Long COVID may result from an overactive immune response in the lungs – The Wire Science

Representative picture. Image: mohamed_hassan/pixabay

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• It is still unclear why and how respiratory diseases can develop into chronic diseases such as COVID-19.
• New research has revealed that it may not be an active viral infection that long causes COVID-19 and similar diseases, but an overactive immune system.
• The immune system facilitates lung recovery after infection by sending signals that activate stem cells but can also maintain harmful inflammatory processes in the lungs.

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Viruses that cause respiratory illnesses like the flu and COVID-19 can cause mild to severe symptoms in the first few weeks after infection. These symptoms usually resolve within a few weeks, sometimes with the help of treatment if severe. However, some people experience persistent symptoms that last for several months to years. It is still unclear why and how respiratory diseases can develop into chronic diseases such as COVID-19.

I’m a graduate student working at the University of Virginia’s Sun Lab. We examine how the immune system sometimes goes awry after fighting off viral infections. We are also developing ways to target the immune system to prevent further complications without weakening its ability to protect against future infections. Our recently published review of research in this area found that it is becoming increasingly clear that it may not be an active viral infection that is long causing COVID-19 and similar conditions, but an overactive immune system.

The lungs in health and disease

It is important that your immune system remains dormant when there is no active infection in order for your lungs to function optimally.

Your airway is in constant contact with your external environment, taking in about 5 to 8 liters (1.3 to 2 gallons) of air – and the toxins and microorganisms it contains – every minute. Despite constant exposure to potential pathogens and pollutants, your body has evolved to rest the immune system in the lungs. In fact, allergies and conditions like asthma are byproducts of an overactive immune system. These excessive immune responses can cause your airways to narrow, making it difficult to breathe. Some severe cases may require treatment to suppress the immune system.

However, during an active infection, the immune system is absolutely essential. When viruses infect your airways, immune cells are recruited into your lungs to fight off the infection. Although these cells are vital in clearing the virus from your body, their activity often leads to collateral damage to your lung tissue. After the virus is removed, your body suppresses your immune system to give your lungs a chance to recover.



Over the past decade, researchers have identified a variety of specialized stem cells in the lungs that can help regenerate damaged tissue. These stem cells can transform into almost any different cell type in the lungs depending on the signals they receive from their environment. Recent studies have highlighted the prominent role played by the immune system in providing signals that facilitate lung recovery. But these signals can produce more than one effect. Not only can they activate stem cells, but they can also maintain harmful inflammatory processes in the lungs. Therefore, your body regulates exactly when, where, and how strong these signals are sent to prevent further damage.

While the reasons are still unclear, some people cannot turn off their immune systems after infection and continue to produce tissue-damaging molecules long after the virus has been flushed out. This not only further damages the lungs, but also disrupts regeneration via the lungs’ own stem cells. This phenomenon can lead to chronic diseases as seen in several respiratory viral infections including COVID-19, Middle East Respiratory Syndrome (MERS), Respiratory Syncytial Virus (RSV) and common cold.

The role of the immune system in chronic diseases

In our review, my colleagues and I found that many different types of immune cells are involved in the development of chronic disease following respiratory viral infections, including prolonged COVID-19.

Scientists have so far identified one type of immune cell, killer T cells, as a potential cause of chronic disease. Also known as cytotoxic or CD8+ T cells, they specialize in killing infected cells, either by interacting with them directly or by producing harmful molecules called cytokines.

Killer T cells are essential to contain the spread of the virus in the body during an active infection. However, their persistence in the lungs after the infection has resolved is associated with prolonged reduced respiratory function. Additionally, animal studies have shown that removing killer T cells from the lungs after infection can improve lung function and tissue repair.

Another type of immune cell, monocytes, are also involved in fighting respiratory infections and serve among first responders by producing virus- and tissue-damaging cytokines. Research has found that these cells continue to accumulate in the lungs of long COVID-19 patients, promoting a pro-inflammatory environment that can cause further damage.

Understanding the immunological mechanisms underlying the long-running COVID-19 is the first step in addressing a rapidly worsening public health problem. Identifying the subtle differences in how the same immune cells that protect you during an active infection can later become harmful could lead to an earlier diagnosis of long-lived COVID-19. Additionally, based on our findings, my team and I believe that treatments that target the immune system could be an effective approach to manage long-standing COVID-19 symptoms. We believe this strategy could prove useful not only for COVID-19, but also for other respiratory viral infections that also lead to chronic diseases.

Harish NarasimhanPhD Student in Immunology, University of Virginia.

This article is republished by The conversation under a Creative Commons license. Read the original article.