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Cryopreserved T Cells Hold Answers to COVID-19 Immunity

Feb 16, 2021 10:05:00 AM / by Nancy Andon, MSc

AdobeStock_329121451-1In a recent publication, researchers at Cellular Technology Ltd. in the U.S., and Complutense University in Madrid, Spain cites using cryopreserved PBMCs from HemaCare for their COVID-19 research. [1]

The scientific group set out to answer one of the most important questions of the COVID-19 pandemic - how can we truly know whether someone has been exposed to the virus?

Widespread COVID-19 testing is helping governments and healthcare workers track the spread of the virus in an ongoing effort to isolate those who may be contagious from those who have not been exposed. However, most people exposed to SARS-CoV-2, the virus responsible for COVID-19, experience mild disease or are asymptomatic. This means that the presence of SARS-CoV-2-specific antibodies may fade quickly after infection, increasing the chance of a false-negative test result.

Since antibody detection proved not to be ideal for COVID-19 testing, scientists have been investigating the possibility of using the presence of SARS-CoV-2 specific T cell memory cell response as a more reliable means of determining previous exposure to the virus. Unfortunately, recent studies show that cross-reactivity with related yet harmless types of coronavirus, such as those that cause the common cold, are present in most individuals and can muddy test results.

In this current publication, scientists may finally have found an answer to this conundrum. The research group realized that if they could distinguish between cross-reactive T cells and T cells that were truly specific for SARS-CoV-2, they could reliably determine which individuals had been infected with COVID-19 and elucidate their current immune protective status.

However, before this research could be carried out, the researchers faced another imposing challenge - getting access to healthy donor material in the middle of a pandemic and making sure those donors had never been exposed to the SARS-CoV-2 virus. The solution to both requirements lay in using pre-pandemic cryopreserved donor cells.

Cryopreserved donor material has been critically important to research and medicine during the COVID-19 pandemic. As we have discussed previously, restricted access to healthy donors could easily have resulted in a crisis of biomedical shortages and delayed cell-based treatments. Instead, many labs and hospitals turned to cryopreserved materials to help meet their demands.

Cryopreserved T Cells Blog Feb 2021All living cells are highly temperature-sensitive, so COVID-19 impacts on shipping logistics continue to be a significant risk to cell viability and clinical efficacy of any cell-based product. Cryopreservation preserves the stability of cell-based products and grants researchers the ability to stockpile critical cellular starting materials for future use.

Even prior to the current pandemic, cryopreservation has been acknowledged as a logistical necessity for long-distance shipping. The technique allows for “off-the-shelf” deployment of cellular products, which is often necessary to support complicated, unpredictable schedules.

For the purposes of this study, the scientists sourced their starting materials from HemaCare, which maintains an extensive bank of cryopreserved cells, including GMP-compliant cells suitable to clinical and pre-clinical studies. The group acquired PBMCs collected from healthy donors prior to the COVID-19 outbreak. These cells would be used to compare with cryopreserved PBMCs collected from donors 2 weeks to 3 months after recovering from COVID-19 infection.

PBMCs are often used as a convenient and efficient way to enrich for T cells, since T cell subtypes make up 45-70% of the total PBMC population. The researchers set out to characterize T cell memory response to SARS-CoV-2 antigens in both donor groups. They chose Immunospot analysis to identify SARS-CoV-2-specific T cell memory cells due to the assay’s established sensitivity; SAR-CoV-2 specific T cell memory cells occur at low frequencies compared to the response induced by many more common viruses. The Immunospot assay is designed to detect any antigen-specific T cells present in the PMBC population that are actively producing cytokines.

To account for the presence of non-specific cross-reactivity, the scientists first documented memory T cell reactivity to mega-peptide pools composed of hundreds of peptides covering all possible T cell recognition epitopes within the SARS-CoV-2 virus. They would then be able to compare responses of the naïve T cell population of pre-pandemic donors to the T cell response of donors whom they knew had been exposed to COVID-19.

The results showed the experiments to be a success. In a blinded study, the research group could clearly distinguish between pre-pandemic cross-reactivity and SARS-CoV-2 specific responses from individuals who had been exposed to COVID-19. This work should lead to more accurate COVID-19 testing, as well as furthering scientific understanding of COVID-19 immune response and immune protective status.

To learn more about cryopreserved HemaCare starting materials, please visit our website here.


  1. Lehmann P. et al. Deconvoluting the T cell response to SARS-CoV-2: specificity versus chance- and cognate cross-reactivity. Cold Spring Harbor Laboratory-bioRxiv preprint. Nov 2020.

Topics: PBMCs, T Cells

Nancy Andon, MSc

Written by Nancy Andon, MSc

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