"CAPA in Progress": A New Real-Life Approach for the Management of Critically Ill COVID-19 Patients

Abstract

(1) Background: COVID-19-associated pulmonary aspergillosis (CAPA) has worsened the prognosis of patients with pneumonia and acute respiratory distress syndrome admitted to the intensive care unit (ICU). The lack of specific diagnosis criteria is an obstacle to the timely initiation of appropriate antifungal therapy. Tracheal aspirate (TA) has been employed under special pandemic conditions. Galactomannan (GM) antigens are released during active fungal growth. (2) Methods: We proposed the term "CAPA in progress" (CAPA-IP) for diagnosis at an earlier stage by GM testing on TA in a specific population admitted to ICU presenting with clinical deterioration. A GM threshold ≥0.5 was set as the mycological inclusion criterion. This was followed by a pre-emptive short-course antifungal. (3) Results: We prospectively enrolled 200 ICU patients with COVID-19. Of these, 164 patients (82%) initially required invasive mechanical ventilation and GM was tested in TA in 93 patients. A subset of 19 patients (11.5%) fulfilled the CAPA-IP criteria at a median of 9 days after ICU admittance. The median GM value was 3.25 ± 2.82. CAPA-IP cases showed significantly higher ICU mortality [52.6% (10/19) vs. 34.5% (50/145), p = 0.036], as well as a much longer median ICU stay than those with a normal GM index [27 (7-64) vs. 11 (9-81) days, p = 0.008]. All cases were treated with a pre-emptive systemic antifungal for a median time of 19 (3-39) days. (4) Conclusions: CAPA-IP highlights a new real-life early approach in the field of fungal stewardship in ICU programs.

Keywords: Aspergillus spp.; CAPA; COVID-19; acute respiratory distress syndrome; critically ill patients; galactomannan; tracheal aspirate; “CAPA in progress”.

Figure 1

Galactomannan values in consecutive tracheal aspirate samples during ICU stay in patients diagnosed with COVID-19 pneumonia and CAPA in progress. Green lines and symbols denote patients who died, and those who survived are indicated in yellow.

Figure 2

Algorithm for diagnosis and management of “CAPA in progress” in patients admitted to ICU diagnosed with COVID-19 pneumonia and ARDS requiring IMV. Possible approaches depend on hospital characteristics. The protocol followed in our study is shown on the left side while the previously described screening protocols on the right one [5,6,10]. Key aspects supporting our protocol in the algorithm are: ^a GM from TA is a subrogate of the emerging invasive process as the antigen is released during active fungal growth, providing the pathophysiologic basis of the CAPA-IP concept [8]. ^b Detection of Aspergillus spp. in respiratory samples (TA) by culture or PCR is associated with mortality [10]. ^c These three factors were independently associated with proven, probable, or possible CAPA in two large cohorts of critically ill patients diagnosed with COVID-19 pneumonia and ARDS [10,13]. ^d Diagnostic performance of GM in TA is improved using a cutoff value of 2 ODI, with a negative predictive value (NPV) of over 90% for CAPA probable diagnosis [6]. ^e Mean serum BDG value in patients with proven and probable invasive fungal disease is significantly higher than in those with fungal colonization, with an NPV of 83% [14]. ICU: intensive care unit; IMV: invasive mechanical ventilation; ARDS: acute respiratory distress syndrome; APR: acute phase reactants; TA: tracheal aspirate; GM: galactomannan; PCR: polymerase chain reaction; ODI: optical density index; BDG: (1-3)-β-d glucan; CT: computer tomography. Ref. [4] and refs. [1,4] refer to respective bibliographic references.