SARS-CoV-2 causes immune paralysis in severe cases of COVID-19 – The Science Board

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SARS-CoV-2 causes immune paralysis in severe cases of COVID-19 – The Science Board



August 12, 2020— The SARS-CoV-2 virus can cause the paralysis of key immune cells as the COVID-19 disease progresses, and this immune paralysis can be the difference between severe and mild cases of COVID-19, according to a study published inScienceon August 11.

Most COVID-19 patients exhibit mild-to-moderate symptoms, with around 15% progressing to severe or critical disease that requires hospitalization, primarily due to the development of acute respiratory distress syndrome (ARDS). The underlying cause behind the high mortality rate of COVID-19 is unknown but may be due to an impaired interferon and dysregulated inflammatory responses.

In response to infection with the virus, the body initially launches the rapid — through somewhat indiscriminate — innate immune response, followed by a more targeted but slower adaptive immune response. Classifying the dynamic interactions between both types of immune responses and SARS-CoV-2 is an important step in understanding what contributes to the clinical severity of COVID-19 — and can inform the design of therapeutic strategies.

In theSciencepaper, researchers used a systems biological approach with mass cytometry and single-cell transcriptomics of leukocytes, transcriptomics of bulk peripheral blood mononuclear cells (PBMCs), and multiplex analysis of cytokines in plasma to analyze the immune response of 76 COVID-19 patients from two geographically distant cohorts.

The Stanford University researchers found an increase in the frequency of plasmablast (immature blood cells that mature into antigen-presenting cells) and effector CD8 T cells in infected individuals. Conversely, there was a decreased frequency of plasmacytoid dendritic cells — the major producers of type I interferons (IFNs) — in infected individuals.

The results suggest that patients with COVID-19 may have impaired capacity to produce IFN-alpha. Indeed, they observed reduced production of IFN-alpha in response to stimuli in dendritic cells of infected individuals. This finding suggests that periphery innate immune cells are suppressed during SARS-CoV-2 infection.

Cytokine suspects

Next, the team detected 43 cytokines (including common mediators such as interleukin-6 (IL-6), MCP-6, CXCL10) that were upregulated in infected samples. This upregulated inflammatory response is despite the impaired interferon response in the blood. The researchers believe that the molecules originate from elsewhere in the body, likely in the lungs at the site of infection.

Three inflammatory mediators were strongly correlated with clinical severity of COVID-19:

  • Tumor necrosis factor superfamily member 14 (TNFSF14; LIGHT), expressed in human lung fibroblasts with implications in lung tissue fibrosis, remodeling, and inflammation
  • Extracellular newly identified receptor for advanced glycation end products (EN-RAGE), which expresses S100A12, a biomarker of pulmonary injury, and is implicated in pathogenesis of sepsis-induced ARDS
  • Oncostatin-M (OSM), a regulator of IL-6

“These three molecules and their receptors could r

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