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

Abstract

COVID-19 associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complication affecting critically ill patients with acute respiratory distress syndrome following SARS-CoV-2 infection, with incidence rates varying from 8 to 33% depending on the study. However, definitive diagnosis of CAPA is challenging. Standardised diagnostic algorithms and definitions are lacking, clinicians are reticent to perform aerosol-generating bronchoalveolar lavages for galactomannan testing and microscopic and cultural examination, and questions surround the diagnostic sensitivity of different serum biomarkers. Between 11th March and 14th July 2020, the UK National Mycology Reference Laboratory received 1267 serum and respiratory samples from 719 critically ill UK patients with COVID-19 and suspected pulmonary aspergillosis. The laboratory also received 46 isolates of Aspergillus fumigatus from COVID-19 patients (including three that exhibited environmental triazole resistance). Diagnostic tests performed included 1000 (1-3)-β-d-glucan and 516 galactomannan tests on serum samples. The results of this extensive testing are presented here. For a subset of 61 patients, respiratory specimens (bronchoalveolar lavages, tracheal aspirates, sputum samples) in addition to serum samples were submitted and subjected to galactomannan testing, Aspergillus-specific PCR and microscopy and culture. The incidence of probable/proven and possible CAPA in this subset of patients was approximately 5% and 15%, respectively. Overall, our results highlight the challenges in biomarker-driven diagnosis of CAPA especially when only limited clinical samples are available for testing, and the importance of a multi-modal diagnostic approach involving regular and repeat testing of both serum and respiratory samples.

COVID‐19–associated pulmonary aspergillosis: a prospective single‐center dual case series

“…From our cohort, two patients had an environmental TR 34 /L98H azole‐resistant isolate, one of these elsewhere published as a case report 20 . This mutation has also been identified in CAPA patients in Ireland, 38 France 39 and the UK 2 underscoring the challenges faced in patient management, the importance of early diagnostics and (inter)national surveillance programs.…”

“…Recently published small case series describe an overall high incidence of CAPA in SARS‐CoV‐2‐positive patients admitted to the ICU with acute respiratory distress syndrome requiring mechanical ventilation. The United Kingdom, 1,2 The Netherlands, 3,4 Belgium, 5 Germany, 6 Italy 7 and France 8,9 report incidences of 12.3%–33.3%. In Denmark, 10 a 25% ( n = 2/8) incidence of invasive aspergillosis in COVID‐19 patients undergoing extracorporeal membrane oxygenation (ECMO) was described, totalling 7.4% when adding the non‐ECMO ICU population ( n = 19).…”

“…Recently published small case series describe an overall high incidence of CAPA in SARS-CoV-2-positive patients admitted to the ICU with acute respiratory distress syndrome requiring mechanical ventilation. The United Kingdom, 1,2 The Netherlands, 3,4 Belgium, 5 Germany, 6 Italy 7 and France 8,9 report incidences of 12.3%-33.3%.…”

Covid-19-Associated Pulmonary Aspergillosis: The Other Side of the Coin

“…Recent extensive diagnosic testing has been performed in 719 critically ill COVID-19 patients. In a subset of 61 patients for whom both serum and respiratory samples were available, rates of 5% (3/61) and 15% (10/61) of proven/probable and possible CAPA, respectively, were reported [ 26 ].…”

Innate and Adaptive Immune Responses Induced by A. Fumigatus Conidia and Hyphae

“…With the widespread use of broad-spectrum antibiotics and immunosuppressive agents, the high incidence of aspergillosis remains to be a public concern [5][6][7][8]. Moreover, the ongoing pandemic of coronavirus disease 2019 (COVID-19) has shown a high frequency of co-infection with aspergillus spp., leading to terrible clinical results and a heavy medical burden [9][10][11][12][13][14].Aspergillus fumigatus (A. fumigatus) is the most common etiologic species of aspergillosis. In its life cycle, numerous asexual conidia are produced and spread, which can be inhaled by humans and easily reach the alveoli owing to their tiny size [15].…”