Pathogens and Immunity最新文献

{"title":"Immune Dysregulation in Acute SARS-CoV-2 Infection.","authors":"Lauren Grimm,&nbsp;Chinyere Onyeukwu,&nbsp;Grace Kenny,&nbsp;Danielle M Parent,&nbsp;Jia Fu,&nbsp;Shaurya Dhingra,&nbsp;Emily Yang,&nbsp;James Moy,&nbsp;P J Utz,&nbsp;Russell Tracy,&nbsp;Alan Landay","doi":"10.20411/pai.v7i2.537","DOIUrl":"https://doi.org/10.20411/pai.v7i2.537","url":null,"abstract":"<p><strong>Introduction: </strong>Neutralizing antibodies have been shown to develop rapidly following SARS-CoV-2 infection, specifically against spike (S) protein, where cytokine release and production is understood to drive the humoral immune response during acute infection. Thus, we evaluated the quantity and function of antibodies across disease severities and analyzed the associated inflammatory and coagulation pathways to identify acute markers that correlate with antibody response following infection.</p><p><strong>Methods: </strong>Blood samples were collected from patients at time of diagnostic SARS-CoV-2 PCR testing between March 2020-November 2020. Plasma samples were analyzed using the MesoScale Discovery (MSD) Platform using the COVID-19 Serology Kit and U-Plex 8 analyte multiplex plate to measure anti-alpha and beta coronavirus antibody concentration and ACE2 blocking function, as well as plasma cytokines.</p><p><strong>Results: </strong>A total of 230 (181 unique patients) samples were analyzed across the 5 COVID-19 disease severities. We found that antibody quantity directly correlated with functional ability to block virus binding to membrane-bound ACE2, where a lower SARS-CoV-2 anti-spike/anti-RBD response corresponded with a lower antibody blocking potential compared to higher antibody response (anti-S1 r = 0.884, <i>P</i> < 0.001; anti-RBD r = 0.75, <i>P</i> < 0.001). Across all the soluble proinflammatory markers we examined, ICAM, IL-1β, IL-4, IL-6, TNFα, and Syndecan showed a statistically significant positive correlation between cytokine or epithelial marker and antibody quantity regardless of COVID-19 disease severity. Analysis of autoantibodies against type 1 interferon was not shown to be statistically significant between disease severity groups.</p><p><strong>Conclusion: </strong>Previous studies have shown that proinflammatory markers, including IL-6, IL-8, IL-1β, and TNFα, are significant predictors of COVID-19 disease severity, regardless of demographics or comorbidities. Our study demonstrated that not only are these proinflammatory markers, as well as IL-4, ICAM, and Syndecan, correlative of disease severity, they are also correlative of antibody quantity and quality following SARS-CoV-2 exposure.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"7 2","pages":"143-170"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9973727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9388591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on the Pathogenesis, Virulence, and Treatment of <i>Candida auris</i>.","authors":"Richard R Watkins,&nbsp;Rachael Gowen,&nbsp;Michail S Lionakis,&nbsp;Mahmoud Ghannoum","doi":"10.20411/pai.v7i2.535","DOIUrl":"https://doi.org/10.20411/pai.v7i2.535","url":null,"abstract":"<p><p><i>Candida auris</i> is an emerging, multidrug resistant fungal pathogen that causes considerable morbidity and mortality. First identified in Japan in 2009, it has since been reported in more than 40 countries. <i>C. auris</i> can persist for long periods on different environmental surfaces as well as the skin. Clinical isolates are typically resistant to commonly prescribed antifungal drugs. Increasingly recognized as a cause of infections and outbreaks in nosocomial settings, <i>C. auris</i> is difficult to identify using traditional microbiological methods. One of the main reasons for the ongoing spread of <i>C. auris</i> is the multitude of virulence factors it possesses and uses against its human host that enables fungal persistence on the skin surface. Yet, many of the virulence mechanismsare unknown or remain incompletely understood. In this review, we summarize the evolution of virulence of <i>C. auris</i>, offer recommendations for combating this important human pathogen, and suggest directions for further research.