Plasma SARS‐CoV‐2 RNA elimination and RAGE kinetics distinguish COVID‐19 severity

OBJECTIVES: Identifying biomarkers causing differential SARS‐CoV‐2 infection kinetics associated with severe COVID‐19 is fundamental for effective diagnostics and therapeutic planning. METHODS: In this work, we applied mathematical modelling to investigate the relationships between patient characteristics, plasma SARS‐CoV‐2 RNA dynamics and COVID‐19 severity. Using a straightforward mathematical model of within‐host viral kinetics, we estimated key model parameters from serial plasma viral RNA (vRNA) samples from 256 hospitalised COVID‐19(+) patients. RESULTS: Our model predicted that clearance rates distinguish key differences in plasma vRNA kinetics and severe COVID‐19. Moreover, our analyses revealed a strong correlation between plasma vRNA kinetics and plasma receptor for advanced glycation end products (RAGE) concentrations (a plasma biomarker of lung damage), collected in parallel to plasma vRNA from patients in our cohort, suggesting that RAGE can substitute for viral plasma shedding dynamics to prospectively classify seriously ill patients. CONCLUSION: Overall, our study identifies factors of COVID‐19 severity, supports interventions to accelerate viral clearance and underlines the importance of mathematical modelling to better understand COVID‐19.