scholarly journals COVID-19 severity and in-hospital mortality in an area with high HIV prevalence

2022 ◽  
Author(s):  
Michael T Boswell ◽  
Tshegofatso Maimela ◽  
Dan Hameiri-Bowen ◽  
George Riley ◽  
Albertus Malan ◽  
...  
Keyword(s):  
T Cell ◽  
Hospital Mortality ◽  
Respiratory Disease ◽  
Severe Disease ◽  
Hiv Prevalence ◽  
People Living With Hiv ◽  
Inflammatory Biomarker ◽  
Cell Counts ◽  
Increased Risk ◽  
Hiv Negative

Abstract Background: HIV is moderate risk factor for developing severe COVID-19 and is associated with increased risk of COVID-19 mortality. HIV infection causes immune dysregulation characterised by progressive lymphopenia, chronic immune activation, immunological senescence, and T cell exhaustion. These changes are partly reversed by effective antiretroviral therapy (ART), which reduces morbidity and mortality in people living with HIV (PWH). We investigated the associations among clinical phenotypes, laboratory biomarkers, and hospitalisation outcomes in a cohort of people hospitalised with COVID-19 in a high HIV prevalence area.Methods: We conducted a prospective observational cohort study in the Tshwane District Hospital complex in Pretoria, South Africa. We analysed data for patients admitted from April to November 2020, before the SARS-CoV-2 Beta variant-driven second wave. Respiratory disease severity was quantified using the respiratory oxygenation (ROX) score. Analysed biomarkers included full blood counts, differential white cell counts, C-reactive protein (CRP), ferritin, procalcitonin (PCT), D-dimer (DDIM), creatinine, alanine aminotransferase (ALT), CD4 T cell counts, and HIV-1 viral loads (HIVVL).Results: The analysis included 558 patients, of whom 112 (21.7%) died during admission. The mean age of the cohort was 54 (SD ±16) years, and numbers of males (50.5%) and females (49.5%) were equivalent. A total of 82 (15%) were HIV-positive. PWH were younger (mean age 46 years) than HIV-negative people; most were on ART with a suppressed HIVVL (72%) and the median CD4 count was 159 (IQR 66-397) cells/µL at the time of admission. After adjusting for age, HIV was not associated with significantly increased risk of mortality during hospitalisation (aHR=1.1, 95% CI: 0.6-2.0). Levels of supportive care were similar in HIV-negative patients and PWH. Inflammatory biomarker levels were equivalent in PWH and HIV-negative patients. A total of 15 PWH had detectable HIVVLs (>1000 copies/mL). Detectable HIVVL was associated with higher ROX scores - indicating less severe respiratory disease. In PWH, mortality was associated with higher levels of CRP, ferritin, PCT and DDIM. When compared to HIV-negative patients who died, PWH who died were younger, had higher DDIM levels, and were more likely to have tuberculosis.Conclusions: HIV per se was not associated with substantively increased risk of severe disease, or in-hospital mortality from COVID-19. Respiratory disease was less severe in PWH with detectable HIVVL. Inflammatory biomarker levels were equivalent in PWH and HIV-negative people, regardless of HIVVL. Increased levels of inflammatory biomarkers and DDIM were associated with in-hospital mortality irrespective of HIV status.

scholarly journals COVID-19 severity and in-hospital mortality in an area with high HIV prevalence

2021 ◽  
Author(s):  
Michael T Boswell ◽  
Tshegofatso Maimela ◽  
Dan Hameiri-Bowen ◽  
George Riley ◽  
Albertus Malan ◽  
...  
Keyword(s):  
T Cell ◽  
Hospital Mortality ◽  
Respiratory Disease ◽  
Severe Disease ◽  
Hiv Prevalence ◽  
People Living With Hiv ◽  
Inflammatory Biomarker ◽  
Cell Counts ◽  
Increased Risk ◽  
Hiv Negative

