The long-term effects of SARS-CoV-2 infection on T cell activation: autoimmune disorders and endothelial cell dysfunction

In a recent review published in Frontiers in Medicine, a group of authors explored the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on thymus (T) cell activation, autoimmune disorders, endothelial dysfunction, and vascular impairments.

Study: Endothelial dysfunction in autoimmune, pulmonary, and kidney systems, and exercise tolerance following SARS-CoV-2 infection. Image Credit: JuanGaertner/Shutterstock.com

Background

The coronavirus disease 2019 (COVID-19) pandemic, instigated by SARS-CoV-2, has caused over a million fatalities in the United States from January 2020 to May 2023.

Symptoms can vary from mild to severe, and pre-existing conditions such as high blood pressure and diabetes can exacerbate the severity of the disease. Several studies suggest a bidirectional relationship between type 2 diabetes and COVID-19.

SARS-CoV-2 infiltrates host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, with variations in human genes influencing infection susceptibility and outcomes.

Endocrine glands expressing ACE2 and transmembrane serine protease two messenger ribonucleic acid (TMPRSS2 mRNA) are vulnerable to COVID-19, potentially causing organ dysfunction.

Autoimmune endocrine disorders and SARS-CoV-2

Thyroid disease

SARS-CoV-2 infection can stimulate immune responses similar to those in autoimmune thyroid disorders. Patients may present with hyperthyroidism or hypothyroidism, with subacute thyroiditis (SAT) being the most common in acute COVID settings.

A retrospective analysis showed a slight increase in SAT incidence in 2020, coinciding with COVID-19 case peaks. SAT can occur during or after acute COVID-19 infection, with varying symptoms. Post-COVID-19 fatigue may be due to residual post-SAT hypothyroidism.

Adrenal disease

SARS-CoV-2 can impact adrenal function through various mechanisms, including hypothalamic–pituitary–adrenal (HPA) axis dysfunction, direct cytopathic impact, immune-mediated inflammation, etc.

Hyponatremia is common in acute COVID-19 infection and may be associated with poorer outcomes.

Pancreas disorder

SARS-CoV-2 can infect human pancreatic beta cells, inducing beta cell death similar to that detected in type 1 diabetes. Hyperglycemia is common in acute COVID-19 infections, even in patients who do not have diabetes.

A meta-analysis revealed a pooled proportion of 14.4% in cases of newly diagnosed diabetes in COVID-19 patients.

The complex interplay between pancreas/diabetes and SARS-CoV-2 continues to be an extensively researched area.

Gonads disorder

Men with acute COVID-19 were found to have hormonal imbalances indicating possible primary testicular damage. The underlying mechanism of SARS-CoV-2 action on the gonads remains unclear.

Concerns regarding long-term spermatogenic failure and male infertility are still areas of uncertainty. Most studies have not reported the impact of COVID-19 on female fertility, but further studies are needed.

Impact on pulmonary vasculature and lung function

The severity of the respiratory failure usually determines the mortality of acute COVID. Endothelial dysfunction and coagulopathy have been observed in acute COVID pathogenesis. Persistent dyspnea is common in long COVID, with various hypothesized mechanisms.

On pulmonary function testing, the common abnormality is the impairment in diffusing capacity. The prolonged respiratory complications experienced by individuals who survived SARS-CoV-2 infection may be associated with many vascular issues.

SARS-CoV-2 and kidney disease

Acute kidney injury (AKI) is mostly common in COVID-19 infection, with more than 20% of hospitalized patients developing AKI.

The pathogenesis of AKI in acute COVID infection is multifactorial and includes activation of the immune system, endothelial injury, coagulation cascade, and the renin-angiotensin-aldosterone system.

SARS-CoV-2 viral effects may continue long after clinical resolution of the infection, potentially triggering increased predisposition to recurring AKI and thus increased probabilities of chronic kidney disease (CKD) development.

The interaction of SARS-CoV-2 infection with other predisposing genetic risk factors for progressive CKD needs further exploration.

Exercise intolerance

Individuals with long COVID often experience exercise intolerance. A meta-analysis of nine studies found that peak oxygen consumption (VO₂) was 4.9 mL/kg/min lower in those with prolonged COVID symptoms than those without.

Exercise intolerance in individuals with long COVID may be related to impaired peripheral oxygen extraction, influenced by factors like hematocrit level, oxygen off-loading from hemoglobin, capillary transit time, capillary density, diffusional oxygen conductance, and muscle oxidative capacity.

Endothelial and autonomic dysfunction and skeletal muscle alterations due to SARS-CoV-2 infection may also reduce oxygen extraction.

Balancing exercise and symptom management

Although preliminary findings hint at exercise benefits in long COVID rehabilitation, it's not universally applicable due to potential post-exertional symptom exacerbation.

Specifically, individuals diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or experiencing post-exertional malaise, should avoid it. In such cases, alternative energy management strategies, such as pacing, are recommended.

Future research should explore optimal exercise dosage, targeted symptoms, and patient suitability for effective management of long COVID.

Written by

Vijay Kumar Malesu

Vijay holds a Ph.D. in Biotechnology and possesses a deep passion for microbiology. His academic journey has allowed him to delve deeper into understanding the intricate world of microorganisms. Through his research and studies, he has gained expertise in various aspects of microbiology, which includes microbial genetics, microbial physiology, and microbial ecology. Vijay has six years of scientific research experience at renowned research institutes such as the Indian Council for Agricultural Research and KIIT University. He has worked on diverse projects in microbiology, biopolymers, and drug delivery. His contributions to these areas have provided him with a comprehensive understanding of the subject matter and the ability to tackle complex research challenges.