Nucleocapsid 203 mutations enhance SARS-CoV-2 immune evasion

Previous work indicated that the nucleocapsid 203 mutation increase the virulence and transmission of the SARS-CoV-2 Alpha variant. However, Delta later outcompeted Alpha and other lineages, promoting a new wave of infections. Delta also possesses a nucleocapsid 203 mutation, R203M. Large-scale epidemiological analyses suggest a synergistic effect of the 203 mutation and the spike L452R mutation, associated with Delta expansion. Viral competition experiments demonstrate the synergistic effect in fitness and infectivity. More importantly, we found that the combination of R203M and L452R brings in a 3.2-fold decrease in neutralizing titers to the neutralizing serum relative to L452R-only virus. R203M/L452R show an increased fitness after the initiation of global vaccination programmes, possibly associated with the enhanced immune evasion. Another rapidly emerging variant Omicron also bears the 203 mutation. Thus, we proposed that nucleocapsid mutations play an essential role for the rise and predominance of variants in concern.

Effect of Asymptomatic Transmission and Emergence Time on Multi-strain Viral Disease Severity

Background: In a viral epidemic, the emergence of a novel strain with increased transmissibility (larger value of basic reproduction number R 0) sparks the fear that the increase in transmissibility is likely to lead to an increase in disease severity. It is required to investigate if a new, more contagious strain will be necessarily dominant in the population and resulting in more disease severity. Methods: The impact of the asymptomatic transmission and the emergence time of a more transmissible variant of a multi-strain viral disease on the disease prevalence, disease severity, and the dominant variant in an epidemic was investigated by a proposed 2-strain epidemic model. Results: The simulation results showed that considering only R0 , is insufficient to predict the outcome of a new, more contagious strain in the population. A more transmissible strain with a high fraction of asymptomatic cases can substantially reduce the mortality rate. If the emergence time of the new strain is closer to the start of the epidemic, the new, more contagious variant has more chance to win the viral competition and be the dominant strain; otherwise, despite being more contagious, it cannot dominate previous strains. Conclusions: Three factors of R0 , the fraction of asymptomatic transmission, and the emergence time of the new strain are required to correctly determine the prevalence, disease severity, and the winner of the viral competition.

Effect of asymptomatic transmission and emergence time on multi-strain viral disease severity

BackgroundIn a viral epidemic, the emergence of a novel strain with increased transmissibility (larger value of basic reproduction number R0) sparks the fear that the increase in transmissibility is likely to lead to an increase in disease severity. It is required to investigate if a new, more contagious strain will be necessarily dominant in the population and resulting in more disease severity.MethodsThe impact of the asymptomatic transmission and the emergence time of a more transmissible variant of a multi-strain viral disease on the disease prevalence, disease severity, and the dominant variant in an epidemic was investigated by a proposed 2-strain epidemic model, called 2-SEICARD model, that is an extension of the SEIRD model.ResultsThe simulation results showed that considering only R0, is insufficient to predict the outcome of a new, more contagious strain in the population. A more transmissible strain with a high fraction of asymptomatic cases can substantially reduce the mortality rate. If the emergence time of the new strain is closer to the start of the epidemic, the new, more contagious variant has more chance to win the viral competition and be the dominant strain; otherwise, despite being more contagious, it cannot dominate previous strains.ConclusionsThree factors of R0, the fraction of asymptomatic transmission, and the emergence time of the new strain are required to correctly determine the prevalence, disease severity, and the winner of the viral competition.

Estimating Relative Fitness in Viral Competition Experiments

ABSTRACT The relative fitness of viral variants has previously been defined as the slope of the logarithmic ratio of the genotype or phenotype frequencies in time plots of pairwise competition experiments. Developing mathematical models for such experiments by employing the conventional coefficient of selection s, we demonstrate that this logarithmic ratio gives the fitness difference, rather than the relative fitness. This fitness difference remains proportional to the actual replication rate realized in the particular experimental setup and hence cannot be extrapolated to other situations. Conversely, the conventional relative fitness (1 + s) should be more generic. We develop an approach to compute the generic relative fitness in conventional competition experiments. This involves an estimation of the total viral replication during the experiment and requires an estimate of the average lifetime of productively infected cells. The novel approach is illustrated by estimating the relative fitness, i.e., the relative replication rate, of a set of zidovudine-resistant human immunodeficiency virus type 1 variants. A tool for calculating the relative fitness from observed changes in viral load and genotype (or phenotype) frequencies is publically available on the website athttp://www-binf.bio.uu.nl/∼rdb/fitness.html .