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"7 2","pages":"46-65"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9620957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9182906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to: Use of a MAIT-Activating Ligand, 5-OP-RU, as a Mucosal Adjuvant in a Murine Model of <i>Vibrio cholerae</i> O1 Vaccination.","authors":"Owen Jensen,&nbsp;Shubhanshi Trivedi,&nbsp;Jackson G Cacioppo,&nbsp;Kelin Li,&nbsp;Jeffrey Aubé,&nbsp;J Scott Hale,&nbsp;Edward T Ryan,&nbsp;Daniel T Leung","doi":"10.20411/pai.v7i1.541","DOIUrl":"https://doi.org/10.20411/pai.v7i1.541","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.20411/pai.v7i1.525.].</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"7 1","pages":"145-146"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential CD4+ T-Cell Cytokine and Cytotoxic Responses Between Reactivation and Latent Phases of Herpes Zoster Infection.","authors":"Wenjie Jin,&nbsp;Mike Fang,&nbsp;Ismail Sayin,&nbsp;Carson Smith,&nbsp;Jeffrey L Hunter,&nbsp;Brian Richardson,&nbsp;Jackelyn B Golden,&nbsp;Christopher Haley,&nbsp;Kenneth E Schmader,&nbsp;Michael R Betts,&nbsp;Stephen K Tyring,&nbsp;Cheryl M Cameron,&nbsp;Mark J Cameron,&nbsp;David H Canada","doi":"10.20411/pai.v7i2.560","DOIUrl":"https://doi.org/10.20411/pai.v7i2.560","url":null,"abstract":"Background: CD4+ T cells are a critical component of effective immune responses to varicella zoster virus (VZV), but their functional properties during the reactivation acute vs latent phase of infection remain poorly defined. Methods: Here we assessed the functional and transcriptomic properties of peripheral blood CD4+ T cells in persons with acute herpes zoster (HZ) compared to those with a prior history of HZ infection using multicolor flow cytometry and RNA sequencing. Results: We found significant differences between the polyfunctionality of VZV-specific total memory, effector memory, and central memory CD4+ T cells in acute vs prior HZ. VZV-specific CD4+ memory T-cell responses in acute HZ reactivation had higher frequencies of IFN-γ and IL-2 producing cells compared to those with prior HZ. In addition, cytotoxic markers were higher in VZV-specific CD4+ T cells than non-VZV-specific cells. Transcriptomic analysis of ex vivo total memory CD4+ T cells from these individuals showed differential regulation of T-cell survival and differentiation pathways, including TCR, cytotoxic T lymphocytes (CTL), T helper, inflammation, and MTOR signaling pathways. These gene signatures correlated with the frequency of IFN-γ and IL-2 producing cells responding to VZV. Conclusions: In summary, VZV-specific CD4+ T cells from acute HZ individuals had unique functional and transcriptomic features, and VZV-specific CD4+ T cells as a group had a higher expression of cytotoxic molecules including Perforin, Granzyme-B, and CD107a.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"7 2","pages":"171-188"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9973729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9525686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Diagnosis of Recurrent Paucibacillary Tuberculosis.","authors":"Claudia Jafari,&nbsp;Ioana D Olaru,&nbsp;Franziska Daduna,&nbsp;Christoph Lange,&nbsp;Barbara Kalsdorf","doi":"10.20411/pai.v7i2.565","DOIUrl":"https://doi.org/10.20411/pai.v7i2.565","url":null,"abstract":"<p><strong>Introduction: </strong>The rapid diagnosis of tuberculosis recurrence can be challenging due to persistently positive detection of <i>Mycobacterium tuberculosis</i>-specific DNA from sputum and bronchopulmonary samples in the absence of active disease.</p><p><strong>Methods: </strong>We compared the diagnostic accuracy of the detection of <i>M. tuberculosis</i>-specific DNA by either Xpert (January 2010-June 2018) or Xpert Ultra (July 2018-June 2020) and <i>M. tuberculosis</i>-specific ELISPOT in bronchoalveolar lavage (BAL) samples with <i>M. tuberculosis</i> culture results from sputum or bronchopulmonary samples in patients with suspected recurrence of pulmonary tuberculosis.</p><p><strong>Results: </strong>Among 44 individuals with previous tuberculosis and a presumptive diagnosis of recurrent pulmonary tuberculosis, 4/44 (9.1%) were diagnosed with recurrent tuberculosis by culture. DNA of <i>M. tuberculosis</i> was detected by Xpert in BAL fluid in 1/4 (25%) individuals with recurrent tuberculosis and in 2/40 (5%) cases with past tuberculosis without recurrence, while BAL-ELISPOT with a cut-off of >4,000 early secretory antigenic target-6-specific or culture filtrate protein-10-specific interferon-γ-producing lymphocytes per 1 million BAL-lymphocytes was positive in 4/4 (100%) individuals with recurrent tuberculosis and in 2/40 (5%) cases of past tuberculosis without recurrence.