PHILADELPHIA (February 1, 2022)—Patients recovering from COVID-19 who continue to have certain debilitating symptoms such as chronic fatigue may need long-term support, including evaluation of the endocrine system, according to a recent review.
“We looked at involvement of the endocrine system related to two things, post-COVID syndrome and long COVID,” said Christian A. Koch, MD, PhD, FACP, MACE, professor and director of the Division of Endocrinology at Fox Chase Cancer Center and the study’s senior author.
“Post-COVID syndrome consists of signs and symptoms that develop during or after infection that are consistent with COVID-19 or its variants and continue for more than 12 weeks but are not explained by an alternative diagnosis,” he said. The term long COVID is used to characterize both post-COVID syndrome and ongoing symptomatic COVID-19 infection anywhere from four to 12 weeks, Koch added.
Long COVID has many similarities with chronic fatigue syndrome, otherwise known as myalgic encephalomyelitis, a condition known to occur after many viral infections, including with the Epstein-Barr virus.
This heterogeneous condition can involve immune, virologic, psychological, and endocrine factors. As such, endocrine evaluations should be part of the management of patients with long COVID, with a specific focus on the hypothalamus-pituitary-adrenal (HPA) axis, adrenal function, and thyroid function.
In the review, Koch and colleagues walked through the known associations between long COVID and these systems. ACE2 receptors are the route of entry for the SARS-CoV-2 virus, which causes COVID-19, into the body, Koch said. These receptors are expressed in a variety of tissues, including the small intestine, heart, kidneys, adipose tissue, muscle, hypothalamus, pituitary, adrenal gland, thyroid, testes, ovaries, and pancreatic islets.
Koch said autopsies of patients who died of SARS infection showed evidence of viral genome, edema, and neuronal degeneration in the hypothalamus. Another study of patients who recovered from SARS infection showed hypocortisolism for up to one year in the majority of patients, along with hypothyroidism.
Studies linking COVID-19 and the HPA axis are somewhat limited. However, one study of patients hospitalized with acute COVID-19 found that about one-third had subnormal cortisol levels and those with severe disease had subnormal cortisol and ACTH levels.
“This suggested a direct association between the degree of COVID-19 infection and impaired glucocorticoid response,” Koch said. Another important endocrine consideration is the use of corticosteroids in the treatment of COVID-19, he added.
“If a patient is given high-dose glucocorticoids and they are not properly tapered off treatment, they can develop adrenal insufficiency and/or abnormal thyroid blood tests,” Koch said.
Adrenal insufficiency should be considered as part of the differential diagnosis in patients experiencing chronic fatigue, dizziness, hypotension, and nausea. Koch and colleagues suggest early adrenal axis testing for patients with COVID-19 and suspicion of adrenal insufficiency.
Finally, Koch said it is conceivable that a virus infection could trigger Type 1 diabetes because of damage to pancreatic islet cells. “There are not many mechanistic case studies of this, but there are two excellent review articles.”
By looking into possible endocrine-related causes of chronic fatigue syndrome after COVID-19, clinicians can rule out anything related to endocrine function. If issues related to the HPA axis, adrenal function, or thyroid function are identified, symptoms of fatigue may be resolved with appropriate treatment.
The paper, “COVID-19 and Chronic Fatigue Syndrome: An Endocrine Perspective,” was published in the Journal of Clinical and Translational Endocrinology in a special issue on COVID-19 and endocrinology, along with another paper that Koch was a co-author on, “Hypertension and COVID-19: Updates From the Era of Vaccines and Variants.”