Invasive mould disease in fatal COVID-19: a systematic review of autopsies.

Invasive mould disease (IMD) might affect up to a third of critically ill patients with COVID-19. COVID-19-associated pulmonary aspergillosis (CAPA) is typically diagnosed on the basis of a combination of non-specific clinical, radiographical, and mycological findings, but whether most cases represent invasive disease is unresolved. We systematically reviewed autopsy series of three or more decedents with COVID-19 for evidence of IMD. We searched PubMed, Web of Science, OVID (Embase), and medRxiv for studies in English or French published from Jan 1, 2019, to Sept 26, 2020. We identified 1070 references, of which 50 studies met the criteria. These studies described autopsies from 677 decedents, with individual-level data for 443 decedents. The median age was 70·0 years (IQR 57·0-79·0). Of decedents with individual-level data, 133 (30%) had diabetes, 97 (22%) had pre-existing lung disease, and 27 (6%) had immunocompromising conditions. Of 548 decedents with such data, 320 (58%) received invasive mechanical ventilation; among 140 decedents for whom this was known, ventilation was for a median of 9·0 days (IQR 5·0-20·0). Treatment included immunomodulation in 60 decedents and antifungals in 50 decedents. Autopsy-proven IMD occurred in 11 (2%) of 677 decedents, including eight CAPA, two unspecified IMD, and one disseminated mucormycosis. Among 320 decedents who received mechanical ventilation, six (2%) had IMD. We conclude that IMD, including CAPA, is an uncommon autopsy finding in COVID-19.
Competing Interests: BEK has no competing interests. CJC reports grants and personal fees from Astellas and Merck, grants from Melinta and Cidara, personal fees from The Medicines Company, Cidara, Scynexis, Shinogi, Opex, Needham & Company, and other support from Merck and T2Biosystems, outside the submitted work. MHN reports grants from the Centers for Disease Control and Prevention, Astellas, and the National Institutes of Health during the conduct of this study. ISS reports personal fees from AVIR Pharma, outside the submitted work.
(© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)