Population Dynamics and Structural Effects at Short and Long Range Support the Hypothesis of the Selective Advantage of the G614 SARS-CoV-2 Spike Variant.

SARS-CoV-2 epidemics quickly propagated worldwide, sorting virus genomic variants in newly established propagules of infections. Stochasticity in transmission within and between countries or an actual selective advantage could explain the global high frequency reached by some genomic variants. Using statistical analyses, demographic reconstructions, and molecular dynamics simulations, we show that the globally invasive G614 spike variant 1) underwent a significant demographic expansion in most countries explained neither by stochastic effects nor by overrepresentation in clinical samples, 2) increases the spike S1/S2 furin-like site conformational plasticity (short-range effect), and 3) modifies the internal motion of the receptor-binding domain affecting its cross-connection with other functional domains (long-range effect). Our results support the hypothesis of a selective advantage at the basis of the spread of the G614 variant, which we suggest may be due to structural modification of the spike protein at the S1/S2 proteolytic site, and provide structural information to guide the design of variant-specific drugs.

The impact of non-pharmaceutical interventions on COVID-19 epidemic growth in the 37 OECD member states.

We estimated the impact of a comprehensive set of non-pharmeceutical interventions on the COVID-19 epidemic growth rate across the 37 member states of the Organisation for Economic Co-operation and Development during the early phase of the COVID-19 pandemic and between October and December 2020. For this task, we conducted a data-driven, longitudinal analysis using a multilevel modelling approach with both maximum likelihood and Bayesian estimation. We found that during the early phase of the epidemic: implementing restrictions on gatherings of more than 100 people, between 11 and 100 people, and 10 people or less was associated with a respective average reduction of 2.58%, 2.78% and 2.81% in the daily growth rate in weekly confirmed cases; requiring closing for some sectors or for all but essential workplaces with an average reduction of 1.51% and 1.78%; requiring closing of some school levels or all school levels with an average reduction of 1.12% or 1.65%; recommending mask wearing with an average reduction of 0.45%, requiring mask wearing country-wide in specific public spaces or in specific geographical areas within the country with an average reduction of 0.44%, requiring mask-wearing country-wide in all public places or all public places where social distancing is not possible with an average reduction of 0.96%; and number of tests per thousand population with an average reduction of 0.02% per unit increase. Between October and December 2020 work closing requirements and testing policy were significant predictors of the epidemic growth rate. These findings provide evidence to support policy decision-making regarding which NPIs to implement to control the spread of the COVID-19 pandemic.

Effectiveness of the measures to flatten the epidemic curve of COVID-19. The case of Spain.

After the cases of COVID-19 skyrocketed, showing that it was no longer possible to contain the spread of the disease, the governments of many countries launched mitigation strategies, trying to slow the spread of the epidemic and flatten its curve. The Spanish Government adopted physical distancing measures on March 14; 13 days after the epidemic outbreak started its exponential growth. Our objective in this paper was to evaluate ex-ante (before the flattening of the curve) the effectiveness of the measures adopted by the Spanish Government to mitigate the COVID-19 epidemic. Our hypothesis was that the behavior of the epidemic curve is very similar in all countries. We employed a time series design, using information from January 17 to April 5, 2020 on the new daily COVID-19 cases from Spain, China and Italy. We specified two generalized linear mixed models (GLMM) with variable response from the Gaussian family (i.e. linear mixed models): one to explain the shape of the epidemic curve of accumulated cases and the other to estimate the effect of the intervention. Just one day after implementing the measures, the variation rate of accumulated cases decreased daily, on average, by 3.059 percentage points, (95% credibility interval: -5.371, -0.879). This reduction will be greater as time passes. The reduction in the variation rate of the accumulated cases, on the last day for which we have data, has reached 5.11 percentage points. The measures taken by the Spanish Government on March 14, 2020 to mitigate the epidemic curve of COVID-19 managed to flatten the curve and although they have not (yet) managed to enter the decrease phase, they are on the way to do so.