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

Abstract

The opportunistic fungus Aspergillus fumigatus has 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 of A. fumigatus causing 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 with A. fumigatus from 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 wider A. fumigatus population, 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-associated cyp51A polymorphism. CAPA isolates are drawn from the wider A. fumigatus population rather than forming a unique genetic background showing that COVID-19 patients are susceptible to the entire A. fumigatus population. However, the relatively high prevalence of azole-resistance alleles that we document poses a threat to treatment success rates, warranting enhanced detection and surveillance of A. fumigatus genotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes.

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“…Recent research has revealed that strains of A. flavus, the second largest cause and one of the main agents of serious comorbidities, including Aspergillosis; also causing co-infections in patients with severe infection by the SARS-CoV-2 virus, leading to pulmonary aspergillosis associated with COVID-19 (Mariscal et al, 2023;Simmons et al, 2023) were tested after exposure to the same azoles agricultural products had the MIC (Minimum Inhibitory Concentration) for drugs of the same class, posaconazole, voriconazole and itraconazole increased, showing that agricultural pesticides can, in fact, reduce the effectiveness of antifungals used in the clinic (Meireles et al, 2019).…”