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Article ; Online: The benefits and consequences of the COVID-19 pandemic for patients diagnosed with cancer and their family caregivers.

Steel, Jennifer L / Amin, Aarshati / Peyser, Tristen / Olejniczak, Donna / Antoni, Michael / Carney, Maureen / Tillman, Emily / Hecht, Carol Lynn / Pandya, Niva / Miceli, Jessica / Reyes, Vincent / Nilsen, Marci / Johnson, Jonas / Kiefer, Gauri / Pappu, Bhanu / Zandberg, Dan P / Geller, David A

Psycho-oncology

2022 Volume 31, Issue 6, Page(s) 1003–1012

Abstract: Background: The objectives of this study were to examine benefits and consequences of the COVID-19 pandemic for patients diagnosed with cancer and their family caregivers.: Methods: A 23-item questionnaire assessing COVID-19-related issues, the ... ...

Abstract	Background: The objectives of this study were to examine benefits and consequences of the COVID-19 pandemic for patients diagnosed with cancer and their family caregivers. Methods: A 23-item questionnaire assessing COVID-19-related issues, the Patient Health Questionnaire-2, Generalized Anxiety Disorder-2, Pittsburgh Sleep Quality Index, and the Perceived Stress Scale (PSS)-4 were administered to patients diagnosed with cancer and their family caregivers. Results: Of the 161 patients and 78 caregivers who participated, 38.1% and 32.8 were male, 95% and 84.6% Caucasian, and the mean age was 66 and 64.6 years, respectively. A total of 16.5% and 15.2% reported depressive symptoms, 18.4% and 19% reported anxiety; 35.5% and 26.6% reported poor sleep quality, and 66% and 63.3% scored one standard deviation above the norms for the PSS, respectively. Predictors of poorer patient- and caregiver-reported outcomes included greater loneliness, worry about self or family being infected by the COVID-19, and worsening relationships with family. The fear of COVID-19 led to 20.8% of patients and 24.4% of family caregivers cancelling medical appointments, procedures, and treatments. A total of 52.5% of patients and 53.2% caregivers reported that the pandemic led to benefit finding but these changes were not associated with any of the measured patient- or caregiver-related outcomes. Conclusions: Psychological functioning for patients and caregivers was similar to that of pre-pandemic levels, however the decrease in health care utilization secondary to fear of COVID-19 was notable. While there were many negative effects of the pandemic, the majority of patients and caregivers reported some benefit to the pandemic.
MeSH term(s)	Anxiety/epidemiology ; Anxiety/psychology ; COVID-19/epidemiology ; Caregivers/psychology ; Cross-Sectional Studies ; Depression/epidemiology ; Depression/psychology ; Female ; Humans ; Male ; Neoplasms/therapy ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2022-02-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1118536-3
ISSN	1099-1611 ; 1057-9249
ISSN (online)	1099-1611
ISSN	1057-9249
DOI	10.1002/pon.5891
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Zs.A 3550: Show issues

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Article ; Online: The next generation of collaborative care: The design of a novel web-based stepped collaborative care intervention delivered via telemedicine for people diagnosed with cancer.

Steel, Jennifer L / Reyes, Vincent / Zandberg, Dan P / Nilsen, Marci / Terhorst, Lauren / Richards, Geena / Pappu, Bhanu / Kiefer, Gauri / Johnson, Jonas / Antoni, Michael / Vodovotz, Yoram / Spring, Michael / Walker, Jon / Geller, David A

Contemporary clinical trials

2021 Volume 105, Page(s) 106295

Abstract: Background: The NIH consensus statement on cancer-related symptoms concluded the most common and debilitating were depression, pain and fatigue [1-6]. Although the comorbidity of these symptoms is well known and may have similar underlying biological ... ...

