scholarly journals Persistently Increased Systemic ACE2 Activity Is Associated With an Increased Inflammatory Response in Smokers With COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Gagandeep Kaur ◽  
Shaiesh Yogeswaran ◽  
Thivanka Muthumalage ◽  
Irfan Rahman
Keyword(s):  
Multiplex Assay ◽  
Lipid Mediators ◽  
Smoking History ◽  
Infectious Agents ◽  
Serum Samples ◽  
Pronounced Increase ◽  
Enzymatic Action ◽  
Cytokine Levels ◽  
Associated Proteins ◽  
History Of

Background: Tobacco smoking is known to be involved in the pathogenesis of several cardiopulmonary diseases. Additionally, smokers are highly susceptible to infectious agents due to weakened immunity. However, the progression of lung injury based on SARS-CoV-2-mediated COVID-19 pathogenesis amongst smokers and those with pre-existing pulmonary diseases is not known. We determined the systemic levels and activity of COVID-19 associated proteins, cytokine/chemokines, and lipid mediators (lipidomics) amongst COVID-19 patients with and without a history of smoking to understand the underlying susceptible factor in the pathogenesis of COVID-19.Methods: We obtained serum from healthy (CoV−), COVID-19 positive (CoV+), and COVID-19 recovered (CoV Rec) subjects with and without a history of smoking. We conducted a Luminex multiplex assay (cytokine levels), LC/MS (eicosanoids or oxylipin panel), and ACE2 enzymatic activity assays on the serum samples to determine the systemic changes in COVID-19 patients.Results: On comparing the levels of serum ACE2 amongst COVID-19 (positive and recovered) patients and healthy controls, we found a pronounced increase in serum ACE2 levels in patients with COVID-19 infection. Furthermore, ACE2 enzyme activity was significantly increased amongst COVID-19 patients with a smoking history. Also, we analyzed the levels of Angiotensin 1–7 (Ang1–7) peptide, the product of enzymatic action of ACE2, in the serum samples. We found significantly high levels of Ang1–7 in the serum of both CoV+ and CoV Rec patients. Our data further demonstrated a smoking-induced increase in serum furin and inflammatory cytokine [IFNγ(p = 0.0836), Eotaxin (p < 0.05), MCP-1 (p < 0.05), and IL-9 (p = 0.0991)] levels in COVID-19 patients as compared to non-smoking controls. Overall, our results show that smoking adversely affects the levels of systemic inflammatory markers and COVID-19 associated proteins, thus suggesting that COVID-19 infection may have severe outcomes amongst smokers.

scholarly journals Persistently increased systemic ACE2 activity and Furin levels are associated with increased inflammatory response in smokers with SARS-CoV-2 COVID-19

2021 ◽  
Author(s):  
Gagandeep Kaur ◽  
Shaiesh Yogeswaran ◽  
Thivanka Muthumalage ◽  
Irfan Rahman
Keyword(s):  
Enzymatic Activity ◽  
Inflammatory Cytokines ◽  
Lipid Mediators ◽  
Smoking History ◽  
Serum Samples ◽  
Cytokine Analysis ◽  
Cytokine Levels ◽  
History Of ◽  
Ifn Γ ◽  
Related Proteins

AbstractBackgroundTobacco 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.MethodsWe 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.ResultsOn 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-1α, 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-γ, 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 patient’s 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 PGF2α, 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.

scholarly journals The Influence of Depression, Body Mass Index, and Smoking on Serum Inhibin B Levels in Late Reproductive-Aged Women

2006 ◽  
Vol 91 (4) ◽  
pp. 1496-1500 ◽  
Author(s):  
G. M. Lambert-Messerlian ◽  
B. L. Harlow
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Ovarian Reserve ◽  
Psychosocial Functioning ◽  
Reproductive Function ◽  
Inhibin B ◽  
Smoking History ◽  
Serum Samples ◽  
History Of ◽  
History Of Depression

Context: Women experiencing depression have difficult psychosocial functioning, and recent data suggest an earlier onset of menopause. Understanding the biological mechanism for the impairment of reproductive function associated with depression is important. Objective: The objective of the study was to determine whether a lifetime history of depression is associated with reduced ovarian reserve as reflected in serum levels of the granulosa cell product, inhibin B. Design: Residual serum samples from a subset of patients in the Harvard Study of Cycles and Moods were collected. Setting: Patients were recruited from seven Boston-area communities. Patients: Women with or without a history of major depression, based on structured clinical interviews for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were enrolled. A subset of patients who had provided an early follicular phase blood specimen at study enrollment and two or more other samples over the first 18-month period of follow-up were included. Intervention: There were no interventions. Main Outcome Measure: Serum inhibin B levels were measured. Results: Serum FSH levels were higher in women with a history of depression, whereas inhibin B levels did not differ between groups. Body mass index and age were significantly and inversely related to serum inhibin B levels. Smoking history was noted, for the first time, to have a significant negative association with inhibin B levels. Conclusions: Smoking has a direct negative effect on ovarian reserve, as suggested by decreased serum inhibin B levels. In contrast, effects of depression on the reproductive axis may occur at the level of the pituitary and/or hypothalamus rather than at the gonadal level, as suggested by increased serum FSH levels.

