Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2024 Jan 4:14:1329026.
doi: 10.3389/fimmu.2023.1329026. eCollection 2023.

Reduced monocyte proportions and responsiveness in convalescent COVID-19 patients

Eugene V Ravkov  1 , Elizabeth S C P Williams  2 , Marc Elgort  1 , Adam P Barker  1   3 , Vicente Planelles  3 , Adam M Spivak  2 , Julio C Delgado  1   3 , Leo Lin  1   3 , Timothy M Hanley  1   3
Affiliations
Comment

Reduced monocyte proportions and responsiveness in convalescent COVID-19 patients

Eugene V Ravkov et al. Front Immunol. .

Abstract

Introduction: The clinical manifestations of acute severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) suggest a dysregulation of the host immune response that leads to inflammation, thrombosis, and organ dysfunction. It is less clear whether these dysregulated processes persist during the convalescent phase of disease or during long COVID. We sought to examine the effects of SARS-CoV-2 infection on the proportions of classical, intermediate, and nonclassical monocytes, their activation status, and their functional properties in convalescent COVID-19 patients.

Methods: Peripheral blood mononuclear cells (PBMCs) from convalescent COVID-19 patients and uninfected controls were analyzed by multiparameter flow cytometry to determine relative percentages of total monocytes and monocyte subsets. The expression of activation markers and proinflammatory cytokines in response to LPS treatment were measured by flow cytometry and ELISA, respectively.

Results: We found that the percentage of total monocytes was decreased in convalescent COVID-19 patients compared to uninfected controls. This was due to decreased intermediate and non-classical monocytes. Classical monocytes from convalescent COVID-19 patients demonstrated a decrease in activation markers, such as CD56, in response to stimulation with bacterial lipopolysaccharide (LPS). In addition, classical monocytes from convalescent COVID-19 patients showed decreased expression of CD142 (tissue factor), which can initiate the extrinsic coagulation cascade, in response to LPS stimulation. Finally, we found that monocytes from convalescent COVID-19 patients produced less TNF-α and IL-6 in response to LPS stimulation, than those from uninfected controls.

Conclusion: SARS-CoV-2 infection exhibits a clear effect on the relative proportions of monocyte subsets, the activation status of classical monocytes, and proinflammatory cytokine production that persists during the convalescent phase of disease.

