Why COVID-19 Makes Some People So Much Sicker Than Others

Yale researcher explains what a ‘cytokine storm’ is and how immune responses vary.

For some people, COVID-19 will be a mild illness, sometimes barely even noticeable. Others, however, can become severely ill and end up in the intensive care unit (ICU) fighting for their lives.  

Yale School of Medicine researchers are trying to understand why COVID-19 can affect people so differently. The answer, says Aiko Iwasaki, PhD, a Yale immunobiologist, appears to involve an overactive response from the body’s immune system.   

Normally, the body recruits white blood cells to clear viruses. Part of the virus-clearing process includes secreting cytokines, small proteins released by cells that calm down the immune response.  

“With a COVID-19 infection, the immune system starts responding to the virus as it normally would, but in certain patients, something goes wrong,” says Iwasaki, who is the Waldemar Von Zedtwitz Professor of Immunobiology and professor of molecular, cellular, and developmental biology at Yale, and an investigator for the Howard Hughes Medical Institute.  

For these people, rather than simply targeting the virus, the immune system goes into overdrive and creates what is known as a “cytokine storm.”  

“Instead of helping the host cope with the infection, the cytokines can cause damage to the tissue, such as breaking down protective lining of the lung and the blood vessels,” Iwasaki explains.  

When the lining of the blood vessels in the airway is diminished, fluids and proteins seep out of blood vessels and fill the alveoli (tiny air sacs in the lungs). This disrupts oxygen exchange and causes people to experience shortness of breath, Iwasaki says. “They can no longer have enough oxygen in the blood coming in through the alveoli, because they're filled with fluids,” she adds.  

The prevailing theory is that this overdrive of the immune response is what leads to severe cases of COVID-19, Iwasaki says. “It might actually also lead to death in some cases, because if you imagine the patients that are unable to breathe because of all this fluid coming into the alveoli, that may be the cause of lethality in some cases,” she adds.

Iwasaki’s laboratory is working to identify the type of immune responses needed to recover from the infection and what types are driving the disease. “If we can figure this out, we can have better therapy and better vaccine strategies to try to promote the protective type of immune response, and to dampen the toxic immune pathology,” she says.    

That, she adds, will help physicians determine if a patient is likely to recover easily from COVID-19 or develop a severe case. This insight will guide treatment.  

In the meantime, as there is no vaccine or specific medications for COVID-19, the public can do its part by continuing to practice social distancing and keeping a healthy lifestyle, Iwasaki says. “Washing your hands, eating healthy, exercising, and getting enough sleep can help your immune system be as optimal as it can be,” she says. “I know this is difficult for many people because they're under such stress from this COVID-19 outbreak, but it's really important to keep up with self-care.” 

Click here to learn more about Yale’s research efforts and response to COVID-19.