Touro College of Osteopathic Medicine, New York, New York, United States of America.
Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, United States of America.
PLoS Pathog. 2021 Oct 29;17(10):e1010025. doi: 10.1371/journal.ppat.1010025. eCollection 2021 Oct.
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.
全球 SARS-CoV-2 冠状病毒大流行在许多地区仍造成严重破坏。治疗方案有限，许多中心已使用恢复期供者血浆将被动中和抗体转移给有呼吸道受累的患者。结果因机构而异，并且受供者血浆本身的性质和质量、给药时机以及受者的临床方面等因素影响而变得复杂。众所周知，SARS-CoV-2 感染与几种炎症细胞因子/趋化因子的血液浓度升高有关，这是对病毒的整体免疫反应的一部分，也是介导的肺部病理学的结果。其中一些相关因素导致细胞因子风暴综合征和急性呼吸窘迫综合征，通常导致死亡。我们机构进行的一项 IIa 期临床试验使用高中和效价恢复期血浆转移，使我们有机会在输注后 10 天内研究相关因素的升高。血浆受者分为未（Track 2）或需要（Track 3）机械通气的住院 COVID-19 肺炎患者。每个 Track 的患者中都有几种细胞因子升高，有些细胞因子在第 10 天仍在升高，而另一些细胞因子最初升高然后消退。此外，MIP-1α、MIP-1β 和 CRP 的升高与 Track 2 受者的疾病进展相关。总体而言，我们的观察结果为进一步研究这些相关因素以及确定潜在的生物标志物提供了基础，以改善恢复期血浆治疗并促进更成功的患者结局。
