المؤلفون: Park, Han-Sol, Yin, Anna, Barranta, Caelan, Lee, John, Caputo, Christopher, Sachithanandham, Jaiprasath, Li, Maggie, Yoon, Steve, Sitaras, Ioannis, Jedlicka, Anne, Eby, Yolanda, Ram, Malathi, Fernandez, Reinaldo, Baker, Owen, Shenoy, Aarthi, Mosnaim, Giselle, Fukuta, Yuriko, Patel, Bela, Heath, Sonya, Levine, Adam, Meisenberg, Barry, Spivak, Emily, Anjan, Shweta, Huaman, Moises, Blair, Janis, Zand, Martin, Cachay, Edward, Raval, Jay, Kassaye, Seble, Marshall, Christi, Yarava, Anusha, Lane, Karen, McBee, Nichol, Gawad, Amy, Karlen, Nicky, Singh, Atika, Ford, Daniel, Jabs, Douglas, Appel, Lawrence, Shade, David, Lau, Bryan, Ehrhardt, Stephan, Baksh, Sheriza, Shapiro, Janna, Ou, Jiangda, Na, Yu, Knoll, Maria, Ornelas-Gatdula, Elysse, Arroyo-Curras, Netzahualcoyotl, Gniadek, Thomas, Caturegli, Patrizio, Wu, Jinke, Ndahiro, Nelson, Betenbaugh, Michael, Hanley, Daniel, Casadevall, Arturo, Shoham, Shmuel, Bloch, Evan, Gebo, Kelly, Tobian, Aaron, Laeyendecker, Oliver, Pekosz, Andrew, Klein, Sabra, Sullivan, David, Paxton, James, Gerber, Jonathan, Petrini, Joann, Broderick, Patrick, Rausch, William, Cordisco, Marie, Hammel, Jean, Greenblatt, Benjamin, Cluzet, Valerie, Cruser, Daniel, Oei, Kevin, Abinante, Matthew, Hammitt, Laura, Sutcliffe, Catherine, Currier, Judith, Forthal, Donald, Ziman, Alyssa

المصدر: JCI Insight. 9(8)

مصطلحات موضوعية: COVID-19, Immunoglobulins, Immunotherapy, Humans, COVID-19, COVID-19 Serotherapy, Antibodies, Viral, Immunization, Passive, Hospitalization, SARS-CoV-2, Male, Female, Middle Aged, Adult, Immunoglobulin G, Antibodies, Neutralizing, Double-Blind Method, Aged, Blood Donors, Outpatients

الوصف: BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2jb6z62bTest
https://escholarship.org/content/qt2jb6z62b/qt2jb6z62b.pdfTest

المؤلفون: Moctezuma, Sananda, Perez, Jonathan L., Baraban, Ezra, Caturegli, Patrizio, Morris-Wiseman, Lilah, Salvatori, Roberto

المصدر: AACE Clinical Case Reports ; ISSN 2376-0605

مصطلحات موضوعية: Endocrinology, Diabetes and Metabolism

الإتاحة: https://doi.org/10.1016/j.aace.2024.01.007Test
https://api.elsevier.com/content/article/PII:S2376060524000075?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2376060524000075?httpAccept=text/plainTest

المؤلفون: Randad, Pranay R, Pisanic, Nora, Kruczynski, Kate, Manabe, Yukari C, Thomas, David, Pekosz, Andrew, Klein, Sabra L, Betenbaugh, Michael J, Clarke, William A, Laeyendecker, Oliver, Caturegli, Patrizio P, Larman, H Benjamin, Detrick, Barbara, Fairley, Jessica K, Sherman, Amy C, Rouphael, Nadine, Edupuganti, Srilatha, Granger, Douglas A, Granger, Steve W, Collins, Matthew, Heaney, Christopher D

المصدر: JOURNAL OF CLINICAL MICROBIOLOGY. 59(1)

مصطلحات موضوعية: SARS-CoV-2, COVID-19, saliva, oral fluid, serology, antibody test, multiplex, diagnostics, immunoserology, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/83b9d2d3Test

