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  • Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged >= 65 Years - United States, January-March 2021 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Tenforde, M. W., Olson, S. M., Self, W. H., Talbot, H., Lindsell, C. J., Steingrub, J. S., Shapiro, N., Ginde, A. A., Douin, D. J., Prekker, M. E., Brown, S. M., Peltan, I. D., Gong, M. N., Mohamed, A., Khan, A., Aline, M. C., Files, D., Gibbs, K. W., Stubblefield, W. B., Casey, J. D., Rice, T. W., Grijalva, C. G., Hager, D. N., Shehu, A., Qadir, N., Chang, S. Y., Wilson, J. G., Gaglani, M., Murthy, K., Calhoun, N., Monto, A. S., Martin, E. T., Malani, A., Zimmerman, R. K., Silveira, F. P., Middleton, D. B., Zhu, Y., Wyatt, D., Stephenson, M., Baughman, A., Womack, K. N., Hart, K. W., Kobayashi, M., Verani, J. R., Patel, M. M., IVY Network, HAIVEN Invest 2021; 70 (18): 674?79

    Abstract

    Adults aged ?65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination? with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ?65 years. Among 417 hospitalized adults aged ?65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ?65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ?65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ?65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.

    View details for Web of Science ID 000647643800003

    View details for PubMedID 33956782

  • Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged >= 65 Years - United States, January-March 2021 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Tenforde, M. W., Olson, S. M., Self, W. H., Talbot, H., Lindsell, C. J., Steingrub, J. S., Shapiro, N., Ginde, A. A., Douin, D. J., Prekker, M. E., Brown, S. M., Peltan, I. D., Gong, M. N., Mohamed, A., Khan, A., Exline, M. C., Files, D., Gibbs, K. W., Stubblefield, W. B., Casey, J. D., Rice, T. W., Grijalva, C. G., Hager, D. N., Shehu, A., Qadir, N., Chang, S. Y., Wilson, J. G., Gaglani, M., Murthy, K., Calhoun, N., Monto, A. S., Martin, E. T., Malani, A., Zimmerman, R. K., Silveira, F. P., Middleton, D. B., Zhu, Y., Wyatt, D., Stephenson, M., Baughman, A., Womack, K. N., Hart, K. W., Kobayashi, M., Verani, J. R., Patel, M. M., IVY Network, HAIVEN Investigators 2021; 70 (19): 674-679
  • Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI insight Wilson, J. G., Simpson, L. J., Ferreira, A., Rustagi, A., Roque, J. A., Asuni, A., Ranganath, T., Grant, P. M., Subramanian, A. K., Rosenberg-Hasson, Y., Maecker, H., Holmes, S., Levitt, J. E., Blish, C., Rogers, A. J. 2020

    Abstract

    BACKGROUND: Elevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare to those observed in critically ill patients with ARDS or sepsis due to other causes.METHODS: We used a luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNFalpha) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTS: 15 hospitalized COVID-19 patients, 9 of whom were critically ill, were compared to critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNFalpha between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONS: Levels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDING: A.J.R.: Stanford ICU Biobank NHLBI K23 HL125663. C.A.B.: Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687; NIH/NIAID U19AI057229-16 (PI MM Davis); Stanford Maternal Child Health Research Institute; Chan Zuckerberg Biohub.

    View details for DOI 10.1172/jci.insight.140289

    View details for PubMedID 32706339

  • A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nature medicine Wilk, A. J., Rustagi, A., Zhao, N. Q., Roque, J., Martinez-Colon, G. J., McKechnie, J. L., Ivison, G. T., Ranganath, T., Vergara, R., Hollis, T., Simpson, L. J., Grant, P., Subramanian, A., Rogers, A. J., Blish, C. A. 2020

    Abstract

    There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide1. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care2. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines3,4 that may be produced by a subset of inflammatory monocytes5,6, lymphopenia7,8 and T cell exhaustion9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.

    View details for DOI 10.1038/s41591-020-0944-y

    View details for PubMedID 32514174

  • A single-cell atlas of the peripheral immune response to severe COVID-19. medRxiv : the preprint server for health sciences Wilk, A. J., Rustagi, A., Zhao, N. Q., Roque, J., Martinez-Colon, G. J., McKechnie, J. L., Ivison, G. T., Ranganath, T., Vergara, R., Hollis, T., Simpson, L. J., Grant, P., Subramanian, A., Rogers, A. J., Blish, C. A. 2020

    Abstract

    There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2. Here, we apply single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells (PBMCs) of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. We identify substantial reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene (ISG) signature, HLA class II downregulation, and a novel B cell-derived granulocyte population appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines, suggesting that circulating leukocytes do not significantly contribute to the potential COVID-19 cytokine storm. Collectively, we provide the most thorough cell atlas to date of the peripheral immune response to severe COVID-19.

    View details for DOI 10.1101/2020.04.17.20069930

    View details for PubMedID 32511639

  • A generalizable 29-mRNA neural-network classifier for acute bacterial and viral infections. Nature communications Mayhew, M. B., Buturovic, L., Luethy, R., Midic, U., Moore, A. R., Roque, J. A., Shaller, B. D., Asuni, T., Rawling, D., Remmel, M., Choi, K., Wacker, J., Khatri, P., Rogers, A. J., Sweeney, T. E. 2020; 11 (1): 1177

    Abstract

    Improved identification of bacterial and viral infections would reduce morbidity from sepsis, reduce antibiotic overuse, and lower healthcare costs. Here, we develop a generalizable host-gene-expression-based classifier for acute bacterial and viral infections. We use training data (N=1069) from 18 retrospective transcriptomic studies. Using only 29 preselected host mRNAs, we train a neural-network classifier with a bacterial-vs-other area under the receiver-operating characteristic curve (AUROC) 0.92 (95% CI 0.90-0.93) and a viral-vs-other AUROC 0.92 (95% CI 0.90-0.93). We then apply this classifier, inflammatix-bacterial-viral-noninfected-version 1(IMX-BVN-1), without retraining, to an independent cohort (N=163). In this cohort, IMX-BVN-1 AUROCs are: bacterial-vs.-other 0.86 (95% CI 0.77-0.93), and viral-vs.-other 0.85 (95% CI 0.76-0.93). In patients enrolled within 36h of hospital admission (N=70), IMX-BVN-1 AUROCs are: bacterial-vs.-other 0.92 (95% CI 0.83-0.99), and viral-vs.-other 0.91 (95% CI 0.82-0.98). With further study, IMX-BVN-1 could provide a tool for assessing patients with suspected infection and sepsis at hospital admission.

    View details for DOI 10.1038/s41467-020-14975-w

    View details for PubMedID 32132525

  • Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients. The New England journal of medicine National Heart, L., Ginde, A. A., Brower, R. G., Caterino, J. M., Finck, L., Banner-Goodspeed, V. M., Grissom, C. K., Hayden, D., Hough, C. L., Hyzy, R. C., Khan, A., Levitt, J. E., Park, P. K., Ringwood, N., Rivers, E. P., Self, W. H., Shapiro, N. I., Thompson, B. T., Yealy, D. M., Talmor, D. 2019

    Abstract

    BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study.METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality.RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality.CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).

    View details for DOI 10.1056/NEJMoa1911124

    View details for PubMedID 31826336

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