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Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma
The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by instit...
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Published in: | PLoS pathogens 2021-10, Vol.17 (10), p.e1010025-e1010025 |
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description | The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes. |
doi_str_mv | 10.1371/journal.ppat.1010025 |
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Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1010025</identifier><identifier>PMID: 34714894</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Antibodies ; Bacterial pneumonia ; Biology and Life Sciences ; Biomarkers ; Blood ; Care and treatment ; Chemokines ; Clinical aspects ; Clinical trials ; Coronaviruses ; COVID-19 ; Cytokine storm ; Cytokines ; Health aspects ; Hospitalization ; Immune response ; Infections ; Infectious diseases ; Inflammation ; Intubation ; Measurement ; Mechanical ventilation ; Medicine and Health Sciences ; Mortality ; Neutralizing ; Pandemics ; Pathogens ; Patients ; Peripheral blood ; Plasma ; Pneumonia ; Proteins ; Respiratory distress syndrome ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Vascular endothelial growth factor ; Ventilation ; Ventilators ; Viral diseases ; Viral infections ; Viruses</subject><ispartof>PLoS pathogens, 2021-10, Vol.17 (10), p.e1010025-e1010025</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Fanning et al. 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Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.</description><subject>Antibodies</subject><subject>Bacterial pneumonia</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>Care and treatment</subject><subject>Chemokines</subject><subject>Clinical aspects</subject><subject>Clinical trials</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Cytokine storm</subject><subject>Cytokines</subject><subject>Health aspects</subject><subject>Hospitalization</subject><subject>Immune response</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Inflammation</subject><subject>Intubation</subject><subject>Measurement</subject><subject>Mechanical ventilation</subject><subject>Medicine and Health 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cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma</title><author>Fanning, Stacey L ; Korngold, Robert ; Yang, Zheng ; Goldgirsh, Kira ; Park, Steven ; Zenreich, Joshua ; Baker, Melissa ; McKiernan, Phyllis ; Tan, Ming ; Zhang, Bingsong ; Donato, Michele L ; Perlin, David S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c638t-1019ac3a77c771e066b15828bbbe7c59c274b2eb8fb47d5aaf8f7e2af2445cfe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Bacterial pneumonia</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Blood</topic><topic>Care and treatment</topic><topic>Chemokines</topic><topic>Clinical aspects</topic><topic>Clinical trials</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Cytokine 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in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. 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subjects | Antibodies Bacterial pneumonia Biology and Life Sciences Biomarkers Blood Care and treatment Chemokines Clinical aspects Clinical trials Coronaviruses COVID-19 Cytokine storm Cytokines Health aspects Hospitalization Immune response Infections Infectious diseases Inflammation Intubation Measurement Mechanical ventilation Medicine and Health Sciences Mortality Neutralizing Pandemics Pathogens Patients Peripheral blood Plasma Pneumonia Proteins Respiratory distress syndrome Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Vascular endothelial growth factor Ventilation Ventilators Viral diseases Viral infections Viruses |
title | Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma |
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