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    Invasive Mould Disease in Fatal COVID-1 19: A Systematic Review of Autopsies

    Authors: Brittany Kula; Cornelius J Clancy; Minh Hong Nguyen; Ilan S. Schwartz

    doi:10.1101/2021.01.13.21249761 Date: 2021-01-20 Source: medRxiv

    Background Invasive mould disease ( IMD MESHD) - most commonly pulmonary aspergillosis MESHD - is reported to affect up to a third of critically ill COVID-19 MESHD patients. Most reported cases are diagnosed with probable/putative COVID-19 MESHD associated pulmonary aspergillosis MESHD (CAPA) based on a combination of non-specific clinical, radiographic, and mycological findings, but the clinical significance - and whether these cases represent true invasive disease - is unresolved. Methods We performed a systematic review of autopsy series of decedents with COVID-19 MESHD for evidence of IMD MESHD. We searched PubMed, Web of Science, OVID (Embase) and MedRxiv for English- or French-language case series published between January 1, 2019 to September 26, 2020. We included series describing lung histology of [≥]3 decedents, and authors were contacted for missing information as necessary. Results We identified 51 case series describing autopsies of 702 decedents. Individual-level data was available for 430 decedents. The median age was 72 (IQR 61 to 80) years. Diabetes mellitus MESHD, pre-existing lung disease MESHD, and immunocompromising conditions were reported for 129 (32%), 95 (22%), and 25 (6%) decedents, respectively. The median hospitalization length was 10 (IQR 5-22) days. 51.6% of decedents had received mechanical ventilation for a median of nine (IQR 5-20) days. Treatment included immunomodulation in 60 (most often steroids or tocilizumab) and antifungals in 41 decedents. Eleven decedents (1.6%) had autopsy-confirmed IMD (6 with CAPA, 4 with invasive pulmonary mycosis MESHD not specified and 1 with disseminated mucormycosis). Among 173 decedents who received mechanical ventilation, 5 had IMD (2.9%). Conclusions Autopsy-proven IMD, including CAPA, is uncommon in fatal COVID-19 MESHD.

    Genomic and phenotypic analysis of COVID-19 MESHD-associated pulmonary aspergillosis isolates of Aspergillus fumigatus

    Authors: Jacob L. Steenwyk; Matthew E Mead; Patricia A. Castro; Clara Valero; Andre Damasio; Renato A. C. Santos; Abigail L. LaBella; Yuanning Li; Sonja L. Knowles; Huzefa A. Raja; Nicholas H. Oberlies; Xiaofan Zhou; Oliver A. Cornely; Frieder Fuchs; Philipp Koehler; Gustavo Goldman; Antonis Rokas; Tiberio Oggionni; Federica Meloni; Hassan Abolhassani; Federico Bertoglio; Maren Schubert; Miranda Byrne-Steele; Jian Han; Michael Hust; Yintong Xue; Lennart Hammarstrom; Fausto Baldanti; Harold Marcotte; Qiang Pan-Hammarstrom

    doi:10.1101/2020.11.06.371971 Date: 2020-11-06 Source: bioRxiv

    The ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 MESHD ( COVID-19 MESHD) first described from Wuhan, China. A subset of COVID-19 MESHD patients has been reported to have acquired secondary infections by microbial pathogens, such as fungal opportunistic pathogens from the genus Aspergillus. To gain insight into COVID-19 MESHD associated pulmonary aspergillosis MESHD (CAPA), we analyzed the genomes and characterized the phenotypic profiles of four CAPA isolates of Aspergillus fumigatus obtained from patients treated in the area of North Rhine-Westphalia, Germany. By examining the mutational spectrum of single nucleotide polymorphisms, insertion-deletion polymorphisms, and copy number variants among 206 genes known to modulate A. fumigatus virulence, we found that CAPA isolate genomes do not exhibit major differences from the genome of the Af293 reference strain. By examining virulence in an invertebrate moth model, growth in the presence of osmotic, cell wall, and oxidative stressors, and the minimum inhibitory concentration of antifungal drugs, we found that CAPA isolates were generally, but not always, similar to A. fumigatus reference strains Af293 and CEA17. Notably, CAPA isolate D had more putative loss of function mutations in genes known to increase virulence when deleted (e.g., in the FLEA gene, which encodes a lectin recognized by macrophages). Moreover, CAPA isolate D was significantly more virulent than the other three CAPA isolates and the A. fumigatus reference strains tested. These findings expand our understanding of the genomic and phenotypic characteristics of isolates that cause CAPA.

The ZB MED preprint Viewer preVIEW includes all COVID-19 related preprints from medRxiv and bioRxiv, from ChemRxiv, from ResearchSquare, from arXiv and from Preprints.org and is updated on a daily basis (7am CET/CEST).
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MeSH Disease
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SARS-CoV-2 Proteins


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