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

Abstract

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.

Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report

“…Second, type-2 diabetes, which remains a major comorbidity for severe COVID-19 [10,27] and increases the risk of mortality, especially in individuals with poorly controlled blood glucose [28]. Third, superinfection, which represents a new albeit scarcely studied condition in COVID-19 [5], particularly for invasive fungal infections [14,29]. The peculiar pathophysiology of either diabetes [11] or COVID-19 [30] may account for the occurrence of bacterial and fungal coinfections in our case, as in other cases [3,31].…”

Bacterial and fungal superinfections in critically ill patients with COVID-19

“…More than 30 cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been published to date [9]. Overall, the possible development of invasive pulmonary aspergillosis in some critically ill COVID-19 patients is somewhat expected, considering the following, likely cumulative risk factors: (1) the epithelial lung damage caused by either the virus or the dysregulated host response; (2) the frequent use of corticosteroids [10]; (3) a possible similarity with influenza-associated invasive aspergillosis (IAPA) [11].…”

COVID-19-Associated Invasive Aspergillosis: Data from the UK National Mycology Reference Laboratory

“…Since late 2019, a novel betacoronavirus (SARS-CoV-2) has rapidly spread around the world, causing a global pandemic of coronavirus-19 disease (COVID-19) with over 13 million cases and in excess of 500 000 deaths to date (14 th July 2020). The disease spectrum in COVID-19 ranges from asymptomatic infection to severe illness with acute respiratory distress syndrome (ARDS) requiring critical care, with 20-40% of hospitalised symptomatic patients developing ARDS (10)(11)(12). An increasing number of anecdotal case reports and case series have identified COVID-19 associated pulmonary aspergillosis (CAPA) as an additional infective complication of COVID-19 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

“…The disease spectrum in COVID-19 ranges from asymptomatic infection to severe illness with acute respiratory distress syndrome (ARDS) requiring critical care, with 20-40% of hospitalised symptomatic patients developing ARDS (10)(11)(12). An increasing number of anecdotal case reports and case series have identified COVID-19 associated pulmonary aspergillosis (CAPA) as an additional infective complication of COVID-19 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Depending on the study and the region of origin, reported incidence rates for CAPA ranged from approximately 5% (14) to 20-35% (17)(18)(19)(20)(21).…”

“…Depending on the study and the region of origin, reported incidence rates for CAPA ranged from approximately 5% (14) to 20-35% (17)(18)(19)(20)(21). Similarly to IAPA, many questions remain concerning the diagnostic criteria used to define CAPA (12), and diagnosis remains challenging. Radiological findings in COVID- 19 and IA in non-neutropenic patients are non-specific and show considerable overlap.…”