Pathogens and Immunity最新文献

{"title":"Evaluation of 2 Ultraviolet-C Light Boxes for Decontamination of N95 Respirators.","authors":"Jennifer L Cadnum,&nbsp;Basya S Pearlmutter,&nbsp;Daniel F Li,&nbsp;Annette L Jencson,&nbsp;Jacob G Scott,&nbsp;Ian C Charnas,&nbsp;Curtis J Donskey","doi":"10.20411/pai.v6i1.432","DOIUrl":"https://doi.org/10.20411/pai.v6i1.432","url":null,"abstract":"<p><strong>Background: </strong>Ultraviolet-C (UV-C) light devices are effective in reducing contamination on N95 filtering facepiece respirators. However, limited information is available on whether UV-C devices meet the Food and Drug Administration's (FDA) microbiological requirements for Emergency Use Authorization (EUA) for respirator bioburden reduction.</p><p><strong>Methods: </strong>We tested the ability of 2 UV-C light boxes to achieve the 3-log₁₀ microorganism reductions required for EUA for reuse by single users. Whole 3M 1860 or Moldex 1513 respirators were inoculated on the exterior facepiece, interior facepiece, and internal fibers with bacteriophage MS2 and/or 4 strains of bacteria and treated with UV-C cycles of 1 or 20 minutes. Colorimetric indicators were used to assess penetration of UV-C through the respirators.</p><p><strong>Results: </strong>For 1 UV-C box, a 20-minute treatment achieved the required bioburden reduction for Moldex 1513 but not 3M 1860 respirators. For the second UV-C box, a 1-minute treatment achieved the required bioburden reduction in 4 bacterial strains for the Moldex 1513 respirator. Colorimetric indicators demonstrated penetration of UV-C through all layers of the Moldex 1513 respirator but not the 3M 1860 respirator.</p><p><strong>Conclusions: </strong>Our findings demonstrate that UV-C box technologies can achieve bioburden reductions required by the FDA for EUA for single users but highlight the potential for variable efficacy for different types of respirators.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"6 1","pages":"104-115"},"PeriodicalIF":0.0,"publicationDate":"2021-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39238685","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":"COVID-19 Outcomes in Patients Undergoing B Cell Depletion Therapy and Those with Humoral Immunodeficiency States: A Scoping Review.","authors":"Jessica M Jones, Aiman J Faruqi, James K Sullivan, Cassandra Calabrese, Leonard H Calabrese","doi":"10.20411/pai.v6i1.435","DOIUrl":"10.20411/pai.v6i1.435","url":null,"abstract":"<p><strong>Background: </strong>The role of humoral immunity has been well established in reducing infection risk and facilitating viral clearance in patients with COVID-19. However, the relationship between specific antibody responses and severity of COVID-19 is less well understood.</p><p><strong>Methods: </strong>To address this question and identify gaps in knowledge, we utilized the methodology of a scoping review to interrogate risk of infection and clinical outcomes of COVID-19 in patients with iatrogenic and inborn humoral immunodeficiency states based on existing literature.</p><p><strong>Results: </strong>Among patients with iatrogenic B-cell depletion, particularly with agents targeting CD20, our analysis found increased risk of severe COVID-19 and death across a range of underlying disease states. Among patients with humoral inborn errors of immunity with COVID-19, our synthesis found that patients with dysregulated humoral immunity, predominantly common variable immunodeficiency (CVID), may be more susceptible to severe COVID-19 than patients with humoral immunodeficiency states due to X-linked agammaglobulinemia and other miscellaneous forms of humoral immunodeficiency. There were insufficient data to appraise the risk of COVID-19 infection in both populations of patients.</p><p><strong>Conclusions: </strong>Our work identifies potentially significant predictors of COVID-19 severity in patients with humoral immunodeficiency states and highlights the need for larger studies to control for clinical and biologic confounders of disease severity.