Whole-Blood Cellular Responses: A Promising Indicator of SARS-CoV-2 Immunity Compared to Serology.

Background

Currently available immunological tests for SARS-CoV-2 assess only antibody responses. Despite the growing evidence that T cells play a crucial role in protection, especially against emerging viral variants, no routine test is available to determine T cell immunity. The prognostic value of SARS-CoV-2-specific antibodies for determining whether individuals are immune and protected against disease remains uncertain. This is in part due to the following: (a) specificity and limitations such as the sensitivity of antibody tests, and (b) the lack of correlation between antibody titers (quantity) and the antiviral function of antibodies (quality). Approximately a quarter of SARS-CoV-2-infected patients with symptoms fail to show seroconversion in serological assays.

Methods

The current report describes the development and application of a whole-blood-based assay to detect previous exposure to SARS-CoV-2. Whole blood is stimulated with SARS-CoV-2-derived peptides identified during assay development and stimulation-induced cytokines quantified using a multiplex testing platform. The resulting cytokine profiles are generated using computational tools to identify previous exposure to the virus.

Results

The application of the assay revealed a lack of self-awareness of individuals' COVID-19 infection history and demonstrated the value of this new assay to assess the prevalence of SARS-CoV-2 exposure history and immunity in populations.

Conclusions

Positive responses in this assay can facilitate the identification of underlying causes of unexplained symptoms and provide clinically actionable insights for healthcare applications, including in the continued conundrum of post-acute sequela of SARS-CoV-2 infection (PASC or "long COVID"), for which both diagnosis and management remain challenging.