المؤلفون: Pisanic, Nora, Randad, Pranay R, Kruczynski, Kate, Manabe, Yukari C, Thomas, David L, Pekosz, Andrew, Klein, Sabra L, Betenbaugh, Michael J, Clarke, William A, Laeyendecker, Oliver, Caturegli, Patrizio P, Larman, H Benjamin, Detrick, Barbara, Fairley, Jessica K, Sherman, Amy C, Rouphael, Nadine, Edupuganti, Srilatha, Granger, Douglas A, Granger, Steve W, Collins, Matthew H, Heaney, Christopher D

المصدر: Journal of clinical microbiology. 59(1)

مصطلحات موضوعية: Saliva, Humans, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Antibodies, Viral, Female, Male, Spike Glycoprotein, Coronavirus, COVID-19, SARS-CoV-2, COVID-19 Nucleic Acid Testing, Coronavirus Nucleocapsid Proteins, antibody test, diagnostics, immunoserology, multiplex, oral fluid, saliva, serology, Antibodies, Viral, Spike Glycoprotein, Coronavirus, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Microbiology

الوصف: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (n = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2358n7ctTest

المؤلفون: Sanchez, Sandra, Fang, Diana, Xiao, Shaoming, Rezavi, Lu Ann, Howard, Brittney M., Caturegli, Patrizio, Cihakova, Daniela

المصدر: Practical Laboratory Medicine ; volume 33, page e00307 ; ISSN 2352-5517

مصطلحات موضوعية: Clinical Biochemistry, Radiological and Ultrasound Technology

الإتاحة: https://doi.org/10.1016/j.plabm.2023.e00307Test
https://api.elsevier.com/content/article/PII:S235255172300001X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S235255172300001X?httpAccept=text/plainTest

المؤلفون: Caturegli, Patrizio, Laeyendecker, Oliver, Tobian, Aaron A. R., Sullivan, David J.

المساهمون: Yotam, Bar-On, Bloomberg Family Foundation, HHS | NIH | NIAID | Division of Intramural Research, National Institute of Allergy and Infectious Diseases

المصدر: Microbiology Spectrum ; volume 11, issue 6 ; ISSN 2165-0497

الوصف: Natural infection with the SARS-CoV-2 virus and vaccination increase the serum spike antibody levels. These levels, which differ among the various commercial assays, are used by the FDA to qualify individuals as potential COVID-19 convalescent plasma (CCP) donors. Over a 3-year period (April 2020–February 2023), we performed a retrospective analysis of spike IgG antibodies measured by a tertiary hospital clinical immunology laboratory using the Euroimmun SARS-CoV-2 IgG ELISA. The 3-year interval was classified into five periods based on the SARS-CoV-2 strain variant epidemiology. A total of 15,820 sera, derived from 11,022 individuals (6,362 females and 4,660 males) ranging from severe immunocompromised state to routine health visits, were tested. Spike IgG levels rose significantly over time, from a median ELISA 0.13 Arbitrary Units (AU) in the first period to 48.7 in the last period ( P < 0.0001). The 80th percentile of the spike IgG distribution was 0.55, 8.1, 9.6, 64.9, and 151 AU in the five periods. Using 3.5 AU, the FDA threshold for qualifying CCP donors with this Euroimmun assay, the percentage of subjects eligible for CCP donation would have been 11%, 44%, 61%, 81%, and 91% in the five time periods. Overall, spike antibody levels have risen more than 100-fold during the pandemic, while SARS-CoV-2 variants have become resistant to monoclonal antibodies. Since CCP containing high titers of spike antibodies is known to be most effective against variants, restricting CCP donors to those with antibody values in the upper two deciles may allow greater therapeutic transfusion protection. IMPORTANCE Despite the evolution of SARS-CoV-2 variants of concern and ongoing transmission, COVID-19 hospitalization and mortality rates continue to decline. Both the percent seropositive and antibody levels have risen over the past 3 years. Here, we observe more than 90% seropositivity as well as more than a hundred-fold increase in spike IgG levels in a tertiary hospital clinical immunology laboratory setting. ...

