Stanford Study Shows Memory T Cells Are Active Defense Against Severe COVID-19

Patients with COVID-19 who experienced milder symptoms were more likely to have had previous exposure to other coronavirus infections, according to the results of a recent Stanford study.The study, which was published in Science Immunology, demonstrated that killer T cells taken from the sickest patients with COVID-19 showed fewer signs of previous exposure to cold-causing coronaviruses.

For the study, investigators studied blood samples from patients diagnosed with COVID-19. Senior study investigator Mark Davis, PhD, a professor of microbiology and immunology, reported that patients with COVID-19 patients with milder symptoms were more likely to exhibit killer-T memory cells directed at peptide proteins SARS-CoV-2 shared with other coronavirus strains. Sicker patients’ expanded killer T-cell counts were mainly among those T cells typically targeting peptides unique to SARS-CoV-2, indicating that they had likely started from scratch in their response to the virus.¹

“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,” Davis said. “Memory cells are by far the most active in infectious-disease defense.”

According to the investigators, killer T cells whose receptors target peptide sequences unique to SARS-CoV-2 must multiply over several days to get up to speed after exposure to the virus and the lost time can be the difference between a severe reaction and a mild reaction.1

To see why some individuals became very ill or die from COVID-19 while others were asymptomatic, the study’s first author Vamsee Mallajosyula, PhD, postdoctoral fellow, first confirmed that some portions of the coronavirus SARS-CoV-2 sequence are nearly identical to portions of 1 or more of the 4 widespread common-cold–causing coronavirus strains.

The investigators determined that unexposed individuals’ killer T cells targeting SARS-CoV-2 peptide proteins that were shared with other coronaviruses were more likely to multiply than killer T cells targeting peptides found only on SARS-CoV-2. The T cells targeting those shared peptide sequences had probably previously encountered 1 or another gentler coronavirus strain. Many of these killer T cells were in memory mode, the investigators noted.

The findings of this study provide insight into who is more likely to develop severe COVID-19 and may explain why some individuals, such as young children, appear to be more resilient than others to infection by COVID-19.

“Sniffles and sneezes typify the daycare setting and coronavirus-caused common colds are a big part of the reason,” Davis said. “As many as 80% of kids in the United States get exposed within the first couple of years of life.”

Reference

1. News release; July 1, 2021. Accessed July 14, 2021. https://med.stanford.edu/news/all-news/2021/07/stanford-study-ties-milder-covid-19-symptoms-to-prior-run-ins-wi.html.