The causes of many long-COVID symptoms are not detectable using standard lab tests. While some doctors still dismiss some people’s symptoms as psychosomatic, scientists have found visible signs of dysfunction throughout patients’ bodies. Researchers have also identified four factors that appear to increase the risk of developing long COVID:

• High levels of viral RNA early during a patient’s COVID-19 infection 
• The presence of certain autoantibodies
• The reactivation of Epstein-Barr virus 
• Having Type 2 diabetes

While the exact causes of long COVID are still uncertain, new research provides clues as to why the syndrome, comprised of a wide range of possible symptoms, can take such a harsh toll on the body and prove so debilitating.

The Immune System

Long-COVID patients seem to have disrupted immune systems, and chronic immune dysfunction can set off chain reactions throughout your body. This may occur because:

• Your body is still fighting off remnants of the virus. SARS-CoV-2 spreads widely during initial infection and can remain in various tissues for many months.
• Viral reservoirs (places in the body where the virus can hide) cause inflammation, which can damage by itself, and also reactivate other viruses which have lain dormant in your body, sometimes for decades. 
• The virus may trigger autoimmune responses, in which autoantibodies attack the body’s own healthy cells.

These explanations may exist singularly or in combination in any given patient and may require different treatments. A patient with autoantibodies, for example, might benefit from immunosuppressants, while a patient with COVID remnants would receive antiviral medications.

The Circulatory System

In addition to reactivating dormant viruses, chronic inflammation can damage the nerve fibers that help control circulation. This nerve fiber damage, called small fiber neuropathy, has been associated with the malfunction of automatic processes such as heart rate, breathing, and digestion–a condition called dysautonomia–frequently seen in long-COVID patients. 

Nerve fiber damage can hinder oxygen flow from small blood vessels to muscles and tissues, leading to fatigue and limited aerobic ability. The strain on the body’s metabolism may explain why so many long-COVID patients struggle with exercise, and even basic physical activity, long after their initial infections. Other possible causes of circulatory dysfunction include:

• Microscopic blood clots thought to result from hyperactive platelets 
• Protein compounds called cytokines that may injure your cells’ mitochondria 
• Inflamed blood vessel walls

Circulatory problems that cause low oxygen levels are also found in patients with chronic fatigue syndrome, which often follows viral infections. 

The Nervous System

Long-COVID patients have reported a number of lingering neurological symptoms, including:

• Problems with attention and concentration
• Slower information processing  and word-finding
• Impaired memory

It’s not clear how often the virus directly attacks the brain, but a recent study found that infections may trigger the hyper-activation of immune cells called microglia, in a manner that mimics some cognitive problems seen in aging, cancer therapy-related cognitive impairment (CRCI), and certain neurodegenerative diseases. Even patients who had mild infections can experience these long-term effects.

The Respiratory System

Shortness of breath and other breathing difficulties are among the most common complaints of long-COVID patients. Much to their frustration, the results of standard lung tests such as chest X-rays, CT scans, and functional tests often come back normal. Recently, however, British scientists using specialized MRI technology discovered evidence of lung damage in a small group of patients who had not been hospitalized. Tests indicated that, despite their normal lung appearance, most patients had less efficient oxygen uptake than healthy people.

According to the researchers, possible explanations for the shortness of breath include microclots in the lungs and/or thickening of the blood-air barrier that regulates oxygen uptake. The study findings, they said, need to be confirmed with a larger study group. 

*Keller, J. (2022, Feb. 19). How Long Covid Exhausts the Body. The New York Times.      https://www.nytimes.com/interactive/2022/02/19/science/long-covid-causes.html?referringSource=articleShare