Combination of Mycological Criteria: a Better Surrogate to Identify COVID-19-Associated Pulmonary Aspergillosis Patients and Evaluate Prognosis?

Abstract

Introduction: Diagnosis of COVID-19 associated pulmonary aspergillosis remains unclear especially in non-immunocompromised patients. The aim of this study was to evaluate seven mycological criteria and their combination in a large homogenous cohort of patients. Methods: All successive patients (n=176) hospitalized for COVID-19 requiring mechanical ventilation and who clinically worsened despite appropriate standard of care were included over a one-year period. Direct examination, culture, Aspergillus qPCR ( Af -qPCR) and galactomannan was performed on all respiratory samples (n=350). Serum galactomannan, ß-D-glucan and plasma Af -qPCR were also assessed. Criteria were analyzed alone or in combination in relation to mortality rate. Results: Mortality was significantly different in patients with 0, ≤2 and ≥3 positive criteria (logrank test, p=0.04) with death rate of 43.1, 58.1 and 76.4% respectively. Direct examination, plasma qPCR and serum galactomannan were associated with a 100% mortality rate. Bronchoalveolar lavage (BAL) galactomannan and positive respiratory sample culture were often found as isolated markers (28.1 and 34.1%) and poorly repeatable when a second sample was obtained. Aspergillus DNA was detected in 13.1% of samples (46/350) with significantly lower Cq when associated with at least one other criteria (30.2 vs 35.8) (p<0.001). Conclusion: Combination of markers and/or blood biomarkers and/or direct respiratory sample examination seems more likely to identify patients with CAPA. Af -qPCR may help identifying false positive results of BAL galactomannan testing and culture on respiratory samples while quantifying fungal burden accurately.

Utility of Serum 1,3-β- d -Glucan Testing for Diagnosis and Prognostication in COVID-19-Associated Pulmonary Aspergillosis

“…Angioinvasion typically occurs only in later stages of the disease, resulting in limited sensitivity of serum biomarker testing ( 7 ). Combining results of our study with those from prior studies ( 1 , 2 ), per-patient sensitivity and specificity of serum BDG for CAPA were 56% (49/87) and 56% (112/199), respectively. While prevalence of CAPA varies, a median prevalence of 10% ( 4 ) and 15% ( 8 ) has been reported in the largest multicenter studies conducted to date.…”

“…COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a life-threatening complication in patients admitted to intensive care units (ICUs) for COVID-19-associated acute respiratory failure (ARF). Two recent studies on the prognostic potential of serum 1,3-β- d -glucan (BDG) in ICU patients with COVID-19 ARF ( 1 , 2 ) found positive serum BDG to be associated with 75% to 90% mortality, versus 42% to 47% mortality in those with negative serum BDG ( P < 0.01; adjusted odds ratio of 1.3 per 10-point increase of BDG among patient with CAPA). While in some studies serum BDG results were also utilized as mycological evidence ( 3 ), the diagnostic potential of serum BDG for CAPA in ICUs remains controversial and larger analyses are lacking.…”

COVID‐19‐associated aspergillosis in a Brazilian referral centre: Diagnosis, risk factors and outcomes

“…The diagnosis of CAPA is challenging, and the combination of different diagnostic tools may be necessary for its diagnosis. 21 If only tracheal aspirate cultures were considered for CAPA diagnosis, several cases would have been treated unnecessarily in our centre. Serum galactomannan was requested for 43 patients in our cohort.…”

Nebulized Amphotericin B in Mechanically Ventilated COVID-19 Patients to Prevent Invasive Pulmonary Aspergillosis: A Retrospective Cohort Study

“…In our cohort, three out of 11 patients in whom a bronchoscopy was performed a probable CAPA was detected, despite the nebulization of c-AmB. One of these patients was diagnosed with CAPA based solely on a positive BAL-galactomannan, while BAL PCR and cultures remained negative for Aspergillus, which may indicate a false positive BAL-galactomannan (24,25). The other two patients had positive sputum cultures prior to intubation, indicating Aspergillus colonization or infection before prophylaxis was initiated.…”