Extended Data Fig. 3: Correlation between COVID-19 clinical characteristics with endothelial cell death or RBC haemolysis.
From: Ischaemic endothelial necroptosis induces haemolysis and COVID-19 angiopathy
a-e. Pearson correlation coefficient (PCC) showing little correlation between postmortem time (a), ventilation time (b), time from symptom onset to death (c), time from hospitalization to death (d), with the extent of EC death (left) and RBC haemolysis (right). The PCC is represented in the indicated COVID-19 patient organ microvasculature, with the r value included for each correlation type. n = 6 patients. e, Comparison of EC death and RBC haemolysis between control autopsies and biopsies to show EC death and RBC haemolysis are independent of postmortem changes in autopsy tissues, with graphs quantifying the percentage (%) of EC death (left) and vessels containing lysed RBCs (right) in cardiac autopsy samples and biopsies from non-COVID-19 and non-ischaemic patients (n = 4 autopsies, n = 3 biopsies). f-i, Mouse 16-hour postmortem tissues without microvascular RBC haemolysis. Representative H&E and confocal immunofluorescence images showing a lack of intravascular RBC haemolysis (white arrowheads) (3 mice) (f), and quantification of microvascular haemolysis (g) and EC death (h) in the indicated organs. Note: Tissue injury in the gut (villus sloughing) and kidney (mild tubule epithelial detachment) are highlighted by yellow arrowheads and white broken lines in H&E and IF images (n = 3 mice). Scale bars: 100 µm, 20 µm in magnified images. i, Percentage of vessels with EC death in sham-operated LAD hearts (PL) (4 mice). j, CD235+H staining is specific to fragmented and deformed RBCs in COVID-19 patient microvasculature. Confocal/DIC images showing CD235+H staining only on fragmented/deformed haemolysed RBCs (1), but not on ghost RRCs (2) or non-lysed RBCs (3) (marked by white dotted lines) in COVID-19 patient kidney microvasculature (vessel marked by white broken lines) (n = 4 patients). Scale bar, 5 μm. k, Ischaemic injury in COVID-19 patient kidney. Representative H&E images (progressively magnified in lower panels) depicting acute tubular necrosis (ATN) with viable distal tubules (arrowheads), and an adjacent vessel containing lysed RBCs (arrows) but not platelet thrombi or fibrin; Scale bars, 100 and 20 µm; Graph shows the percentage of renal tubules exhibiting ATN, (n = 6 kidney tissues); Data represents mean ± SD. One-sided Pearson’s r (a-d), two-sided t-test (e).
