# COVID-19-associated Pulmonary Aspergillosis in Mechanically Ventilated Patients at 7 US Hospitals: Epidemiology and Estimated Likelihood of Invasive Pulmonary Aspergillosis—Results of the Prospective MSG-017 Study

## TL;DR

A US study found that 7% of ventilated COVID-19 patients had CAPA, but only 30% of these cases likely involved invasive fungal infection.

## Contribution

This is the first prospective US multicenter study to estimate the likelihood of invasive aspergillosis in CAPA patients.

## Key findings

- CAPA incidence was 7% among ventilated COVID-19 patients.
- Single positive mycologic tests are insufficient for diagnosing invasive aspergillosis.
- Median estimated likelihood of invasive aspergillosis in CAPA patients was 30%.

## Abstract

There is no prospective, US multicenter study of COVID-19–associated pulmonary aspergillosis (CAPA). CAPA definitions do not differentiate invasive aspergillosis (IPA) from colonization. Validity of single mycologic test results is unclear.

We performed a prospective 7-center US study of mechanically ventilated adults with COVID-19 (April 2021–May 2022). Mycoses Study Group (MSGERC) CAPA criteria include host and clinical factors, imaging and test results (histopathology; bronchoalveolar lavage [BAL] culture and/or BAL or serum galactomannan-immunoassay). Proven, putative, and unlikely IPA were defined by clinical criteria. CAPA-unlikely IPA criteria included survival or negative autopsy following no/limited antifungal treatment. IPA likelihood was estimated using sensitivity/specificity of tests from autopsy data.

CAPA incidence was 7% (14/212). Independent CAPA risk factors were EORTC/MSGERC host factor and cavitary lesions. Seven percent, 79%, and 14% of CAPA patients had proven, putative, and unlikely IPA, respectively. Respective estimated IPA likelihoods were 84%, 7%–99%, and 1%–8%. Overall, median estimated IPA likelihood was 30%. Patients with CAPA-unlikely IPA had a single positive BAL galactomannan-immunoassay with other negative tests. CAPA mortality (71%) was not impacted by antifungal treatment or significantly different than without CAPA. CAPA incidence was 10% and 16% by European Confederation of Medical Mycology and Public Health Wales definitions, respectively. IPA was unlikely in 75% (6/8) and 57% (13/23) diagnosed by these definitions but not MSGERC.

CAPA is associated with high mortality, but IPA's contribution is unclear. Single positive tests are insufficient for diagnosing CAPA-IPA. IPA likelihood is best estimated by combining test results (both positive and negative).

COVID-19–associated pulmonary aspergillosis (CAPA) incidence was 7% in US intensive care units. CAPA represents a continuum encompassing invasive pulmonary aspergillosis (IPA) and noninvasive colonization. Median estimated likelihood of IPA in patients with CAPA was 30%. Acceptance of single positive mycologic test results likely over-estimates IPA.