الإتاحة: https://doi.org/10.1128/spectrum.02183-23Test

المؤلفون: Hunt, Joanne H, Laeyendecker, Oliver, Rothman, Richard E, Fernandez, Reinaldo E, Dashler, Gaby, Caturegli, Patrizio, Hansoti, Bhakti, Quinn, Thomas C, Hsieh, Yu-Hsiang

المصدر: Open Forum Infectious Diseases; May2024, Vol. 11 Issue 5, p1-8, 8p

مصطلحات موضوعية: MEDICAL screening, SYPHILIS, HOSPITAL emergency services, CHILDBEARING age, HIV

مستخلص: Background Syphilis diagnosis in the emergency department (ED) setting is often missed due to the lack of ED-specific testing strategies. We characterized ED patients with high-titer syphilis infections (HTSIs) with the goal of defining a screening strategy that most parsimoniously identifies undiagnosed, untreated syphilis infections. Methods Unlinked, de-identified remnant serum samples from patients attending an urban ED, between 10 January and 9 February 2022, were tested using a three-tier testing algorithm, and sociodemographic variables were extracted from ED administrative database prior to testing. Patients who tested positive for treponemal antibodies in the first tier and positive at high titer (≥1:8) for nontreponemal antibodies in the second tier were classified as HTSI. Human immunodeficiency virus (HIV) status was determined with Bio-Rad enzyme-linked immunosorbent assay and confirmatory assays. Exact logistic regression and classification and regression tree (CART) analyses were performed to determine factors associated with HTSI and derive screening strategies. Results Among 1951 unique patients tested, 23 (1.2% [95% confidence interval,.8%–1.8%]) had HTSI. Of those, 18 (78%) lacked a primary care physician, 5 (22%) were HIV positive, and 8 (35%) were women of reproductive age (18–49 years). CART analysis (area under the curve of 0.67) showed that using a screening strategy that measured syphilis antibodies in patients with HIV, without a primary care physician, and women of reproductive age would have identified most patients with HTSI (21/23 [91%]). Conclusions We show a high prevalence of HTSI in an urban ED and propose a feasible, novel screening strategy to curtail community transmission and prevent long-term complications. [ABSTRACT FROM AUTHOR]

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المؤلفون: Saraf, Sharada, Zhu, Xianming, Shrestha, Ruchee, Bonny, Tania S., Baker, Owen R., Beck, Evan J., Fernandez, Reinaldo E., Eby, Yolanda, Akinde, Olivia, Ruff, Jessica E., Caturegli, Patrizio, Redd, Andrew D., Bloch, Evan M., Quinn, Thomas C., Tobian, Aaron A. R., Laeyendecker, Oliver

المساهمون: Wu, Han-Chung, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Allergy and Infectious Diseases

المصدر: PLOS ONE ; volume 17, issue 6, page e0264298 ; ISSN 1932-6203

الوصف: The association between COVID-19 symptoms and antibody responses against SARS-CoV-2 is poorly characterized. We analyzed antibody levels in individuals with known SARS-CoV-2 infection to identify potential antibody-symptom associations. Convalescent plasma from 216 SARS-CoV-2 RNA+ individuals with symptomatology information were tested for the presence of IgG to the spike S1 subunit (Euroimmun ELISA), IgG to receptor binding domain (RBD, CoronaCHEK rapid test), and for IgG, IgA, and IgM to nucleocapsid (N, Bio-Rad ELISA). Logistic regression was used to estimate the odds of having a COVID-19 symptom from the antibody response, adjusting for sex and age. Cough strongly associated with antibodies against S1 (adjusted odds ratio [aOR] = 5.33; 95% CI from 1.51 to 18.86) and RBD (aOR = 4.36; CI 1.49, 12.78). In contrast, sore throat significantly associated with the absence of antibodies to S1 and N (aOR = 0.25; CI 0.08, 0.80 and aOR = 0.31; 0.11, 0.91). Similarly, lack of symptoms associated with the absence of antibodies to N and RBD (aOR = 0.16; CI 0.03, 0.97 and aOR = 0.16; CI 0.03, 1.01). Cough appeared to be correlated with a seropositive result, suggesting that SARS-CoV-2 infected individuals exhibiting lower respiratory symptoms generate a robust antibody response. Conversely, those without symptoms or limited to a sore throat while infected with SARS-CoV-2 were likely to lack a detectable antibody response. These findings strongly support the notion that severity of infection correlates with robust antibody response.

