It is unclear why people’s immune response to the SARS-CoV-2 coronavirus varies so widely. Tracking patient responses over time sheds light on this issue, and has implications for efforts to predict disease severity.
A dysregulated immune response, a cytokine storm and cytokine-release syndrome are some of the terms used to describe the overexuberant defence response that is thought to contribute to disease severity in certain people who become seriously ill with COVID-19. However, a precise definition of this type of immune dysfunction remains elusive. Writing in Nature, Lucas et al. fill in some gaps in our knowledge.
A holy grail of COVID-19 research is the ability to assess a person’s immune response, to pinpoint early the individuals who have mild symptoms but who are on track to develop the intense defence response that is associated with severe disease. This is important because there is a broad spectrum of clinical disease in people infected with SARS-CoV-2, the coronavirus that causes COVID-19: some infected individuals can be asymptomatic, whereas others are at risk of dying, and require hospitalization in an intensive-care unit and use of a ventilator machine to breathe. Identifying those whose dysregulated immune-response signature predicts the development of severe disease would enable them to be monitored more intensively to minimize disease progression.
Lucas and colleagues performed extensive analyses of immune responses over time (longitudinal studies) in 113 people hospitalized with COVID-19 who had moderate or severe disease, and assessed a similar number of SARS-CoV-2-free healthy people as controls. The authors analysed molecules in blood plasma and monitored peripheral blood mononuclear cells — white blood cells of the immune system such as CD4 T cells, CD8 T cells and B cells. The longitudinal nature of this study enables conclusions to be drawn that wouldn’t be possible from analysing cross-sectional studies that don’t follow individuals over time.
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