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"6 1","pages":"76-103"},"PeriodicalIF":0.0,"publicationDate":"2021-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39033342","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":"Life As Haiku","authors":"D. Douek","doi":"10.20411/PAI.V6I1.442","DOIUrl":"https://doi.org/10.20411/PAI.V6I1.442","url":null,"abstract":"Life is no haikuAnd I would tell you why notIf I had the timeTo","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42950765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV-2-Priming Protease TMPRSS2.","authors":"Nurit P Azouz, Andrea M Klingler, Victoria Callahan, Ivan V Akhrymuk, Katarina Elez, Lluís Raich, Brandon M Henry, Justin L Benoit, Stefanie W Benoit, Frank Noé, Kylene Kehn-Hall, Marc E Rothenberg","doi":"10.20411/pai.v6i1.408","DOIUrl":"10.20411/pai.v6i1.408","url":null,"abstract":"<p><strong>Background: </strong>Host proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry.</p><p><strong>Methods: </strong>We developed a cell-based assay to identify TMPRSS2 inhibitors. Inhibitory activity was established in SARS-CoV-2 viral load systems.</p><p><strong>Results: </strong>We identified the human extracellular serine protease inhibitor (serpin) alpha 1 anti-trypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity.</p><p><strong>Conclusions: </strong>Our data support the key role of extracellular serine proteases in SARS CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"6 1","pages":"55-74"},"PeriodicalIF":0.0,"publicationDate":"2021-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38896896","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":"The Intersection of COVID-19 and Autoimmunity: What is Our Current Understanding?","authors":"N Winchester, C Calabrese, L H Calabrese","doi":"10.20411/pai.v6i1.417","DOIUrl":"10.20411/pai.v6i1.417","url":null,"abstract":"<p><p>Viral infections have historically had a complex relationship with autoimmune diseases. For patients with preexisting autoimmune disorders, often complicated by immunosuppressive therapies, there are numerous potential effects of COVID-19, a disease of complex immunobiology, including the potential for an altered natural history of COVID-19 when infected. In addition, individuals without recognized autoimmune disease may be vulnerable to virally induced autoimmunity in the forms of autoantibody formation, as well as the development of clinical immune-mediated inflammatory diseases. Until quite recently in the pandemic, this relationship between COVID-19 and autoimmune diseases has been relatively underexplored; yet such investigation offers potential insights into immunopathogenesis as well as for the development of new immune-based therapeutics. Our review examines this relationship through exploration of a series of questions with relevance to both immunopathogenic mechanisms as well as some clinical implications.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"6 1","pages":"31-54"},"PeriodicalIF":0.0,"publicationDate":"2021-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38896894","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":"COVID-19 Outcomes in Patients Undergoing B Cell Depletion Therapy and Those with Humoral Immunodeficiency States: A Scoping Review","authors":"Jessica M Jones, Aiman J Faruqi, J. Sullivan, C. Calabrese, L. Calabrese","doi":"10.21203/RS.3.RS-224753/V1","DOIUrl":"https://doi.org/10.21203/RS.3.RS-224753/V1","url":null,"abstract":"Background: The role of humoral immunity has been well established in reducing infection risk and facilitating viral clearance in patients with COVID-19. However, the relationship between specific antibody responses and severity of COVID-19 is less well understood. Methods: To address this question and identify gaps in knowledge, we utilized the methodology of a scoping review to interrogate risk of infection and clinical outcomes of COVID-19 in patients with iatrogenic and inborn humoral immunodeficiency states based on existing literature. Results: Among patients with iatrogenic B-cell depletion, particularly with agents targeting CD20, our analysis found increased risk of severe COVID-19 and death across a range of underlying disease states. Among patients with humoral inborn errors of immunity with COVID-19, our synthesis found that patients with dysregulated humoral immunity, predominantly common variable immunodeficiency (CVID), may be more susceptible to severe COVID-19 than patients with humoral immunodeficiency states due to X-linked agammaglobulinemia and other miscellaneous forms of humoral immunodeficiency. There were insufficient data to appraise the risk of COVID-19 infection in both populations of patients. Conclusions: Our work identifies potentially significant predictors of COVID-19 severity in patients with humoral immunodeficiency states and highlights the need for larger studies to control for clinical and biologic confounders of disease severity.