Highly-transmissible Variants of SARS-CoV-2 May Be More Susceptible to Drug Therapy Than Wild Type Strains
Verena Schöning, Charlotte Kern, Carlos Chaccour, Felix Hammann
doi:10.21203/rs.3.rs-379291/v1
As of March 2021, no antiviral drug regimen has proved effective against SARS-CoV-2 infection. With the pandemic showing no signs of slowing down, and vaccine campaigns only starting to be rolled out, we appear to have few options other than non-pharmacological measures. Emerging Variants of Concern (VOCs), e.g. B1.1.7, B.1.351, and B.1.1.248, however, are characterized by higher transmissibility (R0). Here we model and simulate the effect of altered R0 on viral load profiles, and its impact on antiviral therapy. As a hypothetical case study, we simulated treatment with ivermectin 600µg/kg for 3 days initiated at different time points around the infection. Simulated mutations range from 1.25 to 2-fold greater infectivity, but also include putative co-adapted variants with lower transmissibility (0.75-fold). Antiviral efficacy was correlated with R0, making highly transmissible VOCs more sensitive to antiviral therapy. Viral exposure was reduced by 42% compared to 22% in wild type if treatment was started on inoculation. Less transmissible variants appear less susceptible. Our findings suggest there may be a role for pre-or post-exposure prophylactic antiviral treatment in areas with presence of highly transmissible variants. Furthermore, clinical trials with borderline efficacious results should consider identifying VOCs and examine their impact in post-hoc analysis.
Author contributions VS: formal analysis, investigation, methodology, software, visualisation, writing -review & editing; CK: methodology, software, writing -review & editing; CC: validation, funding acquisition, writing -review & editing; FH: conceptualisation, formal analysis, funding acquisition, methodology, software, supervision, validation, visualisation, writing -original draft, writing -review & editing. All authors contributed to the final version.
Additional Information
Competing interests The author(s) declare no competing interests. above the serological positivity threshold (b). Black: wild type, blue: less transmissible, orange to red: highly transmissible.
Supplementary Files This is a list of supplementary les associated with this preprint. Click to download. 20210330Sars2variantssupplements.pdf
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' <jats:p>As of March 2021, no antiviral drug regimen has proved effective against '
'SARS-CoV-2 infection. With the pandemic showing no signs of slowing down, and vaccine '
'campaigns only starting to be rolled out, we appear to have few options other than '
'non-pharmacological measures. Emerging Variants of Concern (VOCs), e.g. B1.1.7, B.1.351, and '
'B.1.1.248, however, are characterized by higher transmissibility (R0). Here we model and '
'simulate the effect of altered R0 on viral load profiles, and its impact on antiviral '
'therapy. As a hypothetical case study, we simulated treatment with ivermectin 600µg/kg for 3 '
'days initiated at different time points around the infection. Simulated mutations range from '
'1.25 to 2-fold greater infectivity, but also include putative co-adapted variants with lower '
'transmissibility (0.75-fold).Antiviral efficacy was correlated with R0, making highly '
'transmissible VOCs more sensitive to antiviral therapy. Viral exposure was reduced by 42% '
'compared to 22% in wild type if treatment was started on inoculation. Less transmissible '
'variants appear less susceptible.Our findings suggest there may be a role for pre- or '
'post-exposure prophylactic antiviral treatment in areas with presence of highly transmissible '
'variants. Furthermore, clinical trials with borderline efficacious results should consider '
'identifying VOCs and examine their impact in post-hoc analysis.</jats:p>',
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