Unraveling the Immune Response in Severe COVID-19
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COMMENTARY
Unraveling the Immune Response in Severe COVID-19 Lucie Rodriguez 1 & Petter Brodin 1,2 Received: 15 August 2020 / Accepted: 18 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
An outbreak of coronavirus disease 2019 (COVID-19) emerged in China’s Hubei province and spread rapidly across the globe leading to millions of cases worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel enveloped RNA-virus of the family of beta-coronavirus, was quickly identified and sequences distributed, initiating a race to develop vaccines and therapeutics that is unprecedented in history. A striking feature of the COVID-19 disease is the wide range of disease severity across different infected individuals. The SARS-CoV-2 infection is almost exclusively mild in children [1], while older individuals, as well as those with specific preexisting illnesses, are more likely to develop severe disease and require intensive care [2]. One exception from this general rule is the postinfectious condition termed multisystem inflammatory syndrome (MIS-C) affecting children with COVID-19, a life-threatening syndrome developing 2–6 weeks after the acute SARS-CoV-2 infection [3]. The immunology of this condition is currently under intense investigation [4]. Overall, there is an urgent need to better understand the determinants of this difference in COVID-19 disease presentation, the underlying genetic and functional differences between mild and severe disease patients [5], and ideally also identification of useful biomarkers that can be used to monitor disease progression and distinguish productive from deleterious immune responses. SARS-CoV-2 infection and the immune response to the virus can be divided into two phases. In the first phase, the virus replicates in the respiratory epithelium and alveoli and the principal antiviral response mechanism is the type-I IFN response aimed at limiting viral replication. If this is * Petter Brodin [email protected] 1
Science for life Laboratory, Department of Women’s and Children Health, Karolinska Institutet, Stockholm, Sweden
2
Pediatric Rheumatology, Karolinska University Hospital, Stockholm, Sweden
insufficient at limiting the infection, there is a second phase in patients with more severe disease course, in which cell death and local inflammation triggers the induction of additional cytokines and chemokines that draw additional immune cells into the lung. At the same time, danger signals and alarmins like HMGB1 are released and possibly trigger a self-enhancing inflammatory response giving rise to acute respiratory distress syndrome (ARDS) and clinical deterioration. There has been much discussion around the specifics of this second phase dysregulated immune response in severe COVID-19 but the actual data remain scarce [6]. We know that lymphopenia is a hallmark of severe disease and the degree of lymphopenia, and neutrophil-to-lymphocyte ratio correlates with disease severity [7]. The same is true for plasma l
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