</p><p><strong>Conclusion: </strong><i>M. tuberculosis</i>-specific BAL-ELISPOT is more accurate than BAL-Xpert for the diagnosis of paucibacillary tuberculosis recurrence.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"7 2","pages":"189-202"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9868976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is France Once Again Looking for a Scapegoat?","authors":"Michael M Lederman,&nbsp;Jeffrey S Flier,&nbsp;Peter Hale,&nbsp;Ashley T Haase,&nbsp;William Powderly,&nbsp;Peter Reiss,&nbsp;Guido Silvestri,&nbsp;Rafick P Sekaly,&nbsp;Mirko Paiardini,&nbsp;Drew Weissman,&nbsp;Daniel R Kuritzkes,&nbsp;Leonard H Calabrese,&nbsp;Peter Agre,&nbsp;Gustavo Reyes-Teran,&nbsp;Alan L Landay,&nbsp;Sharon Lewin,&nbsp;Douglas D Richman,&nbsp;Paul Volberding,&nbsp;Peter W Hunt,&nbsp;Mauro Schechter","doi":"10.20411/pai.v6i2.490","DOIUrl":"https://doi.org/10.20411/pai.v6i2.490","url":null,"abstract":"<p><p>On September 10, 2021, a special tribunal established by the French government launched an inquiry into the activities of former health minister Dr. Agnes Buzyn who was charged with \"endangering the lives of others\". It is surprising to learn of this accusation and inquiry into the actions of a public health official whose response to the epidemic was, to all appearances, exemplary.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":" ","pages":"149-152"},"PeriodicalIF":0.0,"publicationDate":"2021-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39573417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soluble Tumor Necrosis Factor Receptor 1 is Associated With Cardiovascular Risk in Persons With Coronary Artery Calcium Score of Zero.","authors":"Tony Dong,&nbsp;Graham Bevan,&nbsp;David A Zidar,&nbsp;Miguel Cainzos Achirica,&nbsp;Khurram Nasir,&nbsp;Imran Rashid,&nbsp;Sanjay Rajagopalan,&nbsp;Sadeer Al-Kindi","doi":"10.20411/pai.v6i2.477","DOIUrl":"https://doi.org/10.20411/pai.v6i2.477","url":null,"abstract":"<p><strong>Background: </strong>A coronary artery calcium (CAC) score of zero confers a low but nonzero risk of atherosclerotic cardiovascular events (CVD) in asymptomatic patient populations, and additional risk stratification is needed to guide preventive interventions. Soluble tumor necrosis factor receptors (sTNFR-1 and sTNFR-2) are shed in the context of TNF-alpha signaling and systemic inflammation, which play a role in atherosclerosis and plaque instability. We hypothesized that serum sTNFR-1 concentrations may aid in cardiovascular risk stratification among asymptomatic patients with a CAC score of zero.</p><p><strong>Methods: </strong>We included all participants with CAC=0 and baseline sTNFR-1 measurements from the prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA). The primary outcome was a composite CVD event (myocardial infarction, stroke, coronary revascularization, cardiovascular death).</p><p><strong>Results: </strong>The study included 1471 participants (mean age 57.6 years, 64% female), with measured baseline sTNFR-1 ranging from 603 pg/mL to 5544 pg/mL (mean 1294 pg/mL ±378.8 pg/mL). Over a median follow-up of 8.5 years, 37 participants (2.5%) experienced a CVD event. In multivariable analyses adjusted for Framingham Score, doubling of sTNFR-1 was associated with a 3-fold increase in the hazards of CVD (HR 3.0, 95% CI: 1.48-6.09, <i>P</i> = 0.002), which remained significant after adjusting for traditional CVD risk factors individually (HR 2.29; 95% CI: 1.04-5.06, <i>P</i>=0.04). Doubling of sTNFR-1 was also associated with progression of CAC >100, adjusted for age (OR 2.84, 95% CI: 1.33-6.03, <i>P</i>=0.007).</p><p><strong>Conclusions: </strong>sTNFR-1 concentrations are associated with more CVD events in participants with a CAC score of zero. Utilizing sTNFR-1 measurements may improve cardiovascular risk stratification and guide primary prevention in otherwise low-risk individuals.