Levels of ACE2 mRNA, ACE2 protein, CD8+ T cells, NK cells, and cytokines in lung cells, lung tissues, and COVID-19 patient samples. (a and b) Pearson R and −log10
P values of correlations between 1,000 randomly sampled genes and the levels of indicated lymphocytes in lung tissues were determined and plotted. The NK cells were resting and activated NK cells. ACE2 Pearson R and P values are shown as red diamonds. Blue lines indicate means with 95% confidence intervals. Percentiles for ACE2 with respect to the 1,000 random R and P values are shown. Data are from the GTEx data set (n = 578). The P values are from one-sample t tests. (c) Correlations between ACE2 mRNA and protein levels in 52 cell lines. R and P values are from Pearson correlations. (d) Pearson correlation R values between mRNA and protein levels of 12,016 genes are compared to the ACE2 R coefficient (red diamond). The line and box represent the median and interquartile ranges. The ACE2 R percentile is also shown. The P value is from one-sample t test. (e) Bar graph showing the correlation between ACE2 mRNA and protein levels in human tissues. Means plus standard errors of the means (error bars) are shown. Samples are from the Human Protein Atlas. P values were from Kruskal-Wallis test. (f) Meta-analysis scatterplot showing the correlation between ACE2 mRNA and protein levels in 17 human tissues. Data are from nine different studies, as detailed in Table S3 in the supplemental material. R and P values are from Pearson correlation. (g and h) Heatmaps showing Spearman correlations between the levels of ACE2 or indicated cytotoxic lymphocytes and eight cytokines that recruit these cells in human lung tissues from the GTEx data set (n = 578). The colors of the tiles represent Spearman R, per the color bar on the right. Spearman significance levels are shown by asterisks. See also Fig. S5. (i and j) Fold increase in expression levels of indicated cytokines in Calu-3 lung cells 24 h after SARS-CoV-2 infection compared to uninfected Calu-3 cells (i), and in postmortem COVID-19 lung tissues (n = 2) to those in healthy, uninfected lung tissues (n = 2) (j). (k) Comparison of indicated fractions of lymphocyte levels in bronchoalveolar lavage fluids from mild/moderate and severe COVID-19 patients, as determined in two separate studies (46, 47). The second study also determined a tissue resident (TR) score for CD8+ T cells. Numbers in the mild/moderate column on the left show fold increase compared to the respective severe cases on the right. Asterisks in the severe column on the right represent statistical significance levels, as determined by Mann-Whitney U tests (top panel), or t tests (middle and bottom panels) comparing mild/moderate to severe cases. P value symbols: *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; †, P < 2.2 × 10−16.