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

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

AEROBIC PATHOGENIC BACTERIA IN POST-OPERATIVE WOUNDS AT MOI TEACHING AND REFERRAL HOSPITAL

Background: The emergence of bacterial antimicrobial resistance associated withacquired infections has made the choice of empirical therapy more difficult andexpensive, hence the need for continuous research to determine their sensitivity patterns.Objectives: To identify the common aerobic pathogenic bacteria in post-operative woundsat Moi Teaching and Referral Hospital (MTRH) and determine their sensitivity patternsto routine antibiotics used.Design: Cross-sectional study.Setting: Moi Teaching and Referral Hospital (MTRH) Surgical, Obstetrics and Gynaecologywards.Patients: Sixty three patients chosen by convenient sampling between May and June2001 were included in the study. A total of eighty four isolates were obtained fromthese patients.Materials and Methods: Isolation of pathogens and their antibiotic sensitivitydetermination was conducted in the Department of Medical Microbiology Laboratory,Faculty of Health Sciences, Moi University. The bacteria were cultured on blood agar,MacConkey and Nutrient agar followed by identification using biochemical tests (catalaseurease, coagulase, triple sugar iron). Disc diffusion method on Muller-Hinton agar wasused for sensitivity testing.Results: Staphylococcus aureus species were the most common pathogenic bacteriaisolated from the post-operative wounds. Other organisms included Proteus, Pseudomonasand Escherichia coli. There was a multi-drug resistance pattern observed, withminocyline being the most effective drug against S. aureus.Conclusion: There is need for review of policies on prescription practice on the useof existing therapeutics choice to limit the spread of resistance. This will ensure reducedpatient stay and cost incurred

Aerobic pathogenic bacteria in post-operative wounds at Moi Teaching and Referral Hospital

Background: The emergence of bacterial antimicrobial resistance associated with acquired infections has made the choice of empirical therapy more difficult and expensive, hence the need for continuous research to determine their sensitivity patterns. Objectives: To identify the common aerobic pathogenic bacteria in post-operative wounds at Moi Teaching and Referral Hospital (MTRH) and determine their sensitivity patterns to routine antibiotics used. Design: Cross-sectional study. Setting: Moi Teaching and Referral Hospital (MTRH) Surgical, Obstetrics and Gynaecology wards. Patients: Sixty three patients chosen by convenient sampling between May and June 2001 were included in the study. A total of eighty four isolates were obtained from these patients. Materials and Methods: Isolation of pathogens and their antibiotic sensitivity determination was conducted in the Department of Medical Microbiology Laboratory, Faculty of Health Sciences, Moi University. The bacteria were cultured on blood agar, MacConkey and Nutrient agar followed by identification using biochemical tests (catalase urease, coagulase, triple sugar iron). Disc diffusion method on Muller-Hinton agar was used for sensitivity testing. Results: Staphylococcus aureus species were the most common pathogenic bacteria isolated from the post-operative wounds. Other organisms included Proteus, Pseudomonas and Escherichia coli. There was a multi-drug resistance pattern observed, with minocyline being the most effective drug against S. aureus. Conclusion: There is need for review of policies on prescription practice on the use of existing therapeutics choice to limit the spread of resistance. This will ensure reduced patient stay and cost incurred. (East African Medical Journal: 2002 79(12): 640-644

Potencial alelopático de espécies nativas na germinação e crescimento inicial de Lactuca sativa L. (Asteraceae) Allelopathic potential of native species in Lactuca sativa L. (Asteraceae) germination and initial growth

A alelopatia caracteriza-se pelos efeitos danosos ou benéficos sobre o desenvolvimento da vegetação, causados por substâncias químicas produzidas e liberadas para o ambiente por uma planta. Com o objetivo de avaliar o potencial alelopático de espécies brasileiras, foram testados extratos foliares de Cecropia pachystachya Trec. (Urticaceae), Peltophorum dubium (Spreng.) Taub. (Fabaceae), Psychotria leiocarpa Cham. & Schltdl (Rubiaceae), Sapium glandulatum (Vell.) Pax (Euphorbiaceae) e Sorocea bonplandii (Baill.) Burg., Lanj. & Boer (Moraceae), utilizando-se bioensaios de germinação e crescimento e alface (Lactuca sativa L.) como planta alvo. Nesses bioensaios, foram usados extratos foliares aquosos nas concentrações de 2 e 4%, preparados por maceração estática com água fria e quente. Os extratos das cinco espécies causaram atraso na germinação dos aquênios da alface, bem como efeitos tóxicos no crescimento das plântulas, com redução e enfraquecimento das raízes. Os resultados obtidos mostraram a presença de substâncias químicas inibidoras nos extratos, revelando potencial alelopático para as cinco espécies avaliadas.<br>Allelopathy is characterized by harmful or beneficial effects on vegetation development, caused by chemical substances produced and released into the environment by the plant. Aiming to assess the allelopathic potential of Brazilian species, aqueous leaf extracts of Cecropia pachystachya Trec. (Urticaceae), Peltophorum dubium (Spreng.) Taub. (Fabaceae), Psychotria leiocarpa Cham. & Schltdl (Rubiaceae), Sapium glandulatum (Vell.) Pax (Euphorbiaceae), and Sorocea bonplandii (Baill.) Burger, Lanj. & Boer (Moraceae) were tested on lettuce using germination and growth bioassays. In these bioassays, aqueous leaf extracts were used at concentrations of 2 and 4%, prepared by static maceration with cold and hot water. The five species extracts delayed lettuce germination and produced toxic effects on seedling growth, with root reduction and debility. The results point to the presence of inhibitorychemical substances in the extracts, indicating an allelopathic potential for the five species evaluated

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease