Longevity of specific and cross-reactive cellular responses to coronaviruses in comparison to serology in COVID-19 convalescent individuals

SARS-CoV-2 is the causative agent of a pandemic of respiratory tract disease,
referred to as coronavirus disease 2019 (COVID-19). Now that several vaccines
have become available, we are entering a phase in which it is crucial to
understand SARS-CoV-2-specific immunity on the individual and population level.
Detection of SARS-CoV-2-specific immune responses relies mostly on antibody
testing. However, asymptomatic and mild cases do not always develop detectable
antibody levels and specific antibodies may not be long-lived. At the same
time, virus-specific T-cell responses appear long-lived, and detectable after
asymptomatic infection as well as after recovery from disease. Therefore,
detection of SARS-CoV-2-specific T-cells could be a valuable diagnostic marker
for prior exposure to SARS-CoV-2.

SARS-CoV-2 is related to a number of seasonal coronaviruses that have been
endemic in humans for decades and usually cause *common cold* symptoms (HCoVs).
Several studies have shown that SARS-CoV-2-specific T-cells can be detected in
individuals never exposed to SARS-CoV-2. This likely reflects the presence of
cross-reactive T-cells, i.e. T-cells induced by HCoVs that cross-recognize
SARS-CoV-2. To study SARS-CoV-2-specific immunity on the individual and
population level, it is of paramount importance that we are able to
discriminate between T-cell responses that recognize SARS-CoV-2, HCoVs or both.
To this end, we will generate and validate unique discriminatory peptide pools.
Using these peptide pools, we will study the longevity of T-cell responses in
comparison to antibody responses in a well-defined cohort of convalescent
COVID-19 patients from the first wave of the COVID-19 pandemic.

Observational cohort study

The study participants will be asked to provide three blood samples in a period
of 12 months (in total 165ml). Venepunctures will be performed by trained
phlebotomists and pose a minimal risk. Participation will require three visits
of max. 20 minutes each. In addition, individuals will be asked prior to each
blood collection time point to answer a short list of questions to capture
relevant clinical details on SARS-CoV-2 re-infections and/or vaccination.