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Abstract	Background:
Language	English
Publishing date	2021-05-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.653045
Database	MEDical Literature Analysis and Retrieval System OnLINE

Article ; Online: Persistently increased systemic ACE2 activity and Furin levels are associated with increased inflammatory response in smokers with SARS-CoV-2 COVID-19

Kaur, Gagandeep / Yogeswaran, Shaiesh / Muthumalage, Thivanka / Rahman, Irfan

medRxiv

Abstract: ... on COVID-19 susceptibility and severity amongst smokers and those with pre-existing pulmonary diseases is ... thus suggesting that COVID-19 infection may have severe outcomes amongst smokers which is reflected systemically. ... not known. We determined the systemic expression and activity of COVID-19 related proteins, cytokine ...

Abstract	Tobacco smoking is known to be involved in the pathogenesis of several cardiopulmonary diseases, and smokers are susceptible to infectious agents. However, the progression of lung injury based on COVID-19 susceptibility and severity amongst smokers and those with pre-existing pulmonary diseases is not known. We determined the systemic expression and activity of COVID-19 related proteins, cytokine, chemokines, and lipid mediators (lipidomics) amongst COVID-19 patients with and without a history of smoking with a view to define biomarkers. We obtained serum from COVID-19 positive and COVID-19 recovered patients with and without a history of smoking. We conducted a Luminex multiplex assay (cytokine levels), LC-MS (eicosanoids or oxylipin panel) and enzymatic activity assays on the serum samples to study the systemic changes in COVID-19 patients. On comparing the cytokine profiles among COVID-19 positive and COVID-19 negative patients, we found a significant upregulation in the production of pro-inflammatory cytokines like IL-1beta, IL-8, IL-2, VEGF and IL-10 in COVID-19 positive patients as compared to the respective controls. Interestingly, smoking history resulted in further augmentation of the release of some hyper-inflammatory cytokines, like IFN-gamma, Eotaxin, MCP-1 and IL-9 amongst COVID-19 positive patients. The enzymatic activity for ACE2, the binding partner for SARS-CoV2 virus in the host cell, was found to be significantly increased in the serum of patients with a smoking history compared to the serum collected from the non-smoking controls. Similarly to our cytokine analysis, our measurement of serum Furin levels was also affected by the patients smoking history, in which we reported a substantial rise in serum Furin levels of COVID-19 patients. The analysis of lipid mediators revealed a distinct signature amongst the COVID-19 positive versus recovered subjects in PGF2alpha, HETEs, LXA4 and LTB4 levels. However, we did not find any changes in the levels of any lipid mediators based on the smoking history of the patients. Overall, our results point towards distinct systemic signatures amongst COVID-19 positive patients. We also show that smoking adversely affects the systemic levels of inflammatory markers and COVID-19 related proteins, thus suggesting that COVID-19 infection may have severe outcomes amongst smokers which is reflected systemically.
Keywords	covid19
Language	English
Publishing date	2021-01-15
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.01.14.21249836
Database	COVID19

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Article: Persistently Increased Systemic ACE2 Activity Is Associated With an Increased Inflammatory Response in Smokers With COVID-19.

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