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

• 成果类型: Article
• 署名作者: Iyaniwura, Sarafa A.; Ribeiro, Ruy M.; Zitzmann, Carolin; Phan, Tin; Ke, Ruian; Perelson, Alan S.
• 署名单位: United States Department of Energy (DOE); Los Alamos National Laboratory; Fred Hutchinson Cancer Center
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9961
• DOI: 10.1073/pnas.2406303121
• 发表日期: 2024-11-12
• 关键词: interferon action; virus-infection; mechanism; DYNAMICS; models

摘要

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 similar to 2 h for viral RNA and similar to 3 h for infectious virus. We estimate that adaptive immunity is initiated similar to 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.