No evidence of tocilizumab treatment efficacy for severe to critical SARS-CoV2 infected patients: Results from a retrospective controlled multicenter study.

ABSTRACT: To assess tocilizumab (TCZ) efficacy associated to standard of care (SOC) compared to SOC alone in severe coronavirus associated disease 2019 (COVID-19) patients. In a matched case-control study from 3 French Hospital COVID-19 Departments, 27 patients with severe COVID-19 treated with TCZ and SOC were matched for baseline epidemiological and clinical features and compared to 27 severe COVID-19 patients treated with SOC alone. Baseline characteristics of the study population were comparable between groups. Eleven patients (20%) died. TCZ was not associated with clinical improvement as compared to SOC regarding oxygen-free status (44% vs 63%) and death (18.5% vs 22%), despite a higher decrease of the C-reactive protein at Day 7 (10.7 vs 52 mg/L; P < 10-3). Compared to the 43 patients alive at the end-of follow-up, patients who died were older (78 vs 64 years; P < 10-3), with 82% of them older than 72 years vs only 23% of live patients (P < 10-3). Age (OR = 1.15; 95%CI = 1.04-1.3; P = .008) and age over 72 years (OR) = 14.85; 95%CI = 2.7-80; P = .002) were independently associated with mortality. TCZ in addition to SOC for severe COVID-19 patients did not reduce mortality, subsequent need for invasive mechanical ventilation nor did it shorten the time of oxygen support, despite better control of the inflammatory response. More powerful and randomized controlled trials are warranted to determine if TCZ is effective in the management of COVID-19.

Toe-to-room temperature gradient correlates with tissue perfusion and predicts outcome in selected critically ill patients with severe infections.

BACKGROUND: Microcirculatory disorders leading to tissue hypoperfusion play a central role in the pathophysiology of organ failure in severe sepsis and septic shock. As microcirculatory disorders have been identified as strong predictive factors of unfavourable outcome, there is a need to develop accurate parameters at the bedside to evaluate tissue perfusion. We evaluated whether different body temperature gradients could relate to sepsis severity and could predict outcome in critically ill patients with severe sepsis and septic shock. METHOD: We conducted a prospective observational study in a tertiary teaching hospital in France. During a 10-month period, all consecutive adult patients with severe sepsis or septic shock who required ICU admission were included. Six hours after initial resuscitation (H6), we recorded the hemodynamic parameters and four temperature gradients: central-to-toe, central-to-knee, toe-to-room and knee-to-room. RESULTS: We evaluated 40 patients with severe sepsis (40/103, 39 %) and 63 patients with septic shock (63/103, 61 %). In patients with septic shock, central-to-toe temperature gradient was significantly higher (12.5 [9.2; 13.8] vs 6.9 [3.4; 12.0] °C, P < 0.001) and toe-to-room temperature gradient significantly lower (1.2 [-0.3; 5.2] vs 6.0 [0.6; 9.5] °C, P < 0.001) than in patients with severe sepsis. Overall ICU mortality rate due to multiple organ failure (MOF) was 21 %. After initial resuscitation, toe-to-room temperature gradient was significantly lower in patients dead from MOF than in the survivors (-0.2 [-1.1; +1.3] °C vs +3.9 [+0.5; +7.2] °C, P < 0.001) and the difference in gradients increased during the first 24 h. Furthermore, toe-to-room temperature gradient was related to tissue perfusion parameters such as arterial lactate level (r = -0.54, P < 0.0001), urine output (r = 0.37, P = 0.0002), knee capillary refill time (r = -0.42, P < 0.0001) and mottling score (P = 0.001). CONCLUSIONS: Toe-to-room temperature gradient reflects tissue perfusion at the bedside and is a strong prognosis factor in critically ill patients with severe infections.