{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:42:16Z","timestamp":1784025736961,"version":"3.55.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hyper-inflammatory immune response, a hallmark of severe COVID-19, is associated with increased mortality. Acute respiratory distress syndrome (ARDS) is a common manifestation. We undertook two phase I\/II studies in five and then 16 subjects with severe\/critical COVID-19 to assess the safety and preliminary efficacy of apoptotic cells (Allocetra\u2122-OTS, Enlivex Therapeutics), a cellular immunomodulatory therapy that reprograms macrophages to reduce hyper-inflammatory response severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eligible patients presenting to the Emergency Room with severe COVID-19 and respiratory dysfunction received one intravenous administration of Allocetra\u2122-OTS and were monitored for adverse events (AEs) for 28 days. The primary aim was to determine the safety profile of treatment; secondary aims were recovery from ARDS, intensive care unit (ICU) and hospital length-of-stay, and mortality. Immune modulator markers were measured to elucidate the mechanism of action of Allocetra\u2122-OTS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>21 patients with severe-critical COVID-19 of Gamma, Alpha and Delta variants, were treated with a single dose of apoptotic cells. 19\/21 patients had mild-to-severe ARDS at presentation. Median age was 53 years, 16\/21 were males, 16\/21 were overweight\/obese. No serious related adverse events (SAEs) were reported. All 21 study subjects survived to day 28 (end of study); 19\/21 recovered completely. Comparable mortality rates at the hospital were 3.8%\u22128.9% for age- and gender-matched patients, and 39%\u221255% for critical patients. Recovering patients exhibited rapid ARDS resolution and parallel resolution of inflammation markers and elevated cytokines\/chemokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with severe\/critical COVID-19 associated with ARDS, Allocetra\u2122-OTS was safe, well-tolerated, and showed promising results for resolution of respiratory failure and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p><jats:ext-link>https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT04513470<\/jats:ext-link>, <jats:ext-link>https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT04590053<\/jats:ext-link>, Identifiers NCT04513470, NCT04590053.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1242551","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T10:14:02Z","timestamp":1690971242000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Apoptotic cells for treatment of acute respiratory distress syndrome associated with COVID-19"],"prefix":"10.3389","volume":"14","author":[{"given":"Peter Vernon","family":"van 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