scholarly journals ‘The long tail of Covid-19’ - The detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 1349
Author(s):  
Ivan Doykov ◽  
Jenny Hällqvist ◽  
Kimberly C. Gilmour ◽  
Louis Grandjean ◽  
Kevin Mills ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Drug Targets ◽  
Multiplex Assay ◽  
The Body ◽  
Medical Complications ◽  
Serum Samples ◽  
Long Tail ◽  
Disease Mechanisms ◽  
Associated Proteins ◽  
Inflammatory Processes

‘Long Covid’, or medical complications associated with post SARS-CoV-2 infection, is a significant post-viral complication that is being more and more commonly reported in patients. Therefore, there is an increasing need to understand the disease mechanisms, identify drug targets and inflammatory processes associated with a SARS-CoV-2 infection. To address this need, we created a targeted mass spectrometry based multiplexed panel of 96 immune response associated proteins. We applied the multiplex assay to a cohort of serum samples from asymptomatic and moderately affected patients. All patients had tested positive for a SARS-CoV-2 infection by PCR and were determined to be subsequently positive for antibodies. Even 40-60 days post-viral infection, we observed a significant remaining inflammatory response in all patients. Proteins that were still affected were associated with the anti-inflammatory response and mitochondrial stress. This indicates that biochemical and inflammatory pathways within the body can remain perturbed long after SARS-CoV-2 infections have subsided even in asymptomatic and moderately affected patients.

scholarly journals DNA methylation and inflammation marker profiles associated with a history of depression

2018 ◽  
Vol 27 (16) ◽  
pp. 2840-2850 ◽  
Author(s):  
Bethany Crawford ◽  
Zoe Craig ◽  
Georgina Mansell ◽  
Isobel White ◽  
Adam Smith ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Dysfunction ◽  
Risk Scores ◽  
Serum Samples ◽  
Markers Of Inflammation ◽  
Genome Wide ◽  
Cytokine Levels ◽  
Exon 1 ◽  
History Of ◽  
History Of Depression

Abstract Depression is a common and disabling disorder, representing a major social and economic health issue. Moreover, depression is associated with the progression of diseases with an inflammatory etiology including many inflammatory-related disorders. At the molecular level, the mechanisms by which depression might promote the onset of these diseases and associated immune-dysfunction are not well understood. In this study we assessed genome-wide patterns of DNA methylation in whole blood-derived DNA obtained from individuals with a self-reported history of depression (n = 100) and individuals without a history of depression (n = 100) using the Illumina 450K microarray. Our analysis identified six significant (Šidák corrected P < 0.05) depression-associated differentially methylated regions (DMRs); the top-ranked DMR was located in exon 1 of the LTB4R2 gene (Šidák corrected P = 1.27 × 10−14). Polygenic risk scores (PRS) for depression were generated and known biological markers of inflammation, telomere length (TL) and IL-6, were measured in DNA and serum samples, respectively. Next, we employed a systems-level approach to identify networks of co-methylated loci associated with a history of depression, in addition to depression PRS, TL and IL-6 levels. Our analysis identified one depression-associated co-methylation module (P = 0.04). Interestingly, the depression-associated module was highly enriched for pathways related to immune function and was also associated with TL and IL-6 cytokine levels. In summary, our genome-wide DNA methylation analysis of individuals with and without a self-reported history of depression identified several candidate DMRs of potential relevance to the pathogenesis of depression and its associated immune-dysfunction phenotype.

On the natural history of hypergastrinemia.

1985 ◽  
Vol 31 (7) ◽  
pp. 1135-1140 ◽  
Author(s):  
G Lindstedt ◽  
D Runsteen ◽  
P A Lundberg ◽  
C Bengtsson ◽  
L Lapidus ◽  
...  
Keyword(s):  
Serum Gastrin ◽  
Reference Group ◽  
Reference Interval ◽  
Serum Samples ◽  
Pronounced Increase ◽  
Pepsinogen I ◽  
Serum Gastrin Concentration ◽  
History Of ◽  
High Concentrations ◽  
Middle Aged Adults

Abstract We determined total gastrin and pepsinogen I in frozen serum samples from 175 overnight-fasted women 54 years old, and from 81 overnight-fasted women 60 years old, who took part in a population study in 1968-69. We also assayed samples from some of these women, who participated in clinical follow-up studies in 1974-75 and 1980-81: all of the women in the initial group whose serum gastrin concentration exceeded the 85th centile value and, as a reference group, a randomized subsample of women whose initial serum gastrin concentration was less than the 80th centile. Samples with total gastrin concentration greater than 400 ng/L were also assayed for gastrin-17 and gastrin-34. We found that: a pronounced increase of serum gastrin persisted throughout the study period for most of these postmenopausal women, indicating that conversion of type A gastritis (antrum-sparing) to pan-gastritis is uncommon; unexplained high concentrations of pepsinogen I in relation to the reference interval for young and middle-aged adults, as well as in relation to serum gastrin, were common; and the gastrin-17/gastrin-34 ratio is not correlated with the outcome of pronounced hypergastrinemia.

