Compartmental immunophenotyping in COVID-19 ARDS: A case series

Abstract

Background Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood. Objective Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS). Methods We consecutively included patients less than 72 hours after intubation following informed consent from their next of kin. Bronchoalveolar lavage fluid was evaluated by microscopy; bronchoalveolar lavage fluid and blood were assessed by 10-color flow cytometry and a multiplex cytokine panel. Results Four mechanically ventilated patients (aged 40-75 years) with moderate-to-severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, whereas CD4 and CD8 T-cell lymphopenia was observed in the 2 compartments. However, regulatory T cells and T H 17 cells were found in higher fractions in the lung. Lung CD4 and CD8 T cells and macrophages expressed an even higher upregulation of activation markers than in blood. A wide range of cytokines were expressed at high levels both in the blood and in the lungs, most notably, IL-1RA, IL-6, IL-8, IP-10, and monocyte chemoattactant protein-1, consistent with hyperinflammation. Conclusion COVID-19 ARDS exhibits a distinct immunologic profile in the lungs, with a depleted and exhausted CD4 and CD8 T-cell population that resides within a heavily hyperinflammatory milieu.

Haemophagocytic syndrome and COVID-19

“…Other coronavirus such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) may also produce an acute lung injury associated with an exaggerated pro-inflammatory cytokine/chemokine systemic response [ 26 ]. In COVID-19 ARDS patients, a recent study has demonstrated a severely hyperinflammatory milieu in both the lungs and peripheral blood but characterised by activated lymphocytes in low numbers, a specific immunologic profile was identified in the lungs, consisting of a depleted and exhausted CD4 and CD8 T cell population prevailing those subtypes involved in both reparative and destructive processes [ 27 ].…”

The role of CD4+FoxP3+ regulatory T cells in the immunopathogenesis of COVID-19: implications for treatment

“…Interestingly, soluble CD25 was increased in the peripheral blood of COVID-19 patients, while its ligand IL-2 was also increased [3,52]. In mechanically ventilated COVID-19 patients with ARDS, in sharp contrast to the lymphopenia in both subsets of CD4 and CD8 T cells, the proportion of Treg cells (defined by CD4 + FoxP3 + ) was increased in the lungs and peripheral blood mononuclear cells (PBMC) [53]. The degree of Treg recruitment into the lungs of COVID-19 patients may determine the severity of the disease since patients with more Treg cells experienced milder disease [54,55].…”

Vascular Inflammation as a Therapeutic Target in COVID-19 “Long Haulers”: HIITing the Spot?

“…Another immune mechanism, which is probably important regardless of whether a type 3 reaction takes place, is the highly proinflammatory cytokine response to SARS-CoV-2, which is prominent both in milder and very severe cases, and which some have designated a “cytokine storm” ( 18 , 19 ). This involves vast elevations in the classical pro-inflammatory cytokines, TNF-α and IL-1β, which have prominent effects on the endothelium.…”