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"6 1","pages":"76 - 103"},"PeriodicalIF":0.0,"publicationDate":"2021-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45238801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Extracellular Vesicle Subtypes May be Useful as Potential Biomarkers of Immune Activation in People With HIV.","authors":"Wilfried Wenceslas Bazié,&nbsp;Julien Boucher,&nbsp;Julien Vitry,&nbsp;Benjamin Goyer,&nbsp;Jean Pierre Routy,&nbsp;Cécile Tremblay,&nbsp;Sylvie Trottier,&nbsp;Mohammad-Ali Jenabian,&nbsp;Patrick Provost,&nbsp;Michel Alary,&nbsp;Caroline Gilbert","doi":"10.20411/pai.v6i1.384","DOIUrl":"https://doi.org/10.20411/pai.v6i1.384","url":null,"abstract":"<p><strong>Background: </strong>Extracellular vesicles (EVs) are intercellular messengers with epigenetic potential since they can shuttle microRNA (miRNA). EVs and miRNA play a role in human immunodeficiency virus (HIV) infection immunopathogenesis. Chronic immune activation and systemic inflammation during HIV infection despite effective antiretroviral therapy (ART) are associated with non-acquired immunodeficiency syndrome (AIDS) comorbidities in people living with HIV (PLWH). Analysis of plasma EVs and their miRNA content may be useful as immune activation or inflammatory biomarkers in PLWH receiving ART. In this study, we hypothesized that the number, size, and miRNA of large and small EVs could reflect immune activation associated with an elevated CD8 T-cell count or a low CD4/CD8 ratio in PLWH.</p><p><strong>Methods: </strong>Plasma EVs subtype purified from PLWH and uninfected controls were sized using dynamic light scattering and quantified using flow cytometry and acetylcholine esterase (AChE) activity. Expression of mature miRNAs miR-92, miR-155, miR-223 was measured by quantitative reverse-transcriptase polymerase chain reaction in EVs and leucocytes.</p><p><strong>Results: </strong>HIV infection induces increased production of small EVs in plasma. EV subtypes were differentially enriched in miR-92, miR-155, and miR-223. Positive correlations between CD8 T-cell count and large EVs abundance and small EVs AChE activity were observed. CD4/CD8 ratio was negatively correlated with small EV AChE activity, and miRNA-155 level per small EV was negatively correlated with CD8 T-cell count.</p><p><strong>Conclusions: </strong>These findings suggest that quantifying large or small EVs and profiling miRNA content per EV might provide new functional biomarkers of immune activation and inflammation.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"6 1","pages":"1-28"},"PeriodicalIF":0.0,"publicationDate":"2021-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38992054","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":"Bittersweet","authors":"Adrian M. Schnall","doi":"10.20411/pai.v6i1.415","DOIUrl":"https://doi.org/10.20411/pai.v6i1.415","url":null,"abstract":"The winner has been declared.A flood of relief!Exultation! Dancing in the streets!And a gasp of horror.How can there be tens of millions on the other side? So many morethan a couple dozen Proud Boys,a few towns of hillbilly farmers, a frenzied rally crowd chanting Lock her up.It’s fathers and mothers, sisters and brothers,face upon human face.Is it them or us? Who are the blind? Fires still flare on the battlefield – one is raging on and off in the distance.  But every blaze is dying as I watch.  