Can You Name an “Unsung Hero” of This Pandemic?

Hint #1: It’s part of our immune system. Hint #2: It’s not antibodies.

A few weeks ago, I spoke to a group of older adults in suburban Philadelphia. At the end of the talk, one participant asked me how she could best protect herself against COVID. Her strategy had been to test her blood for COVID antibodies every 6 months. When antibody levels dropped—which was inevitable—she would get a booster dose of vaccine. She asked me if I thought this was a good idea.

What the questioner hadn’t appreciated was the value of her immune memory cells, which were present even after her antibodies had faded.

SARS-CoV-2 virus has a short incubation period, which is the time from exposure to the virus the onset of symptoms. High levels of antibodies present at the time of exposure can prevent initial symptoms, which are usually mild. Unfortunately, these antibodies are short-lived. Therefore, protection against mild illness is always short-lived. Always.

Severe illness, on the other hand takes a much longer time to develop. To prevent severe illness, all you need is immune memory cells, which take days to become activated but are long-lived. Because memory cells are long-lived, protection against severe disease often lasts for years and sometimes decades.

Three types of immune memory cells are generated after immunization or natural infection: memory B cells, which can be activated to make antibodies; memory T helper cells, which can be activated to help B cells make antibodies; and memory cytotoxic T cells, which can be activated to kill virus-infected cells.

On April 11, 2023, researchers in Australia studied 23 people who had been previously vaccinated but were now reinfected. They wanted to know which of the three different types of immune memory cells best correlated with resolution of symptoms. They found that all three were important. But the cell type that best correlated with faster resolution of symptoms was cytotoxic T cells. (“Cytotoxic” means toxic to cells.)

What are cytotoxic T cells? And how do they know to kill only those cells that have been infected with the virus?

The best way to protect against COVID is to prevent the virus from attaching to cells.  In the case of SARS-CoV-2, the viral protein that binds to cells is called the spike protein. All COVID vaccines induce antibodies against the spike protein. Therefore, all vaccines prevent virus binding to cells. Unlike antibodies, however, cytotoxic T cells don’t prevent the virus from attaching to cells; they only kill cells that have already been infected. Within an hour of SARS-CoV-2 virus entry, infected cells put out a distress signal. They do this by placing a small fragment of the virus (called a peptide) on the surface of the cell. This warning signal alerts cytotoxic T cells to kill the infected cell. The newly infected cell is then killed before hundreds or thousands of new virus particles can be produced inside it. This is the equivalent of a cell throwing itself on a hand grenade. “I’ve been invaded,” shouts the infected cell, “Kill me, so that others might live.” 

People who have been vaccinated or naturally infected can take heart in the power of immune memory cells, which are highly effective in keeping people out of the hospital and out of the morgue. Especially cytotoxic T cells, which are a powerful weapon that most people don’t know about.