Abstract	Background: The NIH consensus statement on cancer-related symptoms concluded the most common and debilitating were depression, pain and fatigue [1-6]. Although the comorbidity of these symptoms is well known and may have similar underlying biological mechanisms no intervention has been developed to reduce these symptoms concurrently. The novel web-based stepped collaborative care intervention delivered by telemedicine is the first to be tested in people diagnosed with cancer. Methods: We plan to test a web-based stepped collaborative care intervention with 450 cancer patients and 200 caregivers in the context of a randomized controlled trial. The primary endpoint is quality of life with other primary outcomes including patient-reported depression, pain, fatigue. Secondary outcomes include patient serum levels of pro-inflammatory cytokines and disease progression. We also will assess informal caregiver stress, depression, and metabolic abnormalities to determine if improvements in patients' symptoms also relate to improvement in caregiver outcomes. Results: The trial is ongoing and a total of 382 patients have been randomized. Preliminary analyses of the screening tools used for study entry suggest that Center for Epidemiological Studies-Depression (CESD) scale has good sensitivity and specificity (0.81 and 0.813) whereas the scale used to assess pain (0.47 and 0.91) and fatigue (0.11 and 0.91) had poor sensitivity but excellent specificity. Using the AUROC, the best cut point for the CES-D was 19, for pain was 4.5; and for fatigue was 2.5. Outcomes not originally proposed included health care utilization and healthcare charges. The first 100 patients who have been followed a year post-treatment, and who were less than 75 years and randomized to the web-based stepped collaborative care intervention, had lower rates of complications after surgery [χ Discussion: This novel web-based stepped stepped collaborative care intervention, delivered via telemedicine, is expected to provide a new strategy to improve the quality of life in those diagnosed with cancer and their caregivers. Trial registration: ClinicalTrials.govNCT02939755.
MeSH term(s)	Depression/diagnosis ; Depression/epidemiology ; Depression/therapy ; Fatigue/epidemiology ; Fatigue/therapy ; Humans ; Internet-Based Intervention ; Neoplasms/therapy ; Quality of Life ; Telemedicine
Language	English
Publishing date	2021-02-05
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	2182176-8
ISSN	1559-2030 ; 1551-7144
ISSN (online)	1559-2030
ISSN	1551-7144
DOI	10.1016/j.cct.2021.106295
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Zs.A 1581: Show issues

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Article ; Online: Measurement of interleukin-17.

Pappu, Bhanu P / Dong, Chen

Current protocols in immunology

2007 Volume Chapter 6, Page(s) Unit 6.25

Abstract: Upon antigenic stimulation, naive CD4+ T cells undergo proliferation and differentiate into cytokine-producing T helper (T(H)) effector cells. T(H)1 cells secrete effector cytokine IFN-gamma and regulate cell-mediated immunity, whereas T(H)2 cells ... ...

Abstract	Upon antigenic stimulation, naive CD4+ T cells undergo proliferation and differentiate into cytokine-producing T helper (T(H)) effector cells. T(H)1 cells secrete effector cytokine IFN-gamma and regulate cell-mediated immunity, whereas T(H)2 cells produce IL-4, IL-5, and IL-13 cytokines, and mediate immunity against extracellular pathogens and allergic reactions. Recent studies have identified a novel T(H) subset, called T(H)17, TH(IL-17), or inflammatory T(H) (THi) cells, characterized by the production of a proinflammatory cytokine, IL-17, and regulating inflammatory responses. In this unit, we describe the protocols for the differentiation of mouse IL-17-expressing T cells in vitro, detection of IL-17-expressing T cells by intracellular cytokine staining, and measurement of IL-17 secretion in culture supernatants by ELISA. Generation of IL-17-expressing T cells in vitro under defined culture conditions allows investigation of their differentiation regulation. Detection of IL-17 in cell culture and tissue samples helps in monitoring inflammatory diseases and determining efficacy of therapeutic interventions.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/secretion ; Cell Culture Techniques ; Cell Differentiation ; Cell Separation ; Flow Cytometry ; Gene Expression Regulation/immunology ; Inflammation Mediators/metabolism ; Interleukin-17/biosynthesis ; Interleukin-17/immunology ; Interleukin-17/secretion ; Mice ; T-Lymphocyte Subsets/cytology ; T-Lymphocyte Subsets/secretion
Chemical Substances	Inflammation Mediators ; Interleukin-17
Language	English
Publishing date	2007-11
Publishing country	United States
Document type	Journal Article
ISSN	1934-368X
ISSN (online)	1934-368X
DOI	10.1002/0471142735.im0625s79
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Article: Potential role of CARMA1 in CD40-induced splenic B cell proliferation and marginal zone B cell maturation.

