Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19.
COVID-19
pneumonia
respiratory infection
viral infection
Journal
Thorax
ISSN: 1468-3296
Titre abrégé: Thorax
Pays: England
ID NLM: 0417353
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
24
09
2020
revised:
09
02
2021
accepted:
27
02
2021
pubmed:
14
4
2021
medline:
30
9
2021
entrez:
13
4
2021
Statut:
ppublish
Résumé
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. 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. 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 ƴδ T 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. 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.
Sections du résumé
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 ƴδ T 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.
Identifiants
pubmed: 33846275
pii: thoraxjnl-2020-216256
doi: 10.1136/thoraxjnl-2020-216256
pmc: PMC8050882
doi:
Substances chimiques
Inflammation Mediators
0
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1010-1019Investigateurs
Esther J Nossent
(EJ)
Janwillem Duitman
(J)
Anno Saris
(A)
Heder De Vries
(H)
Lilian J Meijboom
(LJ)
Lieuwe D Bos
(LD)
Siebe G Blok
(SG)
Alex R Schuurman
(AR)
Tom Dy Reijnders
(TD)
F Hugenholtz
(F)
Juan Garcia Vallejo
(JG)
Hetty Bontkes
(H)
Alexander Pj Vlaar
(AP)
Joost Wiersinga
(J)
René Lutter
(R)
Tom van der Poll
(TV)
Harm Jan Bogaard
(HJ)
Leo Heunks
(L)
S de Bruin
(S)
A R Schuurman
(AR)
R Koing
(R)
M A van Agtmael Ag Algera
(MA)
Fehp van Baarle
(FV)
Djc Bax
(D)
M Beudel
(M)
H J Bogaard
(HJ)
M Bomers
(M)
Ldj Bos
(L)
M Botta
(M)
J de Brabander
(J)
G J de Bree
(GJ)
M Bugiani
(M)
E B Bulle
(EB)
O Chouchane
(O)
Apm Cloherty
(A)
P E Elbers Lm Fleuren
(PE)
S E Geerlings
(SE)
B F Geerts
(BF)
Tbh Geijtenbeek
(T)
Arj Girbes
(A)
A Goorhuis
(A)
M P Grobusch
(MP)
Fmj Hafkamp
(F)
L A Hagens
(LA)
J Hamann
(J)
V C Harris
(VC)
R Hemke
(R)
S M Hermans
(SM)
Lma Heunks
(L)
M W Hollmann
(MW)
J Horn
(J)
J W Hovius
(JW)
M D de Jong
(MD)
N van Mourik
(N)
J F Nellen
(JF)
F Paulus
(F)
Tdy Reijnders
(T)
E Peters
(E)
T van der Poll
(T)
B Preckel
(B)
J M Prins
(JM)
S J Raasveld
(SJ)
M Schinkel
(M)
M J Schultz
(MJ)
K Sigaloff
(K)
M R Smit
(MR)
C Stijnis
(C)
W Stilma
(W)
C E Teunissen
(CE)
P Thoral
(P)
A M Tsonas
(AM)
M van der Valk
(M)
D P Veelo
(DP)
H de Vries
(H)
M van Vugt
(M)
D Wouters
(D)
A H Zwinderman
(AH)
M C Brouwer
(MC)
W J Wiersinga
(WJ)
Apj Vlaar
(A)
D van de Beek
(D)
Commentaires et corrections
Type : CommentIn
Informations de copyright
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.