Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

Stacey L Fanning,Robert Korngold,Melissa Baker,Zheng Yang,Joshua Zenreich,David S Perlin,Michele L Donato,Bingsong Zhang,Ming Tan,Phyllis Mckiernan,Kira Goldgirsh,Steven Park,Shin-Ru Shih

doi:10.1371/journal.ppat.1010025

Abstract

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.

Highlights

Since the emergence of SARS-CoV-2 as a human pathogen in December of 2019 and its global spread resulting in a worldwide pandemic, scientists and clinicians have been working nonstop to understand the biology of the virus and the ensuing host response to discover treatments for COVID-19 disease
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

Summary

Introduction

Since the emergence of SARS-CoV-2 as a human pathogen in December of 2019 and its global spread resulting in a worldwide pandemic, scientists and clinicians have been working nonstop to understand the biology of the virus and the ensuing host response to discover treatments for COVID-19 disease. The inflammatory response to SARS-CoV-2 and resultant cytokine storm is believed to account for much of the severe disease pathology in later stages of disease leading to acute respiratory distress syndrome (ARDS) and multi-organ failure [2,4,5]. Despite the early association of the cytokine response to SARS-CoV-2 infection with CSS, recent reports have indicated that COVID-19 cytokine profiles are not consistent with CSS as characterized in patients with sepsis [7]. Understanding the course of cytokine production and inflammatory markers throughout progression of disease and their contribution to respiratory failure will be critical to optimizing treatment protocols. Determining early predictors of worsening disease will aid in treatment decisions, in the use of immunosuppressants at critical junctures during the clinical course

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