Genomic epidemiology of COVID-19-associated pulmonary aspergillosis from four European countries confirms isolates are drawn from the wider Aspergillus fumigatus population

The opportunistic fungus Aspergillus fumigatus was found to co-infect COVID-19 patients, causing a form of invasive aspergillosis (IA), COVID-19-associated pulmonary aspergillosis (CAPA). In most cases, CAPA is fatal. A recent increase in antifungal drug resistance has been associated with increased treatment failure and poor patient outcomes. Despite advancements in the clinical epidemiological understanding of CAPA, little is understood of A. fumigatus genetics causing CAPA. Here, a population genomic analysis of 29 A. fumigatus from CAPA patients from four Western European countries is presented. Firstly, the CAPA isolates were compared with 11 A. fumigatus isolates from IA patients from the UK, and, secondly, with 232 isolates from the wider A. fumigatus population, from patients (n=158) and the environment (n=74) across Ireland and the UK. Phylogenetic analysis of the 29 CAPA isolates showed a lack of genetic distinction from the wider A. fumigatus population, with isolates distributed within two distinct clades (clades A and B), with the majority of the CAPA isolates found in clade B (75.9%). The prevalence of azole-resistance in CAPA was 27.6% (n=8). However, four CAPA isolates contained novel polymorphisms. A. fumigatus isolates that cause CAPA are drawn from the wider A. fumigatus population rather than CAPA forming a unique genetic background. Therefore, CAPA patients are susceptible to the entire A. fumigatus population. However, high prevalence of azole-resistance poses a threat to treatment success rates, warranting enhanced surveillance of A. fumigatus and potential changes to anti-fungal treatment guidelines, ensuring treatment is successful and improved patient outcomes.