Another study finds cross-reactivity T cell responses against SARS-CoV-2

By Lakshmi Supriya, PhD.Oct 5 2020

Using ELISpot and proliferation assays, researchers show strong responses in SARS-CoV-2 infected patients, but not so much in negative samples. However, there may be cross-reactive T cell responses from other human coronaviruses.

COVID-19, a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading rapidly worldwide in the last ten months. One characteristic of this disease has been the severity of symptoms, often fatal, on one end, and asymptomatic patients, showing no symptoms on the other end. This has led to great efforts to understand how the immune system responds to the virus.

To better understand this, one approach has been to look at the antibodies generated by the immune system. However, there is significant variability in the extent and duration of antibodies seen in infected patients.

Another approach has been to look at the response of T-cells, a type of white blood cell that is a vital part of the immune response. Studies have reported T cell responses to the SARS-CoV-2 virus in almost all cases.

In addition, researchers are also interested in understanding if prior exposure to other human coronaviruses affects the T cell response. A prior study showed reactive responses to SARS-CoV-2 in people who had been infected with SARS-CoV before.

However, different studies have reported different levels of cross-reactive immunity to human coronavirus in people that were unexposed to SARS-CoV-2 ranging from 0–50%.

Study: T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses. Image Credit: Design_Cells / Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Immune response in recovered COVID-19 patients

In the new study published on the preprint server medRxiv*, researchers tried to understand if there were different levels of T cell responses among people with COVID-19 and those without, and if T cell responses can differentiate between people infected by SARS-CoV-2 and other seasonal human coronaviruses.

First, the researchers examined the T cell response using ELISpot assay in 168 people with confirmed SARS-CoV-2 infection and 111 negative samples. They saw interferon-g (IFN-g), a cytokine important in immunity, responses in the convalescent patients to the spike protein, and the structural and accessory proteins of SARS-CoV-2.

However, there was a significant difference in the level of IFN-g response between patients with symptoms and asymptomatic patients, with a more significant response in patients who reported having a fever.

A fever suggests a more significant system response to the virus, and such people may mount a more vigorous T cell response. This may be a result of the early immune system not being able to control the infection, requiring the need for a larger adaptive response.

Although the levels of CD4+ and CD8+ T cells were varied in the different pools for testing response to the structural and accessory proteins, both types of T cells were present in patients infected with SARS-CoV-2. Responses to the M and NP proteins were exceptionally high. These could potentially be used as antigens in testing populations for T cell immunity after SARS-CoV-2 infection.

Previous studies have indicated that the antibodies to SARS-CoV-2 may be short-lived. The T cell responses in this study suggest a peak in the T cell response 4 weeks after symptoms are seen.

T cell response in SAR-CoV-2 negative people

In people who tested negative for SARS-CoV-2, there was no T cell response to the spike protein and structural and accessory proteins in 48 people. However, in 20 people, there were high levels of CD4+ and CD8+ cells, responding to the S1 and S2 subunits of the spike protein, which the authors found using a proliferation assay. There were no or weak responses to the structural and accessory proteins.

The researchers also analyzed cryopreserved samples from before COVID-19. Similar to the COVID-19 seronegative samples, these samples also showed poor T cell response to spike, structural, or accessory proteins, but showed responses to the S1 and S2 proteins.

Responses to M and NP proteins were lesser than those for COVID-19 convalescent patients. Hence, these antigens could be used as markers for T cell response to SARS-CoV-2.

These results suggest people retained cross-reactive central memory responses to spike proteins of other seasonal coronaviruses present in the UK. It is also likely that there is cross-reactivity from other viruses.

While there is a correlation between antibody tests and the ELISpot test in SARS-CoV-2 positive patients, there is a difference in samples that were negative or unexposed to SARS-CoV-2, as there is a strong response to spike proteins in these samples. The authors write that further testing will need to be done to understand this.

Based on these results, the authors write that the ELISpot assay can be used to identify immune responses specific to SARS-CoV-2.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources