Figure 4 (facing page). Numeric Density of Features of intussusceptive and Sprouting Angiogenesis in Lungs from Patients Who Died from Covid-19 or influenza A(H1N1).

Angiogenic features of sprouting and intussusceptive angiogenesis (intussusceptive pillars and sprouts, respectively) were counted per field of view in microvascular corrosion casts of lungs from patients with Covid-19 (red), lungs from patients with influenza A(H1N1) (blue), and control lungs (white). In Panels A and B, the numeric densities of angiogenic features are summarized as box plots for intussusceptive and sprouting angiogenesis. The boxes reflect the interquartile range, and the whiskers indicate the range (up to 1.5 times the interquartile range). Outliers are denoted by singular points. A statistical comparison between lungs from patients Covid-19 and those from patients with influenza and uninfected control lungs showed a significantly higher frequency of angiogenesis in the patients with Covid-19 lungs, especially intussusceptive angiogenesis (P values were calculated with Student’s t-test, controlled for the familywise error rate with a Benjamini–Hochberg false discovery rate threshold of 0.05). Panels C and D show a chronological comparison of intussusceptive and sprouting angiogenesis in lungs from patients with Covid-19 and lungs from patients with influenza A(H1N1) plotted as a function of the duration of hospitalization. The numbers shown are Pearson correlation coefficients and P values (all displayed P values of 0.05 or lower also pass the false discovery rate threshold of 0.05). The median angiogenic feature count for each patient is displayed as one dot. The shaded areas encompassing the dotted linear regression lines are smoothed 95% confidence intervals. As a reference for increased blood-vessel formation in lung diseases, intussusceptive and sprouting angiogenesis as found in end-stage nonspecific interstitial pneumonia (NSIP), a chronic interstitial lung disease, at the time of lung transplantation (a mean of 1650 days from first consultation to lung transplantation) are shown (purple box plots). Findings in healthy control lungs are also indicated (white box plots). The white and purple box plots are displayed in relation to the y axis but not the x axis (as indicated by vertical dashed lines).