COVID-19-associated pulmonary aspergillosis: adding insult to injury
Authors: Giuseppe Bruno, Claudia Fabrizio, Giovanni Battista Buccoliero
Journal: The Lancet Microbe (2020)

Invasive pulmonary aspergillosis might represent a threat in patients with COVID-19. We read with interest the Comment by Paul Verweij and colleagues1Verweij PE Gangneux J-P Bassetti M et al.Diagnosing COVID-19-associated pulmonary aspergillosis.Lancet Microbe. 2020; (published online May 8.)https://doi.org/10.1016/S2666-5247(20)30027-6Summary Full Text Full Text PDF PubMed Scopus (146) Google Scholar on the crucial next research questions regarding COVID-19-associated pulmonary aspergillosis in terms of risk factors, diagnosis, prophylaxis, and treatment. Although some cases of COVID-19-associated pulmonary aspergillosis have been described,2Koehler P Cornely OA Böttiger BW et al.COVID-19 associated pulmonary aspergillosis.Mycoses. 2020; 63: 528-534Crossref PubMed Scopus (372) Google Scholar, 3Blaize M Mayaux J Nabet C et al.Fatal invasive aspergillosis and coronavirus disease in an immunocompetent patient.Emerg Infect Dis. 2020; (published online April 28.)DOI:10.3201/eid2607.201603Crossref PubMed Scopus (109) Google Scholar the burden of this fungal co-infection is still unknown and probably underestimated, particularly in patients with COVID-19 with critical clinical course.1Verweij PE Gangneux J-P Bassetti M et al.Diagnosing COVID-19-associated pulmonary aspergillosis.Lancet Microbe. 2020; (published online May 8.)https://doi.org/10.1016/S2666-5247(20)30027-6Summary Full Text Full Text PDF PubMed Scopus (146) Google Scholar Furthermore, beyond the well recognised risk factors for developing pulmonary aspergillosis, including neutropenia, prolonged use of corticosteroids, and haematological malignancy, it is not clear whether the cytokine storm and immune dysregulation characterising COVID-19 should be considered as additional risk factors.1Verweij PE Gangneux J-P Bassetti M et al.Diagnosing COVID-19-associated pulmonary aspergillosis.Lancet Microbe. 2020; (published online May 8.)https://doi.org/10.1016/S2666-5247(20)30027-6Summary Full Text Full Text PDF PubMed Scopus (146) Google Scholar, 4Chen G Wu D Guo W et al.Clinical and immunological features of severe and moderate coronavirus disease 2019.J Clin Invest. 2020; 130: 2620-2629Crossref PubMed Scopus (3141) Google Scholar We report the case of a 68-year-old immunocompetent man who was admitted on March 16, 2020, to our infectious diseases unit because of severe COVID-19-associated interstitial pneumonia. He developed acute respiratory distress syndrome 2 days later, hence was transferred to the intensive care unit. Therapy with hydroxychloroquine, lopinavir and ritonavir, glucocorticoids, and antibacterials was maintained. In addition, the patient received two doses of tocilizumab. On March 25, he was extubated and admitted to the pneumology unit to continue pulmonary rehabilitation and oxygen therapy. Following the worsening of dry cough and dyspnoea, together with a gradual increase in serum C-reactive protein concentrations, on April 9 the patient underwent a chest CT showing bilateral ground-glass opacities and excavated lesions, one of which with a crescent sign (appendix). Such lesions were absent in a previous CT done on March 28. Therefore, a bronchoscopy was rapidly done and Aspergillus fumigatus colonies were detected in bronchoalveolar lavage fluid. Galactomannan was positive in bronchoalveolar lavage fluid but was negative in serum. The patient was then transferred to the infectious diseases unit where intravenous voriconazole treatment was initiated at a loading dose of 6 mg/kg every 12 h for 1 day and then at 4 mg/kg every 12 h for 2 days. Due to the onset of agitation and insomnia 3 days after starting antifungal treatment, a switch to an oral dose of voriconazole at 200 mg twice daily was decided, which was well tolerated and effective, with regression of cough and shortness of breath, as well as a reduction in serum C-reactive protein concentrations. After 10 days of therapy, the patient was discharged with indication to continue antifungal treatment and follow-up. In summary, pulmonary aspergillosis might complicate the clinical course in individuals with severe COVID-19. Further studies are urgently needed to evaluate the rate and effect of COVID-19-associated pulmonary aspergillosis in critically ill patients. We declare no competing interests. Download .pdf (.19 MB) Help with pdf files Supplementary appendix Diagnosing COVID-19-associated pulmonary aspergillosisThere is increasing concern that patients with coronavirus disease 2019 (COVID-19) might be at risk of developing invasive pulmonary aspergillosis co-infection.1 In a cohort of 221 patients with COVID-19 in China, fungal infections were diagnosed in seven individuals, all of whom were admitted to the intensive care unit (ICU).2 However, causative fungal pathogens were not identified.2 Given that in China, galactomannan testing is rarely available,3 the real burden of invasive pulmonary aspergillosis in patients with COVID-19 requiring ICU admission is probably underestimated. Full-Text PDF Open Access