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  1. Article: Longitudinal Plasma Proteomics Analysis Reveals Novel Candidate Biomarkers in Acute COVID-19

    Mohammed, Yassene / Goodlett, David R. / Cheng, Matthew P. / Vinh, Donald C. / Lee, Todd C. / Mcgeer, Allison / Sweet, David / Tran, Karen / Lee, Terry / Murthy, Srinivas / Boyd, John H. / Singer, Joel / Walley, Keith R. / Patrick, David M. / Quan, Curtis / Ismail, Sara / Amar, Laetitia / Pal, Aditya / Bassawon, Rayhaan /
    Fesdekjian, Lara / Gou, Karine / Lamontagne, Francois / Marshall, John / Haljan, Greg / Fowler, Robert / Winston, Brent W. / Russell, James A.

    Journal of proteome research. 2022 Feb. 10, v. 21, no. 4

    2022  

    Abstract: The host response to COVID-19 pathophysiology over the first few days of infection remains largely unclear, especially the mechanisms in the blood compartment. We report on a longitudinal proteomic analysis of acute-phase COVID-19 patients, for which we ... ...

    Institution ARBs CORONA I
    Abstract The host response to COVID-19 pathophysiology over the first few days of infection remains largely unclear, especially the mechanisms in the blood compartment. We report on a longitudinal proteomic analysis of acute-phase COVID-19 patients, for which we used blood plasma, multiple reaction monitoring with internal standards, and data-independent acquisition. We measured samples on admission for 49 patients, of which 21 had additional samples on days 2, 4, 7, and 14 after admission. We also measured 30 externally obtained samples from healthy individuals for comparison at baseline. The 31 proteins differentiated in abundance between acute COVID-19 patients and healthy controls belonged to acute inflammatory response, complement activation, regulation of inflammatory response, and regulation of protein activation cascade. The longitudinal analysis showed distinct profiles revealing increased levels of multiple lipid-associated functions, a rapid decrease followed by recovery for complement activation, humoral immune response, and acute inflammatory response-related proteins, and level fluctuation in the regulation of smooth muscle cell proliferation, secretory mechanisms, and platelet degranulation. Three proteins were differentiated between survivors and nonsurvivors. Finally, increased levels of fructose–bisphosphate aldolase B were determined in patients with exposure to angiotensin receptor blockers versus decreased levels in those exposed to angiotensin-converting enzyme inhibitors. Data are available via ProteomeXchange PXD029437.
    Keywords COVID-19 infection ; biomarkers ; blood plasma ; cell proliferation ; complement ; fructose-bisphosphate aldolase ; humoral immunity ; inflammation ; longitudinal studies ; pathophysiology ; peptidyl-dipeptidase A ; proteome ; proteomics ; research ; smooth muscle
    Language English
    Dates of publication 2022-0210
    Size p. 975-992.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.1c00863
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Longitudinal Plasma Proteomics Analysis Reveals Novel Candidate Biomarkers in Acute COVID-19.

    Mohammed, Yassene / Goodlett, David R / Cheng, Matthew P / Vinh, Donald C / Lee, Todd C / Mcgeer, Allison / Sweet, David / Tran, Karen / Lee, Terry / Murthy, Srinivas / Boyd, John H / Singer, Joel / Walley, Keith R / Patrick, David M / Quan, Curtis / Ismail, Sara / Amar, Laetitia / Pal, Aditya / Bassawon, Rayhaan /
    Fesdekjian, Lara / Gou, Karine / Lamontagne, Francois / Marshall, John / Haljan, Greg / Fowler, Robert / Winston, Brent W / Russell, James A

    Journal of proteome research

    2022  Volume 21, Issue 4, Page(s) 975–992

    Abstract: The host response to COVID-19 pathophysiology over the first few days of infection remains largely unclear, especially the mechanisms in the blood compartment. We report on a longitudinal proteomic analysis of acute-phase COVID-19 patients, for which we ... ...

