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Review 2: "Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses"

This study introduces a novel therapeutic approach to treating COVID-19. Study motivates further investigation of whether selectively inhibiting FcR receptor driven inflammation could result in more targeted and effective COVID-19 interventions.

Published onAug 26, 2020
Review 2: "Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses"
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Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses
Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses
Description

Abstract For yet unknown reasons, severely ill COVID-19 patients often become critically ill around the time of activation of adaptive immunity. Here, we show that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by human macrophages, which subsequently breaks pulmonary endothelial barrier integrity and induces microvascular thrombosis. The excessive inflammatory capacity of this anti-Spike IgG is related to glycosylation changes in the IgG Fc tail. Moreover, the hyper-inflammatory response induced by anti-Spike IgG can be specifically counteracted in vitro by use of the active component of fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of Syk.One sentence summary Anti-Spike IgG promotes hyper-inflammation.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

This is quite interesting and novel finding. The results are well described. Besides providing evidences from inhibitor and Ab-based neutralization experiments, additional genetic experiments will be more convincing. However, the manuscript does describe a novel therapeutic approach for severely ill COVID patients, which might be quite helpful, thus quick dissemination of this approach might be warranted.

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