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

Rationale: 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.

Objective: SARS-CoV-2 is related to 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, 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.

Study design: Observational cohort study

Study population: Observational cohort study

Intervention (if applicable): Not applicable

Main study parameters/endpoints: The cohort was previously established by Innatoss Laboratories, based on diagnostic studies. The main study parameters of the proposed study are quantification and characterization of SARS-CoV-2-specific T-cells and antibody responses post-infection and/or vaccination. COVID-19 vaccination is not part of this study, volunteers will be offered vaccination through the ongoing national vaccination programs.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: 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. The study does not result in benefits to the participating volunteers.

Virus-specific T-cell responses are more long-lived than antibody responses

3 timepoints in total: The study participants will be asked to provide three blood samples in a period of 12 months. First timepoint was a 1 year post SARS-CoV-2 infection but pre-vaccinaton timepoint, second timepoint is a post-vaccination follow-up, third timepoint is a one year later longevity sample.

The main study parameter in this study is the proportion of COVID-19 convalescent individuals with a detectable SARS-CoV-2-specific adaptive immune response (T-cell and antibody responses for various antigens) at different timepoints between year one and two post initial infection (irrespective of vaccination).

As secondary parameters in this study the quantity, phenotype and activation profile of T-cells specific for SARS-CoV-2 and HCoV will be compared at different times post SARS-CoV-2 infection and vaccination.