Elevated circulating monocytes and monocyte activation in COVID-19 convalescent individuals

Abstract

BackgroundMonocytes and macrophages play a pivotal role in inflammation during acute SARS-CoV-2 infection. However, their contribution to the development of post-acute sequelae of SARS-CoV-2 infection (PASC) are not fully elucidated.MethodsA cross-sectional study was conducted comparing plasma cytokine and monocyte levels among three groups: participants with pulmonary PASC (PPASC) with a reduced predicted diffusing capacity for carbon monoxide [DLCOc, <80%; (PG)]; fully recovered from SARS-CoV-2 with no residual symptoms (recovered group, RG); and negative for SARS-CoV-2 (negative group, NG). The expressions of cytokines were measured in plasma of study cohort by Luminex assay. The percentages and numbers of monocyte subsets (classical, intermediate, and non-classical monocytes) and monocyte activation (defined by CD169 expression) were analyzed using flow cytometry analysis of peripheral blood mononuclear cells.ResultsPlasma IL-1Ra levels were elevated but FGF levels were reduced in PG compared to NG. Circulating monocytes and three subsets were significantly higher in PG and RG compared to NG. PG and RG exhibited higher levels of CD169+ monocyte counts and higher CD169 expression was detected in intermediate and non-classical monocytes from RG and PG than that found in NG. Further correlation analysis with CD169+ monocyte subsets revealed that CD169+ intermediate monocytes negatively correlated with DLCOc%, and CD169+ non-classical monocytes positively correlated with IL-1α, IL-1β, MIP-1α, Eotaxin, and IFN-γ.ConclusionThis study present evidence that COVID convalescents exhibit monocyte alteration beyond the acute COVID-19 infection period even in convalescents with no residual symptoms. Further, the results suggest that monocyte alteration and increased activated monocyte subsets may impact pulmonary function in COVID-19 convalescents. This observation will aid in understanding the immunopathologic feature of pulmonary PASC development, resolution, and subsequent therapeutic interventions.

Single‐cell RNA sequencing reveals characteristics of myeloid cells in post-acute sequelae of SARS-CoV-2 patients with persistent respiratory symptoms

“…Our scRNA-seq analysis identified pronounced alterations in myeloid cells. Furthermore, we found that elevated circulating monocyte levels and their activation were observed in COVID-19 convalescents ( 76 ). Thus, we focused our attention on myeloid cells, particularly CD14 + and CD16 + monocytes, as well as dendritic cells, for downstream analysis hereafter referred to as myeloid-lineage cells (MLCs).…”

“…We recently reported persisting elevation of circulating monocytes in COVID-19 convalescents and cell activation was negatively correlated with lung function in individuals with PPASC ( 76 ). Consistent with this finding, our scRNA-seq data demonstrate continued dysregulation of the peripheral immune system, particularly MLCs, months after acute infection.…”

Organ-Dysfunction Markers in Mild-to-Moderate COVID-19 Convalescents

“…In our study, we did not find any differences in sCD163 levels between convalescents and never-infected subjects. The study performed by Park et al showed that convalescents four weeks after recovery still present with an increased number and activity of the monocyte/macrophage population [28]. However, it should also be considered that our study group consisted of healthy individuals who had been infected with SARS-CoV-2 at least 6 months earlier and had fully recovered.…”

COVID-19 and trained immunity: the inflammatory burden of long covid

“…Research has demonstrated that the number of circulating monocytes is increased in both COVID-19-recovered patients and pneumonia patients compared to the healthy group, and this increase is associated with elevated levels of inflammatory factors ( 56 ). Recent studies have found that COVID-19 can induce epigenetic changes in (HSPCs), leading to enhanced pro-inflammatory phenotypes in monocytes ( 17 ).…”