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Aspergillus test profiles and mortality in critically-ill COVID-19 patients

, , , , Andreas van Arkel, Robbert G. Bentvelsen, Tom Rijpstra, Simone Van Der Sar-Van Der Brugge, Katrien Lagrou, Nico A.F. Janssen,
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Abstract: Background The literature regarding COVID-19 associated pulmonary aspergillosis (CAPA) has shown conflicting observations, including survival of CAPA patients not receiving antifungal therapy and discrepancy between CAPA diagnosis and autopsy findings. To gain insight into the pathophysiology of CAPA we performed a case-control study, in which we compared Aspergillus test profiles in CAPA patients and controls in relation to ICU-mortality. Methods A multinational case-control study, in which Aspergillus test results, use of antifungal therapy and mortality were collected from critically-ill COVID-19 patients. Patients were classified using the 2020 ECMM/ISHAM consensus case definitions. Results 219 critically-ill COVID-19 cases were analyzed, including one proven, 38 probable, 19 possible CAPA cases, 21 Aspergillus colonized patients, seven patients only positive for serum (1, 3)-ß-D-glucan (BDG), and 133 cases with no evidence of CAPA. Mortality was 53.8% in CAPA patients compared to 24.1% in patients without CAPA (p=0.001). Positive serum galactomannan (GM) and BDG were associated with increased mortality compared to serum biomarker negative CAPA patients (87.5% versus 41.7%, p=0.046; 90.0% versus 42.1%, p=0.029, respectively). For each point increase in GM or ten-point BDG serum concentration, the odds of death increased (GM, OR 10.208, 95%CI 1.621-64.291, p=0.013; BDG, OR 1.247, 95%CI 1.029-1.511, p=0.024). Conclusions CAPA is a complex disease, probably involving a continuum of respiratory colonization, tissue-invasion and angioinvasion. Serum biomarkers are useful for staging CAPA disease progression and, if positive, indicate angioinvasion and a high probability of mortality. There is need for a biomarker that distinguishes between respiratory tract colonization and tissue invasive CAPA disease.
Keywords: mortality / CAPA patients / survival / BDG / biomarker / colonization / Aspergillus

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