الإتاحة: https://doi.org/10.1371/journal.pone.0264298Test

المؤلفون: Pani, Fabiana, Yasuda, Yoshinori, Rousseau, Sylvie T, Bermea, Kevin C, Roshanmehr, Solmaz, Wang, Rulin, Yegnasubramanian, Srinivasan, Caturegli, Patrizio, Adamo, Luigi

المساهمون: National Institutes of Health

المصدر: Journal for ImmunoTherapy of Cancer ; volume 10, issue 12, page e005538 ; ISSN 2051-1426

الوصف: Background The response of solid tumors such as papillary thyroid cancer (PTC) to immune checkpoint inhibitors (ICIs) is highly variable. The biological basis of this variability remains unknown. Methods To test the hypothesis that preconditioning of the immune system modulates the therapeutic effect of ICIs, we used a murine model where PTC and iodine exacerbated thyroiditis (IET) can be induced in a temporally predictable fashion. A total of 122 mice were divided into 3 experimental groups. In the first one, named concomitant IET and PTC (No.=40), IET, and PTC were induced at the same time; in the second one, named pre-existing IET (No.=44), IET was induced prior to the induction of PTC; in the third one, named no IET (No.=38), only PTC was induced. Following disease induction, mice of each group were treated with anti-PD-1 antibody, anti-lymphocyte activation gene 3 antibody (anti-Lag3), anti-T-cell immunoglobulin and mucin domain 3 antibody (anti-Tim3), or IgG control. Ten weeks after the initial ICI injection, mice were sacrificed to collect the thyroid gland for histological analysis, to quantify the incidence and burden of PTC, and to perform high-throughput single-cell RNA sequencing of infiltrating CD45 + cells. Results In the concomitant IET and PTC group, ICI treatment reduced PTC incidence (p=0.002 comparing treatment with any ICI vs control), while it had no effect in the pre-existing IET and no IET groups. Single-cell sequencing of thyroidal CD45 + cells showed that the different ICIs tested had both specific and shared effects on all the components of the thyroidal immune cell infiltrate. The shared effect of the tested ICIs was dependent on the presence of pre-existing versus concomitant IET. In the context of concomitant IET, ICI treatment resulted in the modulation of a greater number of pathways related to both innate and adaptive immunity. Conclusions Response to ICIs depends on the status of the immune system of the treated individual. Modulation of the immune system should be explored as a ...

الإتاحة: https://doi.org/10.1136/jitc-2022-005538Test

المؤلفون: Angkeow, Julia W., Monaco, Daniel R., Chen, Athena, Venkataraman, Thiagarajan, Jayaraman, Sahana, Valencia, Cristian, Sie, Brandon M., Liechti, Thomas, Farhadi, Payam N., Funez-dePagnier, Gabriela, Sherman-Baust, Cheryl A., Wong, May Q., Ruczinski, Ingo, Caturegli, Patrizio, Sears, Cynthia L., Simner, Patricia J., Round, June L., Duggal, Priya, Laserson, Uri, Steiner, Theodore S., Sen, Ranjan, Lloyd, Thomas E., Roederer, Mario, Mammen, Andrew L., Longman, Randy S., Rider, Lisa G., Larman, H. Benjamin

المصدر: Immunity ; volume 55, issue 6, page 1051-1066.e4 ; ISSN 1074-7613

مصطلحات موضوعية: Infectious Diseases, Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.1016/j.immuni.2022.05.002Test
https://api.elsevier.com/content/article/PII:S1074761322002229?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1074761322002229?httpAccept=text/plainTest