{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:34:36Z","timestamp":1768466076758,"version":"3.49.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"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>Introduction<\/jats:title><jats:p>In the present study, the impact of BromAc\u00ae, a specific combination of bromelain and acetylcysteine, on the SARS-CoV-2-specific inflammatory response was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An in vitro stimulation system was standardized using blood samples from 9 healthy donors, luminex assays and flow cytometry were performed. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>BromAc\u00ae demonstrated robust anti-inflammatory activity in human peripheral blood cells upon SARS-CoV-2 viral stimuli, reducing the cytokine storm, composed of chemokines, growth factors, and proinflammatory and regulatory cytokines produced after short-term in vitro culture with the inactivated virus (iSARS-CoV-2). A combined reduction in vascular endothelial growth factor (VEGF) induced by SARS-CoV-2, in addition to steady-state levels of platelet recruitment-associated growth factor-PDGFbb, was observed, indicating that BromAc\u00ae may be important to reduce thromboembolism in COVID-19. The immunophenotypic analysis of the impact of BromAc\u00ae on leukocytes upon viral stimuli showed that BromAc\u00ae was able to downmodulate the populations of CD16+ neutrophils and CD14+ monocytes observed after stimulation with iSARS-CoV-2. Conversely, BromAc\u00ae treatment increased steady-state HLA-DR expression in CD14+ monocytes and preserved this activation marker in this subset upon iSARS-CoV-2 stimuli, indicating improved monocyte activation upon BromAc\u00ae treatment. Additionally, BromAc\u00ae downmodulated the iSARS-CoV-2-induced production of TNF-a by the CD19+ B-cells. System biology approaches, utilizing comprehensive correlation matrices and networks, showed distinct patterns of connectivity in groups treated with BromAc\u00ae, suggesting loss of connections promoted by the compound and by iSARS-CoV-2 stimuli. Negative correlations amongst proinflammatory axis and other soluble and cellular factors were observed in the iSARS-CoV-2 group treated with BromAc\u00ae as compared to the untreated group, demonstrating that BromAc\u00ae disengages proinflammatory responses and their interactions with other soluble factors and the axis orchestrated by SARS-CoV-2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results give new insights into the mechanisms for the robust anti-inflammatory effect of BromAc\u00ae in the steady state and SARS-CoV-2-specific immune leukocyte responses, indicating its potential as a therapeutic strategy for COVID-19.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1308477","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T04:27:59Z","timestamp":1702441679000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Taming the 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