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. 2022 Mar 3;9(5):ofac081.
doi: 10.1093/ofid/ofac081. eCollection 2022 May.

Coronavirus Disease 2019-Associated Pulmonary Aspergillosis: Reframing the Debate

Cornelius J Clancy  1   2 , M Hong Nguyen  1   3
Affiliations

Coronavirus Disease 2019-Associated Pulmonary Aspergillosis: Reframing the Debate

Cornelius J Clancy et al. Open Forum Infect Dis. .

Abstract

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has been reported in ~5%-10% of critically ill COVID-19 patients. However, incidence varies widely (0%-33%) across hospitals, most cases are unproven, and CAPA definitions and clinical relevance are debated.

Methods: We reframed the debate by asking, what is the likelihood that patients with CAPA have invasive aspergillosis? We use diagnostic test performance in other clinical settings to estimate positive predictive values (PPVs) and negative predictive values (NPVs) of CAPA criteria for invasive aspergillosis in populations with varying CAPA incidence.

Results: In a population with CAPA incidence of 10%, anticipated PPV/NPV of diagnostic criteria are ~30%-60%/≥97%; ~3%-5% of tested cohort would be anticipated to have true invasive aspergillosis. If CAPA incidence is 2%-3%, anticipated PPV and NPV are ~8%-30%/>99%.

Conclusions: Depending on local epidemiology and clinical details of a given case, PPVs and NPVs may be useful in guiding antifungal therapy. We incorporate this model into a stepwise strategy for diagnosing and managing CAPA.

Keywords: Aspergillus; CAPA; COVID-19; coronavirus disease 2019-associated pulmonary aspergillosis; galactomannan.

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Figures

Figure 1.
Figure 1.
Coronavirus disease 2019-associated pulmonary aspergillosis (CAPA) and invasive pulmonary aspergillosis (IPA). The relationship between CAPA and IPA in critically ill patients with coronavirus disease 2019 (COVID-19) is represented by a Venn diagram. Coronavirus disease 2019-associated pulmonary aspergillosis criteria (large circle on left) signify the likely presence of Aspergillus in the respiratory tract. Invasive pulmonary aspergillosis (small circle on right) is defined by Aspergillus invasion and attendant damage of respiratory tract tissue. Some patients who fulfill CAPA diagnostic criteria have IPA (group 2), but others do not (group 1). In groups 1 and 2, a diagnosis of CAPA can be considered false positive (FP) or true positive (TP) for IPA, respectively. Several critically ill patients with COVID-19 may have IPA without fulfilling criteria for CAPA (group 3, represented by the asterisk in the Venn diagram). In this group, CAPA is false negative (FN) for IPA. It is plausible, but as yet unproven, that IPA in some patients is preceded by CAPA that represents Aspergillus colonization of the respiratory tract.
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