tetano
Editor, Senior Moderator
Cell Rep
. 2022 May 25;110945.
doi: 10.1016/j.celrep.2022.110945. Online ahead of print.
Baricitinib attenuates the proinflammatory phase of COVID-19 driven by lung-infiltrating monocytes
Brian Dobosh[SUP] 1 [/SUP], Keivan Zandi[SUP] 2 [/SUP], Diego Moncada Giraldo[SUP] 1 [/SUP], Shu Ling Goh[SUP] 2 [/SUP], Kathryn Musall[SUP] 2 [/SUP], Milagros Aldeco[SUP] 1 [/SUP], Julia LeCher[SUP] 2 [/SUP], Vincent D Giacalone[SUP] 1 [/SUP], Junkai Yang[SUP] 3 [/SUP], Devon J Eddins[SUP] 3 [/SUP], Manoj Bhasin[SUP] 4 [/SUP], Eliver Ghosn[SUP] 3 [/SUP], Vikas Sukhatme[SUP] 5 [/SUP], Raymond F Schinazi[SUP] 2 [/SUP], Rabindra Tirouvanziam[SUP] 6 [/SUP]
Affiliations
Abstract
SARS-CoV-2-infected subjects are generally asymptomatic during initial viral replication but may suffer severe immunopathology after the virus has receded and monocytes have infiltrated the airways. In bronchoalveolar lavage fluid from severe COVID-19 patients, monocytes express mRNA encoding inflammatory mediators and contain SARS-CoV-2 transcripts. We leverage a human small airway model of infection and inflammation, whereby primary blood monocytes transmigrate across SARS-CoV-2-infected lung epithelium to characterize viral burden, gene expression, and inflammatory mediator secretion by epithelial cells and monocytes. In this model, lung-infiltrating monocytes acquire SARS-CoV-2 from the epithelium and upregulate expression and secretion of inflammatory mediators, mirroring in vivo data. Combined use of baricitinib (Janus kinase inhibitor) and remdesivir (nucleoside analog) enhances antiviral signaling and viral clearance by SARS-CoV-2-positive monocytes while decreasing secretion of proneutrophilic mediators associated with acute respiratory distress syndrome. These findings highlight the role of lung-infiltrating monocytes in COVID-19 pathogenesis and their importance as a therapeutic target.
Keywords: CP: Immunology; CP: Microbiology; Janus kinase; RNA-seq; cytokine release syndrome; inflammation; interferon; therapy.
. 2022 May 25;110945.
doi: 10.1016/j.celrep.2022.110945. Online ahead of print.
Baricitinib attenuates the proinflammatory phase of COVID-19 driven by lung-infiltrating monocytes
Brian Dobosh[SUP] 1 [/SUP], Keivan Zandi[SUP] 2 [/SUP], Diego Moncada Giraldo[SUP] 1 [/SUP], Shu Ling Goh[SUP] 2 [/SUP], Kathryn Musall[SUP] 2 [/SUP], Milagros Aldeco[SUP] 1 [/SUP], Julia LeCher[SUP] 2 [/SUP], Vincent D Giacalone[SUP] 1 [/SUP], Junkai Yang[SUP] 3 [/SUP], Devon J Eddins[SUP] 3 [/SUP], Manoj Bhasin[SUP] 4 [/SUP], Eliver Ghosn[SUP] 3 [/SUP], Vikas Sukhatme[SUP] 5 [/SUP], Raymond F Schinazi[SUP] 2 [/SUP], Rabindra Tirouvanziam[SUP] 6 [/SUP]
Affiliations
- PMID: 35688145
- PMCID: PMC9130711
- DOI: 10.1016/j.celrep.2022.110945
Abstract
SARS-CoV-2-infected subjects are generally asymptomatic during initial viral replication but may suffer severe immunopathology after the virus has receded and monocytes have infiltrated the airways. In bronchoalveolar lavage fluid from severe COVID-19 patients, monocytes express mRNA encoding inflammatory mediators and contain SARS-CoV-2 transcripts. We leverage a human small airway model of infection and inflammation, whereby primary blood monocytes transmigrate across SARS-CoV-2-infected lung epithelium to characterize viral burden, gene expression, and inflammatory mediator secretion by epithelial cells and monocytes. In this model, lung-infiltrating monocytes acquire SARS-CoV-2 from the epithelium and upregulate expression and secretion of inflammatory mediators, mirroring in vivo data. Combined use of baricitinib (Janus kinase inhibitor) and remdesivir (nucleoside analog) enhances antiviral signaling and viral clearance by SARS-CoV-2-positive monocytes while decreasing secretion of proneutrophilic mediators associated with acute respiratory distress syndrome. These findings highlight the role of lung-infiltrating monocytes in COVID-19 pathogenesis and their importance as a therapeutic target.
Keywords: CP: Immunology; CP: Microbiology; Janus kinase; RNA-seq; cytokine release syndrome; inflammation; interferon; therapy.