Pappu, Bhanu P / Lin, Xin

European journal of immunology

2006 Volume 36, Issue 11, Page(s) 3033–3043

Abstract: NF-kappaB activation through B cell receptor (BCR) ligation is critical for B cell development, survival and antigen-mediated activation of B cells. CARD domain and MAGUK-domain containing protein-1 (CARMA1), recently identified adaptor molecule, has ... ...

Abstract	NF-kappaB activation through B cell receptor (BCR) ligation is critical for B cell development, survival and antigen-mediated activation of B cells. CARD domain and MAGUK-domain containing protein-1 (CARMA1), recently identified adaptor molecule, has been shown to play an essential role in BCR-induced NF-kappaB activation. CARMA1-deficient B cells fail to proliferate upon BCR stimulation, leading to defective humoral responses. Surprisingly, CARMA1-deficient B cells are also defective in CD40-induced proliferation. The mechanisms responsible for CD40-induced proliferation defect have not yet been characterized. In this study, we show that signaling cascades activated by CD40 stimulation are largely unaffected in CARMA1-deficient B cells. Instead, we have found that the defective proliferation of CARMA1-deficient B cells is due to two events. First, CARMA1-deficient B cells show defective cell-cycle progression. Secondly, the numbers of marginal zone (MZ) B cells, which are the main responders upon CD40 stimulation, are greatly diminished in CARMA1-deficient mice. Since B cell maturation requires basal signaling through BCR and NF-kappaB activation, we propose that impaired BCR signaling in CARMA1-deficient mice leads to defective maturation of MZ B cell population, which in turn, contributes to impaired proliferation upon CD40 stimulation.
MeSH term(s)	Animals ; Apoptosis ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/physiology ; B-Lymphocytes/cytology ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; CARD Signaling Adaptor Proteins/genetics ; CARD Signaling Adaptor Proteins/physiology ; CD40 Antigens/immunology ; CD40 Antigens/pharmacology ; Cell Cycle/drug effects ; Cell Movement ; Cell Proliferation ; Lymphocyte Activation/genetics ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase Kinases/metabolism ; NF-kappa B/agonists ; Spleen/cytology ; Spleen/drug effects ; Spleen/immunology
Chemical Substances	Apoptosis Regulatory Proteins ; CARD Signaling Adaptor Proteins ; CD40 Antigens ; Card11 protein, mouse ; NF-kappa B ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2)
Language	English
Publishing date	2006-11
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.200535663
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 85: Show issues

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Article: Regulatory mechanisms of helper T cell differentiation: new lessons learned from interleukin 17 family cytokines.

Pappu, Bhanu P / Angkasekwinai, Pornpimon / Dong, Chen

Pharmacology & therapeutics

2008 Volume 117, Issue 3, Page(s) 374–384

Abstract: Interleukin 17 (IL-17) family consists of six cytokines in mammals. Among them, IL-17 and IL-17F are expressed by a novel subset of CD4+ helper T (Th) cells and play critical function in inflammation and autoimmunity. On the other hand, IL-17E, also ... ...

Abstract	Interleukin 17 (IL-17) family consists of six cytokines in mammals. Among them, IL-17 and IL-17F are expressed by a novel subset of CD4+ helper T (Th) cells and play critical function in inflammation and autoimmunity. On the other hand, IL-17E, also called IL-25, has been associated with allergic responses. Here we summarize recent work by us as well as other investigators in understanding the regulation and function of these three cytokines. From these studies, IL-17 family cytokines may serve as novel targets for pharmaceutical intervention of immune and inflammatory diseases.
MeSH term(s)	Animals ; Asthma/immunology ; Cell Differentiation ; Humans ; Interleukin-17/biosynthesis ; Interleukin-17/immunology ; Interleukin-17/physiology ; Mice ; Parasitic Diseases/immunology ; Signal Transduction ; T-Lymphocytes, Helper-Inducer/cytology ; T-Lymphocytes, Helper-Inducer/immunology
Chemical Substances	Interleukin-17
Language	English
Publishing date	2008-01-19
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2007.12.003
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Zs.A 1183: Show issues

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Article: Alteration of cell surface sialylation regulates antigen-induced naive CD8+ T cell responses.

Pappu, Bhanu P / Shrikant, Protul A

Journal of immunology (Baltimore, Md. : 1950)

2004 Volume 173, Issue 1, Page(s) 275–284

Abstract: The strength of interactions with APC instructs naive T cells to undergo programmed expansion and differentiation, which is largely determined by the peptide affinity and dose as well as the duration of TCR ligation. Although, most ligands mediating ... ...

Abstract	The strength of interactions with APC instructs naive T cells to undergo programmed expansion and differentiation, which is largely determined by the peptide affinity and dose as well as the duration of TCR ligation. Although, most ligands mediating these interactions are terminally sialylated, the impact of the T cell sialylation status on Ag-dependent response remains poorly understood. In this study, by monitoring TCR transgenic CD8+ T cells, OT-I, we show that biochemical desialylation of naive OT-I T cells increases their sensitivity for agonist as well as partial agonist peptides. Desialylation enhances early activation and shortens the duration of TCR stimulation required for proliferation and differentiation, without increasing apoptosis. Moreover, desialylation of naive OT-I T cells augments their response to tumor-presented Ag. These results provide direct evidence for a regulatory role for sialylation in Ag-dependent CD8+ T cell responses and offer a new approach to sensitize or dampen Ag-specific CD8+ T cell responses.
MeSH term(s)	Animals ; Antigen-Presenting Cells/physiology ; Antigens, CD/analysis ; Antigens, Differentiation, T-Lymphocyte/analysis ; Apoptosis ; CD8-Positive T-Lymphocytes/immunology ; Fluoresceins/metabolism ; Interferon-gamma/biosynthesis ; Lectins, C-Type ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; N-Acetylneuraminic Acid/metabolism ; Succinimides/metabolism
Chemical Substances	5-(6)-carboxyfluorescein diacetate succinimidyl ester ; Antigens, CD ; Antigens, Differentiation, T-Lymphocyte ; CD69 antigen ; Fluoresceins ; Lectins, C-Type ; Succinimides ; Interferon-gamma (82115-62-6) ; N-Acetylneuraminic Acid (GZP2782OP0)
Language	English
Publishing date	2004-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.173.1.275
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Ud II Zs.37: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 28: Show issues

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Article ; Online: Quantifying the impact of the COVID-19 pandemic on cancer center clinical trial operations.

George, Thomas J / Lin, Tara L / Adrales Bentz, Tricia / Grant, Stefan / Houston, Collette M / Nashawati, Melissa A / Pappu, Bhanu / Peck, Helen / Zafirovski, Alex / Kerstann, Kimberly / LoRusso, Patricia / Schnatterly, Anne / Hofacker, Janie / Cameron, Kendra / Honeycutt, Hailey / Werner, Theresa L

JNCI cancer spectrum

2023 Volume 7, Issue 4

Abstract: Background: Oncology clinical trials are complex, and the COVID-19 pandemic caused major disruptions in 2020.: Methods: Using its networking and sharing of best practices, the Association of American Cancer Institutes, comprising 105 cancer centers, ... ...