Abstract Background: HIV is moderate risk factor for developing severe COVID-19 and is associated with increased risk of COVID-19 mortality. HIV infection causes immune dysregulation characterised by progressive lymphopenia, chronic immune activation, immunological senescence, and T cell exhaustion. These changes are partly reversed by effective antiretroviral therapy (ART), which reduces morbidity and mortality in people living with HIV (PWH). We investigated the associations among clinical phenotypes, laboratory biomarkers, and hospitalisation outcomes in a cohort of people hospitalised with COVID-19 in a high HIV prevalence area.Methods: We conducted a prospective observational cohort study in the Tshwane District Hospital complex in Pretoria, South Africa. We analysed data for patients admitted from April to November 2020, before the SARS-CoV-2 Beta variant-driven second wave. Respiratory disease severity was quantified using the respiratory oxygenation (ROX) score. Analysed biomarkers included full blood counts, differential white cell counts, C-reactive protein (CRP), ferritin, procalcitonin (PCT), D-dimer (DDIM), creatinine, alanine aminotransferase (ALT), CD4 T cell counts, and HIV-1 viral loads (HIVVL).Results: The analysis included 558 patients, of whom 112 (21.7%) died during admission. The mean age of the cohort was 54 (SD ±16) years, and numbers of males (50.5%) and females (49.5%) were equivalent. A total of 82 (15%) were HIV-positive. PWH were younger (mean age 46 years) than HIV-negative people; most were on ART with a suppressed HIVVL (72%) and the median CD4 count was 159 (IQR 66-397) cells/µL at the time of admission. After adjusting for age, HIV was not associated with significantly increased risk of mortality during hospitalisation (aHR=1.1, 95% CI: 0.6-2.0). Levels of supportive care were similar in HIV-negative patients and PWH. Inflammatory biomarker levels were equivalent in PWH and HIV-negative patients. A total of 15 PWH had detectable HIVVLs (>1000 copies/mL). Detectable HIVVL was associated with higher ROX scores - indicating less severe respiratory disease. In PWH, mortality was associated with higher levels of CRP, ferritin, PCT and DDIM. When compared to HIV-negative patients who died, PWH who died were younger, had higher DDIM levels, and were more likely to have tuberculosis.Conclusions: HIV per se was not associated with substantively increased risk of severe disease, or in-hospital mortality from COVID-19. Respiratory disease was less severe in PWH with detectable HIVVL. Inflammatory biomarker levels were equivalent in PWH and HIV-negative people, regardless of HIVVL. Increased levels of inflammatory biomarkers and DDIM were associated with in-hospital mortality irrespective of HIV status.

scholarly journals COVID-19 Vaccination in People Living with HIV (PLWH) in China: A Cross Sectional Study of Vaccine Hesitancy, Safety, and Immunogenicity

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1458
Author(s):  
Ying Liu ◽  
Junyan Han ◽  
Xin Li ◽  
Danying Chen ◽  
Xuesen Zhao ◽  
...  
Keyword(s):  
T Cell ◽  
Negative Impact ◽  
Immunological Response ◽  
Cd4 T Cell ◽  
Vaccine Hesitancy ◽  
People Living With Hiv ◽  
Cross Sectional ◽  
Cell Counts ◽  
Increased Risk ◽  
Living With Hiv

The administration of COVID-19 vaccines is the primary strategy used to prevent further infections by COVID-19, especially in people living with HIV (PLWH), who are at increased risk for severe symptoms and mortality. However, the vaccine hesitancy, safety, and immunogenicity of COVID-19 vaccines among PLWH have not been fully characterized. We estimated vaccine hesitancy and status of COVID-19 vaccination in Chinese PLWH, explored the safety and impact on antiviral therapy (ART) efficacy and compared the immunogenicity of an inactivated vaccine between PLWH and healthy controls (HC). In total, 27.5% (104/378) of PLWH hesitated to take the vaccine. The barriers included concerns about safety and efficacy, and physician counselling might help patients overcome this vaccine hesitancy. A COVID-19 vaccination did not cause severe side effects and had no negative impact on CD4+ T cell counts and HIV RNA viral load. Comparable spike receptor binding domain IgG titer were elicited in PLWH and HC after a second dose of the CoronaVac vaccine, but antibody responses were lower in poor immunological responders (CD4+ T cell counts < 350 cells/µL) compared with immunological responders (CD4+ T cell counts ≥ 350 cells/µL). These data showed that PLWH have comparable safety and immune response following inactivated COVID-19 vaccination compared with HC, but the poor immunological response in PLWH is associated with impaired humoral response.

scholarly journals Using Real World Data to Understand HIV and COVID-19 in the U.S.A. and Spain: Characterizing Co-Infected Patients Across the Care Cascade

