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1.
Horm Metab Res ; 53(2): 85-93, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33395706

ABSTRACT

Our aim was to assess the association between obesity and the risk of unfavourable outcomes (composite of severe disease and mortality) in inpatients with COVID-19. We conducted a systematic search of databases between December 2019 and 28th June 2020. Studies were included if they reported or allowed estimation of an odds ratio (OR) for unfavourable outcome in obese compared to non-obese patients hospitalised for COVID-19. Twenty cohort studies of 28 355 hospitalised patients with COVID-19 infection were included. Meta-analysis estimated a pooled OR of 2.02 (1.41-2.89, p<0.001) for an unfavourable outcome in obese versus non-obese patients when adjusted for age, sex and co-morbidities. When unadjusted for confounders, the OR for unfavourable outcomes was 1.25 (CI 1.07-1.45, p=0.005). An increased adjusted OR was also seen for death (OR 1.51; CI 1.13-2.21, p=0.006) and severe illness (OR 2.26; CI 1.47-3.48, p<0.001). Compared to a normal BMI, the risk of an unfavourable outcome was increased even in overweight patients, with severe obesity having an escalated risk.Obesity is independently associated with an unfavourable outcome of COVID-19 illness, with obese patients having twice the risk of a composite outcome of severe disease or mortality, and a 50% increased risk of death.


Subject(s)
COVID-19/complications , COVID-19/therapy , Obesity/complications , COVID-19/mortality , Humans , Obesity, Morbid/complications , Overweight/complications , Risk Factors , Treatment Outcome
2.
mSphere ; 3(3)2018 06 27.
Article in English | MEDLINE | ID: mdl-29950379

ABSTRACT

Much of our understanding of the activity of anthrax toxin is based on in vitro systems, which delineate the interaction between Bacillus anthracis toxins and the cell surface. However, these systems fail to account for the intimate association of B. anthracis with the circulatory system, including the contribution of serum proteins to the host response and processing of anthrax toxins. Using a variety of immunological techniques to inhibit serum processing of B. anthracis protective antigen (PA) along with mass spectrometry analysis, we demonstrate that serum digests PA via 2 distinct reactions. In the first reaction, serum cleaves PA83 into 2 fragments to produce PA63 and PA20 fragments, similarly to that observed following furin digestion. This is followed by carboxypeptidase-mediated removal of the carboxy-terminal arginine and lysines from PA20IMPORTANCE Our findings identify a serum-mediated modification of PA20 that has not been previously described. These observations further imply that the processing of PA is more complex than currently thought. Additional study is needed to define the contribution of serum processing of PA to the host response and individual susceptibility to anthrax.


Subject(s)
Antigens, Bacterial/metabolism , Bacterial Toxins/metabolism , Carboxypeptidases/metabolism , Hydrolysis , Serum/enzymology , Antigens, Bacterial/chemistry , Bacterial Toxins/chemistry , Mass Spectrometry
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