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      Associations between HIV infection and clinical spectrum of COVID-19: a population level analysis based on US National COVID Cohort Collaborative (N3C) data

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      , PhD a , b , f , , * , , PhD g , , , MD i , j , , Prof, PhD a , c , f , , MS a , c , f , , PhD g , , MS k , , PhD a , d , f , , Prof, MD a , e , f , , PhD l , , MD h , , PhD m , , Prof, MD g , , Prof, PhD a , b , f , National COVID Cohort Collaborative Consortium
      The Lancet. HIV
      Elsevier Ltd.

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          Abstract

          Background

          Evidence of whether people living with HIV are at elevated risk of adverse COVID-19 outcomes is inconclusive. We aimed to investigate this association using the population-based National COVID Cohort Collaborative (N3C) data in the USA.

          Methods

          We included all adult (aged ≥18 years) COVID-19 cases with any health-care encounter from 54 clinical sites in the USA, with data being deposited into the N3C. The outcomes were COVID-19 disease severity, hospitalisation, and mortality. Encounters in the same health-care system beginning on or after January 1, 2018, were also included to provide information about pre-existing health conditions (eg, comorbidities). Logistic regression models were employed to estimate the association of HIV infection and HIV markers (CD4 cell count, viral load) with hospitalisation, mortality, and clinical severity of COVID-19 (multinomial). The models were initially adjusted for demographic characteristics, then subsequently adjusted for smoking, obesity, and a broad range of comorbidities. Interaction terms were added to assess moderation effects by demographic characteristics.

          Findings

          In the harmonised N3C data release set from Jan 1, 2020, to May 8, 2021, there were 1 436 622 adult COVID-19 cases, of these, 13 170 individuals had HIV infection. A total of 26 130 COVID-19 related deaths occurred, with 445 among people with HIV. After adjusting for all the covariates, people with HIV had higher odds of COVID-19 death (adjusted odds ratio 1·29, 95% CI 1·16–1·44) and hospitalisation (1·20, 1·15–1·26), but lower odds of mild or moderate COVID-19 (0·61, 0·59–0·64) than people without HIV. Interaction terms revealed that the elevated odds were higher among older age groups, male, Black, African American, Hispanic, or Latinx adults. A lower CD4 cell count (<200 cells per μL) was associated with all the adverse COVID-19 outcomes, while viral suppression was only associated with reduced hospitalisation.

          Interpretation

          Given the COVID-19 pandemic's exacerbating effects on health inequities, public health and clinical communities must strengthen services and support to prevent aggravated COVID-19 outcomes among people with HIV, particularly for those with pronounced immunodeficiency.

          Funding

          National Center for Advancing Translational Sciences, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.

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          Most cited references24

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          Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries.

          With advances in the effectiveness of treatment and disease management, the contribution of chronic comorbid diseases (comorbidities) found within the Charlson comorbidity index to mortality is likely to have changed since development of the index in 1984. The authors reevaluated the Charlson index and reassigned weights to each condition by identifying and following patients to observe mortality within 1 year after hospital discharge. They applied the updated index and weights to hospital discharge data from 6 countries and tested for their ability to predict in-hospital mortality. Compared with the original Charlson weights, weights generated from the Calgary, Alberta, Canada, data (2004) were 0 for 5 comorbidities, decreased for 3 comorbidities, increased for 4 comorbidities, and did not change for 5 comorbidities. The C statistics for discriminating in-hospital mortality between the new score generated from the 12 comorbidities and the Charlson score were 0.825 (new) and 0.808 (old), respectively, in Australian data (2008), 0.828 and 0.825 in Canadian data (2008), 0.878 and 0.882 in French data (2004), 0.727 and 0.723 in Japanese data (2008), 0.831 and 0.836 in New Zealand data (2008), and 0.869 and 0.876 in Swiss data (2008). The updated index of 12 comorbidities showed good-to-excellent discrimination in predicting in-hospital mortality in data from 6 countries and may be more appropriate for use with more recent administrative data. © The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved.
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            A minimal common outcome measure set for COVID-19 clinical research

