COVID-19 Safe?

People who recovered from SARS 17 years ago and others who never had SARS or COVID-19 have immune cells that could provide immunity against COVID-19.

One of the mysteries of SARS-CoV-2, the virus that causes COVID-19, is the unpredictable way it affects people. Risk factors such as genes, route of infection and the immunity built up from previous viral infections are believed to influence a person’s susceptibility to becoming infected by SARS-CoV-2 and the severity of COVID-19 if they do get infected. However, much is still unknown about how these factors work to affect disease progression

A study published in the journal Nature on 20 August 2020 has characterised differences in immunity among different groups of people. This may explain some of the variation in COVID-19 severity and susceptibility from one person to the next. The authors included researchers from the Duke-NUS Medical School, led by Dr Nina Le Bert and Professor Antonio Bertoletti; the NUS Yong Loo Lin School of Medicine, with Associate Professor Tan Yee Joo and Professor Paul A. Tambyah; the National Centre for Infectious Diseases; and the Singapore General Hospital.

The researchers found that people in Singapore who had recovered from mild to severe COVID-19 or SARS had T-cells (part of our immune response, together with antibodies) that could recognise SARS-CoV-2.

The researchers found that people in Singapore who had recovered from mild to severe COVID-19 or SARS had T-cells (part of our immune response, together with antibodies) that could recognise SARS-CoV-2. People who recovered from SARS still harboured these T-cells 17 years after the infection.

SARS-CoV-2 contains both structural and nonstructural proteins (NSP). Among the structural proteins, the spike protein has been the most widely used in vaccine and antiviral drug candidates. However, to find out which SARS-CoV-2 proteins were recognised by the T-cells, the authors decided to focus on the nucleocapsid protein (NP) as well because of its abundance in the virus and its similarity across many viruses in the same class as SARS-CoV-2, such as the virus that causes the common cold.

The researchers found that all of the 36 people who had recovered from COVID-19 had T-cells that were specific for two regions of the SARS-CoV-2 NP: NP-1 and NP-2. These two regions were also recognised by the T-cells from the 23 people who had recovered from SARS 17 years earlier.

“This is a really important study to help us understand the immune response to COVID-19. Together with other studies which came out soon after, this gives us hope that there might indeed be long-lasting immunity to COVID-19, either from natural infection or a vaccine.”

— Prof Paul Tambyah, Division of Infectious Diseases, NUS Medicine

Even more striking, these NP-specific T-cells could multiply after being activated in cell culture with NP peptides. These findings suggest that previous SARS infection facilitated the production of T-cells that help to protect against or lessen the effects of SARS-CoV-2 infection, when these cells are exposed to the SARS-CoV-2-virus. In contrast, only one third of people who recovered from COVID-19 and one eighth of the SARS-recovered people produced T-cells that recognised the other type of viral protein, NSP. Currently, the reason for the difference is not clear.

To determine whether these potentially protective T-cells were present only in people who recovered from COVID-19 or SARS, the researchers also examined the T-cell response in 37 people who had not been exposed to either SARS-CoV-1 or SARS-CoV-2. Surprisingly, many of these unexposed individuals did have T-cells that were specific for SARS-CoV-2 (both NP and NSP). Strikingly, the T-cell response in these individuals was more likely to be dominated by T-cells that recognised NSP, in contrast to the NP-dominated T-cell response in people who recovered from COVID-19 or SARS.

It is possible that these unexposed individuals had not developed COVID-19 or SARS may have been exposed to common cold viruses and other related (possibly even unknown) viruses, provoking their immune systems to produce T-cells for these viruses. Some of the T-cells remained after the individuals had cleared the infection, and these T-cells were able to recognise SARS-CoV-2.

More work is needed to determine whether these differences in T-cell specificity between SARS-CoV-1/2 recovered and unexposed people are associated with different degrees of protection against COVID-19.

The study, one of the first to characterise in detail the T-cell responses against SARS-CoV-2, lays the groundwork for understanding how existing T-cell responses in people influence their susceptibility to getting infected with SARS-CoV-2, as well as the severity of the disease that they experienced if they contract COVID-19. It also shows that long-lasting T-cell immune responses can be produced from exposure to SARS-CoV-1 and the potential of a vaccine containing or expressing parts of SARS-CoV-2 or SARS-CoV-1.

“This is a really important study to help us understand the immune response to COVID-19,” said Prof Paul Tambyah from the Division of Infectious Disease at NUS Medicine. “Together with other studies which came out soon after, this gives us hope that there might indeed be long-lasting immunity to COVID-19, either from natural infection or a vaccine.”