    Abstract The host response to COVID-19 pathophysiology over the first few days of infection remains largely unclear, especially the mechanisms in the blood compartment. We report on a longitudinal proteomic analysis of acute-phase COVID-19 patients, for which we used blood plasma, multiple reaction monitoring with internal standards, and data-independent acquisition. We measured samples on admission for 49 patients, of which 21 had additional samples on days 2, 4, 7, and 14 after admission. We also measured 30 externally obtained samples from healthy individuals for comparison at baseline. The 31 proteins differentiated in abundance between acute COVID-19 patients and healthy controls belonged to acute inflammatory response, complement activation, regulation of inflammatory response, and regulation of protein activation cascade. The longitudinal analysis showed distinct profiles revealing increased levels of multiple lipid-associated functions, a rapid decrease followed by recovery for complement activation, humoral immune response, and acute inflammatory response-related proteins, and level fluctuation in the regulation of smooth muscle cell proliferation, secretory mechanisms, and platelet degranulation. Three proteins were differentiated between survivors and nonsurvivors. Finally, increased levels of fructose-bisphosphate aldolase B were determined in patients with exposure to angiotensin receptor blockers versus decreased levels in those exposed to angiotensin-converting enzyme inhibitors. Data are available via ProteomeXchange PXD029437.
    MeSH term(s) Biomarkers ; COVID-19 ; Humans ; Plasma ; Proteomics ; Retrospective Studies
    Chemical Substances Biomarkers
    Language English
    Publishing date 2022-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.1c00863
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Successful management of severe group A streptococcal soft tissue infections using an aggressive medical regimen including intravenous polyspecific immunoglobulin together with a conservative surgical approach.

    Norrby-Teglund, Anna / Muller, Matthew P / Mcgeer, Allison / Gan, Bing Siang / Guru, Veena / Bohnen, John / Thulin, Pontus / Low, Donald E

    Scandinavian journal of infectious diseases

    2005  Volume 37, Issue 3, Page(s) 166–172

    Abstract: Intravenous polyspecific immunoglobulin G (IVIG) has been reported to be efficacious as adjunctive therapy in patients with toxic shock syndrome caused by a group A streptococci (GAS). GAS is also an important cause of necrotizing fasciitis, for which an ...

    Abstract Intravenous polyspecific immunoglobulin G (IVIG) has been reported to be efficacious as adjunctive therapy in patients with toxic shock syndrome caused by a group A streptococci (GAS). GAS is also an important cause of necrotizing fasciitis, for which an early and extensive surgical intervention is currently advocated. Here we report on the use of an aggressive medical regimen including high-dose IVIG together with a conservative surgical approach in severe GAS soft tissue infection. We describe 7 patients with severe soft tissue infection caused by GAS, who all were treated with effective antimicrobials and high-dose IVIG. Surgery was either not performed or only limited exploration was carried out. Six of the patients had toxic shock syndrome. All patients survived. Immunostaining of tissue biopsies from 2 of the patients revealed high levels of GAS, superantigen and pro-inflammatory cytokines initially, which were dramatically reduced in a repeat biopsy of the initial operative site collected from 1 of the patients 66 h post-IVIG administration. The study suggests that the use of a medical regimen including IVIG in patients with severe GAS soft tissue infections may allow an initial non-operative or minimally invasive approach, which can limit the need to perform immediate wide debridements and amputations in unstable patients.
    MeSH term(s) Adult ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/therapeutic use ; Combined Modality Therapy ; Fasciitis, Necrotizing/drug therapy ; Fasciitis, Necrotizing/microbiology ; Female ; Humans ; Immunoglobulins, Intravenous/administration & dosage ; Immunoglobulins, Intravenous/therapeutic use ; Male ; Middle Aged ; Shock, Septic/drug therapy ; Shock, Septic/microbiology ; Soft Tissue Infections/microbiology ; Soft Tissue Infections/physiopathology ; Soft Tissue Infections/surgery ; Soft Tissue Infections/therapy ; Streptococcal Infections/microbiology ; Streptococcal Infections/physiopathology ; Streptococcal Infections/surgery ; Streptococcal Infections/therapy ; Streptococcus pyogenes/drug effects ; Streptococcus pyogenes/isolation & purification ; Treatment Outcome
    Chemical Substances Anti-Bacterial Agents ; Immunoglobulins, Intravenous
    Language English
    Publishing date 2005
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390956-6
    ISSN 1651-1980 ; 0036-5548
    ISSN (online) 1651-1980
    ISSN 0036-5548
    DOI 10.1080/00365540410020866
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Frailty Hinders Recovery From Acute Respiratory Illness in Older Adults

    Andrew, Melissa K / Lees, Caitlin / Godin, Judith / Black, Karen / McElhaney, Janet / Ambrose, Ardith / Boivin, Guy / Bowie, William R / Elsherif, May / Green, Karen / Halperin, Scott A / Hatchette, Todd / Johnstone, Jennie / Katz, Kevin / Langley, Joanne M / Leblanc, Jason / Lagace-Wiens, Philippe / Loeb, Mark / Mackinnon-Cameron, Donna /
    Mccarthy, Anne / Mcgeer, Allison / Powis, Jeff / Richardson, David / Semret, Makeda / Smith, Stephanie / Smyth, Daniel / Taylor, Geoffrey / Trottier, Sylvie / Valiquette, Louis / Webster, Duncan / Ye, Lingyun / McNeil, Shelly

    Open Forum Infect Dis

    Abstract: BACKGROUND: Influenza vaccination programs aim to prevent serious outcomes. Given that frailty may impact recovery from influenza, we examined frailty as a predictor of recovery in older adults hospitalized with acute respiratory illness. METHODS: Data ... ...

