The future of intensive care: the study of the microcirculation will help to guide our therapies.

The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients.

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

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.