Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19

Abstract

BackgroundKnowledge 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.MethodsThis 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.FindingsPaired 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.InterpretationThe 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.

CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity

“…Indeed, CD169 + monocytes were present in both blood and BALF of these patients (Figure 2H and Figure S3F). CD169 was also expressed in alveolar macrophages, as we described previously (40). The expression of HLA-DR was also consistently higher in CD169 + cells monocytes/macrophages (Figure 2I).…”

“…Antibody clones and dilutions used are listed in Table S2. Antibodies and reagents used for the ArtDECO cohort have been listed elsewhere (40). BALF samples were excluded when too few viable CD45 + cells were measured (i.e., less than 2,000) or during active therapy with corticosteroids, as described previously (40).…”

“…Antibodies and reagents used for the ArtDECO cohort have been listed elsewhere (40). BALF samples were excluded when too few viable CD45 + cells were measured (i.e., less than 2,000) or during active therapy with corticosteroids, as described previously (40). PBMC samples were only included if a paired BALF sample was available.…”

Immune responses to SARS-CoV-2 in the lung

“…2 In this issue, Saris et al present a study in which the authors characterised the cellular immune composition of paired blood and BAL samples from 17 patients with severe COVID-19 infection, of which 4 patients were deceased. 3 They observed a significant increase in monocyte populations in BAL of all patients, consistent with the idea that activated blood monocytes migrate to the lung in response to infection. The human leukocyte antigen class DR (HLA-DR) levels were also significantly higher in the BAL monocytes than in the peripheral blood mononuclear cell (PBMC) counterpart.…”

Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

“…No significant differences in the differentiation of CD4 T cells were found between healthy donors and patients with mild COVID-19, but patients with severe disease showed an expansion of central memory CCR7+CD45RO+ CD4 T cells [ 40 ]. A high prevalence of central memory CD45RA−CD27+CD28+CCR7+ CD4 T cells in PBMCs was also detected by Saris et al in patients with mild COVID-19 compared to healthy donors [ 41 ].…”