Mycobiome analyses of critically ill COVID-19 patients

Abstract

AbstractRationaleCOVID-19-associated pulmonary aspergillosis (CAPA) is a life-threatening complication in patients with severe COVID-19. Previously, acute respiratory distress syndrome in patients with COVID-19 has been associated with lung fungal dysbiosis, evidenced by reduced microbial diversity andCandidacolonisation. Increased fungal burden in the lungs of critically ill COVID-19 patients is linked to prolonged mechanical ventilation and increased mortality. However, specific mycobiome signatures associated with severe COVID-19 in the context of survival and antifungal drug prophylaxis have not yet been determined and such knowledge could have an important impact on treatment.ObjectivesTo understand the composition of the respiratory mycobiome in critically ill COVID-19 patients with and without CAPA and the impact of antifungal use in patient outcome.MethodsWe performed a multi-national study of 39 COVID-19 patients in intensive care units (ICU) with and without CAPA. Respiratory mycobiome was profiled using ITS1 sequencing andAspergillus fumigatusburden was further validated using qPCR. Fungal communities were investigated using alpha diversity, beta diversity, taxa predominance and taxa abundances.ResultsRespiratory mycobiomes of COVID-19 patients were dominated byCandidaandAspergillus.There was no significant association with corticosteroid use or CAPA diagnosis and respiratory fungal communities. IncreasedA. fumigatusburden was associated with mortality and, the use of azoles at ICU admission was linked with an absence ofA. fumigatus.ConclusionsOur findings suggest that mould-active antifungal treatment at ICU admission may be linked with reducedA. fumigatus-associated mortality in severe COVID-19. However, further studies are warranted on this topic.