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).

No abstract

Background Radical orchidectomy in patients who are subsequently diagnosed with benign testicular tumours represents an overtreatment due to the deleterious effects on endogenous testosterone, fertility and body image. For these reasons, the option of partial orchidectomy (PO) should be considered in certain groups of patients. Patients with bilateral tumours (synchronous or metachronous) or a solitary testis where the lesion is no greater than 30% of the volume of the testis could be considered for a PO. Evidence has shown that PO is effective for small testicular masses with excellent survival and recurrence rates. Objectives Highlight the feasibility of maintaining post‐operative fertility or normal semen parameters and endocrine function following PO. Materials and Methods Data for this review were obtained through a search of the PubMed database. Papers were required to be in English and focus on adult human males. Results Eligible and relevant papers were assessed for data regarding fertility, semen parameters and endocrine function following PO for a small testicular mass (STM). Conclusion It is possible to preserve both fertility and endocrine function after PO. Although patients may still require adjuvant radiotherapy for concomitant intratubular germ cell neoplasia (ITGCN) which results in subfertility, endocrine function is still conserved. However, it is possible to postpone radiotherapy and continue with clinical surveillance for the purposes of fertility preservation.

In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.