Staff at Royal Free London help scientists to better understand COVID-19 immunity

23 December 2020

New research published today shows COVID-19 immunity for those who had a mild version of the disease lasts at least four months.

Staff at the Royal Free London were among healthcare staff taking part in a study by scientists at UCL, Imperial College London, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Barts Health NHS Trust, Public Health England, as well as the Royal Free London NHS Foundation Trust.

The study analysed antibody and T cell responses in 136 London healthcare workers, 76 of whom had mild or asymptomatic infection dating back to the start of lockdown in March 2020.

The team found that 89% of those analysed carried neutralizing antibodies 16-18 weeks following infection, and this was usually complemented by a multi-pronged T cell response. 

However, the research also suggests that these two arms of protective immunity can become uncoupled, with some individuals showing T cell immunity but no evidence of antibodies, and vice versa. 

From the outset of the pandemic, scientists across the globe have been working to understand how our immune system protects us against SARS-CoV-2, the virus that causes COVID-19 disease, and how long this protection lasts. 

Much of the debate around protective immunity has focused on the different roles of B cells, which make antibodies, and T cells, white blood cells which work in several different ways to help protect from viruses. Some previous studies have highlighted that binding antibody levels wane relatively quickly, while T cells may provide more durable protection. 

Understanding how this careful choreography of immune responses works in people with mild or asymptomatic infection is particularly important as they represent the largest infected group. With this in mind, the study team set out to establish whether working adults with mild or asymptomatic infection would still show SARS-CoV-2 specific antibody and T cell responses more than four months after infection. 

They found that 16-18 weeks following infection 89% still had neutralizing antibodies capable of blocking virus entry, with 66% showing high levels. Most also had T cells capable of recognising multiple different parts of the virus. 

Overall, however, just over half of the healthcare workers had mismatched antibody and T cell responses and did not produce a T cell response specific to the virus' spike protein, with 15 per cent not producing a response to 'N', another key virus protein. 

Importantly, the team found that T cell responses tended to be higher in those with the classic, defining symptoms of COVID-19 disease in comparison to those with asymptomatic infection. Asymptomatic infection resulted in weaker T cell immunity than symptomatic infection, but equivalent neutralizing antibody responses. 

The study highlights potential issues around using simple antibody binding tests to comment on past exposure or immunity to SARS-CoV-2. For example, 16% of healthcare workers with proven infection with SARS-CoV-2 had a negative  antibody binding test four months after infection, but demonstrated potentially protective neutralizing antibodies and/or T cell responses. Also, three per cent of healthcare workers with proven infection and a positive antibody binding test had no detectable neutralizing antibodies. 

This study, published in Science Immunology, offers one of the most granular datasets yet of what happens in the most common type of SARS-CoV-2 infection – exposed asymptomatic adults or adults without severe disease or hospitalisation. For the majority of these working adults, there is evidence of immunity at 16-18 weeks comprising neutralizing antibodies (often at a level likely to protect), and this is usually complemented by multi-specific T cell responses. 

This suggests that understanding protective immunity in the population will require careful and simultaneous scrutiny of T cell and antibody responses.

With the emergence of a new SARS-CoV-2 variant, many are asking what implications this poses for immunity either after natural infection or vaccination. The results of the current study reinforce the idea that most people, even following mild infection, carry antibody and T cell immunity to many parts of the virus. While the new variant makes 17 changes to the virus' coding sequence, most aren’t necessarily within parts that will be recognised by immune cells. Therefore, the immune system will likely still be able to recognise and respond to the virus. 

Professor Marianna Fontana, principal investigator of the study site at the National Amyloidosis Centre, based at the Royal Free Hospital, said: “At the start of the pandemic we recruited staff in four days. Over 16 weeks they were swabbed, provided blood samples and answered questionnaires. There was also a follow-up visit in October. It was an incredible effort on behalf of the staff who took part and our research team. The results are important because they have helped us increase our knowledge of how our immune system responds to the virus and what long-term protection it offers.”

Members of the team who ran the study at the Royal Free Hospital - recruiting healthcare workers in just four days