Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

摘要

Circulating CTSL is elevated in patients with COVID-19. A total of 87 patients with COVID-19, including 20 with severe disease and 67 with nonsevere disease, and 125 healthy volunteers were enrolled in this study. a Plasma CTSL, CTSB, and CTSL/CTSB levels patients with severe (n = 20) and nonsevere COVID-19 (n = 67) upon hospital admission (day 0). Statistical significance was assessed by the Mann–Whitney U test (two-sided). b Plasma CTSL, CTSB and CTSL/CTSB levels in COVID-19 patients (day 0) (n = 87) and age-/sex-matched healthy volunteers (n = 125). The green lines in panels a and b indicate the reference ranges for each parameter, established as the mean values ± 2 SD in the healthy participants. Statistical significance was assessed by the Mann–Whitney U test (two-sided). c Correlation between CTSL in plasma from COVID-19 patients (n = 87) and the number of days from symptom onset to blood collection before therapy. Statistical significance was assessed by Spearman correlation analysis (two-sided). d Flowchart of the follow-up study. Patients were admitted to the hospital on day 0 and experienced a mean hospitalization time of 14 days (day 14). Then, they were followed up on the 14th day (day 28) and the 28th day (day 42) after discharge from the hospital. Blood samples were collected on days 0, 28, and 42. e CTSL levels in plasma from COVID-19 patients (n = 87) on days 0, 28, and 42 after enrollment. Statistical significance was assessed by the Kruskal–Wallis test with Dunn’s post hoc test. f Comparison of plasma CTSL levels between patients with nonsevere (n = 67) and severe COVID-19 (n = 20) on days 0, 28, and 42. The data are shown as the medians ± interquartile ranges. Statistical significance was assessed by the Mann–Whitney U test (two-sided). g Summary forest plot of candidate predictor variables associated with the severity of COVID-19 (n = 87) by univariable logistic regression. h Summary forest plot of candidate predictor variables associated with COVID-19 severity (n = 87) in multivariable logistic regression. The predictor variables used in the final model were hypertension, diabetes, sex, age, Ang(1–7), ACE2, CTSB and CTSL