Pervasive but Neglected: A Perspective on COVID-19-Associated Pulmonary Mold Infections Among Mechanically Ventilated COVID-19 Patients

Mona Ghazanfari; Amir Arastehfar; Lotfollah Davoodi; Jamshid Yazdani Charati; Maryam Moazeni; Mahdi Abastabar; Iman Haghani; Roghayeh Mirzakhani; Sabah Mayahi; Wenjie Fang; Wanqing Liao; M Hong Nguyen; David S Perlin; Martin Hoenigl; Weihua Pan; Mohammad T Hedayati

doi:10.3389/fmed.2021.649675

Pervasive but Neglected: A Perspective on COVID-19-Associated Pulmonary Mold Infections Among Mechanically Ventilated COVID-19 Patients

Front Med (Lausanne). 2021 Jun 14:8:649675. doi: 10.3389/fmed.2021.649675. eCollection 2021.

Authors

Mona Ghazanfari^{1

2}, Amir Arastehfar³, Lotfollah Davoodi⁴, Jamshid Yazdani Charati⁵, Maryam Moazeni^{1

2}, Mahdi Abastabar^{1

2}, Iman Haghani^{1

2}, Roghayeh Mirzakhani^{1

2}, Sabah Mayahi^{1

2}, Wenjie Fang⁶, Wanqing Liao⁶, M Hong Nguyen⁷, David S Perlin³, Martin Hoenigl^{8

9

10}, Weihua Pan⁶, Mohammad T Hedayati^{1

2}

Affiliations

¹ Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.
² Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
³ Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United States.
⁴ Antimicrobial Resistance Research Center/Department of Infectious Diseases, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
⁵ Department of Biostatistics, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran.
⁶ Medical Mycology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
⁷ Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
⁸ Clinical and Translational Fungal-Working Group, University of California, San Diego, La Jolla, CA, United States.
⁹ Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
¹⁰ Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, San Diego, CA, United States.

Abstract

Background: Recent studies from multiple countries have shown a high prevalence of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) among severely ill patients. Despite providing valuable insight into the clinical management of CAPA, large-scale prospective studies are limited. Here, we report on one of the largest multicenter epidemiological studies to explore the clinical features and prevalence of COVID-19-associated pulmonary mold infections (CAPMIs) among mechanically ventilated patients. Methods: Bronchoalveolar lavage (BAL) and serum samples were collected for culture, galactomannan (GM), and β-D-glucan (BDG) testing. Patients were classified as probable CAPMI based on the presence of host factors, radiological findings, and mycological criteria. Results: During the study period, 302 COVID-19 patients were admitted to intensive care units (ICUs), among whom 105 were mechanically ventilated for ≥4 days. Probable CAPMI was observed among 38% of patients (40/105), among whom BAL culture of 29 patients turned positive for molds, while galactomannan testing on BAL (GM index ≥1) and serum (GM index >0.5) samples were positive for 60% (24/40) and 37.5% (15/39) of patients, respectively. Aspergillus (22/29; 75.8%) and Fusarium (6/29; 20.6%) constituted 96.5% of the molds isolated. Diaporthe foeniculina was isolated from a COVID-19 patient. None of the patients who presented with CAPMI were treated with antifungal drugs. Conclusion: Despite being prevalent, the absence of appropriate antifungal treatment highlights that CAPMI is a neglected complication among mechanically ventilated COVID-19 patients admitted to ICUs. CAPMI can be caused by species other than Aspergillus.

Keywords: Aspergillus; COVID-19-associated pulmonary mold infections; Fusarium; galactomannan; mechanically ventilation.