Coronavirus Disease 2019-Associated Pulmonary Aspergillosis: Reframing the Debate

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.