Involvement of Circulating Fibrocytes in Pathophysiology and Prognosis of COVID-19 Pneumonia

ABSTRACT

Rationale SARS-CoV-2 infection, responsible of COVID-19, can lead to severe acute pneumonia in 15-20% of patients. Circulating fibrocytes are fibroblasts precursors involved in the repair process. Increased blood fibrocytes count is associated with a poor prognosis in fibrotic lung diseases and acute respiratory distress syndrome (ARDS). We aimed to quantify the % of circulating fibrocytes in patients hospitalized for COVID-19 and included in the French COVID cohort, in order to determine their prognosis value in this disease. Methods:SARS-CoV-2 infection was confirmed by PCR in all patients. Blood fibrocytes were quantified by flow cytometry as CD45+/CD15-/CD34+/Collagen-1+. Clinical and imaging data were obtained at inclusion and after 3 months. In a subgroup of patients admitted in ICU, we quantified fibrocytes in blood and broncho-alveolar lavage fluid (BALF). Serum amyloid protein (SAP), a known regulator of fibrocytes differentiation, was quantified by ELISA in serum samples. Results:We included 57 patients admitted for hypoxemic COVID-19 pneumonia (mean age 60 years [23-87]) and 15 sex- and age-matched healthy controls. Samples were taken 0 to 10 days after admission, and 14 days (4-48 days) after first symptom. The median % of circulating fibrocytes was higher in patients compared to controls (2,49% vs 1,82%, p<0,05). The % was lower in patients who died of COVID-19 (6/57) as compared to survivors (1.25% versus 2.52%, p=0.03). Fibrocyte count was lower in patients receiving corticosteroids before blood sample collection (2.28% vs 2.82%, p=0.04). Fibrocyte % did not correlate with biological severity markers (lymphocytes, LDH, ferritin, CRP). Thirty-two patients were evaluated 3 months after admission. Complete resolution of CT abnormalities was observed in 13 patients (40%). It was associated with a significantly higher initial fibrocyte count compared with patients with an incomplete resolution (2.95% vs 2.18%, p=0.03). SAP concentration in serum was higher in COVID-19 patients compared to controls (96.3 vs 65,0 mg/L, p = 0.0021);it did not correlate with fibrocyte count. We studied 7 ICU patients (mean age 62 years [50-73]). In these patients, median blood fibrocyte count was 0.94% while median BALF fibrocyte count was 5.43%, suggesting a recruitment of fibrocytes to the lung in severe cases. Conclusion: Circulating fibrocytes were increased in patients with hypoxemic COVID-19 pneumonia. Lower fibrocyte count were associated with an increased risk of in-hospital death and a slower resolution of lung CT opacities, and may be due to the recruitment of fibrocytes to the lung in the most severe cases.