July 1, 2020

expert reaction to preprint paper looking at T cell response in people with mild or asymptomatic COVID-19

A preprint, an unpublished non peer-reviewed study posted on bioRxiv, looked at T cell response in people with mild or asymptomatic COVID-19.

Dr Elizabeth Bateman, Chair, Association for Clinical Biochemistry and Laboratory Medicine (ACB) Immunology Professional Committee, said:

“We welcome this study of T cell responses to SARS-CoV-2. It is important to understand how T cells respond to this virus and how this varies with severity of infection. Though this study found some people with no symptoms of COVID-19 had T cells that recognised the virus, more work is needed to show if they are protected from getting infected again, i.e.  if they are “immune”.

“T-cells are an important part of the immune system and have many different functions. They are needed to help make long-lived antibody responses. They also fight viral infections. There are T-cells that remember past infections, and can help fight it if the person catches it again. These cells can last many years, depending on the infection. It depends on the pathogen if T-cell memory alone is enough to fight the infection. T-cell immunity may vary as a person ages.

“As we learn more about SARS-CoV-2 and the immune response to it, we will be able to see how useful antibody testing and other immune responses, such as T cells are at predicting immunity. For some infections looking at the T cell response is more helpful than the antibody response, such as in Tuberculosis, where a T-cell test is used for diagnosis of latent (asymptomatic) TB.

“As T cells are such an important part of the immune system, Immunologists from across the world are looking at T cell responses to SARS-CoV-2.”

Prof Francois Balloux, Professor of Computational Systems Biology and Director of UCL Genetics Institute, University College London (UCL), said:

(Comment more generally on T-cell responses)

“Over the last weeks, a substantial amount of new evidence has become available about immunity to SARSCoV2. This information can be difficult to process and integrate.

“The immune system is highly complex and comprises a series of different arms. Innate immunity represents mostly first-line responses with no memory of prior infections. Acquired immunity can be broken down into ‘antibody-mediated’ and ‘T-cell-mediated’ immunity.

Antibody-mediated (humoral) immunity is based on B‐lymphocytes that are reactivated to produce antibodies when exposed to a pathogen upon reinfection. Until recently, all the attention in the SARSCoV2 debate has been on antibodies.

“Antibodies are fairly easy to quantify which is the basis of serological tests that inform whether someone has been infected with SARSCoV2. Though, it is becoming apparent that not everyone infected mounts detectable levels of antibodies.

“Antibody levels to SARSCoV2 also wane fairly fast, in line with other coronaviruses. As such, antibody tests can fail to detect prior infection in particular for asymptomatic or mild infections. Serological surveys may underestimate the proportion of people infected.

“T-cell-mediated immunity against SARSCoV2 has received little attention until recently. The main reasons are that T-cell response is less straightforward to measure and it is generally considered less important for vaccine efficacy.

“T-cell response is a late immune response and does not generally make the host refractory to infection. As such, a vaccine blocking infection would need to elicit a strong antibody-mediated response. Though, T-cell immunity is essential for controlling an infection and reducing symptoms. SARSCoV2 seems to elicit robust T-cell response even in asymptomatic/mild patients. There is also evidence for widespread cross-immunity with ‘common cold’ coronaviruses.

“There are four known coronaviruses (229E, NL63, OC43, and HKU1) that cause 15-30% of “common colds”. They circulate primarily in young children. Most people get infected with one or more of these viruses at some point in their lives.

“In contrast to antibody-mediated immunity, T-cell response is extremely long-lived. For example, people infected in 2003 with SARS (SARSCoV1 ) still mount a robust T-cell immune response to SARSCoV2 17 years later, which suggests they should be largely protected from developing severe symptoms when infected with SARSCoV2.

“While there is still no established case of SARSCoV2 reinfection to date, it is likely those will be observed soon due to fairly fast waning antibodies. Though, anyone with a prior exposure to SARSCoV2 is expected to experience far less severe symptoms upon reinfection.

“Most ‘hight-tech’ vaccines tend to focus on eliciting narrow antibody responses as they generally target a single SARSCoV2 protein. Such vaccines are not expected to generate a robust T-cell response. Indeed, T-cell-mediated immunity works best when a host is exposed to the entire diversity of a virus. This raises the question whether there should not be more efforts towards ‘traditional’ vaccines (i.e. attenuated/inactivated).”

Prof Danny Altmann, British Society for Immunology spokesperson and Professor of Immunology at Imperial College London, said:

“Among the many studies of cellular (T cell) immunity to SARS-CoV-2 that have appeared in the past few months, this is one of the most robust, impressive and thorough in the approaches used. It adds to the growing body of evidence that many people who were antibody-negative actually have a specific immune response as measured in T cell assays, confirming that antibody testing alone under-estimates immunity. However, the big unknown for the moment is which parameters of immunity offer the most faithful indicator of true, protective immunity from future infection. So far, there is a sense from some studies that functional, virus-neutralising antibody is one such correlate of protection. We urgently need experimental studies to help confirm whether T cell immunity alone can give protection.”

“Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19” by Takuya Sekine et al. was uploaded onto bioRxiv on 29 June.

doi: https://doi.org/10.1101/2020.06.29.174888

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www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.