Fig. 6: Molecular characteristics of the ISG^high and ISG^low COVID-19 lung profiles.

a Representative immunohistochemistry for p53 and Ki67. Size bar 100 μm. At least two different tissue blocks from different areas of the lungs were evaluated for each case. b Expression of C1QA and C1QB in ISG^high and ISG^low lung samples (n = 31 independent samples). Box-plots elements indicate the median (center line), upper, and lower quartiles (box limits). Whiskers extend to the most extreme value included in 1.5× interquartile range. Groups were compared using a two-sided Wilcoxon rank-sum test. c Representative IHC stainings for complement activation products C5b-9 and C3d in ISG^high, ISG^low COVID-19, and normal control lungs. Size bar 100 μm. At least two different tissue blocks from different areas of the lungs were evaluated for each case. ISG^high samples, red; ISG^low samples, blue. d Schematic time course of COVID-19 lung disease based on lung autopsy findings. Early in the disease, an ISG^high lung profile is observed, with high viral load, high expression of cytokines and ISGs, and sparse immune infiltrates. Late in the disease, an ISG^low lung profile is observed, with low viral load, low local expression of cytokines and ISGs, and strong infiltration of macrophages and lymphocytes. Patients who die early are not able to adequately control SARS-CoV-2, while patients who die late suffer from DAD and immunopathology. Infectious dose and individual predisposition to mount immune responses likely define whether or not a patient survives COVID-19. Green line: Relative viral loads, red line: Relative expression of lung ISGs and cytokines, blue line: pulmonary immune infiltrates and complement deposition. Dark gray area: lethal outcomes, arrows: individual variability.