Post-COVID-19 surveillance: To establish T cell assays for assessing T cell responses and identify individual and immunological factors that account for different disease outcomes

Study code
NBR87

Lead researcher
Dr Nyarie Sithole

Study type
Samples and data

Institution or company
Cambridge University Hospital NHS Foundation Trust

Researcher type
Academic

Speciality area
Infection, COVID

Summary

The current COVID-19 pandemic, which is caused by coronavirus, SARS-CoV-2 has already infected close to eleven and half million people and claimed over half a million lives. Hardly anything is yet known regarding the medium to long term sequelae of COVID-19, the different immunological responses and their contribution or lack of, to prolonged symptoms.  During the initial phase, COVID-19 has been shown to be driven primarily by the viral infection and later by the immune response.  What is surprising and not well understood is a sub-group of COVID-19 patients who do not appear to produce antibodies to the virus; it is not known whether they generate cellular immune response (T cells) to SARS-CoV-2. There is also a significant group of patients with clinical history/symptoms highly suggestive of COVID-19 infection who are being referred from the primary care with persistent post-viral symptoms; these patients never had a SARS-CoV-2 swab test done at the appropriate time in the trajectory of their illness. The current challenge is how to retrospectively determine whether the cause of the initial illness was due to SARS-CoV-2 infection, especially in those who are seronegative for the virus - serological assays can have limited sensitivity and specificity, often depending on the target antigen.   There is also a significant group of patients with clinical history/symptoms highly suggestive of COVID-19 infection who are being referred from the primary care with persistent post-viral symptoms; these patients never had a SARS-CoV-2 swab test done at the appropriate time in the trajectory of their illness. The current challenge is how to retrospectively determine whether the cause of the initial illness was due to SARS-CoV-2 infection, especially in those who are seronegative for the virus - serological assays can have limited sensitivity and specificity, often depending on the target antigen.  In collaboration with other researchers, I will utilise the vast expertise available in Cambridge to explore these important research questions to better understand disease progression and identify ways to mitigate COVID-19 disease.

The hypotheses I am working with is that we can utilise T cell assays to retrospectively diagnose exposure or previous infection with SARS-CoV-2 and, also, to better understand T cell response in COVID-19 infection. There is proof of concept in retrospectively diagnosing exposure or previous infection based on cellular immune responses in Mycobacterium Tuberculosis and T cell responses to SARS-CoV-2 have been detected in seronegative patient. Therefore, our work may potentially lead to a clinical diagnostic test.