LONDON – People infected with COVID-19 are likely to have T-cell immunity six months after contracting the virus, according to a U.K. study of 100 subjects who had an asymptomatic or mild to moderate infection.

T cells against SARS-CoV-2 were found in all 100 participants at six months post infection, including in those who had no detectable antibodies.

“To our knowledge, our study is the first in the world to show robust, cellular immunity remains at six months after infection in individuals who experienced either mild/moderate or asymptomatic COVID-19,” said Paul Moss, professor at the Institute of Immunology and Immunotherapy, Birmingham University, and leader of the U.K. Coronavirus Immunology Consortium.

“While our findings cause us to be cautiously optimistic about the strength and length of immunity generated after SARS-CoV-2 infection, this is just one piece of the puzzle,” Moss said.

The cellular immune response detected at six months was directed against a range of proteins from the virus, including the spike protein that is targeted by most COVID-19 vaccines. However, comparable immunity was present against nucleoprotein and other proteins, suggesting further targets for vaccines developers.

“We looked at the spike protein that a lot a vaccines are based on, and also saw really good, robust immune responses against other proteins,” said Shamez Ladhani, consultant epidemiologist at the Immunisation and Countermeasure Division of Public Health England, and a co-author of the study published as a preprint on Biorxiv on Nov. 2.

As yet, there is not enough information to say which of those would be the best targets, Ladhani said. “The cellular immune response recognized a number of proteins, but we don’t know which are the most important,” he said.

The 100 participants are part of a cohort of more than 2,000 clinical and non-clinical health care workers who volunteered to donate serum and blood samples very early in 2020. The subset of 100 all tested seropositive for SARS-CoV-2 after the pandemic took hold in the U.K. in March. Their antibody levels were subsequently measured each month, and blood samples were taken at six months to assess the T-cell response.

“We were recruiting colleagues even before there was an antibody test. That’s the advantage we’ve got. We identified people who got the infection very early and there have been very few reinfections since then, so it’s an important cohort,” Ladhani said.

The study of T-cell response involved looking at the magnitude of response, as well as the response to different SARS-CoV-2 proteins, requiring analyses that are much more complex than antibody testing, Moss noted. Largeish blood donations are needed that must be processed within three hours. It took three weeks to analyze all the samples.

In addition to looking at the longest time point post-infection in any T-cell immunity study to date, the research is important in testing volunteers who were not ill enough to be hospitalized.

“The majority of T-cell studies have looked at hospitalized patients,” Ladhani said. “The difference here is mild or asymptomatic disease, which represents the vast number of infections. The fact you can see persistence in this cohort of people in the community is more reassuring, because you would expect people who are very sick to have a bigger immune response.”

That alignment with severity is reflected in the fact that T-cell responses were 50% higher in the participants who experienced symptomatic infection. Although saying that means the nature of the initial infection determines long-term cellular immunity, Moss said it is not known if this provides more protection in people with severe initial disease.

“It raises the question: Are people with asymptomatic disease simply more able to suppress the virus without the need to generate a large immune response?” he said.

While “reassuring,” the research does not mean people cannot get reinfected. Large-scale population studies are required to show how antibody, and T-cell and B-cell profiles, act to protect people over time, said Moss. A separate U.K. study is looking at B-cell responses, but has not reported any data as yet.

All participants had antibody responses when they entered the study, but in some antibodies fell below detectable levels over the six months. That indicates T-cell and B-cell measurements are needed to track population level immunity in the longer term, the researchers say.

Based on data accumulated so far, 90% to 95% of people with a confirmed COVID-19 infection have a detectable antibody response. Ladhani said antibodies are a definitive marker of past exposure to the virus, and there is little evidence to suggest there is a cellular immune response without an antibody response.

Ladhani has been tracking the antibody response of all the 2,000-plus cohort. However, he has not yet published any data because the plateau has not been reached. In general, the decline in antibodies is rapid immediately after an infection and then flattens to a stable level. “We have not got to that point,” he said.

The data are consistent with previous observations on T-cell immunity to SARS, with some patients having T cells more than 10 years after infection, said Charles Bangham, chair of immunology at Imperial College London, who was not involved in the research. “These results provide reassurance that, although the titer of antibody to SARS-CoV-2 can fall below detectable levels within a few months of infection, a degree of immunity to the virus may be maintained.”

The critical question remains as to whether these persistent T cells provide efficient protection against reinfection. It also will be important to follow antibody and T-cell immunity in people who develop “long COVID”, the persistent condition that follows acute SARS-CoV-2 infection in a still-uncertain proportion of people, Banham said.