Genomic epidemiology of EuropeanAspergillus fumigatuscausing COVID-19-associated pulmonary aspergillosis in Europe

Abstract

AbstractThe opportunistic fungusAspergillus fumigatushas been found to cause coinfections in patients with severe SARS-CoV-2 virus infection, leading to COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA all-cause mortality rate is approximately 50% and may be complicated by azole-resistance. Genomic epidemiology can help shed light on the genetics ofA. fumigatuscausing CAPA including the prevalence of alleles that are associated with azole-resistance. Here, a population genomic analysis of 21 CAPA isolates from four European countries is presented. The CAPA isolates were compared withA. fumigatusfrom a wider population of 167 non-CAPA clinical isolates and 73 environmental isolates. Bioinformatic analysis and antifungal susceptibility testing were performed to quantify resistance and identify possible genetically-encoded azole-resistant mechanisms. Phylogenetic analysis of the 21 CAPA isolates showed a lack of genetic distinction from the widerA. fumigatuspopulation, with isolates distributed within two distinct clades (A and B), with the majority of the CAPA isolates in clade B (71.4%). The prevalence of phenotypic azole-resistance in CAPA was 14.3% (n=3/21); all three CAPA isolates contained a known resistance-associatedcyp51Apolymorphism. CAPA isolates are drawn from the widerA. fumigatuspopulation rather than forming a unique genetic background showing that COVID-19 patients are susceptible to the entireA. fumigatuspopulation. However, the relatively high prevalence of azole-resistance alleles that we document poses a threat to treatment success rates, warranting enhanced detection and surveillance ofA. fumigatusgenotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes.