Timing of antiviral treatment initiation is critical to reduce SARS-Cov-2 viral load

Abstract

word count: 100/100) 38We modeled the viral dynamics of 13 untreated patients infected with SARS-CoV-2 to infer 39 viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak 40 viral load by more than 2 logs, drug efficacy needs to be greater than 80% if treatment is 41 administered after symptom onset; an efficacy of 50% could be sufficient if treatment is 42 initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, 43 current investigated drugs may be in a range of 20-70% efficacy. They may help control virus 44 if administered very early, but may not have a major effect in severe patients. 45 46 All rights reserved. No reuse allowed without permission.was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data

“…It could be argued that the timing of antiviral treatment initiation might be critical in reducing SARS-Cov-2 viral load 20. In the recent lopinavir-ritonavir trial, a post hoc subgroup analysis suggested that lopinavir-ritonavir might have a clinical benefit when started earlier than 12 days after symptom onset 21.…”

Kinetics of SARS-CoV-2 infection in the human upper and lower respiratory tracts and their relationship with infectiousness

“…Dynamics of early infection. As in previous work (33,35), we first constructed a target cell limited (TCL) model (see Methods) to quantify the early dynamics of SARS-CoV-2 infection in both the URT and the LRT. We used this model to estimate key parameters, such as the time to peak viremia and the within-host basic reproductive number (R0) and their relationships with the time from infection to symptom onset, i.e.…”

“…(5). Because we used the known infection dates, we could estimate the initial dynamics more carefully than previous studies (32)(33)(34)(35)(36). In particular, we found infected individuals with a longer incubation period had lower rates of viral growth, and higher potential for presymptomatic transmission.…”

“…Mathematical modeling plays a crucial role in understanding the pathogenesis of viral diseases and in the development of effective therapeutics and treatment strategies for viruses such as HIV, hepatitis C, influenza, Zika and Ebola (26)(27)(28)(29)(30)(31). Mathematical modeling has been applied, by us and others (32)(33)(34)(35)(36), to understand SARS-CoV-2 infection in hospitalized patients and the potential impact of therapy. However, these studies modeled a single physiological compartment even though SARS-CoV-2 infects both the URT and the LRT and there were large uncertainties in the parameter estimates because the patient infection dates were unknown.…”

A pharmacological perspective of chloroquine in SARS-CoV-2 infection: An old drug for the fight against a new coronavirus?

“…In general, the results so far obtained can be explained by recent calculations taking into account the pharmacokinetics of CQ/HCQ. Taking into account the mathematical model developed by Gonçalves et al [104] , recent pharmacokinetic analyses [105] and some immune-modulating properties of the drug [106] , Savarino and Tarek calculated that CQ/HCQ may have a limited impact on viral clearance, being evident only within a narrow window of tissue concentrations immediately below those causing toxicity [107] . The results of this modelling study also highlight a problem underlying many of the aforementioned clinical studies, which were conducted in patients already hospitalised: an antiviral effect of HCQ is to be expected when the drug is administered immediately early after diagnosis, before patients are hospitalised.…”