TY - JOUR
T1 - Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19
AU - Amsterdam UMC COVID study group
AU - Saris, Anno
AU - Reijnders, Tom D. Y.
AU - Nossent, Esther J.
AU - Schuurman, Alex R.
AU - Verhoeff, Jan
AU - Asten, Saskia Van
AU - Bontkes, Hetty
AU - Blok, Siebe
AU - Duitman, Janwillem
AU - Bogaard, Harm-Jan
AU - Heunks, Leo
AU - Lutter, Rene
AU - van der Poll, Tom
AU - Garcia Vallejo, Juan J.
AU - Study group members AMC, null
AU - Hollmann, Markus W.
AU - Preckel, Prof. dr. , Benedikt
AU - Veelo, Denise P.
AU - ArtDeco consortium
AU - Bugiani, M
N1 - Funding Information: Funding AS and TDYR were funded in part by NACTAR (grant number 16447) of the Dutch research council (NWO) and JWD was supported by a personal grant of the NWO (VENI grant 016.186.046). Publisher Copyright: © Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Background Knowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses. Methods This was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU). Mononuclear cells were purified from bronchoalveolar lavage fluid (BALF) and blood, and analysed by spectral flow cytometry; inflammatory mediators were measured in BALF and plasma. Findings Paired blood and BALF samples were obtained from 17 patients, four of whom died in the ICU. Macrophages and T cells were the most abundant cells in BALF, with a high percentage of T cells expressing the γ δT cell receptor. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells (87·3% and 83·8%, respectively), and these cells expressed higher levels of the exhaustion marker programmad death-1 than in peripheral blood. Prolonged ICU stay (>14 days) was associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma. Interpretation The bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood. Fully elucidating COVID-19 pathophysiology will require investigation of the pulmonary immune response.
AB - Background Knowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses. Methods This was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU). Mononuclear cells were purified from bronchoalveolar lavage fluid (BALF) and blood, and analysed by spectral flow cytometry; inflammatory mediators were measured in BALF and plasma. Findings Paired blood and BALF samples were obtained from 17 patients, four of whom died in the ICU. Macrophages and T cells were the most abundant cells in BALF, with a high percentage of T cells expressing the γ δT cell receptor. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells (87·3% and 83·8%, respectively), and these cells expressed higher levels of the exhaustion marker programmad death-1 than in peripheral blood. Prolonged ICU stay (>14 days) was associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma. Interpretation The bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood. Fully elucidating COVID-19 pathophysiology will require investigation of the pulmonary immune response.
KW - COVID-19
KW - Pneumonia
KW - Respiratory infection
KW - Viral infection
UR - http://www.scopus.com/inward/record.url?scp=85104054830&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/thoraxjnl-2020-216256
DO - https://doi.org/10.1136/thoraxjnl-2020-216256
M3 - Article
C2 - 33846275
SN - 0040-6376
VL - 76
SP - 1010
EP - 1019
JO - Thorax
JF - Thorax
IS - 10
M1 - thoraxjnl-2020-216256
ER -