HighlightsWhat are the main findings?A definite diagnosis of invasive pulmonary aspergillosis is elusive in patients with severe COVID-19.Experimental and clinical data indicate that delayed initiation of antifungal therapy could be detrimental to IA.What is the implication of the main finding?The persistence of a respiratory co-infection in SARS-CoV-2 patients despite the administration of broad-spectrum antibiotics should lead to the pursuit of the confirmation or exclusion of IPA, especially in those patients who present risk factors for invasive pulmonary aspergillosis.Early treatment should be initiated, even in the absence of a definite diagnosis, when clinical suspicion is high.AbstractInvasive pulmonary aspergillosis (IPA) presents a known risk to critically ill patients with SARS-CoV-2; quantifying the global burden of IPA in SARS-CoV-2 is extremely challenging. The true incidence of COVID-19-associated pulmonary aspergillosis (CAPA) and the impact on mortality is difficult to define because of indiscriminate clinical signs, low culture sensitivity and specificity and variability in clinical practice between centers. While positive cultures of upper airway samples are considered indicative for the diagnosis of probable CAPA, conventional microscopic examination and qualitative culture of respiratory tract samples have quite low sensitivity and specificity. Thus, the diagnosis should be confirmed with serum and BAL GM test or positive BAL culture to mitigate the risk of overdiagnosis and over-treatment. Bronchoscopy has a limited role in these patients and should only be considered when diagnosis confirmation would significantly change clinical management. Varying diagnostic performance, availability, and time-to-results turnaround time are important limitations of currently approved biomarkers and molecular assays for the diagnosis of IA. The use of CT scans for diagnostic purposes is controversial due to practical concerns and the complex character of lesions presented in SARS-CoV-2 patients. The key objective of management is to improve survival by avoiding misdiagnosis and by initiating early, targeted antifungal treatment. The main factors that should be considered upon selection of treatment options include the severity of the infection, concomitant renal or hepatic injury, possible drug interactions, requirement for therapeutic drug monitoring, and cost of therapy. The optimal duration of antifungal therapy for CAPA is still under debate.