Accelarated immune ageing is associated with COVID-19 disease severity

Background The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. Results We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01). Conclusions Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease

Control System for Active Camouflage

Implementation of a control system for an active camouflage system based on thermal elements and LED technology

B-type natriuretic peptide predicts long-term survival after major non-cardiac surgery

Background. The prediction of long-term survival after surgery is complex. Natriuretic peptides can predict short-term postoperative cardiac morbidity and mortality. This study aims to determine the long-term prognostic significance of preoperative B-type natriuretic peptide (BNP) concentration after major non-cardiac surgery. Methods. We conducted a prospective single-centre observational cohort study in a West of Scotland teaching hospital. Three hundred and forty-five patients undergoing major non-cardiac surgery were included. The primary endpoint was long-term all-cause mortality. Results. Overall survival was 67.8% (234/345), with 27 postoperative deaths (within 42 days) and 84 deaths at subsequent follow-up (median follow-up 953 days). A BNP concentration of &gt;87.5 pg ml(-1) best predicted mortality, and the mean survival of patients with an elevated BNP (&gt;87.5 pg ml(-1)) was 731.9 (95% CI 613.6-850.2) days compared with 1284.6 days [(95% CI 1219.3-1350.0), P&lt;0.001] in patients with a BNP&lt;87.5 pg ml(-1). BNP was an independent predictor of survival. Conclusions. BNP is an independent predictor of long-term survival after major non-cardiac surgery. A simple preoperative blood test can provide predictive information on future risk of death, and potentially has a role in preoperative risk assessment

Genomic and ecologic characteristics of the airway microbial-mucosal complex

S ummary paragraph Lung diseases due to infection and dysbiosis affect hundreds of millions of people world-wide 1-4 . Microbial communities at the airway mucosal barrier are conserved and highly ordered 5 , reflecting symbiosis and co-evolution with human host factors 6 . Freed of selection to digest nutrients for the host, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the results of the first systematic culture and whole-genome sequencing of the principal airway bacterial species, identifying abundant novel organisms within the genera Streptococcus, Pauljensenia, Neisseria and Gemella . Bacterial genomes were enriched for genes encoding antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. RNA-targeting CRISPR elements in some taxa suggest the potential to prevent or treat specific viral infections. Homologues of human RO60 present in Neisseria spp. provide a possible respiratory primer for autoimmunity in systemic lupus erythematosus (SLE) and Sjögren syndrome. We interpret the structure and biogeography of airway microbial communities from clinical surveys in the context of whole-genome content, identifying features of airway dysbiosis that may presage breakdown of homeostasis during acute attacks of asthma and chronic obstructive pulmonary disease (COPD). We match the gene content of isolates to human transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways that can sustain host interactions with the microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosal immunity in lung diseases of global significance