Lost in Translation: Evaluation of Subcutaneous Interferon-ß Treatment for SARS-CoV-2 Infection in Real Life.

Despite in vitro activity of interferon-ß (IFN-ß) against SARS-CoV-2 infection, its clinical efficacy remains controversial. We evaluated the impact of IFN-ß treatment in a cohort of 3590 patients hospitalized with COVID-19 during March−April 2020. The primary endpoint was a composed variable of admission to intensive care unit (ICU)/death. Overall, 153 patients (4%) received IFN-ß. They were significantly more severely ill, with a worse clinical and analytical situation, explaining a higher ICU admission (30% vs. 17%; p < 0.01), and a shorter time to the composed variable. In a Cox regression analysis, older age, lymphopenia, renal failure, or increased neutrophil-to-lymphocyte ratio were associated with a greater hazard ratio (HR) of admission at ICU/death. Notably, the HR of IFN-ß for the outcome variable was no longer significant after adjustment (HR, 1.03; 95% CI, 0.82−1.30), and different sensitivity analysis (early IFN use, ICU admission) showed no changes in the estimates. A propensity score matching analysis showed no association of IFN-ß therapy and outcome. In conclusion, in this large cohort of hospitalized COVID-19 patients, IFN-ß was used mainly in patients with advanced disease, reflecting an important bias of selection. After adjusting by severity, IFN-ß was not associated with a higher rate of ICU admission or mortality.

Altered Ecology of the Respiratory Tract Microbiome and Nosocomial Pneumonia.

Nosocomial pneumonia is one of the most frequent infections in critical patients. It is primarily associated with mechanical ventilation leading to severe illness, high mortality, and prolonged hospitalization. The risk of mortality has increased over time due to the rise in multidrug-resistant (MDR) bacterial infections, which represent a global public health threat. Respiratory tract microbiome (RTM) research is growing, and recent studies suggest that a healthy RTM positively stimulates the immune system and, like the gut microbiome, can protect against pathogen infection through colonization resistance (CR). Physiological conditions of critical patients and interventions as antibiotics administration and mechanical ventilation dramatically alter the RTM, leading to dysbiosis. The dysbiosis of the RTM of ICU patients favors the colonization by opportunistic and resistant pathogens that can be part of the microbiota or acquired from the hospital environments (biotic or built ones). Despite recent evidence demonstrating the significance of RTM in nosocomial infections, most of the host-RTM interactions remain unknown. In this context, we present our perspective regarding research in RTM altered ecology in the clinical environment, particularly as a risk for acquisition of nosocomial pneumonia. We also reflect on the gaps in the field and suggest future research directions. Moreover, expected microbiome-based interventions together with the tools to study the RTM highlighting the "omics" approaches are discussed.

Serum cystatin C concentration as a marker of acute renal dysfunction in critically ill patients.

INTRODUCTION: In critically ill patients sudden changes in glomerular filtration rate (GFR) are not instantly followed by parallel changes in serum creatinine. The aim of the present study was to analyze the utility of serum cystatin C as a marker of renal function in these patients. METHODS: Serum creatinine, serum cystatin C and 24-hour creatinine clearance (CCr) were determined in 50 critically ill patients (age 21-86 years; mean Acute Physiology and Chronic Health Evaluation II score 20 +/- 9). They did not have chronic renal failure but were at risk for developing renal dysfunction. Serum cystatin C was measured using particle enhanced immunonephelometry. Twenty-four-hour body surface adjusted CCr was used as a control because it is the 'gold standard' for determining GFR. RESULTS: Serum creatinine, serum cystatin C and CCr (mean +/- standard deviation [range]) were 1.00 +/- 0.85 mg/dl (0.40-5.61 mg/dl), 1.19 +/- 0.79 mg/l (0.49-4.70 mg/l), and 92.74 +/- 52.74 ml/min per 1.73 m2 (8.17-233.21 ml/min per 1.73 m2), respectively. Our data showed that serum cystatin C correlated better with GFR than did creatinine (1/cystatin C versus CCr: r = 0.832, P < 0.001; 1/creatinine versus CCr: r = 0.426, P = 0.002). Cystatin C was diagnostically superior to creatinine (area under the curve [AUC] for cystatin C 0.927, 95% confidence interval 86.1-99.4; AUC for creatinine 0.694, 95% confidence interval 54.1-84.6). Half of the patients had acute renal dysfunction. Only five (20%) of these 25 patients had elevated serum creatinine, whereas 76% had elevated serum cystatin C levels (P = 0.032). CONCLUSION: Cystatin C is an accurate marker of subtle changes in GFR, and it may be superior to creatinine when assessing this parameter in clinical practice in critically ill patients.