Assessment of risks associated with SARS-CoV-2 experimental human infection studies

Controlled human infection (CHI) models for the novel coronavirus (SARS-CoV-2) have been proposed as a tool to accelerate the development of vaccines and drugs. Such models carry inherent risks. Participants may develop severe disease or complications after deliberate infection. Prolonged isolation may negatively impact their wellbeing. Through secondary infection of study personnel or participant household contacts, the experimental virus strain may cause a community outbreak. We identified risks associated with such a SARS-CoV-2 CHI model and assessed their likelihood and impact and propose strategies that mitigate these risks. In this report, we show that risks can be minimized with proper risk mitigation strategies; the residual risk however should be weighed carefully against the scientific and social values of such a CHI model.

Monocytes, B-cells and dendritic cells during rhinovirus-induced asthma exacerbation

Aim. In this study we aimed to investigate circulating blood cells during experimental virus-induced asthma exacerbation vs baseline.Materials and methods. Rhinovirus 16 (RV16) experimental infections were induced in RV16-seronegative moderate and mild atopic asthmatic and healthy non-atopic subjects. PBMC from 8 mild, 12 moderate asthmatics and 6 normal subjects obtained at baseline (14 day) and at day 4 after infection with RV16 were analyzed by flow cytometry. B-cells were identified as CD19+. Monocytes were identified as MHC II, CD14high cells. The MHC II, CD14neg-low cells were further classified by CD123 and CD11c expression into myeloid DC (CD11chigh, mDC), plasmacytoid DC (CD123+, pDC).Results. There were no differences at baseline in frequencies of blood monocytes, mDC and pDC in asthmatic compared to normal subjects, but we found increased amount of B-cells in asthma group (p < 0.05). At day 4 after RV16 infection we found decreased percentages of pDC in both moderate and mild asthmatics (p < 0.05) compared to baseline.Conclusion. These data suggest an increased migratory potential of circulating pDCs during virus-induced asthma exacerbation. In patients with asthma pDCs could be recruited to the airways. It is possible that the distinct subsets of DCs may be recruited at different time points to the effector sites of allergic inflammation.

Landscapes

This chapter begins by discussing fitness landscape, an idea first introduced by evolutionary geneticist Sewall Wright and later extended by several other authors. The fitness landscape is defined in terms of some particular traits that are implicit in the virus particle phenotype and are usually described in terms of replication rate or infectivity. The landscape appears in most textbook plots as a multi-peaked surface. Local maxima represent optimal fitness values, which can be reached through mutation from a subset of lower-fitness neighbors. Given an initial condition defined by a quasi-species distribution localized somewhere in the sequence space, the population will evolve by exploring nearest positions through mutation. The remainder of the chapter deals with symmetric competition, epistasis in RNA viruses, experimental virus landscapes, the survival of the flattest effect, and virus robustness.

Optimal Perturbations of Systems with Delayed Argument for Control of Dynamics of Infectious Diseases Based on Multicomponent Actions

In this paper, we apply optimal perturbations to control mathematical models of infectious diseases expressed as systems of nonlinear differential equations with delayed argument. We develop the method for calculation of perturbations of the initial state of a dynamical system with delayed argument producing maximal amplification in the given local norm taking into account weights of perturbation components. For the model of experimental virus infection, we construct optimal perturbation for two types of stationary states, with low or high virus load, corresponding to different variants of chronic virus infection flow.