Abstract	Background: Oncology clinical trials are complex, and the COVID-19 pandemic caused major disruptions in 2020. Methods: Using its networking and sharing of best practices, the Association of American Cancer Institutes, comprising 105 cancer centers, solicited a longitudinal series of voluntary surveys from members to assess how clinical trial office operations were affected. The surveys showed that centers were able to keep oncology trials available to patients while maintaining safety. Data were collected regarding interventional clinical trial accruals for the calendar years 2019, 2020, and 2021. Results: Data demonstrated a sizeable decrease in interventional treatment trial accruals in both 2020 and 2021 compared with prepandemic figures in 2019. No cancer center reported an increase in interventional treatment trial accruals in 2020 compared with 2019, with most centers reporting a moderate decrease. In mid-2022, 15% of respondents reported an increasing trend, 31% reported no significant change, and 54% continued to report a decrease. Conclusions: The pandemic necessitated rapid adoption of trial operations, with the emergence of several best practices, including remote monitoring, remote consenting, electronic research charts, and work-from-home strategies for staff. The national infrastructure to conduct trials was significantly affected by the pandemic, with noteworthy resiliency, evidenced by improvements in efficiencies and patient-centered care delivery but with residual capacity challenges that will be evident for the foreseeable future.
MeSH term(s)	Humans ; United States/epidemiology ; COVID-19/epidemiology ; Pandemics ; Neoplasms/epidemiology ; Neoplasms/surgery ; Medical Oncology ; Research Design
Language	English
Publishing date	2023-08-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2515-5091
ISSN (online)	2515-5091
DOI	10.1093/jncics/pkad048
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Article ; Online: Prospective Evaluation of Coronavirus Disease 2019 (COVID-19) Vaccine Responses Across a Broad Spectrum of Immunocompromising Conditions: the COVID-19 Vaccination in the Immunocompromised Study (COVICS).

Haidar, Ghady / Agha, Mounzer / Bilderback, Andrew / Lukanski, Amy / Linstrum, Kelsey / Troyan, Rachel / Rothenberger, Scott / McMahon, Deborah K / Crandall, Melissa D / Sobolewksi, Michele D / Nathan Enick, P / Jacobs, Jana L / Collins, Kevin / Klamar-Blain, Cynthia / Macatangay, Bernard J C / Parikh, Urvi M / Heaps, Amy / Coughenour, Lindsay / Schwartz, Marc B /

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2022 Volume 75, Issue 1, Page(s) e630–e644

Abstract: ... and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater ... with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody ...

Abstract	Background: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. Methods: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. Results: A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. Conclusions: Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.
MeSH term(s)	Adult ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; HIV Infections/complications ; Humans ; Immunocompromised Host ; Prospective Studies ; SARS-CoV-2 ; Vaccination
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciac103
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Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E.

Chang, Seon Hee / Reynolds, Joseph M / Pappu, Bhanu P / Chen, Guangjie / Martinez, Gustavo J / Dong, Chen

Immunity

2011 Volume 35, Issue 4, Page(s) 611–621

Abstract: Although several interleukin-17 (IL-17) family members and their receptors have been recently appreciated as important regulators in inflammatory diseases, the function of other IL-17 cytokines and IL-17 receptor-like molecules is unclear. Here we show ... ...

Abstract	Although several interleukin-17 (IL-17) family members and their receptors have been recently appreciated as important regulators in inflammatory diseases, the function of other IL-17 cytokines and IL-17 receptor-like molecules is unclear. Here we show that an IL-17 cytokine family member, IL-17C, was induced in a Th17 cell-dependent autoimmune disease and was required for its pathogenesis. IL-17C bound to IL-17RE, a member of IL-17 receptor family whose full-length isoform was selectively expressed in Th17 cells and signaled via an IL-17RA-RE receptor complex and the downstream adaptor Act1. IL-17C-IL-17RE induced the expression of a nuclear IkappaB family member, IκBζ, in Th17 cells to potentiate the Th17 cell response. Thus, our work has identified a cytokine-receptor pair with important function in regulating proinflammatory responses. This pathway may be targeted to treat autoimmune diseases.
MeSH term(s)	Animals ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Encephalomyelitis, Autoimmune, Experimental/pathology ; I-kappa B Kinase/metabolism ; Interleukin-17/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Interleukin-17/deficiency ; Receptors, Interleukin-17/immunology ; Receptors, Interleukin-17/metabolism ; Signal Transduction ; Th17 Cells/cytology ; Th17 Cells/immunology
Chemical Substances	Interleukin-17 ; Receptors, Interleukin-17 ; I-kappa B Kinase (EC 2.7.11.10)
Language	English
Publishing date	2011-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2011.09.010
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 69: Show issues

