Blood fibrocytes are associated with severity and prognosis in COVID-19 pneumonia

Abstract

Increased blood fibrocytes are associated with a poor prognosis in fibrotic lung diseases. We aimed to determine whether the percentage of circulating fibrocytes could be predictive of severity and prognosis during Coronavirus disease 2019 (COVID-19) pneumonia. Blood fibrocytes were quantified by flow cytometry as CD45+/CD15-/CD34+/Collagen-1+cells in patients hospitalized for COVID-19 pneumonia. In a subgroup of patients admitted in ICU, fibrocytes were quantified in blood and broncho-alveolar lavage (BAL). Serum amyloid P (SAP), TGF-b1,CXCL12, CCL2, and FGF2 serum concentration were measured in serum. We included 57 patients in the Hospitalized group (median age 59 years [23-87]) and 16 Healthy controls. The median percentage of circulating fibrocytes was higher in patients compared to controls (3.6% [0.2-9.2] vs. 2.1% [0.9-5.1], p=0.04). Blood fibrocyte count was lower in the 6 patients who died compared to survivors (1.6% [0.2-4.4] vs. 3.7% [0.6-9.2], p=0.02). Initial fibrocyte count was higher in patients showing a complete lung CT resolution at 3 months. Circulating fibrocyte count was decreased in the ICU group (0.8% [0.1-2.0]) whereas BAL fibrocyte count was 6.7% [2.2-15.4]. Serum SAP and TGF-b1 concentrations were increased in Hospitalized patients. SAP was also increased in ICU patients. CXCL12 and CCL2 were increased in ICU patients, and negatively correlated with circulating fibrocyte count. We conclude that circulating fibrocytes were increased in patients hospitalized for COVID-19 pneumonia and a lower fibrocyte count was associated with an increased risk of death and a slower resolution of lung CT opacities.

COVID‐19 plasma proteome reveals novel temporal and cell‐specific signatures for disease severity and high‐precision disease management

“…59 A range of biomarkers reflecting ECM remodelling and fibrosis were identified predicting the decline of the lung function. 37,55 Overactive fibroblasts (EPIC software output) are suspected of fibrillar collagens (type I, III, V collagens) production, which are not permeable to oxygen, unlike the networking collagens of the basement membrane (types IV and VIII). 36 To manage this condition, we propose MMP inhibitors as potential therapeutic agents for severe COVID-19 lung injury, including Aprotinin, a nonspecific protease inhibitor.…”

“…53,54 Moreover, polymerized type I collagen given by intramuscular injection (Fibroque IMR drug) is able to downregulate the 'cytokine storm' and combat the ECM degradation by reducing the expression of IL-1β, IL-8, TNFα, IL-17, and upregulate certain key adhesion molecules (ELAM-1, VCAM-1, ICAM-1). ECM disintegration would release cells from the affected tissues, 55 and a broken ECM may trigger not only aberrant T-cell homing but also their 'exhaustion' followed by apoptosis. 14,36 In addition, impaired adhesion can also stimulate massive chemokine release in COVID-19 plasma, stimulating cell migration which could ultimately F I G U R E 7 Summary cartoon illustrating the proposed deconvoluted mechanisms of COVID-19 based on Olink analysis of the patient cohorts be detrimental to tissue stability.…”

Potential marker subset of blood-circulating cytokines on hematopoietic progenitor-to-Th1 pathway in COVID-19

“…Previous COVID-19 studies have clarified several diagnostic markers and biomarkers, such as IP-10, CRP, and various ILs and IFNs ( 26 ) such as CD163 ( 27 ), MIF ( 28 ), IL-8 ( 29 ), IL-18 ( 30 ), FGF-basic ( 30 ), and CHI3L1 ( 31 ). Of great interest are MMP-3 as a progression marker ( 32 ), MCP-3 as a urine marker ( 33 ), and IL-2 as a heart disease marker ( 34 ).…”

Interstitial lung disease following coronavirus disease 2019

“…Circulating fibrocytes were found to be increased at the acute phase and persisted 3 months after hospital admission. Interestingly, higher circulating fibrocytes percentage was more frequently observed when there was a complete resolution of CT scan abnormalities at 3 months post-COVID [34] suggesting that fibrocytes could be a marker for efficient repair in this context of postacute injury.…”