Increased sCD163 and sCD14 Plasmatic Levels and Depletion of Peripheral Blood Pro-Inflammatory Monocytes, Myeloid and Plasmacytoid Dendritic Cells in Patients With Severe COVID-19 Pneumonia

Zingaropoli, Maria Antonella; Nijhawan, Parni; Carraro, Anna; Pasculli, Patrizia; Zuccalà, Paola; Perri, Valentina; Marocco, Raffaella; Kertusha, Blerta; Siccardi, Guido; Borgo, Cosmo Del; Curtolo, Ambrogio; Ajassa, Camilla; Iannetta, Marco; Ciardi, Maria Rosa; Mastroianni, Claudio Maria; Lichtner, Miriam

doi:10.3389/fimmu.2021.627548

Cited by 173 publications

(89 citation statements)

References 52 publications

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“…A very recent paper, performed on hospitalized COVID-19 patients, showed significantly increased sCD163 and sCD14 and a reduction of non-classical monocytes, mDCs and pDCs in COVID-19. However, in this study, the Slan positive population was classified within DCs, while our unbiased flow cytometry data analysis, as well as previous evaluations, performed through genome-wide transcriptional profiling, demonstrated that those cells cluster together with non-classical monocyte population (22)(23)(24)(25).…”

Section: Discussionmentioning

confidence: 54%

Severe COVID-19 Recovery Is Associated with Timely Acquisition of a Myeloid Cell Immune-Regulatory Phenotype

et al. 2021

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After more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an urgent need for understanding the underlying pathogenic mechanisms to guide therapeutic interventions. This study was designed to assess myeloid cell activation and phenotype leading to recovery in patients surviving severe COVID-19. We evaluated longitudinally patients with COVID-19 related respiratory insufficiency, stratified according to the need of intensive care unit admission (ICU, n = 11, and No-ICU, n = 9), and age and sex matched healthy controls (HCs, n = 11), by flow cytometry and a wide array of serum inflammatory/immune-regulatory mediators. All patients featured systemic immune-regulatory myeloid cell phenotype as assessed by both unsupervised and supervised analysis of circulating monocyte and dendritic cell subsets. Specifically, we observed a reduction of CD14lowCD16+ monocytes, and reduced expression of CD80, CD86, and Slan. Moreover, mDCs, pDCs, and basophils were significantly reduced, in comparison to healthy subjects. Contemporaneously, both monocytes and DCs showed increased expression of CD163, CD204, CD206, and PD-L1 immune-regulatory markers. The expansion of M2-like monocytes was significantly higher at admission in patients featuring detectable SARS-CoV-2 plasma viral load and it was positively correlated with the levels of specific antibodies. In No-ICU patients, we observed a peak of the alterations at admission and a progressive regression to a phenotype similar to HCs at discharge. Interestingly, in ICU patients, the expression of immuno-suppressive markers progressively increased until discharge. Notably, an increase of M2-like HLA-DRhighPD-L1+ cells in CD14++CD16− monocytes and in dendritic cell subsets was observed at ICU discharge. Furthermore, IFN-γ and IL-12p40 showed a decline over time in ICU patients, while high values of IL1RA and IL-10 were maintained. In conclusion, these results support that timely acquisition of a myeloid cell immune-regulatory phenotype might contribute to recovery in severe systemic SARS-CoV-2 infection and suggest that therapeutic agents favoring an innate immune system regulatory shift may represent the best strategy to be implemented at this stage.

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Section: Discussionmentioning

confidence: 54%

Severe COVID-19 Recovery Is Associated with Timely Acquisition of a Myeloid Cell Immune-Regulatory Phenotype

et al. 2021

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“…An elevated level of sCD14 and sCD163 was reported to be strongly associated with clinical laboratory parameters like ferritin, CRP, and procalcitonin and IL-6 in SARS-CoV-2 patients [ 63 ]. In this line of research, a study reported that plasmatic sCD163 level >2032 ng/ml during the time of admission can be used to predict COVID-19 disease severity (p = 0.0022) [ 64 ]. We have earlier reported the correlation of sCD163 & ferritin in dengue disease progression [ 65 , 66 ].…”

Section: Regular Clinical Biomoleculesmentioning

confidence: 99%

Potential biomarkers for the early prediction of SARS-COV-2 disease outcome

Mariappan

Manoharan

Ranganadin

et al. 2021

Microbial Pathogenesis

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The current pandemic due to the fast spreading of SARS-CoV-2 infection has caused severe impairment in health, social, economic, scientific, and medical sectors across the globe. Owing to the not so well understood mechanism of disease pathogenesis in terms of variations in immune responses, there remains obscure why some of the patients who are infected by the novel SARS-CoV-2 develop an unpredictable clinical course that rapidly causes severe and deadly complications/manifestations. Currently, several assays are available for the confirmation of SARS-CoV-2 infection at the point of care. However, none of these assays can predict the severity of the COVID-19 disease. Thus, the identification of a prognostic biomarker that forecasts the condition of SARS-CoV-2 patients to develop a severe form of the disease could enable the clinicians for more efficient patient triage and treatment. In this regard, the present review describes the role of selected biomolecules that are crucially involved in the immune-pathogenesis of SARS-CoV-2 infection such as hyper-immune responsiveness, bradykinin storm and vascular leakage assuming these may serve as an effective prognostic biomarker in COVID-19 to understand the outcome of the disease. Based on the review, we also propose the development of a cost-effective SERS-based prognostic biosensor for the detection and quantification of biomolecules for use as a point-of-care system during a disease outbreak.

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“…They were shown to sense and control, via type I IFN release, infection with both coronaviruses SARS-CoV and Middle East respiratory syndrome coronavirus (MERS) [ 14 – 16 ]. Importantly, pDC were found significantly reduced or absent in the blood of patients with severe COVID-19 [ 17 – 19 ] and were absent in the lungs [ 20 ] and in bronchoalveolar lavage fluids [ 21 ] while showed a higher proportions in moderate disease.…”

Section: Introductionmentioning

confidence: 99%

Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection

et al. 2021

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SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.

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Increased sCD163 and sCD14 Plasmatic Levels and Depletion of Peripheral Blood Pro-Inflammatory Monocytes, Myeloid and Plasmacytoid Dendritic Cells in Patients With Severe COVID-19 Pneumonia

Cited by 173 publications

References 52 publications

Severe COVID-19 Recovery Is Associated with Timely Acquisition of a Myeloid Cell Immune-Regulatory Phenotype

Severe COVID-19 Recovery Is Associated with Timely Acquisition of a Myeloid Cell Immune-Regulatory Phenotype

Potential biomarkers for the early prediction of SARS-COV-2 disease outcome

Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection

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