Resumen En enero de 2020 China identificó un nuevo virus de la familia de los Coronaviridae como causante de varios casos de neumonía de origen desconocido. Inicialmente confinado a la
Spinal cord injuries (SCIs) often lead to impairment of the respiratory system and, consequently, restrictive respiratory changes. Paresis or paralysis of the respiratory muscles can lead to respiratory insufficiency, which is dependent on the level and completeness of the injury. Respiratory complications include hypoventilation, a reduction in surfactant production, mucus plugging, atelectasis, and pneumonia. Vital capacity (VC) is an indicator of overall pulmonary function; patients with severely impaired VC may require assisted ventilation. It is best to proceed with intubation under controlled circumstances rather than waiting until the condition becomes an emergency. Mechanical ventilation can adversely affect the structure and function of the diaphragm. Early tracheostomy following short orotracheal intubation is probably beneficial in selected patients. Weaning should start as soon as possible, and the best modality is progressive ventilator-free breathing (PVFB). Appropriate candidates can sometimes be freed from mechanical ventilation by electrical stimulation. Respiratory muscle training regimens may improve patients' inspiratory function following a SCI.
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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