{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:30:59Z","timestamp":1789587059836,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000090","name":"\u201cCongressionally directed medical research program\u201d (CDMRP) discovery award","doi-asserted-by":"publisher","award":["PR211676"],"award-info":[{"award-number":["PR211676"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCM"],"abstract":"<jats:p>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\u2019 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 \u201clong COVID\u201d), for which both diagnosis and management remain challenging.<\/jats:p>","DOI":"10.3390\/jcm14196889","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T09:12:23Z","timestamp":1759223543000},"page":"6889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Whole-Blood Cellular Responses: A Promising Indicator of SARS-CoV-2 Immunity Compared to Serology"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0005-9985","authenticated-orcid":false,"given":"Lucas M.","family":"Zhou","sequence":"first","affiliation":[{"name":"Immunology Core, Biologics Research & Development, Walter Reed Army Institute of Research\u2014WRAIR, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth H.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Immunology Core, Biologics Research & Development, Walter Reed Army Institute of Research\u2014WRAIR, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupsa C.","family":"Boelig","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research\u2014WRAIR, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Currier","sequence":"additional","affiliation":[{"name":"Viral Diseases Branch, Walter Reed Army Institute of Research\u2014WRAIR, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8571-8956","authenticated-orcid":false,"given":"Elke S.","family":"Bergmann-Leitner","sequence":"additional","affiliation":[{"name":"Immunology Core, Biologics Research & Development, Walter Reed Army Institute of Research\u2014WRAIR, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mushtaq, M.Z., Shakoor, S., Kanji, A., Shaheen, N., Nasir, A., Ansar, Z., Ahmed, I., Mahmood, S.F., Hasan, R., and Hasan, Z. 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