    Abstract BACKGROUND: Influenza vaccination programs aim to prevent serious outcomes. Given that frailty may impact recovery from influenza, we examined frailty as a predictor of recovery in older adults hospitalized with acute respiratory illness. METHODS: Data came from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network during the 2011/12, 2012/13, and 2013/14 influenza seasons; all patients were aged 65+. Frailty was measured using a previously validated Frailty Index (FI) of health and functional deficits; baseline frailty was categorized using published cutoffs (0-.1 non-frail, >.1-.21 pre-frail, >.21-.45 frail, >.45 most frail). Recovery was operationalized as being alive 30 days post-discharge with less than two additional health/functional deficits (<=0.06 FI increase). Logistic regression was used to examine the change in odds of recovery for every 0.1 increase in baseline FI, controlling for age, sex, season, lab-confirmed influenza status, and seasonal influenza vaccination status. RESULTS: Of 5125 hospitalized older adults, 15% were non-frail, 39% pre-frail, 40% frail, and 6% most frail. 11% died, and poor recovery was experienced by 520/4544=11% of survivors. Poor recovery was inversely associated with baseline frailty (11% non-frail, 17% pre-frail, 28% frail, 38% most frail; P < .001). Frailty was associated with lower odds of recovery in all three seasons [2011/12 (OR=0.71; 95% CI 0.60–0.85), 2012/13 (OR=0.72; 0.66–0.78), 2013/14 (OR=0.76; 0.70–0.82)] though results varied by season, influenza status, and vaccination status. In 2011/12, frailty was associated with poor recovery in unvaccinated (OR=0.46. 95% CI=0.32–0.67) but not vaccinated older patients (OR=0.83, 95% CI=0.68–1.02). CONCLUSION: Increasing frailty was consistently associated with lower odds of recovery in older adults admitted with influenza and other acute respiratory illnesses; depending on seasonal factors, vaccination may offer some buffering of this impact. Understanding frailty and functional status is important, both because frailty is predictive of poor recovery and because persistence of new health/functional deficits is an adverse outcome with important implications for patients, families and health systems. DISCLOSURES: M. K. Andrew, GSK: Grant Investigator, Research grant; Pfizer: Grant Investigator, Research grant; Sanofi-Pasteur: Grant Investigator, Research grant; J. McElhaney, GSK Vaccines: Scientific Advisor, Speaker honorarium; M. Elsherif, Canadian Institutes of Health Research: Investigator, Research grant; Public Health Agency of Canada: Investigator, Research grant; GSK: Investigator, Research grant; S. A. Halperin, GSK: Scientific Advisor, Consulting fee; GSK: Grant Investigator, Research grant; T. Hatchette, GSK: Grant Investigator, Grant recipient; Pfizer: Grant Investigator, Grant recipient; Abbvie: Speaker for a talk on biologics and risk of TB reactivation, Speaker honorarium; J. M. Langley, GSK: Investigator, Research grant; Canadian Institutes of Health Research: Investigator, Research grant; A. Mcgeer, Hoffman La Roche: Investigator, Research grant; GSK: Investigator, Research grant; sanofi pasteur: Investigator, Research grant; J. Powis, Merck: Grant Investigator, Research grant; GSK: Grant Investigator, Research grant; Roche: Grant Investigator, Research grant; Synthetic Biologicals: Investigator, Research grant; M. Semret, GSK: Investigator, Research grant; Pfizer: Investigator, Research grant; S. Trottier, Canadian Institutes of Health Research: Investigator, Research grant; L. Valiquette, GSK: Investigator, Research grant; S. McNeil, GSK: Contract Clinical Trials and Grant Investigator, Research grant; Merck: Contract Clinical Trials and Speaker’s Bureau, Speaker honorarium; Novartis: Contract Clinical Trials, No personal renumeration; sanofi pasteur: Contract Clinical Trials, No personal renumeration
    Keywords covid19
    Publisher PMC
    Document type Article ; Online
    DOI 10.1093/ofid/ofx163.1500
    Database COVID19

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