The onset of late severe lung impairment in COVID-19 is associated with high inflammation markers at admission and metabolic syndrome markers (preprint)

Background: COVID-19 severity is mainly related to lung impairment. However, preexisting patient characteristics and biomarkers at admission associated with this event are not precisely known. Methods. We report 205 patients admitted for a proven COVID-19 in our institution between March 7 and April 22, 2020, particularly their comorbidities, respiratory severity, immune profile, and metabolic profile. Findings. Median age was 70 years [interquartile range (IQR) 25-75: 60;79]; 115 (56.1%) patients were men. Oxygen supplementation of >2L/min was required in 107 patients (52.2%) after a median time of 8 days [IQR: 6;10] after the first symptoms; 67 (32.7%) patients were admitted to the intensive care unit (ICU), almost exclusively due to severe hypoxia. Patients requiring >2L/min oxygen therapy and/or ICU admission were older and more frequently males, with a significantly higher body mass index (BMI), a significantly higher total cholesterol (TC) / HDL cholesterol ratio, and higher triglycerides. They also had higher plasma levels of C-reactive protein (CRP) and interleukin 6 (IL-6); IL-6 >20 ng/L and CRP >70 mg/L were significantly associated with ICU admission and/or (for patients with a decision of limitation of life-support therapy) death. Higher BMI and TC/HDL-c ratio were associated with higher CRP and IL-6 levels. Steroid therapy was performed in 61 patients; while its clinical impact was inconclusive due to heterogeneous situations, IL-6 levels decreased significantly more in these patients. Interpretation. Severe COVID-19 mostly relates to late-onset pneumonia associated with preexisting metabolic syndrome markers and a surge in inflammatory markers, allowing the early identification of at-risk patients.

Almitrine as a non ventilatory strategy to improve intrapulmonary shunt in COVID-19 patients (preprint)

In severe COVID-19 pulmonary failure, hypoxia is mainly related to pulmonary vasodilation with altered hypoxic pulmonary vasoconstriction (HPV). Besides prone positioning, other non-ventilatory strategies may reduce the intrapulmonary shunt. This study has investigated almitrine, a pharmacological option to improve oxygenation. Patients and Method. A case control series of 17 confirmed COVID-19 mechanically ventilated patients in prone or supine positioning was collected: 10 patients received two doses of almitrine (4 and 12 mcg/kg/min) at 30-45 min interval each, and were compared to 7 control COVID-matched patients conventionally treated. The end-point was the reduction of intra-pulmonary shunt increasing the PaO2 and ScvO2. Results Patients were male (59%) with median (25th, 75th percentiles) age of 70 (54-78) years and a BMI of 29 (23-34). At stable mechanical ventilatory settings, PaO2 (mmHg) at FiO2 1 (135 (85, 195) to 214 (121, 275); p = 0.06) tended to increase with almitrine. This difference was significant when the best PaO2 between the 2 doses was used : 215 (123,294) vs baseline (p = 0.01). A concomitant increase in ScvO2 occurred ((73 (72, 76) to 82 (80, 87); p = 0.02). Eight over 10 almitrine-treated patients increased their PaO2, with no clear dose-effect. During the same time, the controls did not change PaO2. In conclusion, in early COVID-19 with severe hypoxemia, almitrine infusion is associated with improved oxygenation in prone or supine positioning. This pharmacological intervention may offer an alternative and/or an additional effect to proning and might delay or avoid more demanding modalities such as ECMO.