Great conflagrations are turning to ash.The forecast is for snowon the mountaintops, in the streets,in the corridors of State.Pride needs to go into hibernation.I think the air will be clearin the morning. I think I will hear music in the trees.But no one is surrenderinghis gun.","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":"84 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41308273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV.","authors":"Netanya S Utay,&nbsp;Ana N Monczor,&nbsp;Anoma Somasunderam,&nbsp;Sofia Lupo,&nbsp;Zhi-Dong Jiang,&nbsp;Ashley S Alexander,&nbsp;Malcolm Finkelman,&nbsp;Karen J Vigil,&nbsp;Jordan E Lake,&nbsp;Blake Hanson,&nbsp;Herbert L DuPont,&nbsp;Roberto C Arduino","doi":"10.20411/pai.v5i1.388","DOIUrl":"https://doi.org/10.20411/pai.v5i1.388","url":null,"abstract":"<p><strong>Background: </strong>Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.</p><p><strong>Methods: </strong>Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured.</p><p><strong>Results: </strong>Median age at week 0 was 39 years, CD4⁺ T cell count 496 cells/mm³, HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. α diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest α diversity at week 0. At week 26, α diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low α diversity that improved between weeks 0 and 6 with a shift in distribution.</p><p><strong>Conclusions: </strong>Weekly FMT was safe and well-tolerated. α diversity increased in participants with the lowest baseline α diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":" ","pages":"364-381"},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38864256","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":"Changes in the Serum Metabolome of Patients Treated With Broad-Spectrum Antibiotics.","authors":"George E Jaskiw,&nbsp;Mark E Obrenovich,&nbsp;Sirisha Kundrapu,&nbsp;Curtis J Donskey","doi":"10.20411/pai.v5i1.394","DOIUrl":"https://doi.org/10.20411/pai.v5i1.394","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiome (GMB) generates numerous small chemicals that can be absorbed by the host and variously biotransformed, incorporated, or excreted. The resulting metabolome can provide information about the state of the GMB, of the host, and of their relationship. Exploiting this information in the service of biomarker development is contingent on knowing the GMB-sensitivity of the individual chemicals comprising the metabolome. In this regard, human studies have lagged far behind animal studies. Accordingly, we tested the hypothesis that serum levels of chemicals unequivocally demonstrated to be GMB-sensitive in rodent models would also be affected in a clinical patient sample treated with broad spectrum antibiotics.</p><p><strong>Methods: </strong>We collected serum samples from 20 hospitalized patients before, during, and after treatment with broad-spectrum antibiotics. We also collected samples from 5 control patients admitted to the hospital but not prescribed antibiotics. We submitted the samples for a non-targeted metabolomic analysis and then focused on chemicals known to be affected both by germ-free status and by antibiotic treatment in the mouse and/or rat.</p><p><strong>Results: </strong>Putative identification was obtained for 499 chemicals in human serum. An aggregate analysis did not show any time x treatment interactions. However, our literature search identified 10 serum chemicals affected both by germ-free status and antibiotic treatment in the mouse or rat. Six of those chemicals were measured in our patient samples and additionally met criteria for inclusion in a focused analysis. Serum levels of 5 chemicals (p-cresol sulfate, phenol sulfate, hippurate, indole propionate, and indoxyl sulfate) declined significantly in our group of antibiotic-treated patients but did not change in our patient control group.</p><p><strong>Conclusions: </strong>Broad-spectrum antibiotic treatment in patients lowered serum levels of selected chemicals previously demonstrated to be GMB-sensitive in rodent models. Interestingly, all those chemicals are known to be uremic solutes that can be derived from aromatic amino acids (L-phenylalanine, L-tyrosine, or L-tryptophan) by anaerobic bacteria, particularly <i>Clostridial</i> species. We conclude that judiciously selected serum chemicals can reliably detect antibiotic-induced suppression of the GMB in man and thus facilitate further metabolome-based biomarker development.</p>","PeriodicalId":36419,"journal":{"name":"Pathogens and Immunity","volume":" ","pages":"382-418"},"PeriodicalIF":0.0,"publicationDate":"2020-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38843584","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}