Faculty Bibliography
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49
CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer
Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.
PMID: 34017137
ISSN: 1546-170x
CID: 4877652
CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer
Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.
PMCID:7872363
PMID: 33564756
ISSN: n/a
CID: 4779702
The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures
In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests.
PMCID:6889798
PMID: 31832342
ISSN: 2215-0013
CID: 4238902
Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci
Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown.We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies.
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EMBASE:615000254
ISSN: 0964-6906
CID: 4901632
Structural mimicry of the antigen binding modes of rhesus macaque and human anti-gp120 V3 antibodies [Meeting Abstract]
ISI:000398396800117
ISSN: 1525-4135
CID: 2541262
Duration of Untreated Psychosis in Community Treatment Settings in the United States
OBJECTIVE: This study is the first to examine duration of untreated psychosis (DUP) among persons receiving care in community mental health centers in the United States. METHODS: Participants were 404 individuals (ages 15-40) who presented for treatment for first-episode psychosis at 34 nonacademic clinics in 21 states. DUP and individual- and site-level variables were measured. RESULTS: Median DUP was 74 weeks (mean=193.5+/-262.2 weeks; 68% of participants had DUP of greater than six months). Correlates of longer DUP included earlier age at first psychotic symptoms, substance use disorder, positive and general symptom severity, poorer functioning, and referral from outpatient treatment settings. CONCLUSIONS: This study reported longer DUP than studies conducted in academic settings but found similar correlates of DUP. Reducing DUP in the United States will require examination of factors in treatment delay in local service settings and targeted strategies for closing gaps in pathways to specialty FEP care.
PMID: 25588418
ISSN: 1557-9700
CID: 1648982
Prescription Practices in the Treatment of First-Episode Schizophrenia Spectrum Disorders: Data From the National RAISE-ETP Study
OBJECTIVE: Treatment guidelines suggest distinctive medication strategies for first-episode and multiepisode patients with schizophrenia. To assess the extent to which community clinicians adjust their usual treatment regimens for first-episode patients, the authors examined prescription patterns and factors associated with prescription choice in a national cohort of early-phase patients. METHOD: Prescription data at study entry were obtained from 404 participants in the Recovery After an Initial Schizophrenia Episode Project's Early Treatment Program (RAISE-ETP), a nationwide multisite effectiveness study for patients with first-episode schizophrenia spectrum disorders. Treatment with antipsychotics did not exceed 6 months at study entry. RESULTS: The authors identified 159 patients (39.4% of the sample) who might benefit from changes in their psychotropic prescriptions. Of these, 8.8% received prescriptions for recommended antipsychotics at higher than recommended dosages; 32.1% received prescriptions for olanzapine (often at high dosages), 23.3% for more than one antipsychotic, 36.5% for an antipsychotic and also an antidepressant without a clear indication, 10.1% for psychotropic medications without an antipsychotic, and 1.2% for stimulants. Multivariate analysis showed evidence for sex, age, and insurance status effects on prescription practices. Racial and ethnic effects consistent with effects reported in previous studies of multiepisode patients were found in univariate analyses. Despite some regional variations in prescription practices, no region consistently had different practices from the others. Diagnosis had limited and inconsistent effects. CONCLUSIONS: Besides prescriber education, policy makers may need to consider not only patient factors but also service delivery factors in efforts to improve prescription practices for first-episode schizophrenia patients.
PMCID:4358323
PMID: 25727536
ISSN: 0002-953x
CID: 1481322
Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry
We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1.
PMCID:4157131
PMID: 25135832
ISSN: 1550-6606
CID: 3763412
Identification of Key Determinants for the Unusual Neutralization Sensitivity of the MW965.26 Env [Meeting Abstract]
ISI:000344774402169
ISSN: 1931-8405
CID: 1882532
Comprehensive molecular profiling of lung adenocarcinoma
ISI:000339566300025
ISSN: 0028-0836
CID: 5270632