2020 ◽  
Author(s):  
Julianna Kohler ◽  
Kristin Kostka ◽  
Rupa Makadia ◽  
Roger Paredes ◽  
Talita Duarte-Salles ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Severe Disease ◽  
Data Sources ◽  
Routine Practice ◽  
People Living With Hiv ◽  
Medication History ◽  
Real World Data ◽  
Care Cascade ◽  
History Of ◽  
Hiv Negative

ABSTRACTObjectiveMost patients severely affected by COVID-19 have been elderly and patients with underlying chronic disease such as diabetes, cardiovascular disease, or respiratory disease. People living with HIV (PLHIV) may have greater risk of contracting or developing severe COVID-19 due to the underlying HIV infection or higher prevalence of comorbidities.DesignThis is a cohort study, including PLHIV diagnosed, hospitalized, or requiring intensive services for COVID-19.MethodsData sources include routine electronic medical record or claims data from the U.S. and Spain. Patient demographics, comorbidities, and medication history are described.ResultFour data sources had a population of HIV/COVID-19 coinfected patients ranging from 288 to 4606 lives. PLHIV diagnosed with COVID-19 were younger than HIV-negative patients diagnosed with COVID-19. PLHIV diagnosed with COVID-19 diagnosis had similar comorbidities as HIV-negative COVID-19 patients with higher prevalence of those comorbidities and history of severe disease. Treatment regimens were similar between PLHIV diagnosed with COVID-19 or PLHIV requiring intensive services.ConclusionsOur study uses routine practice data to explore HIV impact on COVID-19, providing insight into patient history prior to COVID-19. We found that HIV and COVID-19 coinfected patients have higher prevalence of underlying comorbidities such as cardiovascular and respiratory disease as compared to HIV-negative COVID-19 infected patients. We also found that, across the care cascade, co-infected patients who received intensive services were more likely to have more serious underlying disease or a history of more serious events as compared to PLHIV who were diagnosed with COVID-19.

scholarly journals Baseline T-lymphocyte subset absolute counts can predict both outcome and severity in SARS-CoV-2 infected patients: a single center study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marco Iannetta ◽  
Francesco Buccisano ◽  
Daniela Fraboni ◽  
Vincenzo Malagnino ◽  
Laura Campogiani ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Severe Disease ◽  
Laboratory Data ◽  
Lymphocyte Subset ◽  
Multivariable Logistic Regression Analysis ◽  
Double Positive ◽  
Increased Risk ◽  
T Lymphocyte Subset

AbstractThe aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4− CD8− double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p < 0.001). Multivariable logistic regression analysis showed that absolute counts of CD3+ T-lymphocytes < 524 cells/µl, CD3+ CD4+ < 369 cells/µl, and the number of T-lymphocyte subsets below the cutoff (T-lymphocyte subset index [TLSI]) were independent predictors of in-hospital mortality. Baseline T-lymphocyte subset counts and TLSI were also predictive of disease severity (CD3+  < 733 cells/µl; CD3+ CD4+ < 426 cells/µl; CD3+ CD8+ < 262 cells/µl; CD3+ DP < 4.5 cells/µl; CD3+ DN < 18.5 cells/µl). The evaluation of peripheral T-lymphocyte absolute counts in the early stages of COVID-19 might represent a useful tool for identifying patients at increased risk of unfavorable outcomes.

scholarly journals Lymphocyte subset analysis to evaluate the prognosis of HIV-negative patients with pneumocystis pneumonia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fan Jin ◽  
Jing Xie ◽  
Huan-ling Wang
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Lymphocyte Subsets ◽  
Nk Cell ◽  
Cd8 T Cell ◽  
Pneumocystis Pneumonia ◽  
Lymphocyte Subset ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv Negative

Abstract Objectives We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. Methods We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. Results A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597–83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. Conclusion The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.

scholarly journals HIV status alters disease severity and immune cell responses in beta variant SARS-CoV-2 infection wave

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Farina Karim ◽  
Inbal Gazy ◽  
Sandile Cele ◽  
Yenzekile Zungu ◽  
Robert Krause ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Disease Severity ◽  
Immune Cell ◽  
Supplemental Oxygen ◽  
People Living With Hiv ◽  
Cell Counts ◽  
Cell Changes ◽  
Living With Hiv ◽  
Second Wave ◽  
Hiv Negative

