COVID-19 Associated Pulmonary Aspergillosis (CAPA)-From Immunology to Treatment

被引:298
作者
Arastehfar, Amir [1 ]
Carvalho, Agostinho [2 ,3 ]
van de Veerdonk, Frank L. [4 ,5 ]
Jenks, Jeffrey D. [6 ,7 ]
Koehler, Philipp [8 ,9 ,10 ]
Krause, Robert [11 ]
Cornely, Oliver A. [8 ,9 ,10 ,12 ,13 ]
Perlin, David S. [1 ]
Lass-Floerl, Cornelia [14 ]
Hoenigl, Martin [7 ,11 ,15 ]
机构
[1] Hackensack Meridian Hlth, Ctr Discovery & Innovat, Nutley, NJ 07110 USA
[2] Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, P-4710057 Braga, Portugal
[3] ICVS 3Bs PT Govt Associate Lab, P-4710057 Braga, Portugal
[4] Radboud Univ Nijmegen, Dept Internal Med, Med Ctr, NL-6525 Nijmegen, Netherlands
[5] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Med Ctr, NL-6525 Nijmegen, Netherlands
[6] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA
[7] Univ Calif San Diego, Clin & Translat Fungal Working Grp, La Jolla, CA 92093 USA
[8] Univ Cologne, Dept Internal Med 8, Med Fac, D-50937 Cologne, Germany
[9] Univ Cologne, Univ Hosp Cologne, D-50937 Cologne, Germany
[10] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50937 Cologne, Germany
[11] Med Univ Graz, Dept Internal Med, Sect Infect Dis & Trop Med, A-8036 Graz, Austria
[12] Clin Trials Ctr Cologne, Zentrum Klin Studien ZKS Koln, D-50937 Cologne, Germany
[13] Univ Cologne, Med Fac, Partner Site Bonn Cologne, German Ctr Infect Res DZIF, D-50937 Cologne, Germany
[14] Med Univ Innsbruck, Div Hyg & Med Microbiol, A-6020 Innsbruck, Austria
[15] Univ Calif San Diego, Dept Med, Div Infect Dis & Global Publ Hlth, San Diego, CA 92093 USA
关键词
SARS COV-2; Aspergillus; novel coronavirus; superinfection; co-infection; risk factors; prevalence; challenges; immune response; expert statement; European Confederation of Medical Mycology; CRITICALLY-ILL; INVASIVE ASPERGILLOSIS; DIAGNOSIS; DISEASE; SUSCEPTIBILITY; INFLAMMATION; INFECTIONS; PNEUMONIA; SPECTRUM; MICE;
D O I
10.3390/jof6020091
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug-drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles.
引用
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页码:1 / 17
页数:17
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