Aspergillosis is a mycotic disease usually caused by Aspergillus fumigatus, a saprophytic and ubiquitous airborne fungus. Aspergillus-related lung diseases are traditionally classified into four different forms, whose occurrence depends on the immunologic status of the host and the existence of an underlying lung disease. Allergic broncho-pulmonary aspergillosis (ABPA) affects patients with asthma or cystic fibrosis. Saprophytic infection (aspergilloma) occurs in patients with abnormal airways (chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis) or chronic lung cavities. Chronic necrotizing aspergillosis (semi-invasive form) is described in patients with chronic lung pathology or mild immunodeficiency. Invasive aspergillosis (angio-invasive or broncho-invasive forms) occurs in severely immuno-compromised patients. Knowledge of the various radiological patterns for each form, as well as the corresponding associated immune disorders and/or underlying lung diseases, helps early recognition and accurate diagnosis.
Background
High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters.
Methods
The TOCICOVID study included a prospective cohort of patients aged 16–80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology.
Results
Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (
n
= 49) and the control (
n
= 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25–0.56];
p
< 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36–0.94];
p
= 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31–1.748],
p
= 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17–2.37],
p
= 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days;
p
< 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22–2.75];
p
= 0.003). The levels of CRP and fibrinogen post therapy (
p
< 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%;
p
< 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%,
p
= 0.089) including ventilator-acquired pneumonia (8% vs. 26%,
p
= 0.022) were higher in the control group.
Conclusion
These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive ca...
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