The kinetics of SARS-CoV-2 infection based on a human challenge study.

Publication date: Nov 12, 2024

Studying the early events that occur after viral infection in humans is difficult unless one intentionally infects volunteers in a human challenge study. Here, we use data about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in such a study in combination with mathematical modeling to gain insights into the relationship between the amount of virus in the upper respiratory tract and the immune response it generates. We propose a set of dynamic models of increasing complexity to dissect the roles of target cell limitation, innate immunity, and adaptive immunity in determining the observed viral kinetics. We introduce an approach for modeling the effect of humoral immunity that describes a decline in infectious virus after immune activation. We fit our models to viral load and infectious titer data from all the untreated infected participants in the study simultaneously. We found that a power-law with a power h < 1 describes the relationship between infectious virus and viral load. Viral replication at the early stage of infection is rapid, with a doubling time of ~2 h for viral RNA and ~3 h for infectious virus. We estimate that adaptive immunity is initiated ~7 to 10 d postinfection and appears to contribute to a multiphasic viral decline experienced by some participants; the viral rebound experienced by other participants is consistent with a decline in the interferon response. Altogether, we quantified the kinetics of SARS-CoV-2 infection, shedding light on the early dynamics of the virus and the potential role of innate and adaptive immunity in promoting viral decline during infection.

Concepts Keywords
Coronavirus Adaptive Immunity
Mathematical Antibodies, Viral
Postinfection Antibodies, Viral
Severe COVID-19
Volunteers human challenge study
Humans
Immunity, Humoral
Immunity, Innate
infectious disease modeling
Kinetics
mathematical modeling
RNA, Viral
RNA, Viral
SARS-CoV-2
SARS-CoV-2
viral dynamics
Viral Load
Virus Replication

Semantics

Type Source Name
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection
disease MESH viral infection
disease IDO immune response
disease IDO cell
disease MESH viral load
pathway KEGG Viral replication
disease MESH infection
disease IDO role
disease MESH infectious disease
pathway REACTOME Infectious disease
disease IDO replication

Original Article

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