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Background The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. Material and methods A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3–5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. Results Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80–1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%). Conclusion In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.

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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.