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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).

SUMMARY Decapitation of tulips early in extension growth resulted in a 59% reduction in stem length at flowering. Selective removal of the floral parts showed that the gynoecium controlled stem extension. The upper internodes were most affected, and the effect was largely reversed by the application of indol‐3‐ylacetic acid (IAA) but not by gibberellic acid (GA). Soil drenches of ancymidol also reduced tulip stem extension, but in this case the lower internodes were most affected and this effect was reversed by GA. The result of flower removal in narcissus was similar to that in tulip, although the narcissus scope and the tulip stem differ morphologically. Scape extension of narcissus was reduced by decapitation; this was due entirely to the removal of the gynoecium and could be reversed by IAA but not GA. In narcissus, spathe removal led to earlier flowering. Flower blasting in tulip (a drying out of the flower which occurs commercially under some conditions) resulted from a number of treatments, including floral surgery, injections and ancymidol soil drenches. The incidence of flower blasting was reduced by injecting GA or kinetin. The results are discussed in relation to commerical flower production, the control of pot‐plant height, and the prevention of flower blasting.

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