A new study from Stanford University researchers has found previous recent exposure to common coronaviruses could help explain why some people infected with SARS-CoV-2 only suffer mild symptoms. The research showed specific immune cells from patients with mild cases of COVID-19 exhibit signs of prior encounters with common-cold-causing coronaviruses.
One big mystery of SARS-CoV-2, the novel coronavirus that appeared in late 2019, is the variability of effects it generates from person to person. Mark Davis, director of Stanford University’s Institute for Immunity, Transplantation and Infection, wondered if the answer lay in a type of immune cell known as a killer T-cell.
“A lot of people get very sick or die from COVID-19, while others are walking around not knowing they have it,” says Davis. “Why?”
A great deal of early work on SARS-CoV-2 immunity focused on antibodies. These are the immune proteins that quickly home in on a virus and stop it from infecting our cells. But antibodies are just one weapon in our immune system’s arsenal, and Davis points out pathogens can quickly evolve ways to evade antibody attacks.
Killer T-cells, on the other hand, are the immune system’s big fighters. They seek out and destroy infected cells.
After an initial encounter with a virus, trained killer T-cells quieten down and enter a kind of memory mode. They can persist in this surveillance state for years, on guard to quickly jump into action as soon as a targeted pathogen reappears.
“Memory cells are by far the most active in infectious-disease defense,” explains Davis. “They’re what you want to have in order to fight off a recurring pathogen. They’re what vaccines are meant to generate.”
The problem is that tracking killer T-cells is a little more difficult than simply measuring antibody levels. And working out which particular pathogen those cells are trained to attack is even harder still.
SARS-CoV-2 is the seventh coronavirus found to affect humans. Four of these are relatively harmless, responsible for many instances of the common cold. However, the others (MERS, SARS and now SARS-CoV-2) are responsible for some of the most concerning viral outbreaks of the past 20 years.
To investigate whether killer T-cells previously trained to target common coronaviruses could explain why some people experience only mild cases of COVID-19 the researchers first needed to develop a new immune cell screening platform. As SARS-CoV-2 is somewhat related to other coronaviruses, the researchers mapped out several peptide sequences that were shared by the viruses.
A panel of 24 different peptide sequences was created. Some of the sequences were unique to SARS-CoV-2, while others were shared with known seasonal coronaviruses.
Blood samples taken from subjects before the pandemic began were analyzed and the researchers discovered some killer T-cells quickly kicked into gear when exposed to SARS-CoV-2, targeting those shared coronavirus peptide sequences. Instead of taking a few days to identify and destroy a novel pathogen, these immune cells swiftly recognized SARS-CoV-2 due to its similarities to other coronaviruses. Davis says this crucial factor could be playing a role in differentiating those mild COVID-19 cases from the more severe ones.
“That lost time can spell the difference between never even noticing you have a disease and dying from it,” says Davis.
The researchers then tested their new screening platform on blood samples from COVID-19 patients. The hypothesis held strong, with those mild cases of disease showing T-cells targeting peptide sequences common to several coronaviruses, while severe cases primarily targeted sequences unique to SARS-CoV-2.
“It may be that patients with severe COVID-19 hadn’t been infected, at least not recently, by gentler coronavirus strains, so they didn’t retain effective memory killer T cells,” hypothesizes Davis.
The new study offers some clues to why children have been less susceptible to severe COVID-19. Prior research has suggested the frequency of recent exposure to common coronaviruses in children could play a role in reducing disease severity, and Davis believes his new findings back up that hypothesis.
“Sniffles and sneezes typify the daycare setting and coronavirus-caused common colds are a big part of the reason,” he says. “As many as 80 percent of kids in the United States get exposed within the first couple of years of life.”
A recent study from researchers at Johns Hopkins Medicine found this compelling cross-reactive immune response between SARS-CoV-2 and common coronaviruses could mean COVID-19 vaccines generate a small degree of protection against the common cold. The research again looked at T-cell immunity, finding a robust vaccine-induced response to one specific common-cold-causing strain of coronavirus (HCoV-NL63).
The new study was published in the journal Science Immunology.
Source: Stanford Medicine
