVID-19 on the Pituitary Gland?

There have been no reports suggesting that there are direct damages caused to the pituitary gland due to the COVID-19 infection. However, there is some alteration in the pituitary functioning. The pituitary gland displays a low ACE2 expression which could be the reason for lesser damage caused to the gland by the COVID-19 infection.

Acute Effects of the Infection Include:

1. Damage to the vascular supply of the pituitary gland (as it has high expression of ACE2 receptors).

2. Pituitary apoplexy may occur in patients with pituitary tumors.

3. Prothrombotic state due to the altered platelet function and coagulation.

4. High levels of fibrinogen and D-dimer.

Persistent Effects of the Infection Include:

1. Central hypothyroidism was reported in 4.9 % of the patients after six months of getting the infection.

What Are the Effects of COVID-19 on the Thyroid Gland?

It has been reported that patients affected by COVID-19 infections develop reduced thyroid functioning. The post-mortem examination of patients who died of the infection showed severely damaged follicular and non-follicular cells of the thyroid gland. Therefore, the thyroid gland is greatly affected by the COVID-19 infection, and one of the primary reasons for this could be the presence of ACE2 mRNA (messenger ribonucleic acid) in the follicular cells of the thyroid gland.

Acute Effects of the Infection Include:

1. Thyrotoxicosis associated with IL-6 levels (interleukin-6) has been reported in multiple cases of COVID-19.

2. Low levels of thyroid-stimulating hormone (TSH).

3. Thyrotoxicosis was reported in about 10.8 % of the patients, and hypothyroidism was reported in about 0.7 % of the patients.

4. Patients with COVID-induced pneumonia had a lower level of serum TSH and total T3 (triiodothyronine) levels, along with no change in T4 (thyroxin) levels as compared to other forms of pneumonia.

5. Subacute thyroiditis.

Persistent Effects of the Infection:

1. It has been reported that thyroid function values return to baseline after three to six months of getting the infection and following conservative treatment.

2. Some cases showed persistent hypothyroidism even after recovery.

What Are the Effects of COVID-19 on the Adrenal Glands?

The ACE2 receptors have been identified to be present in the adrenal cortex, which facilitates the cellular entry of the virus into the adrenal cortex. It is prevalent in the zona fasciculata (middle zone of the adrenal cortex) and zona reticularis (innermost layer of the adrenal cortex), and it is not present in the zona glomerulosa (outermost region of the adrenal cortex). The autopsy reports of patients who died of severe COVID-19 infections revealed adrenal hemorrhage, ischemic necrosis (death of cells due to loss of blood flow), focal inflammation, etc. The serum sodium levels of the COVID-19 patients were also reported to be decreased in about 30 % of the patients.

Acute Effects of the Infection:

1. Adrenal insufficiency is secondary to adrenal infarction.

2. Adrenal hemorrhage.

3. Serum cortisol levels were significantly raised within 48 hours of admission of patients with COVID-19 (this is also associated with an increased mortality rate).

Persistent Effects of the Infection:

1. Patients were reported to have adequate adrenal reserve after three months of contracting the infection.

What Are the Effects of COVID-19 on the Testes?

The ACE2 receptors are found to be present in the testicular germ cells, Leydig cells, and Sertoli cells using cell RNA sequencing. Some of the autopsy reports of people who died of COVID-19 revealed Coronavirus-like particles at the interstitial compartment of the testes and almost absence of germ cells in the seminiferous tubules.

Acute Effects of the Infections Include:

1. Some patients have reported testicular pain.

2. Epididymo-orchitis has also been reported (swelling or pain in one or both testicles).

3. Testicular spermatogenic dysfunction due to immune or inflammatory reaction.

Persistent Effects of the Infection:

1. There is a reduction in testosterone levels, but it is not persistent for a long time.

What Are the Effects of COVID-19 on the Ovaries?

Menstrual irregularity has been extensively reported in women who were affected by COVID-19 infection. In a new study, about 43 % of the women had increased cases of irregular menstrual cycles, menorrhagia (menstrual bleeding longer than seven days), dysmenorrhea (extreme pain during periods), etc., since the start of the pandemic.

Acute Effects of the Infection:

1. Reduction in anti-Mullerian hormone levels.

2. Serum luteinizing hormone, testosterone, and prolactin are higher in the follicular phase of women affected by COVID-19.

3. Increased cycle length, more than 37 days.

Persistent Effects of the Infection:

1. Irregular periods.

2. Abnormally heavy period.

3. Postmenopausal bleeding.

4. Adverse pregnancy outcomes.

What Are the Effects of COVID-19 on the Pancreas?

Hyperglycemia in patients who were previously not known to have diabetes was reported in a considerably large number of patients affected by COVID-19. Similarly, there were reports of ketosis and a new diagnosis of diabetes in COVID-19 patients. The Coronavirus can infect and replicate the human endocrine pancreas cells. Autopsy reports suggested Coronavirus RNA be present in the beta cells of patients with COVID-19. The ACE2 receptors are prevalent in the microvasculature of the pancreas.

Acute Effects of the Infection:

1. Ketoacidosis occurs due to insufficient insulin secretion to meet the glycemic needs secondary to the autoimmune destruction of beta cells.

2. New onset of type 1 diabetes cases.

3. COVID-19 has also been reported to disrupt beta cells function in patients without a diabetes history.

Persistent Effects of the infection:

1. About 63 % of the people diagnosed with hypoglycemia during the COVID-19 infection recovered after six months.

2. Some people who developed new-onset diabetes during the infection continued to have the disease even after three years.

3. Permanent dysregulation of glucose homeostasis.

Conclusion

COVID-19 may cause several endocrine problems, and it may worsen the condition of people with pre-existing endocrine disorders. Most of the endocrine glands have shown symptoms suggesting COVID-19 complications. However, there are not enough studies and research done to narrow down these complications. Moreover, the increasing number of Coronavirus variants keeps.