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).

The salivary glands of Aedes stimulans (Walker) are the source of an antigen which produces typical bite reactions in men and laboratory rabbits. If the main salivary duct is cut, the reaction is not produced when the mosquito bites. Lack of saliva does not affect the intake or movement of blood into the mid-gut, nor does it prevent the development of eggs. The presence of ain a-nesthetic component in saliva is suggested.

Can. Ent. 102: 501-509 (1970) The piercing mouthparts of three species of mosquitoes were examined with a stereoscan scanning electron microscope. The structures observed are discussed in relation to existing morphological studies. T w o pairs of peg-like organs were seen at the tip of the labrum and sensory-like structures measuring approximately 1.2 p were shown at the tip of the hypopharynx of all species. Differences were observed in the numbers of maxillary teeth of different species. The stylets of Wyeomyia smithii appear functional despite the belief that this species does not take a blood meal.

The maturation of the salivary glands in adult mosquitoes was studied from histological preparations. A striking sexual dimorphism in the glands apparently reflects the blood-feeding habits of the female. The glands of the female undergo a dramatic development, following emergence, whereas those of the male remain small and show little change. Three main regions of secretory activity differentiate in the female: the necks and the acini proper of the lateral lobes and the acinus of the central lobe. These areas are characterized by histochemical criteria. A cycle of secretory activity occurs after ingestion of blood. The possible functions of the secretion products are discussed.

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