The coronavirus disease (COVID-19) attacks the lungs, leading to pneumonia, and eventually, a cascade of serious complications. But how does COVID-19 kill? Is it the virus itself or the result of the person’s immune system response?

The coronavirus has now spread to 185 countries and territories, infecting roughly 2 million people and killing nearly 120,000 people. It is a respiratory virus, which means it can enter and invade the airways and lungs. Many other viruses affect the respiratory system; some may infect the upper part while others, the lower respiratory tract – severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) does both.

Novel Coronavirus SARS-CoV-2 Transmission electron micrograph of a SARS-CoV-2 virus particle, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Respiratory virus

While close to 450,000 people are reported as recovered from COVID-19, health experts believe that the survival of a patient dramatically depends on the condition of the lungs. Since the coronavirus is a respiratory virus, which can infect both the upper and lower respiratory tract, it can cause a multitude of symptoms. The most common symptoms include fever, dry cough, tiredness and difficulty in breathing (severe cases). Once the virus has already entered the lower respiratory tract, the disease progresses to a severe lung infection, called pneumonia, which causes difficulty of breathing.

Commonly, when the virus reaches the lungs, it causes inflammation, resulting in fluid accumulation and difficulty of breathing. When fluid enters the alveoli or the air sacs in the lungs where gas exchange occurs, it leads to low blood oxygen levels. This condition is termed as pneumonia.

According to Narveen Jandu, an assistant professor at the University of Waterloo who specializes in microbiology and infectious diseases, the cell disruption that the coronavirus disease causes in the lungs is a major reason the condition leads to a severe respiratory illness.

“Gas exchange is an important and vital function for life. And that’s the exact function where the virus is disrupting during infection,” Jandu said. “When the virus enters the air sacs, it interacts with a specific type of cell that lines the sacs called the alveolar cells — specifically called type II cells,” she added.

Further, she added that once the virus gets into the cells in the lungs, they proliferate inside the cell. When the cell bursts open, it releases new particles of the virus to infect more cells—the infection then overwhelms the immune system.

Immune response

Some people recover from COVID-19, while others die from the infection. The virus kills and destroys the cellular lining of the air sacs. The way the immune system reacts to the infection play an essential role in the difference between recovery and possibly fatal outcomes.

For instance, those who have more robust immune systems may recover faster. In contrast, those with underlying medical conditions, older adults, and those who are immunocompromised may have a hard time warding off the novel coronavirus.

Clinical data also suggests that the immune response plays a pivotal role in the decline and even death of people with COVID-19. As a result, it overwhelms the vital organs of the body, making it hard for doctors to determine the best way to treat patients who are severely ill with SARS-CoV-2 infection.

With the common notion that the immune system may contribute to the severity of the infection, there had been treatments provided to suppress it. During an active infection, shutting down the immune system is risky and can lead to severe complications.

Some early studies have shown that it might not be the virus that negatively impacts the lungs, but an overactive immune response. In some patients who had been critically-ill with the coronavirus, there had been increased blood levels of cytokines, which are proteins that ramp up the immune response. This event is called a cytokine storm, an overreaction of the body’s immune system.

Different cells in the body, including those of the immune system, release small proteins called cytokines. In some instances, the body’s response to an infection can go into overdrive, just like what happens in COVID-19. When the SARS-CoV-2 enters the lungs, it attracts an immune response in the area, causing localized inflammation. Some people may have hyper inflammation, which can be dangerous and life-threatening.

Some of the diseases that can trigger cytokine storms include COVID-19, influenza, and other coronaviruses, like MERS and SARS. Some patients with HIV infection may also experience this type of immune overreaction.

Health experts suggest that the damage of both the virus and the immune response is not uncommon. In some infections, such as those caused by noroviruses, where the patient immediately gets ill, the virus may be the culprit. However, in coronavirus infections where people do not manifest symptoms until several days after infection, there is collateral damage from the virus and the immune response.