New research highlights the huge variation in how T cells respond to the deadly virus
La Jolla, California – A big question on people’s minds these days: How long does immunity to SARS-CoV-2 last after infection?
A research team from the La Jolla Institute of Immunology (LJI), the University of Liverpool and the University of Southampton has discovered an interesting evidence. Their new study suggests that people with severe cases of COVID-19 may be left with more of the protective “memory” T cells needed to fight infection again.
Professor Pandurangan Vijayanand, co-chair of the study, says: “The data from this study indicate that people with severe COVID-19 cases may have stronger immunity in the long term.”
The research was published January 21 in Immunology, Is the first to describe T cells that fight SARS-CoV-2 in “very fine” detail.
“This study highlights the huge variation in how humans react to the viral challenge,” adds co-leader Christian H. Utensmeier, MD, PhD, FRCP, professor at the University of Liverpool and assistant professor at LJI.
Since the early days of the COVID-19 pandemic, scientists at LJI have investigated the important antibodies and T cells to fight SARS-CoV-2. As experts in genomics, Vijayanand and Ottensmeier used sequencing tools to uncover sub-groups of T cells that might control disease severity. In October, the team published its first detailed look at how CD4 + T cells respond to the virus.
For the new study, the researchers used a technique called single-cell transcriptional analysis to study the expression of individual genes of more than 80,000 CD8 + T cells isolated from both COVID-19 patients and unexposed donors. CD8 + T cells are the cells responsible for destroying virus-infected host cells. The CD8 + T “memory” cells are also important for protecting the body from reinfection against many viruses.
The team studied CD8 + T cells from 39 patients with COVID-19 and 10 people who had never been exposed to the virus (their blood samples were given prior to the pandemic). Among the COVID-19 patients, 17 had a milder condition that did not require hospitalization, 13 patients were hospitalized, and nine required additional ICU support.
To the researchers’ surprise, they saw weaker CD8 + T cell responses in patients with milder cases of COVID-19. Researchers saw the strongest CD8 + T cell responses in critically ill patients who required hospital treatment or intensive care unit support.
“There is an inverse link between how poorly T cells function and how badly the infection is,” Ottensmeier says. “I think that was totally unexpected.”
One can expect to see a stronger CD8 + T cell response in mild cases, given that these are the cases where the immune system is equipped to fight a severe infection – but the study showed the opposite. In fact, CD8 + T cells in milder cases showed the molecular markers of a phenomenon called “depletion” of T cells. In cases of T cell depletion, the cells receive a large amount of stimulation to the immune system during a viral attack so that they are less effective in performing their functions.
While more research is needed, Vijayanand and Uttenmeyer think it is worth examining whether depletion of T cells in mild cases of COVID-19 may impede a person’s ability to build long-term immunity.
“People with severe disease are likely to end up with too many memory cells,” says Vijayanand. “People with milder disease have memory cells, but they seem tired and dysfunctional – so it may not be effective long enough.”
The new study provides a valuable window into CD8 + T cell responses, but it is limited because it relies on CD8 + T cells found in blood samples. As a next step, the researchers hope to shed light on how T cells in tissues are severely affected by SARS-CoV-2, such as the lungs, on the virus. This step will be important because the memory T cells that provide long-term immunity need to live in the tissues.
“This study is largely a first step in understanding the spectrum of immune responses against infectious agents,” says Ottensmeier. Going forward, researchers hope to use single-cell sequencing techniques to screen for CD8 + T cells in cancer patients with COVID-19 infection.
“This research highlights the power of these new tools in understanding human immunology,” says Vijayanand.
The new study, titled “Critically ill COVID-19 patients exhibiting poor depletion features in interactive SARS-CoV-2 CD8 + T cells,” is supported by the National Institutes of Health (Grants U19AI142742, U19AI118626, R01HL114093, R35-GM128938, S10RR027366) , S10OD025052, William K. Bowes Jr Foundation, Whittaker Foundation, Wessex Clinical Research Network and UK National Institute for Health Research.
Additional study authors include first co-authors Anthony Cosnadi, Cerro Ramirez Swasteguoy, Vicente Fajardo and Serena GChe, as well as Benjamin J. Mickaev, Hayley Simon, Emanuela Pelosi, Gregory Somoa, and Farhat I.
DOI: 10.1126 / sciimmunol.abe4782
About La Jolla Immunology Institute
The La Jolla Institute of Immunology is dedicated to understanding the complexities and power of the immune system so that we can apply that knowledge to promote human health and prevent a wide range of diseases. Since its establishment in 1988 as an independent, not-for-profit research organization, the institute has made several developments that have led to the achievement of its goal: life without disease.