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Data from patients with severe clinical manifestations compared to patients with mild symptoms indicate that highly dysregulated exuberant inflammatory responses correlate with severity of disease and lethality. Epithelial-immune cell interactions and elevated cytokine and chemokine levels, i.e. cytokine storm, seem to play a central role in severity and lethality in COVID-19. The present perspective places a central cellular pro-inflammatory signal pathway, NF-\u03baB, in the context of recently published data for COVID-19 and provides a hypothesis for a therapeutic approach aiming at the simultaneous inhibition of whole cascades of pro-inflammatory cytokines and chemokines. The simultaneous inhibition of multiple cytokines\/chemokines is expected to have much higher therapeutic potential as compared to single target approaches to prevent cascade (i.e. redundant, triggering, amplifying, and synergistic) effects of multiple induced cytokines and chemokines in critical stage COVID-19 patients.<\/jats:p>","DOI":"10.3389\/fimmu.2020.598444","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T09:50:43Z","timestamp":1608285043000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":189,"title":["NF-\u03baB Pathway as a Potential Target for Treatment of Critical Stage COVID-19 Patients"],"prefix":"10.3389","volume":"11","author":[{"given":"Ralf","family":"Kircheis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Haasbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lueftenegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willm T.","family":"Heyken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Ocker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Planz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30076-X","article-title":"Pathological findings of COVID-19 associated with acute respiratory distress syndrome","volume":"8","author":"Xu","year":"2020","journal-title":"Lancet Resp Lancet Respir Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.04.021","article-title":"Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis","volume":"81","author":"Zheng","year":"2020","journal-title":"J Infect"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1101\/2020.04.19.20054262","article-title":"Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study","volume":"20","author":"Carsana","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVOD-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"New Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.02.042","article-title":"Proteasome inhibition by peptide-semicarbazones","volume":"16","author":"Leban","year":"2008","journal-title":"Bioorg Med Chem"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0311-8","article-title":"The trinity of COVID-19: immunity, inflammation and intervention","volume":"20","author":"Tay","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0312-7","article-title":"COVID-19: risk for cytokine targeting in chronic inflammatory diseases","volume":"20","author":"Schett","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb8925","article-title":"Cytokine release syndrome in severe COVID-19. 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