Millions of people suffer from long Covid, and the impact of this chronic illness can be debilitating as it affects different parts of the body, Josh Keller writes for the New York Times.

Recovery clinics for Covid-19 long-haulers

How does long Covid develop?

According to Keller, studies estimate that around 10% to 30% of people who are infected with Covid-19 develop long-term symptoms. Although it's not clear why some people develop long Covid while others don't, recent research has uncovered four factors that could potentially increase a person's risk:

1. High levels of viral RNA early in an infection
2. The presence of certain autoantibodies
3. Reactivation of the Epstein-Barr virus
4. Having Type 2 diabetes

Although these findings are still preliminary, Steven Deeks, a professor of medicine at the University of California, San Francisco, said they may help clinicians design interventions to treat patients with long Covid more effectively.

How long Covid affects the body

Long Covid can manifest in different ways depending on the person, causing a wide variety of symptoms that affect different parts of the body.

1. The immune system

Long Covid may continue to disrupt a patient's immune system long after the initial infection.

One potential explanation for this chronic immune dysfunction is that the body may still be fighting remnants of the original virus. According to researchers, the coronavirus spreads widely during an initial infection, and the virus's genetic material can remain in tissues, such as the intestines, lymph nodes, and spleen, for many months.

In addition, there's evidence that Covid-19 may cause a long-term, damaging autoimmune response in the body. Several studies have found high levels of autoantibodies, which mistakenly attack a person's own tissues, several months after a person was first infected.

Another possible cause is that the initial coronavirus infection may reactivate other viruses that are usually dormant, such as the Epstein-Barr virus. The reactivation of this and other viruses may lead to chronic inflammation.

According to Akiko Iwasaki, an immunologist at Yale University, it's important to identify the specific cause of each patient's immune problems to treat them most effectively. For example, a patient with autoantibodies could benefit from immunosuppressive medication, while a patient with lingering viral material could benefit from antivirals.

"Depending on what each person has, the treatment would be quite different," Iwasaki said.

2. The circulatory system

Several studies suggest that many long Covid patients struggle with exercise—a problem that may stem from damage to their circulatory systems. This damage disrupts the flow of oxygen to muscles and other tissues, which then limits aerobic capacity and causes severe fatigue.

Long Covid patients may also suffer from chronic inflammation, which then could damage nerve fibers that help control circulation. This condition is called small fiber neuropathy and is associated with dysautonomia, which causes automatic functions like heart rate and breathing to malfunction.

Long Covid patients may also be affected by microscopic blood clots that form during an initial infection. Although these clots will usually break down naturally, they may linger in long Covid patients and block capillaries that transport oxygen throughout the body.

According to David Systrom, an exercise physiologist at Brigham and Women's Hospital, these findings indicate that long Covid patients are suffering from systemic physical problems rather than just being out of shape or anxious.

"You can't make up small fiber neuropathy by skin biopsy. That isn't in somebody's head," Systrom said. "You can't make up poor oxygen extraction to this degree. All of these are objective measures of disease."

3. The brain

According to Keller, even people with mild Covid-19 infections may experience long-term cognitive impairments, such as reduced attention, memory, and word finding.

Although it is not clear how the coronavirus directly enters the brain, several experts said that even mild infections appear to cause significant brain inflammation. Infections may also lead to the overactivation of immune cells called microglia, a process that is similar to one associated with cognitive problems in aging and some neurodegenerative diseases.

Other research suggests that long Covid may significantly reduce the amount of blood that reaches a person's brain. This reduced blood flow was also observed in patients with chronic fatigue syndrome, a condition that has similar symptoms to long Covid, including memory and cognitive problems, muscle and joint pain, and severe fatigue.

According to Avindra Nath, the clinical director of the National Institute of Neurological Disorders and Stroke, the potential long-term neurological problems long Covid patients face are "a major public health crisis."

4. The lungs

Shortness of breath is a common long Covid symptom, but when doctors test long Covid patients with common lung tests, such as chest X-rays, CT scans, and functional tests, the results usually show no sign of damage.

However, a team of British researchers recently found preliminary evidence of lung damage in a small group of long Covid patients. Using specialized MRI scans, the researchers found that most of the long Covid patients took in oxygen less efficiently compared to healthy people, even if the structure of their lungs looked normal.

These results need to be further confirmed by a larger group of patients, but the researchers say potential explanations for patients' shortness of breath could be microclots in lung tissues or a thickening of the blood-air barrier, which affects oxygen uptake in the lungs. (Keller, New York Times, 2/19)