Fig. 4

Schematic of the mechanistic model. a Illustration of the components of the model. The infection is triggered by an initial inoculum of virus in the upper respiratory tract. The virus invades susceptible cells (S): once cells are infected (I) they can produce more of the virus (V). In this manner, the infection grows exponentially. The presence of infectious cells triggers the immune response. In the model, we capture this using an early immune response and a late immune response (A). Activated by a high density of infected cells, the effect of the early immune response is to reduce susceptibility of cells to the virus, thereby slowing the rate of growth of the infection. The late immune response, which requires a maturation phase before becoming effective, reduces the infectious cell reservoir, eventually resolving the infection. These two mechanisms represent a simplification of a much broader response, involving innate and adaptive mechanisms. The early response, the activation of which coincides with symptom onset, is more representative of the innate immune response, whilst the late response is more representative of the adaptive response. However, we do not attempt to fully distinguish between innate and adaptive responses in this model, due to their complex interplay. b Linking the model’s mechanisms to the observed viral load dynamics. Prior to the activation of the immune responses, viral load grows exponentially. Activation of the early immune response, which causes febrile symptoms, slows the growth rate. After a maturation phase, the late immune response starts clearing the infectious cells, leading to a decline in the circulating virus. Eventually, the infection becomes undetectable when the viral load passes below the limit of detection (LOD)