There are conflicting reports on the effects of HIV on COVID-19. Here we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes.

scholarly journals Occurrence of Accelerated Epigenetic Aging and Methylation Disruptions in Human Immunodeficiency Virus Infection Before Antiretroviral Therapy

2020 ◽  
Author(s):  
Chen Xi Yang ◽  
Emma Schon ◽  
Ma’en Obeidat ◽  
Michael S Kobor ◽  
Lisa McEwen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cellular Aging ◽  
Epigenetic Clock ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Negative Controls ◽  
Hiv Negative

Abstract Background Whether accelerated aging develops over the course of chronic human immunodeficiency virus (HIV) infection or can be observed before significant immunosuppression on is unknown. We studied DNA methylation in blood to estimate cellular aging in persons living with HIV (PLWH) before the initiation of antiretroviral therapy (ART). Methods A total of 378 ART-naive PLWH who had CD4 T-cell counts &gt;500/µL and were enrolled in the Strategic Timing of Antiretroviral Therapy trial (Pulmonary Substudy) were compared with 34 HIV-negative controls. DNA methylation was performed using the Illumina MethylationEPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) in PLWH compared with controls were identified using a robust linear model. Methylation age was calculated using a previously described epigenetic clock. Results There were a total of 56 639 DMPs and 6103 DMRs at a false discovery rate of &lt;0.1. The top 5 DMPs corresponded to genes NLRC5, VRK2, B2M, and GPR6 and were highly enriched for cancer-related pathways. PLWH had significantly higher methylation age than HIV-negative controls (P = .001), with black race, low CD4 and high CD8 T-cell counts, and duration of HIV being risk factors for age acceleration. Conclusions PLWH before the initiation of ART and with preserved immune status show evidence of advanced methylation aging.

CD26+CD4+T cell counts and attack risk in interferon-treated multiple sclerosis

2005 ◽  
Vol 11 (6) ◽  
pp. 641-645 ◽  
Author(s):  
F Sellebjerg ◽  
C Ross ◽  
N Koch-Henriksen ◽  
P Soelberg Sørensen ◽  
J L Frederiksen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Flow Cytometry ◽  
T Cells ◽  
T Cell ◽  
Hazard Ratio ◽  
Cd4 T Cell ◽  
Immunomodulatory Treatment ◽  
Cell Counts ◽  
Increased Risk ◽  
Insufficient Response

Biomarkers that allow the identification of patients with multiple sclerosis (MS) with an insufficient response to immunomodulatory treatment would be desirable, as currently available treatments are only incompletely efficacious. Previous studies have shown that the expression of CD25, CD26 and CCR5 on T cells is altered in patients with active MS. We studied the expression of these molecules by flow cytometry in patients followed for six months during immunomodulatory treatment. In interferon (IFN)-β-treated patients, we found that the hazard ratio for developing an attack was 2.8 in patients with CD26+CD4+T cell counts above median, and this risk was independent of the risk conferred by neutralizing anti-IFN-β antibodies. CD26+CD4+T cell counts may identify patients with MS at increased risk of attack during treatment with IFN-β.

scholarly journals Immunological and Psychological Efficacy of Meditation/Yoga Intervention Among People Living With HIV (PLWH): A Systematic Review and Meta-analyses of 19 Randomized Controlled Trials

2020 ◽  
Author(s):  
Taiyi Jiang ◽  
Jianhua Hou ◽  
Runsong Sun ◽  
Lili Dai ◽  
Wen Wang ◽  
...  
Keyword(s):  
Mental Health ◽  
T Cell ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Cd4 T Cell ◽  
Controlled Trials ◽  
People Living With Hiv ◽  
Yoga Intervention ◽  
Randomized Controlled ◽  
Cell Counts

