Objectives Information on the recently COVID‐19‐associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID‐19), and review the published literature from Western countries. Methods Prospective study (March to May, 2020) that included all COVID‐19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used. Results COVID‐19‐associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non‐immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA‐related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all‐cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%. Conclusions COVID‐19‐associated pulmonary aspergillosis must be considered a serious and potentially life‐threatening complication in patients with severe COVID‐19 receiving immunosuppressive treatment.
Aims Due to bioprosthetic valve degeneration, aortic valve-in-valve (ViV) procedures are increasingly performed. There are no data on long-term outcomes after aortic ViV. Our aim was to perform a large-scale assessment of long-term survival and reintervention after aortic ViV. Methods and results A total of 1006 aortic ViV procedures performed more than 5 years ago [mean age 77.7 ± 9.7 years; 58.8% male; median STS-PROM score 7.3% (4.2–12.0)] were included in the analysis. Patients were treated with Medtronic self-expandable valves (CoreValve/Evolut, Medtronic Inc., Minneapolis, MN, USA) (n = 523, 52.0%), Edwards balloon-expandable valves (EBEV, SAPIEN/SAPIEN XT/SAPIEN 3, Edwards Lifesciences, Irvine, CA, USA) (n = 435, 43.2%), and other devices (n = 48, 4.8%). Survival was lower at 8 years in patients with small-failed bioprostheses [internal diameter (ID) ≤ 20 mm] compared with those with large-failed bioprostheses (ID > 20 mm) (33.2% vs. 40.5%, P = 0.01). Independent correlates for mortality included smaller-failed bioprosthetic valves [hazard ratio (HR) 1.07 (95% confidence interval (CI) 1.02–1.13)], age [HR 1.21 (95% CI 1.01–1.45)], and non-transfemoral access [HR 1.43 (95% CI 1.11–1.84)]. There were 40 reinterventions after ViV. Independent correlates for all-cause reintervention included pre-existing severe prosthesis–patient mismatch [subhazard ratio (SHR) 4.34 (95% CI 1.31–14.39)], device malposition [SHR 3.75 (95% CI 1.36–10.35)], EBEV [SHR 3.34 (95% CI 1.26–8.85)], and age [SHR 0.59 (95% CI 0.44–0.78)]. Conclusions The size of the original failed valve may influence long-term mortality, and the type of the transcatheter valve may influence the need for reintervention after aortic ViV.
Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).
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