Invasive Pulmonary Aspergillosis Common in Intubated COVID-19 Patients

By Will Boggs MD

August 14, 2020

NEW YORK (Reuters Health) - More than a quarter of intubated patients with COVID-19 have evidence of invasive pulmonary aspergillosis, according to a new study.

"Active surveillance for aspergillosis should be implemented in all cases of critical COVID-19 patients and prompt antifungal treatment can be considered," Dr. Michele Bartoletti of Sant'Orsola Malpighi Hospital and the University of Bologna, in Italy, told Reuters Health by email. "Bacterial and fungal superinfection should be carefully evaluated in every patient that is failing to improve with common treatments."

Previous studies have reported invasive pulmonary aspergillosis complicating severe influenza in patients admitted to intensive-care units (ICUs), and preliminary reports suggest a high incidence of invasive aspergillosis in intubated patients with COVID-19.

Dr. Bartoletti and colleagues in the PREDICO study group evaluated the incidence and outcome of coronavirus-associated pulmonary aspergillosis (CAPA) among 108 patients diagnosed with SARS-CoV-2 infection and admitted for mechanical ventilation at four ICUs from three hospitals in Bologna.

Based on revised definitions of possible, probable and proven invasive aspergillosis in immunocompromised patients from the European Organization for Research and Treatment of Cancer/Mycoses Study Group, 27.7% of these patients had probable aspergillosis, diagnosed after a median four days from intubation and a median 14 days from COVID-19 symptom onset.

The incidence of probable CAPA was 38.83 per 10,000 ICU patient-days, and the only factor associated with CAPA was chronic steroid therapy at doses equivalent to or higher than prednisone 16 mg/day for at least 15 days, the researchers report in Clinical Infectious Diseases.

When defined based on a serum galactomannan (GM) index >0.5 or bronchoalveolar lavage (BAL) GM index >1.0, pulmonary aspergillosis was diagnosed in 17.6% of patients.

During a median follow-up of 31 days, 50% of patients were discharged alive, 41% died, and nine patients remained hospitalized.

Patients with probable CAPA had significantly higher 30-day mortality from ICU admission (44%) than did patients without CAPA (19%). Mortality was also higher when pulmonary aspergillosis was defined based on the serum GM index (74% vs. 26%).

The odds of death within 30 days of ICU admission increased by 41% for each point increase in the initial BAL GM index.

Among patients with probable CAPA, voriconazole treatment was associated with a trend toward lower mortality.

"The major limitation of our report was that we were unable to perform serial autopsies on all deceased individuals; therefore, we were unable to assess whether aspergillosis was the real cause of death of these patients," Dr. Bartoletti said.

"These findings should be further confirmed in more specific studies," he said.

Dr. Martin Hoenigl of the University of California, San Diego, and the Medical University of Graz, in Austria, who recently reviewed COVID-19-associated pulmonary aspergillosis, told Reuters Health by email, "The high prevalence of COVID-19-associated aspergillosis in this multicenter study of COVID-19 patients receiving mechanical ventilation is mainly confirming what has been previously reported from other centers and countries. What this study really adds is the clear and strong association between COVID-19-associated aspergillosis and mortality, which remained significant even after adjusting for confounders."

"Physicians should take away that pulmonary aspergillosis is a relatively frequent superinfection in mechanically ventilated COVID-19 patients," said Dr. Hoenigl, who was not involved in the study. "Screening should be performed via, e.g., culture and GM testing of tracheal aspirates as well as serum GM screening. In those with suspicion of COVID-19-associated aspergillosis, aggressive diagnostic approaches (should be used) for establishing the diagnosis, optimally using closed-system bronchoscopies that can be safely performed in COVID-19 patients."

"Early initiation of antifungal treatment with voriconazole, liposomal amphotericin B, or isavuconazole is likely important to improve survival," Dr. Hoenigl said.

SOURCE: Clinical Infectious Diseases, online July 28, 2020.