scholarly journals ‘The long tail of Covid-19’ - The detection of a prolonged inflammatory response after a SARS-CoV-2 infection in asymptomatic and mildly affected patients

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1349
Author(s):  
Ivan Doykov ◽  
Jenny Hällqvist ◽  
Kimberly C. Gilmour ◽  
Louis Grandjean ◽  
Kevin Mills ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Drug Targets ◽  
Multiplex Assay ◽  
The Body ◽  
Medical Complications ◽  
Serum Samples ◽  
Long Tail ◽  
Disease Mechanisms ◽  
Associated Proteins ◽  
Inflammatory Processes

‘Long Covid’, or medical complications associated with post SARS-CoV-2 infection, is a significant post-viral complication that is being more and more commonly reported in patients. Therefore, there is an increasing need to understand the disease mechanisms, identify drug targets and inflammatory processes associated with a SARS-CoV-2 infection. To address this need, we created a targeted mass spectrometry based multiplexed panel of 96 immune response associated proteins. We applied the multiplex assay to a cohort of serum samples from asymptomatic and moderately affected patients. All patients had tested positive for a SARS-CoV-2 infection by PCR and were determined to be subsequently positive for antibodies. Even 40-60 days post-viral infection, we observed a significant remaining inflammatory response in all patients. Proteins that were still affected were associated with the anti-inflammatory response and mitochondrial stress. This indicates that biochemical and inflammatory pathways within the body can remain perturbed long after SARS-CoV-2 infections have subsided even in asymptomatic and moderately affected patients.

LUNGRADS AND UPDATE OF LUNG NODULES SCREENING BY LOW DOSE COMPUTED TOMOGRAPHY

2015 ◽  
pp. 12-19
Author(s):  
Thi Ngoc Ha Hoang ◽  
Trong Khoan Le
Keyword(s):  
Lung Cancer ◽  
Low Dose ◽  
False Negative ◽  
Lung Nodule ◽  
Lung Cancer Mortality ◽  
Smoking History ◽  
Low Dose Ct ◽  
History Of ◽  
Chest X Ray ◽  
Low Dose Computed Tomography

Background: A pulmonary nodule is defined as a rounded or irregular opacity, well or poorly defined, measuring up to 3 cm in diameter. Early detection the malignancy of nodules has a significant role in decreasing the mortality, increasing the survival time and consider as early diagnosis lung cancer. The main risk factors are those of current or former smokers, aged 55 to 74 years with a smoking history of at least 1 pack-day. Low dose CT: screening individuals with high risk of lung cancer by low dose CT scans could reduce lung cancer mortality by 20 percent compared to chest X-ray. Radiation dose has to maximum reduced but respect the rule of ALARA (As Low as Resonably Archivable). LungRADS 2014: Classification of American College of Radiology, LungRADS, is a newly application but showed many advantages in comparison with others classification such as increasing positive predict value (PPV), no result of false negative and cost effectiveness. Key words: LungRADS, screening lung nodule, low dose CT, lung cancer

scholarly journals Predicting COVID-19 mortality with electronic medical records

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hossein Estiri ◽  
Zachary H. Strasser ◽  
Jeffy G. Klann ◽  
Pourandokht Naseri ◽  
Kavishwar B. Wagholikar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Medical Information ◽  
Age Groups ◽  
Prognostic Models ◽  
Smoking History ◽  
Risk Scores ◽  
Gradient Boosting ◽  
Chronic Obstructive ◽  
Clinical Expertise ◽  
History Of

AbstractThis study aims to predict death after COVID-19 using only the past medical information routinely collected in electronic health records (EHRs) and to understand the differences in risk factors across age groups. Combining computational methods and clinical expertise, we curated clusters that represent 46 clinical conditions as potential risk factors for death after a COVID-19 infection. We trained age-stratified generalized linear models (GLMs) with component-wise gradient boosting to predict the probability of death based on what we know from the patients before they contracted the virus. Despite only relying on previously documented demographics and comorbidities, our models demonstrated similar performance to other prognostic models that require an assortment of symptoms, laboratory values, and images at the time of diagnosis or during the course of the illness. In general, we found age as the most important predictor of mortality in COVID-19 patients. A history of pneumonia, which is rarely asked in typical epidemiology studies, was one of the most important risk factors for predicting COVID-19 mortality. A history of diabetes with complications and cancer (breast and prostate) were notable risk factors for patients between the ages of 45 and 65 years. In patients aged 65–85 years, diseases that affect the pulmonary system, including interstitial lung disease, chronic obstructive pulmonary disease, lung cancer, and a smoking history, were important for predicting mortality. The ability to compute precise individual-level risk scores exclusively based on the EHR is crucial for effectively allocating and distributing resources, such as prioritizing vaccination among the general population.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

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