Red Blood cells show increased caspase-3/7 activity in COVID-19
disease which is suppressed by a pan-caspase inhibitor
Recent reports suggest abnormalities in the RBCs in patients with
COVID-19 (36-38). In the process of Ficoll separation, we observed a
layer of RBCs contaminating the PBMC layer that was universally present
in all samples from COVID-19 individuals (Figure 5A ). This
finding was also present in up to 80% of COVID-19 convalescent
subjects. Plasma from acutely infected COVID-19 subjects induced a
similar finding when incubated overnight with plasma depleted whole
blood of healthy patients. Treatment of the plasma samples with trypsin,
DNAse, or heat inactivation did not abolish this effect (data not
shown), suggesting a cell intrinsic process rather than due to cell
surface changes. Cellular caspases are not limited to immune cells. RBCs
do not express caspase-1, but have been shown to have detectable
caspase-3 that increases with various disorders (36). We found that RBCs
from acute COVID-19 subjects showed up-regulation of caspase-3/7
activity compared to healthy controls (Figure 5B ). Plasma from
these patients also upregulated caspase-3 in healthy subjects’ RBCs.
When healthy subjects’ RBCs were incubated with plasma from influenza
infected patients this effect was not observed, although a similar RBC
contamination was observed in these samples after Ficoll separation.
Furthermore, EMR suppressed the caspase-3 up-regulation in samples
incubated with COVID-19 patient-derived plasma, but did not change the
baseline expression levels in influenza-plasma incubated samples.