TY - JOUR
T1 - Incomplete antiviral treatment may induce longer durations of viral shedding during SARS-CoV-2 infection
AU - Kim, Kwang Su
AU - Iwanami, Shoya
AU - Oda, Takafumi
AU - Fujita, Yasuhisa
AU - Kuba, Keiji
AU - Miyazaki, Taiga
AU - Ejima, Keisuke
AU - Iwami, Shingo
N1 - Funding Information:
This study was supported in part by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education 2019R1A6A3A12031316 (to KS Kim); Grants-in-Aid for JSPS Research Fellow 19J12319 (to S Iwanami); Scientific Research (KAKENHI) B 18KT0018 (to S Iwami), 18H01139 (to S Iwami), 16H04845 (to S Iwami), Scientific Research in Innovative Areas 20H05042 (to S Iwami), 19H04839 (to S Iwami), 18H05103 (to S Iwami); AMED CREST 19gm1310002 (to S Iwami); AMED Japan Program for Infectious Diseases Research and Infrastructure, 20wm0325007h0001, 20wm0325004s0201, 20wm0325012s0301, 20wm0325015s0301 (to S Iwami); AMED Research Program on HIV/AIDS 19fk0410023s0101 (to S Iwami); AMED Research Program on Emerging and Re-emerging Infectious Diseases 19fk0108050h0003 (to S Iwami), 19fk0108156h0001 (to S Iwami), 20fk0108140s0801 (to S Iwami) and 20fk0108413s0301 (to S Iwami); AMED Program for Basic and Clinical Research on Hepatitis 19fk0210036h0502 (to S Iwami); AMED Program on the Innovative Development and the Application of New Drugs for Hepatitis B 19fk0310114h0103 (to S Iwami); JST MIRAI (to S Iwami); Moonshot R&D grant Number JPMJMS2021 (to S Iwami) and JPMJMS2025 (to S Iwami); Mitsui Life Social Welfare Foundation (to S Iwami); Shin-Nihon of Advanced Medical Research (to S Iwami); Suzuken Memorial Foundation (to S Iwami); Life Science Foundation of Japan (to S Iwami); SECOM Science and Technology Foundation (to S Iwami); The Japan Prize Foundation (to S Iwami); Daiwa Securities Health Foundation (to S Iwami).
Publisher Copyright:
© 2021 Kim et al.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - The duration of viral shedding is determined by a balance between de novo infection and removal of infected cells. That is, if infection is completely blocked with antiviral drugs (100% inhibition), the duration of viral shedding is minimal and is determined by the length of virus production. However, some mathematical models predict that if infected individuals are treated with antiviral drugs with efficacy below 100%, viral shedding may last longer than without treatment because further de novo infections are driven by entry of the virus into partially protected, uninfected cells at a slower rate. Using a simple mathematical model, we quantified SARS-CoV-2 infection dynamics in non-human primates and characterized the kinetics of viral shedding. We counterintuitively found that treatments initiated early, such as 0.5 d after virus inoculation, with intermediate to relatively high efficacy (30-70% inhibition of virus replication) yield a prolonged duration of viral shedding (by about 6.0 d) compared with no treatment.
AB - The duration of viral shedding is determined by a balance between de novo infection and removal of infected cells. That is, if infection is completely blocked with antiviral drugs (100% inhibition), the duration of viral shedding is minimal and is determined by the length of virus production. However, some mathematical models predict that if infected individuals are treated with antiviral drugs with efficacy below 100%, viral shedding may last longer than without treatment because further de novo infections are driven by entry of the virus into partially protected, uninfected cells at a slower rate. Using a simple mathematical model, we quantified SARS-CoV-2 infection dynamics in non-human primates and characterized the kinetics of viral shedding. We counterintuitively found that treatments initiated early, such as 0.5 d after virus inoculation, with intermediate to relatively high efficacy (30-70% inhibition of virus replication) yield a prolonged duration of viral shedding (by about 6.0 d) compared with no treatment.
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U2 - 10.26508/LSA.202101049
DO - 10.26508/LSA.202101049
M3 - Article
C2 - 34344719
AN - SCOPUS:85112841231
SN - 2575-1077
VL - 4
JO - Life Science Alliance
JF - Life Science Alliance
IS - 10
M1 - e202101049
ER -