Discussion worksheet

Main Research Question?

What's the mechanism for SARS-CoV-2 to infect immune cells and trigger subsequent immune responses?

Flow cytometry (staining for cell death markers) was used to show monocytes in patients with COVID19 undergo pyroptosis. (Fig 1)
flow cytometry (staining for nucleocapsid, N) was used to show mainly intermediate and non-classical monocytes take up SARS-CoV-2(Fig 1)
ELISA was used to quantify inflammatory markers in plasma and showed that patient with COVID19 had elevated IgG, pyroptosis markers and other non-pyroptosis inflammatory markers. Pyroptosis markers are correlated with disease severity(Fig 1).
Imaging flow cytometry (staining for pyroptosis marker) was used to show monocytes in patients with COVID19 has greater expression of inflammasome adaptor ASC, activated caspase-1 and GSDMD (hence inflammatory responses of COVID-19 onset due to greater activation of inflammasomes?) (Fig 2)
Confocal microscopy of lung autopsies was used to show ASC specks are present mainly in CD14+ cells and may activate inflammasomes in uninfected macrophages. (Fig 3)
imaging flow cytometry was used to show monocytes take up antibody opsonied SARS-CoV-2 through FcyR
RE-qPCR was used to show viral replication was aborted in monocytes and monocyte infection did not produce infectious virus

Yes I agree with most of the data as they are supported by data presented.

How did they normalize pooled plasma and account for potential confounding variables due to other plasma components?
How to explain the heterogeneity among COVID patient samples (Fig 2g)

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