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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Autores principales:	Stacey L. Fanning, Robert Korngold, Zheng Yang, Kira Goldgirsh, Steven Park, Joshua Zenreich, Melissa Baker, Phyllis McKiernan, Ming Tan, Bingsong Zhang, Michele L. Donato, David S. Perlin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/91892a739c05473a890b19d51c35fe63
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spelling	oai:doaj.org-article:91892a739c05473a890b19d51c35fe632021-11-18T06:01:31ZElevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma1553-73661553-7374https://doaj.org/article/91892a739c05473a890b19d51c35fe632021-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580259/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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. Author summary COVID-19, the disease caused by the SARS-CoV-2 virus, has a varied clinical course with limited treatment options. While some patients mount a productive immune response leading to recovery, others progress to rapid respiratory deterioration that may require hospitalization and mechanical ventilation. Our institution conducted a clinical trial to evaluate the efficacy of convalescent plasma therapy (CPT) to treat patients hospitalized with COVID-19 pneumonia. In this arm of the study, we sought to examine immune analytes in donor plasma as well as evaluate the recipients’ plasma before CPT infusion, and at Day 3 and Day 10 post-CPT infusion. We found some analytes to be elevated in plasma donors, compared to healthy controls, even after recovery. Plasma composition in CPT recipients prior to infusion showed elevations in several analytes associated with immune activation. Some significant differences were seen in plasma composition in patients in our Track 2 cohort (hospitalized without mechanical ventilation) compared to the Track 3 cohort (hospitalized with mechanical ventilation). In addition, we obtained plasma samples for hospitalized COVID-19 patients that did not receive CPT and noted several differences in the course of immune analyte production over time compared to the CPT-treated patients.Stacey L. FanningRobert KorngoldZheng YangKira GoldgirshSteven ParkJoshua ZenreichMelissa BakerPhyllis McKiernanMing TanBingsong ZhangMichele L. DonatoDavid S. PerlinPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Stacey L. Fanning Robert Korngold Zheng Yang Kira Goldgirsh Steven Park Joshua Zenreich Melissa Baker Phyllis McKiernan Ming Tan Bingsong Zhang Michele L. Donato David S. Perlin Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma
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. Author summary COVID-19, the disease caused by the SARS-CoV-2 virus, has a varied clinical course with limited treatment options. While some patients mount a productive immune response leading to recovery, others progress to rapid respiratory deterioration that may require hospitalization and mechanical ventilation. Our institution conducted a clinical trial to evaluate the efficacy of convalescent plasma therapy (CPT) to treat patients hospitalized with COVID-19 pneumonia. In this arm of the study, we sought to examine immune analytes in donor plasma as well as evaluate the recipients’ plasma before CPT infusion, and at Day 3 and Day 10 post-CPT infusion. We found some analytes to be elevated in plasma donors, compared to healthy controls, even after recovery. Plasma composition in CPT recipients prior to infusion showed elevations in several analytes associated with immune activation. Some significant differences were seen in plasma composition in patients in our Track 2 cohort (hospitalized without mechanical ventilation) compared to the Track 3 cohort (hospitalized with mechanical ventilation). In addition, we obtained plasma samples for hospitalized COVID-19 patients that did not receive CPT and noted several differences in the course of immune analyte production over time compared to the CPT-treated patients.
format	article
author	Stacey L. Fanning Robert Korngold Zheng Yang Kira Goldgirsh Steven Park Joshua Zenreich Melissa Baker Phyllis McKiernan Ming Tan Bingsong Zhang Michele L. Donato David S. Perlin
author_facet	Stacey L. Fanning Robert Korngold Zheng Yang Kira Goldgirsh Steven Park Joshua Zenreich Melissa Baker Phyllis McKiernan Ming Tan Bingsong Zhang Michele L. Donato David S. Perlin
author_sort	Stacey L. Fanning
title	Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma
title_short	Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma
title_full	Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma
title_fullStr	Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma
title_full_unstemmed	Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma
title_sort	elevated cytokines and chemokines in peripheral blood of patients with sars-cov-2 pneumonia treated with high-titer convalescent plasma
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/91892a739c05473a890b19d51c35fe63
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Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma

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