Active screening of COVID-19-associated pulmonary aspergillosis with serum beta-glucan and endotracheal aspirates galactomannan and fungal culture.

BACKGROUND: Since February 2021 active screening of COVID-19-associated pulmonary aspergillosis (CAPA) has been implemented in our institution. OBJECTIVES: To evaluate CAPA incidence in our centre and evaluate performance of our screening protocol. METHODS: We screened once per week, collecting endotracheal aspirates for fungal culture and galactomannan (GM) and serum for 1,3-ß-D-glucan (BG). In case of positivity (GM more than 4.5, platelia assay, and/or BG >7 pg/ml, wako and/or positive fungal culture), second-level investigations were performed to pursue CAPA diagnosis according to ECMM/ISHAM criteria: bronchoalveolar lavage (BAL) fungal culture and GM, chest computed tomography (CT), serum GM. RESULTS: A total of 102 patients were screened (median age 64 years, range 39-79; 28 (27.4%) females). Twenty-two patients were diagnosed with CAPA (21%). 12 patients were positive for serum BG, 17 patients were positive for endotracheal aspirates GM and 27 patients were positive for endotracheal aspirates fungal culture. Thirty-two BALs were performed, and 26 patients underwent CT chest. Following the second level investigations 61% of the patients with positive screening tests were diagnosed with CAPA. Serum BG above 20 pg/ml or positive serum GM were always associated with typical CT chest signs of aspergillosis. Compared with 1 single positive test, having 2 positive screening test was significantly more associated with CAPA diagnosis (p = .0004). CONCLUSIONS: Active CAPA screening with serum 1,3-ß-D-glucan and endotracheal aspirates galactomannan and fungal cultures and consequent second level investigations led to high number of CAPA diagnosis. Combining more positive fungal biomarkers was more predictive of CAPA diagnosis.

"Heparinization" and hyperfibrinogenolysis by wasp sting.

We report on a patient with coagulation abnormalities induced by a wasp sting anaphylaxis. First, we observed an unclottable activated partial thromboplastin time and a significant anti-Xa activity (equivalent to a therapeutic heparin range), whereas the patient had received no heparin. This phenomenon is probably due to activated mast cells that release mediators such as heparin and tryptase. Heparin can then act as an anticoagulant by binding to antithrombin. This "heparinization" explains the anti-Xa activity contributing to the unclottable activated partial thromboplastin time detected in our patient. Second, we noted an extremely low fibrinogen level in the presence of normal platelet count and only a slight increase of D-dimers (absence of important disseminated intravascular coagulation). This is probably due to serum tryptase released during massive mast cell activation. Tryptase cleaves the alpha and beta chains of fibrinogen. This results in the removal of the thrombin cleavage site and of the critical polymerization site from the fibrinogen beta chain. Thrombin- initiated clot formation is therefore inhibited. Tryptase also acts directly on the fibrinolytic pathway by activating the single-chain urinary-type plasminogen activator, resulting in conversion of plasminogen into plasmin and therefore degradation of fibrinogen and other coagulation factors. This hyperfibrinogenolysis explains both the prolonged clotting times and the low fibrinogen level observed. Although our patient did not bleed, in other settings (trauma, during surgery) patients with anaphylaxis may present bleeding disorders. Although the mechanisms underlying these abnormalities have been described in vitro and in vivo animal trials, this is the first time they are described in a human clinical setting.