Simmons Benjamin C, Rhodes Johanna, Rogers Thomas R, Verweij Paul E, Abdolrasouli Alireza, Schelenz Silke, Hemmings Samuel J, Talento Alida Fe, Griffin Auveen, Mansfield Mary, Sheehan David, Bosch Thijs, Fisher Matthew C
Medical Research Council Centre for Global Infectious Disease Analysis, Imperial College London, London W2 1PG, UK.
UK Health Security Agency, London EP14 4PU, UK.
J Fungi (Basel). 2023 Nov 13;9(11):1104. doi: 10.3390/jof9111104.
has been found to coinfect 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 causing CAPA, including the prevalence of resistance-associated alleles. We present a population genomic analysis of 21 CAPA isolates from four European countries with these isolates compared against 240 non-CAPA isolates from a wider population. Bioinformatic analysis and antifungal susceptibility testing were performed to quantify resistance and identify possible genetically encoded azole-resistant mechanisms. The phylogenetic analysis of the 21 CAPA isolates showed that they were representative of the wider population with no obvious clustering. The prevalence of phenotypic azole resistance in CAPA was 14.3% ( = 3/21); all three CAPA isolates contained a known resistance-associated polymorphism. The relatively high prevalence of azole resistance alleles that we document poses a probable threat to treatment success rates, warranting the enhanced surveillance of genotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes when CAPA is suspected.
已发现其可与严重的SARS-CoV-2病毒感染患者合并感染，导致新型冠状病毒肺炎相关肺曲霉病（CAPA）。CAPA的全因死亡率约为50%，且可能并发唑类耐药。基因组流行病学有助于阐明导致CAPA的遗传学特征，包括耐药相关等位基因的流行情况。我们对来自四个欧洲国家的21株CAPA分离株进行了群体基因组分析，并将这些分离株与来自更广泛群体的240株非CAPA分离株进行了比较。进行了生物信息学分析和抗真菌药敏试验，以量化耐药性并确定可能的基因编码唑类耐药机制。对21株CAPA分离株的系统发育分析表明，它们代表了更广泛的群体，没有明显的聚类。CAPA中表型唑类耐药的发生率为14.3%（n = 3/21）；所有三株CAPA分离株都含有一个已知的耐药相关多态性。我们记录的唑类耐药等位基因相对较高的流行率可能对治疗成功率构成威胁，因此有必要加强对这些患者基因型的监测。此外，当怀疑有CAPA时，可能需要对抗真菌一线治疗指南进行潜在调整，以改善患者预后。
