TY - JOUR
T1 - Comprehensive immunologic evaluation of bronchoalveolar lavage samples from human patients with moderate and severe seasonal influenza and severe covid-19
AU - Reynolds, Daniel
AU - Guillamet, Cristina Vazquez
AU - Day, Aaron
AU - Borcherding, Nicholas
AU - Guillamet, Rodrigo Vazquez
AU - Choreño-Parra, José Alberto
AU - House, Stacey L.
AU - O'Halloran, Jane A.
AU - Zúniga, Joaquín
AU - Ellebedy, Ali H.
AU - Byers, Derek E.
AU - Mudd, Philip A.
N1 - Funding Information:
This work was supported by grants from the Barnes Jewish Hospital Foundation awarded to P.A.M. and C.V.G. and by a grant from the Washington University Institute of Clinical and Translational Sciences awarded to P.A.M. The Washington University Institute of Clinical and Translational Sciences is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Office of Extramural Research, National Institutes of Health grant UL1TR002345. The content is solely the responsibility of the authors and does not necessarily represent the official
Funding Information:
view of the National Institutes of Health. Cytokine measurements were supported, in part, by the Bursky Center for Human Immunology and Immunotherapy Programs at Washington University, Immunomonitoring Laboratory. This project also received funding from the National Council of Science and Technology of Mexico (CONACyT) under the research contracts: SECTEI/050/2020, Secretaría de Ciencia, Tecnología e Innovación de la Ciudad de México (SECTEI CDMX); FORDECYT/10SE/2020/05/ 14-06 and FORDECYT/10SE/2020/05/14-07.
Publisher Copyright:
© 2021 by TheAmericanAssociation of Immunologists, Inc.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or seasonal influenza may lead to respiratory failure requiring intubation and mechanical ventilation. The pathophysiology of this respiratory failure is attributed to local immune dysregulation, but how the immune response to viral infection in the lower airways of the human lung differs between individuals with respiratory failure and those without is not well understood. We used quantitative multiparameter flow cytometry and multiplex cytokine assays to evaluate matched blood and bronchoalveolar lavage (BAL) samples from control human subjects, subjects with symptomatic seasonal influenza who did not have respiratory failure, and subjects with severe seasonal influenza or SARS-CoV-2 infection with respiratory failure. We find that severe cases are associated with an influx of nonclassical monocytes, activated T cells, and plasmablast B cells into the lower airways. Cytokine concentrations were not elevated in the lower airways of moderate influenza patients compared with controls; however, 28 of 35 measured cytokines were significantly elevated in severe influenza, severe SARS-CoV-2 infection, or both. We noted the largest elevations in IL-6, IP-10, MCP-1, and IL-8. IL-1 family cytokines and RANTES were higher in severe influenza infection than severe SARS-CoV-2 infection. Interestingly, only the concentration of IP-10-correlated between blood and BAL during severe infection. Our results demonstrate inflammatory immune dysregulation in the lower airways during severe viral pneumonia that is distinct from lower airway responses seen in human patients with symptomatic, but not severe, illness and suggest that measurement of blood IP-10 concentration may predict this unique dysregulation.
AB - Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or seasonal influenza may lead to respiratory failure requiring intubation and mechanical ventilation. The pathophysiology of this respiratory failure is attributed to local immune dysregulation, but how the immune response to viral infection in the lower airways of the human lung differs between individuals with respiratory failure and those without is not well understood. We used quantitative multiparameter flow cytometry and multiplex cytokine assays to evaluate matched blood and bronchoalveolar lavage (BAL) samples from control human subjects, subjects with symptomatic seasonal influenza who did not have respiratory failure, and subjects with severe seasonal influenza or SARS-CoV-2 infection with respiratory failure. We find that severe cases are associated with an influx of nonclassical monocytes, activated T cells, and plasmablast B cells into the lower airways. Cytokine concentrations were not elevated in the lower airways of moderate influenza patients compared with controls; however, 28 of 35 measured cytokines were significantly elevated in severe influenza, severe SARS-CoV-2 infection, or both. We noted the largest elevations in IL-6, IP-10, MCP-1, and IL-8. IL-1 family cytokines and RANTES were higher in severe influenza infection than severe SARS-CoV-2 infection. Interestingly, only the concentration of IP-10-correlated between blood and BAL during severe infection. Our results demonstrate inflammatory immune dysregulation in the lower airways during severe viral pneumonia that is distinct from lower airway responses seen in human patients with symptomatic, but not severe, illness and suggest that measurement of blood IP-10 concentration may predict this unique dysregulation.
UR - http://www.scopus.com/inward/record.url?scp=85113733473&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.2100294
DO - 10.4049/jimmunol.2100294
M3 - Article
C2 - 34348975
AN - SCOPUS:85113733473
SN - 0022-1767
VL - 207
SP - 1229
EP - 1238
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -