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Mathematical modeling explains differential SARS CoV-2 kinetics in lung and nasal passages in remdesivir treated rhesus macaques
Preprint
in English
| bioRxiv
| ID: ppbiorxiv-163550
ABSTRACT
Remdesivir was recently demonstrated to decrease recovery time in hospitalized patients with SARS-CoV-2 infection. In rhesus macaques, early initiation of remdesivir therapy prevented pneumonia and lowered viral loads in the lung, but viral loads increased in the nasal passages five days after therapy. We developed mathematical models to explain these results. We identified that 1) drug potency is slightly higher in nasal passages than in lungs, 2) viral load decrease in lungs relative to nasal passages during therapy because of infection-dependent generation of refractory cells in the lung, 3) incomplete drug potency in the lung that decreases viral loads even slightly may allow substantially less lung damage, and 4) increases in nasal viral load may occur due to a slight blunting of peak viral load and subsequent decrease of the intensity of the innate immune response, as well as a lack of refractory cells. We also hypothesize that direct inoculation of the trachea in rhesus macaques may not recapitulate natural infection as lung damage occurs more abruptly in this model than in human infection. We demonstrate with sensitivity analysis that a drug with higher potency could completely suppress viral replication and lower viral loads abruptly in the nasal passages as well as the lung. One Sentence SummaryWe developed a mathematical model to explain why remdesivir has a greater antiviral effect on SARS CoV-2 in lung versus nasal passages in rhesus macaques.
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Collection:
Preprints
Database:
bioRxiv
Language:
English
Year:
2020
Document type:
Preprint