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Article ; Online: Immunogenicity of COVID-19 Vaccination in Immunocompromised Patients: An Observational, Prospective Cohort Study Interim Analysis

Haidar, Ghady / Agha, Mounzer / Lukanski, Amy / Linstrum, Kelsey / Troyan, Rachel / Bilderback, Andrew / Rothenberger, Scott / McMahon, Deborah K / Crandall, Melissa / Enick, P Nathan / Sobolewksi, Michelle / Collins, Kevin / Schwartz, Marc B / Dueker, Jeffrey M / Silveira, Fernanda P / Keebler, Mary E / Humar, Abhinav / Luketich, James D / Morrell, Matthew R /

Pilewski, Joseph M / McDyer, John F / Pappu, Bhanu / Ferris, Robert L / Marks, Stanley M / Klamar-Blain, Cynthia / Parikh, Urvi M / Heaps, Amy / Kip, Paula L / Wells, Alan / Minnier, Tami / Angus, Derek / Mellors, John W

medRxiv

Abstract: ... significantly lower (p<.001) among immunocompromised patients with Solid organ transplant (SOT), autoimmune ... solid tumor=82.4%, p < 0.05). Over 94% of patients with Human Immunodeficiency Virus were seropositive ... Among seropositive patients, antibody levels were much lower among SOT (4.5 [2.1,13.1], p=.020). Neutralization ...

Abstract	Objectives: Immunocompromised patients were excluded from COVID-19 vaccine clinical trials. The objectives of the study were to measure antibody responses, levels, and neutralization capability after COVID-19 vaccination among immunocompromised patients and compare these variables to those of immunocompetent healthcare workers. Methods This is an interim analysis of an ongoing observational, prospective cohort study which launched on April 14, 2021 across Western Pennsylvania. Participants were healthy healthcare workers (HCW) and immunocompromised patients who had completed their COVID-19 vaccination series. Individuals with a history of COVID-19 were not eligible. Serum was collected to measure for the presence of IgG against the SARS-CoV-2 Spike protein using a semi-quantitative assay; antibody levels were available for comparisons. A quasi-random subset of patients was selected for pseudovirus neutralization assays. Seropositivity with 95% Clopper-Pearson exact confidence intervals and distribution of antibody levels were measured. To identify risk factors for seronegativity, clinical characteristics were univariately compared between antibody reactive and non-reactive individuals within the immunocompromised group. Results: 107 HCW and 489 immunocompromised patients were enrolled. Compared to HCWs, seropositivity was significantly lower (p<.001) among immunocompromised patients with Solid organ transplant (SOT), autoimmune, hematological malignancies, and solid tumors (HCW=98.1%; SOT=37.2%; autoimmune=83.8%; hematological malignancies=54.7%; and solid tumor=82.4%, p < 0.05). Over 94% of patients with Human Immunodeficiency Virus were seropositive. Among seropositive patients, antibody levels were much lower among SOT (4.5 [2.1,13.1], p=.020). Neutralization titers tightly correlated with antibody levels (Spearman r = 0.91, p < 0.0001). Conclusion: Our findings demonstrate the heterogeneity of the humoral immune response to COVID-19 vaccines based on underlying immunosuppressive condition and highlight an urgent need to optimize and individualize COVID-19 prevention in these patients. These findings also have implications on public health guidance, particularly given revised Centers for Disease Control and Prevention recommendations permitting vaccinated individuals to abandon masking and social distancing in most settings. Future studies are warranted to determine assessment of cellular immunity, longitudinal measurement of immune responses, and the safety and efficacy of revaccination.
Keywords	covid19
Language	English
Publishing date	2021-06-30
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.06.28.21259576
Database	COVID19

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