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Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2586-2599页

作者： Yuan Hou Yadi Zhou Michaela U.Gack Justin D.Lathia asha kallianpur Reena Mehra Timothy A.Chan Jae U.Jung Lara Jehi Charis Eng Feixiong Cheng Genomic Medicine Institute Lerner Research InstituteCleveland ClinicClevelandOHUSA Florida Research and Innovation Center Cleveland ClinicPort Saint LucieFLUSA Department of Cardiovascular and Metabolic Science Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA Department of Population and Quantitative Health Sciences Case Western Reserve UniversityClevelandOHUSA Neurological Institute Cleveland ClinicClevelandOHUSA Center for Immunotherapy and Precision Immuno-Oncology Cleveland ClinicClevelandOHUSA Department of Cancer Biology Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Genetics and Genome Sciences Case Western Reserve University School of MedicineClevelandOHUSA Case Comprehensive Cancer Center Case Western Reserve University School of MedicineClevelandOHUSA

Sex differences in the susceptibility of SARS-CoV-2 infection and severity have been controversial,and the underlying mechanisms of COVID-19 in a sex-specific manner remain *** we inspected sex differences in SARS-CoV-2 infection,hospitalization,admission to the intensive care unit(ICU),sera inflammatory biomarker profiling,and single-cell RNA-sequencing(scRNA-seq)profiles across nasal,bronchoalveolar lavage fluid(BALF),and peripheral blood mononuclear cells(PBMCs)from COVID-19 patients with varying degrees of disease *** propensity score-matching observations revealed that male individuals have a 29%elevated likelihood of SARS-CoV-2 positivity,with a hazard ratio(HR)1.32(95%confidence interval[Cl]1.18-1.48)for hospitalization and HR 1.51(95%Cl 1.24-1.84)for admission to *** from male patients at hospital admission had elevated neutrophil-lymphocyte ratio and elevated expression of inflammatory markers(C-reactive protein and procalcitonin).We found that SARS-CoV-2 entry factors,including ACE2,TMPRSS2,FURIN,and NRP1,have elevated expression in nasal squamous cells from male individuals with moderate and severe *** observed male-biased transcriptional activation in SARS-CoV-2-infected macrophages from BALF and sputum samples,which offers potential molecular mechanism for sex-biased susceptibility to viral ***-cell interaction network analysis reveals potential epithelium-immune cell interactions and immune vulnerability underlying male-elevated disease severity and mortality in ***,monocyte-elevated expression of Toll-like receptor 7{TLR7)and Bruton tyrosine kinase{BTK)is associated with severe outcomes in males with *** summary,these findings provide basis to decipher immune responses underlying sex differences and designing sex-specific targeted interventions and patient care for COVID-19.

关键词： elevated epithelium analysis

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The Impact of Depressive Symptoms on Neuropsychological Performance Tests in HIV-Infected Individuals: A Study of the Hawaii Aging with HIV Cohort

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World Journal of AIDS 2011年第4期1卷 139-145页

作者： Sheri M. Shimizu Dominic C. Chow Victor Valcour Kamal Masaki Beau Nakamoto Kalpana J. kallianpur Cecilia Shikuma Hawaii Center for AIDS John A. Burns School of Medicine University of Hawaii at Manoa Honolulu USA.

Background: The frequency of neurocognitive impairment (NCI) in human immunodeficiency virus (HIV) -infected individuals remains high despite the availability of potent antiretroviral therapy (ART). The concurrence of depression among HIV-infected patients with NCI is common, especially among older individuals. Depression has been implicated as a risk factor for impaired neuropsychological performance (NP). This study explored the relationship between depressive symptoms and NP testing in HIV-infected individuals. Methods: A cross-sectional analysis was performed within the Hawaii Aging with HIV Cohort, a large prospective study of cognition of older (50 or more years old) compared to younger (20 to 39 years old) HIV-infected individuals. Results: Two hundred and eighty-five HIV infected participants (157 older and 128 younger) were administered a battery of NP tests to measure performance in major cognitive domains. Depressive symptoms were measured using the Beck Depression Inventory (BDI). The rates of depressive symptoms and neuropsychological impairment were similar in older and younger groups. Multivariate analyses revealed depressive symptoms were associated with NP test impairment in the younger group. In the older group, depressive symptoms were not associated with NP. Conclusion: This study suggests that depressive symptoms are associated with NP test impairment in younger HIV-infected individuals, but not in older individuals.

关键词： Depression HIV Neurocognitive Function Aging

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Impact of Cannabis Use on Brain Structure and Function in Suppressed HIV Infection

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Journal of Behavioral and Brain Science 2020年第8期10卷 344-370页

作者： Kalpana J. kallianpur Rasmus Birn Lishomwa C. Ndhlovu Scott A. Souza Brooks Mitchell Robert Paul Dominic C. Chow Lindsay Kohorn Cecilia M. Shikuma Department of Tropical Medicine Medical Microbiology and Pharmacology University of Hawaii-Manoa Honolulu HI USA Center for Translational Research on Aging Kuakini Medical Center Honolulu HI USA Hawaii Center for AIDS University of Hawaii-Manoa Honolulu HI USA Department of Medical Physics School of Medicine and Public Health University of Wisconsin-Madison Madison WI USA Weill Cornell Medicine New York NY USA The Queen’s Medical Center Honolulu HI USA Missouri Institute of Mental Health University of Missouri-St Louis St. Louis MO USA

Background: Brain atrophy and cognitive deficits persist among individuals with suppressed HIV disease. The impact of cannabis use is unknown. Methods: HIV+ and HIV- participants underwent cross-sectional magnetic resonance imaging and neuropsychological testing. Lifetime frequency, duration (years), and recency of cannabis use were self-reported. Relationships of cannabis use to resting-state functional connectivity (RSFC) and to 9 regional brain volumes were assessed with corrections for multiple comparisons. Peripheral blood cytokines and monocyte subsets were measured in the HIV+ group and examined in relation to cannabis exposure. Results: We evaluated 52 HIV+ [50.8 ± 7.1 years old;100% on antiretroviral therapy ≥ 3 months;83% with plasma viral load 10 times/lifetime was linked to more somatic symptoms, better executive function, and lower CD14+CD16++ monocyte count. Conclusion: HIV+ individuals demonstrated opposing associations with cannabis. Recent use may weaken RSFC and prolonged consumption may exacerbate atrophy of the accumbens and other brain regions. More frequent or recent cannabis use may reduce the inflammation and CD14<

关键词： Resting-State Functional Connectivity Occipital Atrophy Inflammation Monocytes

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