            Summary Clinical research is necessary for an effective response to an emerging infectious disease outbreak. However, research efforts are often hastily organised and done using various research tools, with the result that pooling data across studies is challenging. In response to the needs of the rapidly evolving COVID-19 outbreak, the Clinical Characterisation and Management Working Group of the WHO Research and Development Blueprint programme, the International Forum for Acute Care Trialists, and the International Severe Acute Respiratory and Emerging Infections Consortium have developed a minimum set of common outcome measures for studies of COVID-19. This set includes three elements: a measure of viral burden (quantitative PCR or cycle threshold), a measure of patient survival (mortality at hospital discharge or at 60 days), and a measure of patient progression through the health-care system by use of the WHO Clinical Progression Scale, which reflects patient trajectory and resource use over the course of clinical illness. We urge investigators to include these key data elements in ongoing and future studies to expedite the pooling of data during this immediate threat, and to hone a tool for future needs.
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              Is Open Access

              Risk factors for COVID-19 death in a population cohort study from the Western Cape Province, South Africa

              Abstract Background Risk factors for COVID-19 death in sub-Saharan Africa and the effects of HIV and tuberculosis on COVID-19 outcomes are unknown. Methods We conducted a population cohort study using linked data from adults attending public sector health facilities in the Western Cape, South Africa. We used Cox-proportional hazards models adjusted for age, sex, location and comorbidities to examine the association between HIV, tuberculosis and COVID-19 death from 1 March-9 June 2020 among (i) public sector “active patients” (≥1 visit in the 3 years before March 2020), (ii) laboratory-diagnosed COVID-19 cases and (iii) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19 comparing HIV positive vs. negative adults using modelled population estimates. Results Among 3,460,932 patients (16% HIV positive), 22,308 were diagnosed with COVID-19, of whom 625 died. COVID-19 death was associated with male sex, increasing age, diabetes, hypertension and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR] 2.14; 95% confidence interval [CI] 1.70-2.70), with similar risks across strata of viral load and immunosuppression. Current and previous tuberculosis were associated with COVID-19 death (aHR [95%CI] 2.70 [1.81-4.04] and 1.51 [1.18-1.93] respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95%CI 1.96-2.86); population attributable fraction 8.5% (95%CI 6.1-11.1). Conclusion While our findings may over-estimate HIV- and tuberculosis-associated COVID-19 mortality risks due to residual confounding, both HIV and current tuberculosis were independently associated with increased COVID-19 mortality. The associations between age, sex and other comorbidities and COVID-19 mortality were similar to other settings.
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                Author and article information

                Journal
                Lancet HIV
                Lancet HIV
                The Lancet. HIV
                Elsevier Ltd.
                2405-4704
                2352-3018
                13 October 2021
                13 October 2021
                Affiliations
                [a ]South Carolina SmartState Center for Healthcare Quality, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
                [b ]Department of Health Promotion, Education, and Behavior, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
                [c ]Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
                [d ]Department of Health Services Policy and Management, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
                [e ]Department of Internal Medicine, School of Medicine, University of South Carolina, Columbia, SC, USA
                [f ]Big Data Health Science Center, University of South Carolina, Columbia, SC, USA
                [g ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
                [h ]Schools of Medicine, Public Health, and Nursing, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
                [i ]Department of Medicine, University of Washington, Seattle, WA, USA
                [j ]Department of Global Health, University of Washington, Seattle, WA, USA
                [k ]Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA
                [l ]Center for Immunization and Infection in Cancer, Cancer Epidemiology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
                [m ]Center for Health AI, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
                Author notes
                [* ]Correspondence to: Dr Xueying Yang PhD, South Carolina SmartState Center for Healthcare Quality, Department of Health Promotion, Education, and Behavior, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA
                [†]

                Joint first authors

                Article
                S2352-3018(21)00239-3
                10.1016/S2352-3018(21)00239-3
                8514200
                34655550
                07606a50-ed5e-452d-94d6-2bc8001b8d9a
                © 2021 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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