Cell states during SARS-CoV-2 infection in human tracheal/bronchial epithelial cells. a) 6162 cells (Fiege et al., 2021) covering samples of mock-infected (0 h), 24 hpi (hours post-infection), and 48 hpi visualized with UMAP. b) Average expression of representative viral genes, IFNs, and antiviral genes with each cell cluster (state). c) Cell proportions of clusters at different time points (hpi = 0, 24, and 48). Cell proportions are labeled with corresponding colors in a). d) Average expression (0–48h) of antiviral genes (IFIT1, IFIT2, IFIT3, IFIT5, IFIH1, OAS1, OAS2, OAS3, OASL, DDX58). e) Average expression (0–48h) of viral genes (cov.orf1ab, cov.S, cov.orf3a, cov.orf6, cov.M, cov.N). f) Average expression (0–48h) of interferon genes (IFNB1, IFNL1, IFNL2,IFNL3). 103 cells (1.7%) are IFN-positive. g) Progression of viral infection as indicated by changes in cell proportions of different states. Cells are shown separately at each time point in the leftmost column. The right columns show the average expression of antiviral genes, viral genes, and IFNs in the corresponding cells.

NOVAa model. a) The cell state transitions are included in the NOVAa model. The simpler OVA model bypasses the a and N states, by allowing V to induce direct O → A transitions (Fig. S3). b) Final states of a small lattice (50 × 50) simulations at two different values of Pa (both at IFN spreading radius R = 1). c) The fraction of cells in each state in the final frozen configuration as a function of Pa. A critical transition is observed at Pa = Pc ∼ 27.8%. At lower values of Pa, most cells terminate in the V state, representing an aggressive tissue infection. Simulations were performed on a lattice with linear dimension L = 1000.

Cluster size distribution. a) The distribution of infected cells (s = (N + V )/L2) for different values of Pa, simulated by starting with one infected cell in a 2D square lattice of linear extent L = 2000. b) The exponents from a) are extracted by re-scaling as shown on the y-axis, yielding τ = 1.83. The cut-off exponent is estimated as σ ∼ 1. Simulations plot the final outbreak sizes from 10,000 initial infections of one cell. The histogram is log-binned with 5 bins per decade. The critical point at Pa = Pc = 0.28 is determined as the value with the longest scaling regime.

Range of IFN. a) Typical cluster for an R = 1 simulation at Pa ∼ Pc = 0.278. b) The dependence of Pc with R, approximately reproduced by a fit Pc ∼ 3−R. For comparison the OVA model as well as percolation has Pc ∼ 3−R/2. In all cases, when Pa is above Pc then the virus is prevented from spreading. c) Cluster distribution for R = 5 at Pa ∼ Pc = 0.004, at a 5 times larger linear scale than a).