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":" ","pages":"135-148"},"PeriodicalIF":0.0,"publicationDate":"2021-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39901352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Patient With Multiple Carbapenemase Producers Including an Unusual <i>Citrobacter sedlakii</i> Hosting an IncC <i>bla</i> _NDM-1- and <i>armA</i>-carrying Plasmid.","authors":"Aline I Moser,&nbsp;Peter M Keller,&nbsp;Edgar I Campos-Madueno,&nbsp;Laurent Poirel,&nbsp;Patrice Nordmann,&nbsp;Andrea Endimiani","doi":"10.20411/pai.v6i2.482","DOIUrl":"https://doi.org/10.20411/pai.v6i2.482","url":null,"abstract":"<p><strong>Background: </strong>Patients colonized with multiple species of carbapenemase-producing Enterobacterales (CPE) are increasingly observed. This phenomenon can be due to the high local prevalence of these pathogens, the presence of important host risk factors, and the great genetic promiscuity of some carbapenemase genes.</p><p><strong>Methods: </strong>We analyzed 4 CPE (<i>Escherichia coli, Klebsiella pneumoniae, Providencia stuartii, Citrobacter sedlakii</i>), 1 extended-spectrum cephalosporin-resistant <i>K. pneumoniae</i> (ESC-R-<i>Kp</i>), and 1 carbapenemase-producing <i>Acinetobacter baumannii</i> simultaneously isolated from a patient transferred from Macedonia. Susceptibility tests were performed using a microdilution MIC system. The complete genome sequences were obtained by using both short-read and long-read whole-genome sequencing technologies.</p><p><strong>Results: </strong>All CPE presented high-level resistance to all aminoglycosides due to the expression of the <i>armA</i> 16S rRNA methylase. In <i>C. sedlakii</i> and <i>E. coli</i> (ST69), both the carbapenemase <i>bla</i> _NDM-1 and <i>armA</i> genes were located on an identical IncC plasmid of type 1a. The <i>K. pneumoniae</i> (ST268) and <i>P. stuartii</i> carried chromosomal <i>bla</i> _NDM-1 and <i>bla</i> _OXA-48, respectively, while the ESC-R-<i>Kp</i> (ST395) harbored a plasmid-located <i>bla</i> _CTX-M-15. In the latter 3 isolates, <i>armA</i>-harboring IncC plasmids similar to plasmids found in <i>C. sedlakii</i> and <i>E. coli</i> were also detected. The <i>A. baumannii</i> strain possessed the <i>bla</i> _OXA-40 carbapenemase gene.</p><p><strong>Conclusions: </strong>The characterization of the genetic organization of IncC-type plasmids harbored by 3 different species from the same patient offered insights into the evolution of these broad-host-range plasmids. Moreover, we characterized here the first complete genome sequence of a carbapenemase-producing <i>C. sedlakii</i> strain, providing a reference for future studies on this rarely reported species.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":" ","pages":"119-134"},"PeriodicalIF":0.0,"publicationDate":"2021-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39901351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Memory B-Cell Response to Influenza Immunization in Patients With Common Variable Immunodeficiency (CVID).","authors":"Wei Zhan,&nbsp;Todd Hatchette,&nbsp;Fengyun Yue,&nbsp;Jun Liu,&nbsp;Haihan Song,&nbsp;Hanqi Zhao,&nbsp;Stephen Betschel,&nbsp;Mario Ostrowski","doi":"10.20411/pai.v6i2.405","DOIUrl":"https://doi.org/10.20411/pai.v6i2.405","url":null,"abstract":"<p><strong>Background: </strong>Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency characterized by low serum antibody levels and recurrent infections. The cellular response to immunization in patients with CVID has not been fully investigated. In this study, we aimed to characterize vaccination-induced influenza-specific memory B-cell responses in CVID.</p><p><strong>Methods: </strong>Eleven individuals affected with CVID and 9 unaffected control individuals were immunized with the 2010-2011 non-adjuvanted seasonal influenza vaccine. Blood samples were collected on the day of vaccination and at week 8 and week 16 after vaccination, and PBMCs were immunophenotyped by flow cytometry. Influenza specific serology was determined using hemagglutination inhibition and microneutralization against vaccine antigens. Influenza-specific memory B-cell responses were determined by ELISpot.