Cellular immunity to COVID-19 found at six months in non-hospitalised individuals

Cellular (T cell) immunity against SARS-CoV-2 is likely to be present within most adults six months after primary infection, a new pre-print on bioRxiv suggests. The research from Public Health England and the UK Coronavirus Immunology Consortium (UK-CIC) demonstrates robust T cell responses to SARS-CoV-2 virus peptides at this timepoint in all participants following asymptomatic or mild/moderate COVID-19 infection.

A key question is whether previous infection with SARS-CoV-2 results in immunity to reinfection, and if so for how long.  The immune system is extremely complex and there are many different potential routes whereby it can generate immunity to a disease post-infection. This study examines the role of T cells in contributing to immunity against SARS-CoV-2 at six months post infection.

As part of UK-CIC, researchers from the University of Birmingham, Public Health England and NIHR Manchester Clinical Research Facility collected serum and blood samples from a cohort of more than 2,000 clinical and non-clinical healthcare workers including 100 individuals who tested sero-positive for SARS-CoV-2 in March/April 2020 (average age 41 (range 22–65); 23 men, 77 women). All 100 individuals experienced either mild/moderate symptoms or were asymptomatic (56 versus 44 people) and none were hospitalised for COVID-19. Serum samples were collected monthly to measure antibody levels, and blood samples were taken after six months to assess the cellular (T cell) response. A range of analyses were carried out to assess different aspects of the T cell response including the magnitude of response and the response to different proteins from SARS-CoV-2.

Carrying out these cellular analyses is much more complex than antibody studies – but this study of 100 individuals is one of the largest in the world to date in this field.

T cell responses were present in all individuals at six months after SARS-CoV-2 infection. The cellular immune response was directed against a range of proteins from the virus, including the Spike protein that is being used in most vaccine studies. However, comparable immunity was present against additional proteins, such as nucleoprotein, which suggests that these may be of value for incorporation in future vaccine protocols.

This indicates that a robust cellular memory against the virus persists for at least six months.

The size of T cell response differed between individuals, being considerably (50%) higher in people who had experienced symptomatic disease at the time of infection six months previously. Further research will be needed to determine the significance of this finding. It is possible that heightened cellular immunity might provide increased protection against re-infection in people with initial symptomatic infection, or that asymptomatic individuals are simply able to fight off the virus without the need to generate a large immune response.

Antibodies are also a crucial component of immune defence and cellular immunity was strongly correlated with the peak level of the antibody response. Furthermore, larger cellular responses appeared to protect against antibody ‘waning’ over time, again suggesting the need to ensure that cellular immune responses are elicited in vaccine regimens.

Overall, these findings indicate a robust cellular (T cell) immune response against SARS-CoV-2 at six months post-infection. These findings will feed not only into our understanding of how immunity to SARS-CoV-2 works but also help inform future vaccine strategies. Further research is now needed to assess whether this immune response is maintained over the longer term and to better understand how strength of cellular immune response corresponds to likelihood of reinfection.

Professor Paul Moss, UK Coronavirus Immunology Consortium lead from BHP founder-member the University of Birmingham, said: “Understanding what constitutes effective immunity to SARS-CoV-2 is extremely important, both to allow us to understand how susceptible individuals are to reinfection and to help us develop more effective COVID-19 vaccines.

“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. Interestingly, we found that cellular immunity is stronger at this time point in those people who had symptomatic infection compared with asymptomatic cases. We now need more research to find out if symptomatic individuals are better protected against reinfection in the future.

“Our knowledge of SARS-CoV-2 infection is increasing all the time. 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. There is still a lot for us learn before we have a full understanding of how immunity to COVID-19 works. While we increase our understanding, whether we think we have previously had COVID-19 or not, we all should still follow Government guidelines on social distancing to ensure we play our part in minimising the spread of COVID-19 within our communities.”

Dr Shamez Ladhani, Consultant epidemiologist at Public Health England and the study’s author, said: “Cellular immunity is a complex but potentially very significant piece of the COVID-19 puzzle, and it’s important that more research be done in this area. However, early results show that T-cell responses may outlast the initial antibody response, which could have a significant impact on COVID vaccine development and immunity research.

“Our thanks go to the more than 2,000 staff who have volunteered to provide monthly blood samples since the beginning of the pandemic. Recruiting donors so early in 2020 allowed us significantly longer follow-up than many similar studies have achieved so far.”

Professor Fiona Watt, Executive Chair of the Medical Research Council, part of UKRI, said: “This study shows the benefit of funding world-leading immunologists through the UK Coronavirus Immunology Consortium. Researchers investigated whether previous infection with SARS-CoV-2 results in immunity to reinfection. They found that a robust cellular memory against the virus persists for at least six months. This is promising news – if natural infection with the virus can elicit a robust T cell response then this may mean that a vaccine could do the same.”

Please note, this paper is a pre-print reporting preliminary data that has not yet been peer-reviewed.