Disrupted Resolution Mechanisms Favor Altered Phagocyte Responses in COVID-19

Duco Steven Koenis,Kimberly Pistorius,Charlotte Camille Jouvene,Patricia Regina Souza,Gabriel Amador Aguirre,Gavin Thomas,Ghassan Alusi,Mauro Perretti,Lucy Ly,Jesmond Dalli,William Ricketts,Maria Gonzalez-Nunez,Issa Beegun,Hemant M Kocher,Paul Pfeffer

doi:10.1161/circresaha.121.319142

Abstract

[Figure: see text].

Highlights

The inflammatory response is an essential protective mechanism that evolved to safeguard the host from invading pathogens and facilitate the restoration of tissue function through repair and regeneration of damaged tissues[1,2,3,4]
In order to evaluate whether specialized pro-resolving lipid mediators (SPM) concentrations are differentially regulated in COVID-19 patients we first assessed plasma lipid mediator (LM) profiles in hospitalized patients with COVID-19 (n=38) and compared these with LM profiles obtained from healthy volunteers with no clinical suggestion of COVID19 infection (n=12; see Supplemental Table I for clinical characteristics)
This included an upregulation of SPM from the docosahexaenoic acid (DHA), n-3 docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA) bioactive metabolomes in COVID-19 patients, such as DHAderived MCTR3, PCTR3, and RvD6, and n-3 DPA-derived RvD5n-3 DPA and PD1n-3 DPA

Summary

Introduction

The inflammatory response is an essential protective mechanism that evolved to safeguard the host from invading pathogens and facilitate the restoration of tissue function through repair and regeneration of damaged tissues[1,2,3,4] This finely tuned response becomes unravelled in disease, often resulting in disseminated inflammation. COVID-19 is characterized by a number of clinical presentations that in severe cases include pneumonia, acute respiratory distress syndrome and multiple organ failure[5] This disseminated inflammatory response is thought to involve alveolar damage that can lead to cardiovascular complications and multi-organ failure. This notion is underpinned by results obtained in the RECOVERY Trial, which demonstrated a significant reduction in mortality in critically ill patients treated with the anti-inflammatory corticosteroid dexamethasone[6]

Objectives

Results

Conclusion