</p><p><strong>Results: </strong>Individuals with CVID showed wide variability in the frequency of CD19+ B cells in blood. The CVID group had significantly reduced frequencies of CD19+CD27+ memory B cells. Frequencies of circulating T follicular helper (CD4+CXCR5+) cells were similar between those with CVID and healthy controls. In terms of serology, compared to healthy controls, the CVID group overall showed significantly reduced boosting to vaccine antigens by hemagglutination inhibition and microneutralization assays at 8 weeks compared to controls and failed to maintain responses by 16 weeks compared to controls, resulting in a post-vaccination geometric mean titer (GMT) ≥ 40 to strain A/H1N1 in only 27% at 8 weeks, and 22% at 12 weeks for patients with CVID vs 78% and 75%, respectively for healthy controls. In addition, there was a GMT ≥ 40 to A/H3N2 in only 9% at 8 weeks and 22% at 12 weeks for patients with CVID vs 56% and 50%, respectively for healthy controls. Healthy participants showed significant increases in flu-specific IgM-secreting memory B cells after vaccination, whereas patients with CVID showed non-signifi-cant mild increases. Before vaccination, patients with CVID had significantly lower frequencies of background level influenza-specific IgG and IgA memory B cells. Half of the patients with CVID showed an increase in influenza-specific IgG-secreting memory B cells post vaccination, whereas the other half showed none. All control participants exhibited an increase in influenza-specific IgG-secreting B cells. None of the patients with CVID developed influenza-specific IgA memory B-cell response post vaccination, compared to 5/8 in healthy controls. At week 16, the frequency of influenza-specific memory B-cell responses decayed but to non-zero baseline in healthy controls and to zero baseline in patients with CVID.</p><p><strong>Conclusions: </strong>Together, these data demonstrate that patients with CVID respond heterogeneously, but as a group poorly, to non-adjuvanted influenza vaccine, with a subgroup unable to generate ","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":" ","pages":"105-118"},"PeriodicalIF":0.0,"publicationDate":"2021-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39901350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Red Cell Distribution Width and Low Absolute Lymphocyte Count Associate With Subsequent Mortality in HCV Infection.","authors":"Sofi Damjanovska,&nbsp;Perica Davitkov,&nbsp;Surya Gopal,&nbsp;Lenche Kostadinova,&nbsp;Corrine Kowal,&nbsp;Alyssa Lange,&nbsp;Anita Moreland,&nbsp;Carey L Shive,&nbsp;Brigid Wilson,&nbsp;Taissa Bej,&nbsp;Sadeer Al-Kindi,&nbsp;Yngve Falck-Ytter,&nbsp;David A Zidar,&nbsp;Donald D Anthony","doi":"10.20411/pai.v6i2.467","DOIUrl":"https://doi.org/10.20411/pai.v6i2.467","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis-C virus (HCV) chronic infection can lead to cirrhosis, hepatocellular carcinoma (HCC), end-stage liver disease, cardiovascular disease (CVD), and mortality. Transient Elastography (TE) is used to non-invasively assess fibrosis. Whether immune monitoring provides additive prognostic value is not established. Increased red-cell distribution width (RDW) and decreased absolute lymphocyte count (ALC) predict mortality in those without liver disease. Whether these relationships remain during HCV infection is unknown.</p><p><strong>Materials and methods: </strong>A retrospective cohort of 1,715 single-site VA Liver Clinic patients receiving Transient Elastography (TE) 2014-2019 to evaluate HCV-associated liver damage were evaluated for RDW and ALC in relation to traditional parameters of cardiovascular risk, liver health, development of HCC, and mortality.</p><p><strong>Results: </strong>The cohort was 97% male, 55% African American, 26% with diabetes mellitus, 67% with hypertension, and 66% with tobacco use. After TE, 3% were subsequently diagnosed with HCC, and 12% (n=208) died. Most deaths (n=189) were due to non-liver causes. The TE score associated with prevalent CVD, positively correlated with atherosclerotic cardiovascular disease (ASCVD) 10-Year Risk Score, age, RDW, and negatively correlated with ALC. Patients with anisocytosis (RDW above 14%) or lymphopenia (ALC level under 1.2×10⁹/L) had greater subsequent all-cause mortality, even after adjusting for age, TE score, and comorbidities. TE score, and to a modest degree RDW, were associated with subsequent liver-associated mortality, while TE score, RDW, and ALC were each independently associated with non-liver cause of death.</p><p><strong>Conclusion: </strong>Widely available mortality calculators generally require multiple pieces of clinical information. RDW and ALC, parameters collected on a single laboratory test that is commonly performed, prior to HCV therapy may be pragmatic markers of long-term risk of mortality.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":" ","pages":"90-104"},"PeriodicalIF":0.0,"publicationDate":"2021-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39665341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}