Keywords: 70; COVID-19; IL-6 69; SARS-CoV-2; TNF-α; monocytes; tissue factor.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Monocytes are decreased and lymphocytes increased in convalescent COVID-19 patients. (A) Total monocyte percentage, (B) Total lymphocyte percentage, (C) Myeloid dendritic cell percentage, and (D) Plasmacytoid dendritic cell percentage (of PBMCs) in convalescent COVID-19 (red, n=18) and control (blue, n=31) groups. Mann-Whitney U test. ns, not significant.
Figure 2
Figure 2
T cells are increased in convalescent COVID-19 patients. (A) T cell percentage, (B) B cell percentage, and (C) NK cell percentage (of PBMCs) in convalescent COVID-19 (red, n=18) and control (blue, n=31) groups. Mann-Whitney U test. ns, not significant.
Figure 3
Figure 3
Classical (CD14+ CD16-) monocytes from convalescent COVID-19 patients express less CD142 (tissue factor) in response to LPS. (A) CD142 percentage (of classical monocytes) in convalescent COVID-19 (red, n=18) and control (blue, n=31) groups in the absence (empty) or presence (filled) of 100 ng/mL LPS. (B) CD142 percentage (of intermediate monocytes) in convalescent COVID-19 (blue) and control (red) groups in the absence (empty) or presence (filled) of 100 ng/mL LPS. (C) CD142 percentage (of non-classical monocytes) in convalescent COVID-19 (blue) and control (red) groups in the absence (empty) or presence (filled) of 100 ng/mL LPS. Comparison between groups (control vs. COVID-19) Mann-Whitney U test. Comparison within groups (untreated vs. LPS-treated) Wilcoxon ranked test. ns, not significant.
Figure 4
Figure 4
Expression of activation markers is altered in classical (CD14+ CD16-) monocytes from convalescent COVID-19 patients. (A) CD4 percentage, (B) CD56 percentage, (C) CD69 percentage, (D) CD83 percentage, and (E) CD86 percentage (of classical monocytes) in convalescent COVID-19 (red, n=18) and control (blue, n=31) groups in the absence (empty) or presence (filled) of 100 ng/mL LPS. Comparison between groups (control vs. COVID-19) Mann-Whitney U test. Comparison within groups (untreated vs. LPS-treated) Wilcoxon ranked test. ns, not significant.
Figure 5
Figure 5
Activation marker expression is not altered in intermediate (CD14+ CD16+) monocytes from convalescent COVID-19 patients. (A) CD4 percentage, (B) CD56 percentage, (C) CD69 percentage, (D) CD83 percentage, and (E) CD86 percentage (of intermediate monocytes) in convalescent COVID-19 (red, n=18) and control (blue, n=31) groups in the absence (empty) or presence (filled) of 100 ng/mL LPS. Comparison between groups (control vs. COVID-19) Mann-Whitney U test. Comparison within groups (untreated vs. LPS-treated) Wilcoxon ranked test. ns, not significant.
Figure 6
Figure 6
Classical (CD14+ CD16-) monocytes from convalescent COVID-19 patients express less CD142 (tissue factor) in response to LPS. (A) CD142 percentage (of classical monocytes) in convalescent COVID-19 (red, n=18) and control (blue, n=31) groups in the absence (empty) or presence (filled) of 100 ng/mL LPS. (B) CD142 percentage (of intermediate monocytes) in convalescent COVID-19 (blue) and control (red) groups in the absence (empty) or presence (filled) of 100 ng/mL LPS. (C) CD142 percentage (of non-classical monocytes) in convalescent COVID-19 (blue) and control (red) groups in the absence (empty) or presence (filled) of 100 ng/mL LPS. Comparison between groups (control vs. COVID-19) Mann-Whitney U test. Comparison within groups (untreated vs. LPS-treated) Wilcoxon ranked test. ns, not significant.
Figure 7
Figure 7
Proinflammatory cytokine expression is decreased in monocytes from convalescent COVID-19 patients. (A) TNF-α and (B) IL-6 expression in convalescent COVID-19 (red, n=10) and control (blue, n=10) groups in the absence (empty) or presence (filled) of 100 ng/mL LPS. Comparison between groups (control vs. COVID-19) Mann-Whitney U test. Comparison within groups (untreated vs. LPS-treated) Wilcoxon ranked test. ns, not significant.
See this image and copyright information in PMC

Update of

Comment on

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Harrison AG, Lin T, Wang P. Mechanisms of sars-cov-2 transmission and pathogenesis. Trends Immunol (2020) 41(12):1100–15. doi: 10.1016/j.it.2020.10.004 - DOI - PMC - PubMed
    1. Lamers MM, Haagmans BL. Sars-cov-2 pathogenesis. Nat Rev Microbiol (2022) 20(5):270–84. doi: 10.1038/s41579-022-00713-0 - DOI - PubMed
    1. Vanderbeke L, Van Mol P, Van Herck Y, De Smet F, Humblet-Baron S, Martinod K, et al. . Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of covid-19 disease severity. Nat Commun (2021) 12(1):4117. doi: 10.1038/s41467-021-24360-w - DOI - PMC - PubMed
    1. Guo C, Li B, Ma H, Wang X, Cai P, Yu Q, et al. . Single-cell analysis of two severe covid-19 patients reveals a monocyte-associated and tocilizumab-responding cytokine storm. Nat Commun (2020) 11(1):3924. doi: 10.1038/s41467-020-17834-w - DOI - PMC - PubMed
    1. Subramaniam S, Kothari H, Bosmann M. Tissue factor in covid-19-associated coagulopathy. Thromb Res (2022) 220:35–47. doi: 10.1016/j.thromres.2022.09.025 - DOI - PMC - PubMed

Publication types

Substances