Systems-Level Immunomonitoring from Acute to Recovery Phase of Severe COVID-19

Lucie Rodriguez,Olli Vapalahti,Christian Pou,Kirsten Nowlan,Petter Brodin,Pirkka T Pekkarinen,Santtu Heinonen,Ziyang Tan,Camila Rosat Consiglio,Tomas Strandin,Lev Levanov,Eliisa Kekäläinen,Tadepally Lakshmikanth,Constantin Habimana Mugabo,Anu Kantele,Yang Chen,Jussi Hepojoki,Ngoc-Anh A Nguyen ,Wang Ju ,Jaromír Mikes

doi:10.1016/j.xcrm.2020.100078

Abstract

SummarySevere disease of SARS-CoV-2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5–7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses are required to capture cellular interactions. Here, we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ-eosinophil axis activated before lung hyperinflammation and changes in cell-cell co-regulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.

Highlights

Since its emergence in December 2019, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has infected millions of individuals and caused hundreds of thousands of deaths worldwide
Severe disease of SARS-CoV-2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5–7 days of stable disease
Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome rely on the unraveling of the immune cell interactions and cytokines that drive such responses

Summary

Introduction

Since its emergence in December 2019, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has infected millions of individuals and caused hundreds of thousands of deaths worldwide. Cells recognize the presence of the virus through pathogenrecognition receptors (PRRs) and elicit antiviral response programs.. The two main components of such antiviral programs involve the production of type I and III interferons (IFNs) that induce downstream transcription of hundreds of IFN-stimulated genes (ISGs) that interfere with viral replication in the cell.. The second element of the antiviral response program is the secretion of chemokines that recruit specialized cells of the immune system to clear the virus. SARS-CoV-2, like other viruses, has evolved countermeasures to these defenses, and, in particular, the virus efficiently interferes with IFN signaling and the induction of ISGs in SARS-CoV-2-infected cells.. SARS-CoV-2, like other viruses, has evolved countermeasures to these defenses, and, in particular, the virus efficiently interferes with IFN signaling and the induction of ISGs in SARS-CoV-2-infected cells. In contrast, pro-inflammatory cytokine and chemokine responses are induced normally, and this imbalance between antiviral and pro-inflammatory responses is a key feature of COVID-19.6

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