Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19

Abstract

Immune response dynamics in coronavirus disease 2019 and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyperinflammatory signatures, and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163 + monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract.

CCR2-dependent monocyte-derived cells restrict SARS-CoV-2 infection

“…Similar phenomenon have been noted in human subjects, with one study describing an association between SARS-CoV-2 viral burden, IL-6 levels, and increased risk of death 24 . Similar to studies of post-mortem lung tissue or BALs from patients suffering from COVID-19, we observed a significant increase in the numbers of S100a8+ granulocytes in the lung parenchyma 4,[6][7][8] . S100a8/9 and TLR4 signaling mediate the emergence of a dysregulated neutrophil population that promotes SARS-CoV-2 disease 18 .…”

“…Innate immunity to SARS-CoV-2 begins with a limited interferon (IFN) response and production of inflammatory cytokines (IL-6, Il-1β, TNFα, IL-8) by respiratory epithelial cells or alveolar macrophages [3][4][5][6]7 . As shown in bronchoalveolar lavages (BAL) of COVID-19 patients, this innate immune response coincides with robust infiltration of neutrophils, monocytes, and dendritic cells into the lung airways 6,8 . Monocytes in the lung parenchyma can be divided into subpopulations characterized by their expression of Ly6C; Ly6C high classical monocytes are pro-inflammatory, whereas Ly6C low non-classical monocytes promote wound healing 9,10 .…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…Pathogenic changes in the monocytic compartment regarding phenotypes and function and an increase in immature neutrophils are central hallmarks of COVID-19 [424]. Macrophage activity drives both inflammation and much of the pathology in COVID-19 patients [425,426]. These cells act as sentinels to limit early viral replication by initiating an IFN-I response and an inflammatory response to recruit additional immune cells [427].…”

Monocytes and macrophages in severe COVID‐19 – friend, foe or both?

“…While most COVID-19 patients have mild symptoms, about 15% of patients develop severe COVID-19 often with fatal outcomes, and scientists have been on the hunt to understand the underlying immune mechanisms driving disease severity. In a recent study in Immunity, Szabo et al 1 provide comprehensive longitudinal insights into the phenotypical and functional shifts of T cells, monocytes and macrophages driving inflammation in the lungs of patients with severe COVID-19.…”