Infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2) triggers a series of defense mechanisms in the human body which are collectively known as the adaptive immune response. Adaptive immune response can be subdivided into humoral or antibody-based immune response and cellular immune response, which is mediated by specific immune cells.

To study: Concordance of B and T cell responses to SARS-CoV-2 infection, regardless of symptoms suggestive of COVID-19. Image Credit: Cristoph Burgstedt / Shutterstock.com

Fund

Humoral immunity begins to develop two to three weeks after infection. The initial stage of this immune response is marked by the production of immunoglobulin M (IgM), followed by IgG within a few days. The most common antibody target is the SARS-CoV-2 spike protein, which is also the primary target of current coronavirus disease 2019 (COVID-19) vaccines; however, neutralizing antibodies produced by the humoral immune response can also target the viral nucleocapsid protein.

Measuring the neutralizing antibody response helps assess the virus-fighting potential of an individual’s convalescent serum. The cellular response, for its part, completes the humoral arm of the immune response, using specific immune cells including T lymphocytes, in particular CD4⁺ subset T.

Acute COVID-19 elicits antibody responses in most patients. However, a subset of patients who have had symptoms suggestive of COVID-19, as well as some “long COVID” patients, do not have detectable levels of antibodies. A possible explanation for this lack of detectable antibody levels could be the lack of sensitivity and specificity of the test methods used to measure these antibodies, as well as the possibility that antibody levels may decline over time.

In a recent study published on the preprint server medRxiv,* researchers are assessing a possible correlation between humoral and cell-mediated responses to SARS-CoV-2 in symptomatic and asymptomatic individuals in the UK.

About the study

In the current study, the researchers collected data from the TwinsUK Cohort and the COVID Symptom Study (CSS) Cohort. TwinsUK has over 14,000 registered people, including over 7,000 twins.

A total of 431 people from the TwinsUK cohort participated in a home visiting study between May 2020 and June 2020. Of these 431 home visiting study participants, 384 had also participated sufficiently in CSS. The CSS data was used to form a ‘symptom score’, with a scale ranging from 0 to 1.0. A score above 0.5 on this scale indicates “symptom positive” COVID-19.

All participants were grouped into four categories based on symptom score and anti-spike IgG antibody responses from the initial home visit. The groups were composed of individuals who were “symptom positive” for COVID-19 and had a positive antibody response (group 1), individuals who were “symptom positive” for COVID-19 but negative for antibodies (group 2) , of individuals who were “symptom negative” for COVID-19 with a positive antibody response, thus indicating asymptomatic infection (group 3), and individuals who were “symptom negative” for COVID-19 and antibody negative, implying the healthy control group (Group 4).

At the end of the study, nine people were included in group 1, 12 people were included in group 2, groups 3 and 4 consisting of six and five people respectively.

All study participants provided their sera to analyze for peak and nucleocapsid antibody levels, as well as their T-cell responses. On their second visit, participants again provided serum samples, which were used to isolate peripheral blood mononuclear cells (PBMC) and repeat antibody assays.

Study results

None of the 17 antibody-negative individuals, which included those in groups 2 and 4, showed a T-cell response when their sera were tested against pools of antigens corresponding to SARS matrix and nucleocapsid proteins. -CoV-2, as well as the S1 and S2 domains of the spike protein. In comparison, 14 out of 15 people who were positive for the antibodies showed a clear T cell-mediated immune response against these viral antigens.

The researchers also found that anti-spike IgG levels were strongly correlated with helper T cell responses compared to their levels associated with regulatory T cells. Although this response is not surprising, since T helper cells play an important role in generating B cell antibody responses, a strong correlation between T helper and T-regulatory responses was also observed.

Notably, not all antibody-negative individuals also exhibited a T-cell response to SARS-CoV-2 infection, whether or not they reported experiencing COVID-19-like symptoms.

Consequences

The observed strong correlation between anti-spike IgG levels and T-cell responses demonstrates that T-cell testing is unlikely to add information regarding individual immunity to SARS-CoV-2 when it is tested. is used in addition to measuring levels of neutralizing antibodies. However, since T cell responsiveness and antibody levels may differ at later time points, it may be useful for researchers to assess how the T cell response compares to the decline in antibody levels after several months after infection and/or vaccination.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.