Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus
Jacob L. Steenwyk, Matthew E. Mead, Patrícia Alves de Castro, Clara Valero, André Damásio, Renato Santos, Abigail L. LaBella, Yuanning Li, Sonja L. Knowles, Huzefa A. Raja, Nicholas H. Oberlies, Xiaofan Zhou, Oliver A. Cornely, Frieder Fuchs, Philipp Koehler, Gustavo H. Goldman, Antonis Rokas
Abstract
The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), has already killed millions of people. COVID-19 patient outcome can be further complicated by secondary infections, such as COVID-19-associated pulmonary aspergillosis (CAPA). CAPA is caused by Aspergillus fungal pathogens, but there is little information about the genomic and phenotypic characteristics of CAPA isolates. We conducted genome sequencing and extensive phenotyping of four CAPA isolates of Aspergillus fumigatus from Germany. We found that CAPA isolates were often, but not always, similar to other reference strains of A. fumigatus across 206 genetic determinants of infection-relevant phenotypes, including virulence. For example, CAPA isolate D was more virulent than other CAPA isolates and reference strains in an invertebrate model of fungal disease, but similarly virulent to two other clinical strains. These results expand our understanding of COVID-19-associated pulmonary aspergillosis.