{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:12:55Z","timestamp":1787242375085,"version":"build-2736575974"},"reference-count":65,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T00:00:00Z","timestamp":1710892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Western Institute of Veteran Research, Warren 805","award":["Warren 805"],"award-info":[{"award-number":["Warren 805"]}]},{"name":"Western Institute of Veteran Research, Warren 805","award":["IK2 BX4004219"],"award-info":[{"award-number":["IK2 BX4004219"]}]},{"name":"Department of Veteran Affairs","award":["Warren 805"],"award-info":[{"award-number":["Warren 805"]}]},{"name":"Department of Veteran Affairs","award":["IK2 BX4004219"],"award-info":[{"award-number":["IK2 BX4004219"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>SARS-CoV-2 infection has claimed just over 1.1 million lives in the US since 2020. Globally, the SARS-CoV-2 respiratory infection spread to 771 million people and caused mortality in 6.9 million individuals to date. Much of the early literature showed that SARS-CoV-2 immunity was defective in the early stages of the pandemic, leading to heightened and, sometimes, chronic inflammatory responses in the lungs. This lung-associated \u2018cytokine storm\u2019 or \u2018cytokine release syndrome\u2019 led to the need for oxygen supplementation, respiratory distress syndrome, and mechanical ventilation in a relatively high number of people. In this study, we evaluated circulating PBMC from non-hospitalized, male and female, COVID-19+ individuals over the course of infection, from the day of diagnosis (day 0) to one-week post diagnosis (day 7), and finally 4 weeks after diagnosis (day 28). In our early studies, we included hospitalized and critically care patient PBMC; however, most of these individuals were lymphopenic, which limited our assessments of their immune integrity. We chose a panel of 30 interferon-stimulated genes (ISG) to evaluate by PCR and completed flow analysis for immune populations present in those PBMC. Lastly, we assessed immune activation by stimulating PBMC with common TLR ligands. We identified changes in innate cells, primarily the innate lymphoid cells (ILC, NK cells) and adaptive immune cells (CD4+ and CD8+ T cells) over this time course of infection. We found that the TLR-7 agonist, Resiquimod, and the TLR-4 ligand, LPS, induced significantly better IFN\u03b1 and IFN\u03b3 responses in the later phase (day 28) of SARS-CoV-2 infection in those non-hospitalized COVID-19+ individuals as compared to early infection (day 0 and day 7). We concluded that TLR-7 and TLR-4 agonists may be effective adjuvants in COVID-19 vaccines for mounting immunity that is long-lasting against SARS-CoV-2 infection.<\/jats:p>","DOI":"10.3390\/v16030472","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T05:56:07Z","timestamp":1710914167000},"page":"472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Evaluation of Type 1 Interferon Related Genes in Male and Female-Matched, SARS-CoV-2 Infected Individuals Early in the COVID-19 Pandemic"],"prefix":"10.3390","volume":"16","author":[{"given":"Tom P.","family":"Huecksteadt","sequence":"first","affiliation":[{"name":"Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Myers","sequence":"additional","affiliation":[{"name":"Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA"},{"name":"Department of Neurology, University of Utah, Salt Lake City, UT 84132, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel E.","family":"Aamodt","sequence":"additional","affiliation":[{"name":"Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA"},{"name":"Department of Internal Medicine, Pulmonary Division, University of Utah Health Science Center, Salt Lake City, UT 84132, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhanshi","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA"},{"name":"Department of Internal Medicine, Pulmonary Division, University of Utah Health Science Center, Salt Lake City, UT 84132, USA"},{"name":"Division of Infectious Diseases, University of Utah, Salt Lake City, UT 84132, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi J.","family":"Warren","sequence":"additional","affiliation":[{"name":"Salt Lake City VA Medical Center, Salt Lake City, UT 84148, USA"},{"name":"Department of Internal Medicine, Pulmonary Division, University of Utah Health Science Center, Salt Lake City, UT 84132, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s40121-020-00352-z","article-title":"Chest CT Features of 182 Patients with Mild Coronavirus Disease 2019 (COVID-19) Pneumonia: A Longitudinal, Retrospective and Descriptive Study","volume":"9","author":"Liu","year":"2020","journal-title":"Infect. 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