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).

Purpose: To analyse long-term efficacy, safety, visual and refractive stability and physiological changes of Artiflex Myopia and Toric phakic intraocular lenses (pIOL) separately throughout an 8-year follow-up. Design: Retrospective cohort study. Methods: A total of 67 eyes of 37 patients underwent Artiflex Myopia (47 eyes) or Artiflex Toric (20 eyes) implantation for correcting myopia and/or astigmatism. Follow-up evaluations were performed 1, 3, 5 and 8 years after surgery. Preoperative and postoperative data included corrected (CDVA) and uncorrected distance visual acuity (UDVA), manifest refraction, endothelial cell density (ECD) and intraocular pressure (IOP) assessments. Efficacy and safety indexes were analysed. The vectorial analysis was performed using the Thibos method. Results: Mean CDVA and UDVA of both pIOLs significantly improved from preoperative to 1 year after implantation, and then it remained stable over the 8-year follow-up. The efficacy and safety indexes after 8 years were 0.94 ± 0.16 and 1.07 ± 0.18 for Artiflex Myopia and 1.00 ± 0.11 and 1.10 ± 0.15 for Artiflex Toric, respectively. The spherical equivalent (SE) significantly improved after surgery. J0, J45 and SE refractive components showed no changes between postoperative visits. A total ECD loss of 4.8% ( p < 0.001) and 10.4% ( p = 0.005) was found after 8 years for Artiflex Myopia and Toric, respectively. Conclusions: Artiflex Myopia and Toric pIOLs are a safe, efficient and predictable option for the correction of myopia and/or astigmatism. The vectorial analysis showed excellent rotation stability for the toric version.

To evaluate the clinical outcomes obtained after cataract or crystalline lens surgery with implantation of a new continuous transitional focus (CTF) intraocular lens (IOL).

Background Recent studies seem to confirm the relationship between residual pulmonary obstruction (RPO) in pulmonary embolism (PE) and risk of recurrent thrombosis and chronic thromboembolic pulmonary hypertension (CTEPH). However, the prognostic factors associated with PE resolution on follow‐up computed tomography angiography (CTA) are not clear. Objectives To determine the prognostic factors of resolution of PE diagnosed and monitored by CTA and the impact of RPO on late complications. Methods We retrospectively analyzed 241 patients with PE who had undergone a 12‐month follow‐up and CT scan evaluation at 6 months. Factors related to resolution and the impact of RPO on the outcome were analyzed. Results Resolution was achieved in 74.3% of all cases after 6 months of treatment. Absence of chronic obstructive pulmonary disease (COPD) (OR, 3.22 [1.35–7.71]; p = 0.009), provoked PE (OR, 2.02 [1.08–3.79]; p = 0.028), early initiation of treatment (<7 days) (OR, 2.42 [1.22–4.78]; p = 0.011), and degree of obstruction caused by the initial PE as indicated by a Qanadli score lower than 16 (OR, 2.12 [1.03–4.37]; p = 0.043) were associated with complete resolution. RPO was associated with recurrent PE as well as the combined endpoint consisting of recurrent VTE and/or CTEPH (4.67 [95% CI, 1.26–17.26]; p = 0.02) and (OR 6.4 [95% CI, 1.9–21.2]; p < 0.005), respectively. Conclusions Resolution of PE is associated with a lower risk of recurrent thrombosis. Earlier initiation of treatment improves prognosis as measured by resolution on follow‐up CTA.