Search

Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). Here, we investigate associations between plasma ACE2 and outcome of COVID-19. Methods and results This analysis used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort). Comprehensive clinical data were collected on this cohort, including 28-day outcomes. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. High admission plasma ACE2 in COVID-19 patients was associated with increased maximal illness severity within 28 days with OR = 1.8, 95%-CI: 1.4–2.3 (P < 0.0001). Plasma ACE2 was significantly higher in COVID-19 patients with hypertension compared with patients without hypertension (P = 0.0045). Circulating ACE2 was also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). Conclusion This study suggests that measuring plasma ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 could be a link between COVID-19 illness severity and its established risk factors hypertension, pre-existing heart disease and pre-existing kidney disease.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). COVID-19 is a disease with a very broad spectrum of clinical manifestations, ranging from asymptomatic and subclinical infection to severe hyperinflammatory syndrome and death. Methods This study used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort with Olink Proteomics). Comprehensive clinical data were collected on this cohort, including 28-day outcomes classified according to the World Health Organization (WHO) COVID-19 outcomes scale. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. Findings High baseline levels of ACE2 in plasma from COVID-19 patients were associated with worse WHOmax category at 28 days with OR=0.56, 95%-CI: 0.44-0.71 (P < 0.0001). This association was significant in regression models with correction for baseline characteristics, pre-existing medical conditions, and laboratory test results. High levels of ACE2 in plasma from COVID-19 patients were also significantly associated with worse WHO category at the time of blood sampling at both day 0, day 3, and day 7 (P = 0.0004, P < 0.0001, and P < 0.0001, respectively). The levels of ACE2 in plasma from COVID-19 patients with hypertension were significantly higher compared to patients without hypertension (P = 0.0045). The plasma ACE2 levels were also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). There was no difference in plasma ACE2 levels comparing patients with or without pre-existing lung disease, diabetes, or immunosuppressive conditions (P = 0.953, P = 0.291, and P = 0.237, respectively). The associations between high plasma levels of ACE2 and worse WHOmax category during 28 days were more pronounced in COVID-19 positive patients compared with COVID-19 negative patients but the difference was not significant in the two-way ANOVA analysis. Interpretation This study suggests that measuring ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 levels could be a link between severe COVID-19 disease and its risk factors, namely hypertension, pre-existing heart disease and pre-existing kidney disease. The design of the data analysis using the Olink platform does not allow assessment of quantitative differences. However, previous studies have described a positive correlation between plasma ACE2 and ACE1 activity. This is interesting because ACE1 (serum ACE) analysis is a standardized test in most hospital laboratories. Therefore, our study encourages quantitative investigations of both plasma ACE 1 and 2 in COVID-19. Key Points Question Can plasma levels of the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin converting enzyme 2 (ACE2), predict outcome of coronavirus disease of 2019 (COVID-19). Findings In this study of 306 COVID-19 positive patients, high baseline levels of ACE2 in plasma from COVID-19 patients were associated with worse outcome measured by the World Health Organization (WHO) COVID-19 outcomes scale. Meaning Measuring ACE2 is potentially valuable in predicting COVID-19 outcomes and link COVID-19 disease and the risk factors hypertension, pre-existing heart disease and pre-existing kidney disease.

In plants Zn is commonly found bound to proteins. In barley (Hordeum vulgare) major storage proteins are alcohol soluble prolamin known as hordein and some of them have potentiality to bind/store Zn. 65Zn overlay and blotting techniques have been widely used for detecting zinc binding protein. However, so far of our knowledge this Zn blotting assay was never been applied to detect prolamin fraction in barley grains. A radioactive Zinc (65ZnCl2) blotting technique was optimized to detect zinc binding prolamins, followed by development of an easy to follow non-radioactive colorimetric zinc blotting method using a zinc sensing dye, dithizone (DTZ). Hordeins were extracted from mature barley grain, separated by SDS-PAGE, blotted on membrane, renatured, overlayed and probed with zinc and subsequently zinc binding specificity of certain proteins was detected either by autoradiography or colour formation. The DTZ staining method gave similar reproducibility like the radioactive blotting. The detected zinc binding protein was identified as B-hordein by western blotting experiment. In plants, zinc is commonly found bound to proteins. In barley (Hordeum vulgare), major storage proteins are alcohol-soluble prolamins known as hordeins, and some of them have the potential to bind or store zinc. 65Zn overlay and blotting techniques have been widely used for detecting zinc-binding protein. However, to our knowledge so far this zinc blotting assay has never been applied to detect a prolamin fraction in barley grains. A radioactive zinc (65ZnCl2) blotting technique was optimized to detect zinc-binding prolamins, followed by development of an easy-to-follow nonradioactive colorimetric zinc blotting method with a zinc-sensing dye, dithizone. Hordeins were extracted from mature barley grain, separated by SDS-PAGE, blotted on a membrane, renatured, overlaid, and probed with zinc; subsequently, zinc-binding specificity of certain proteins was detected either by autoradiography or color formation. The dithizone staining method gave similar reproducibility to the radioactive blotting. The detected zinc-binding protein was identified as B-hordein by Western blotting

Psoriasis is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex interplay between T cells, dendritic cells and the epidermis in which T cells and dendritic cells maintain skin inflammation. Anti-tumour necrosis factor (anti-TNF)-α agents have been approved for therapeutic use across a range of inflammatory disorders including psoriasis, but the anti-inflammatory mechanisms of anti-TNF-α in lesional psoriatic skin are not fully understood.We used the Human Gene 1.0 ST Array to analyse gene expression in punch biopsies taken from psoriatic patients before and also 4 and 14 days after initiation of treatment with the anti-TNF-α agent adalimumab. The gene expression was analysed by gene set enrichment analysis using the Functional Annotation Tool from DAVID Bioinformatics Resources. The most enriched pathway was visualised by the Pathview Package on Kyoto Encyclopedia of Genes and Genomes (KEGG) graphs. The analysis revealed new early biological events in psoriasis after adalimumab treatment, which may reflect decreased attraction of immune cells by downregulation of first chemokines and then their ligands (IL-8, CXCL9 and CXCL10 after 4 days of treatment; and IL8RB and CXCR-4 after 14 days). We also found downregulation of angiogenesis by downregulation of chemokines like CCL19 and CCL21 after 4 days of treatment and downregulation of VEGFA after 14 days.Combining microarray data on biopsies from psoriasis patients with pathway analysis allows us to integrate earlier in vitro findings into the identification of mechanisms that may be important in vivo.