Abstract Background An expanding number of mind–body therapies are being used to reduce the psychological burden of peoples living with human immunodeficiency virus (HIV). However, the effects on the immune system and mental health varied among studies. Purpose This meta-analysis was conducted to summarize the randomized controlled trials to draw comprehensive conclusions regarding the psycho-immunological efficacy. Methods Random-effects models were used to assess the outcome of interest. Egger’s tests were used to identify publication bias. Subgroup and meta-regression were used to explore potential moderators. This review was registered on the PROSPERO database (CRD42019148118). Results Nineteen randomized controlled trials with a total sample size of 1,300 were included in this meta-analysis. Regarding immune system outcome, mind–body therapy significantly improved CD4 T-cell counts (Cohen’s d = 0.214, p = .027) and maintained (0.427, p = .049). In addition, baseline CD4 T-cell counts and years since HIV diagnosis significantly moderated the efficacy of mind–body practices on CD4 improvement (all ps &lt; .001). Regarding mental health outcome, mind–body therapy significantly reduced stress, depression, and anxiety symptoms (0.422, p &lt; .001; 0.506, p &lt; .001, and 0.709, p &lt; .001, respectively) while improving quality of life (0.67, p &lt; .001). Conclusions Meditation/yoga intervention could result in potential benefits with regard to improved CD4 T-cell counts immediately after the intervention and at long-term follow-up, while also improving their mental health. The cost-effective meditation/yoga intervention should be integrated into routine care for people living with HIV, especially for those with lower CD4 baseline and fewer years since diagnosis.

Early Recovery of Thymus-Derived Naïve T Cells in Pediatric Patients (pts) Treated with Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation (NMSCT) for Cancer.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 310-310
Author(s):  
Terry J. Fry ◽  
Alison R. Rager ◽  
Frances Hakim ◽  
Cynthia Love ◽  
Paula Layton ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
High Risk ◽  
Peripheral Blood ◽  
T Cell Subsets ◽  
Immune Recovery ◽  
Early Recovery ◽  
Thymic Function ◽  
Cell Counts ◽  
Increased Risk

Abstract Background: Current SCT approaches consistently achieve rapid donor myeloid engraftment, but delayed immune recovery remains a significant obstacle and results in increased risk of infection and relapse. T cells are regenerated via 2 pathways, thymus-derived and peripheral expansion, processes for which IL-7 is critical. We postulated that non-myeloablative pre-transplant conditioning might preserve thymic function in pediatric SCT recipients thus enhancing thymus-derived naïve T cell regeneration. Methods: We analyzed T cell subsets, T cell receptor excision circles (TREC), and IL-7 levels in peripheral blood after SCT in 21 pediatric pts with high-risk malignancies (median age 14, range 4–21). Fludarabine-based induction chemotherapy was administered for disease control and targeted CD4 count reduction. Pre-transplant conditioning consisted of cyclophosphamide (1,200 mg/m2/day) and fludarabine (30 mg/m2/day) × 4 days plus melphalan (100 mg/m2 × 1 dose in sarcoma pts). Grafts consisted of G-CSF mobilized unmodified peripheral blood stem cells from 5–6/6 HLA-matched first-degree relatives (median CD34 dose 11.7 × 10E6/kg, range 4.4–19.1; median CD3 dose 416 × 10E6/kg, range 228–815). Cyclosporine was used for GVHD prophylaxis. Results: Donor-derived engraftment was rapid (absolute neutrophil count > 500/uL median day 9, range 8–11). Complete donor lymphoid chimerism (>95% by VNTR-PCR on CD3 sorted peripheral blood) was achieved in all by day 28. Immune recovery was brisk and sustained. Substantial numbers of naïve (CD45RA+/CD62L+) CD4+ and CD8+ T-cells were detected at day 28 (Fig 1). There was a steady increase in TREC from 3 to 12 months consistent with early, robust thymic-dependant T cell generation (Fig 2). This was not seen in adult pts treated on a parallel trial (data not shown). IL-7 levels were elevated and inversely correlated with T cell counts (r=−0.56, p<0.0001). Conclusions: Targeted immune depletion and NMSCT results in rapid, sustained immune reconstitution in pediatric pts with malignancy. Preserved thymic function appears to contribute to naïve T cell recovery in this setting. We postulate that non-myeloablative conditioning is thymus sparing and that this, in combination with immune depletion-induced IL-7 elevation, promotes early thymic-derived lymphoid recovery. This approach may serve as a strategy to overcome the prolonged immunodeficiency commonly encountered after allogeneic SCT in pediatrics and might be used as a platform to direct allogeneic anti-tumor immune responses in high-risk childhood cancers. Figure 1 Figure 1. Figure 2 Figure 2.

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