The evolution of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths and substantial morbidity worldwide. Intense scientific effort to understand the biology of SARS-CoV-2 has resulted in daunting numbers of genomic sequences. We witnessed evolutionary events that could mostly be inferred indirectly before, such as the emergence of variants with distinct phenotypes, for example transmissibility, severity and immune evasion. This Review explores the mechanisms that generate genetic variation in SARS-CoV-2, underlying the within-host and population-level processes that underpin these events. We examine the selective forces that likely drove the evolution of higher transmissibility and, in some cases, higher severity during the first year of the pandemic and the role of antigenic evolution during the second and third years, together with the implications of immune escape and reinfections, and the increasing evidence for and potential relevance of recombination. In order to understand how major lineages, such as variants of concern (VOCs), are generated, we contrast the evidence for the chronic infection model underlying the emergence of VOCs with the possibility of an animal reservoir playing a role in SARS-CoV-2 evolution, and conclude that the former is more likely. We evaluate uncertainties and outline scenarios for the possible future evolutionary trajectories of SARS-CoV-2.

Optimal vaccination strategies using a distributed model applied to COVID-19.

Optimal distribution of vaccines to achieve high population immunity levels is a desirable aim in infectious disease epidemiology. A distributed optimal control epidemiological model that accounts for vaccination was developed and applied to the case of the COVID-19 pandemic. The model proposed here is nonstandard and takes into account the heterogeneity of the infected sub-population with respect to the time since infection, which is essential in the case of COVID-19. Based on the epidemiological characteristics of COVID-19 we analyze several vaccination scenarios and an optimal vaccination policy. In particular we consider random vaccination over the whole population and the prioritization of age groups such as the elderly and compare the effects with the optimal solution. Numerical results of the model show that random vaccination is efficient in reducing the overall number of infected individuals. Prioritization of the elderly leads to lower mortality though. The optimal strategy in terms of total deaths is early prioritization of those groups having the highest contact rates.

Demographics of COVID-19 hospitalisations and related fatality risk patterns.

The assessment of hospitalisations and intensive care is crucial for planning health care resources needed over the course of the coronavirus disease 2019 (COVID-19) pandemic. Nonetheless, comparative empirical assessments of COVID-19 hospitalisations and related fatality risk patterns on a large scale are lacking. This paper exploits anonymised, individual-level data on SARS-CoV-2 confirmed infections collected and harmonized by the European Centre for Disease Prevention and Control to profile the demographics of COVID-19 hospitalised patients across nine European countries during the first pandemic wave (February - June 2020). We estimate the role of demographic factors for the risk of in-hospital mortality, and present a case study exploring individuals' comorbidities based on a subset of COVID-19 hospitalised patients available from the Dutch health system. We find that hospitalisation rates are highest among individuals with confirmed SARS-CoV-2 infection who are not only older than 70 years, but also 50-69 years. The latter group has a longer median time between COVID-19 symptoms' onset and hospitalisation than those aged 70+ years. Men have higher hospitalisation rates than women at all ages, and particularly above age 50. Consistently, men aged 50-59 years have a probability of hospitalisation almost double than women do. Although the gender imbalance in hospitalisation remains above age 70, the gap between men and women narrows at older ages. Comorbidities play a key role in explaining selection effects of COVID-19 confirmed positive cases requiring hospitalisation. Our study contributes to the evaluation of the COVID-19 burden on the demand of health-care during emergency phases. Assessing intensity and timing dimensions of hospital admissions, our findings allow for a better understanding of COVID-19 severe outcomes. Results point to the need of suitable calibrations of epidemiological projections and (re)planning of health services, enhancing preparedness to deal with infectious disease outbreaks.

Droplets and aerosols: An artificial dichotomy in respiratory virus transmission.

In the medical literature, three mutually non-exclusive modes of pathogen transmission associated with respiratory droplets are usually identified: contact, droplet, and airborne (or aerosol) transmission. The demarcation between droplet and airborne transmission is often based on a cut-off droplet diameter, most commonly 5 µm. We argue here that the infectivity of a droplet, and consequently the transmissivity of the virus, as a function of droplet size is a continuum, depending on numerous factors (gravitational settling rate, transport, and dispersion in a turbulent air jet, viral load and viral shedding, virus inactivation) that cannot be adequately characterized by a single droplet diameter. We propose instead that droplet and aerosol transmission should be replaced by a unique airborne transmission mode, to be distinguished from contact transmission.

On the Transmission Dynamics of SARS-CoV-2 in a Temperate Climate.

An epidemiological model, which describes the transmission dynamics of SARS-CoV-2 under specific consideration of the incubation period including the population with subclinical infections and being infective is presented. The COVID-19 epidemic in Greece was explored through a Monte Carlo uncertainty analysis framework, and the optimal values for the parameters that determined the transmission dynamics could be obtained before, during, and after the interventions to control the epidemic. The dynamic change of the fraction of asymptomatic individuals was shown. The analysis of the modelling results at the intra-annual climatic scale allowed for in depth investigation of the transmission dynamics of SARS-CoV-2 and the significance and relative importance of the model parameters. Moreover, the analysis at this scale incorporated the exploration of the forecast horizon and its variability. Three discrete peaks were found in the transmission rates throughout the investigated period (15 February-15 December 2020). Two of them corresponded to the timing of the spring and autumn epidemic waves while the third one occurred in mid-summer, implying that relaxation of social distancing and increased mobility may have a strong effect on rekindling the epidemic dynamics offsetting positive effects from factors such as decreased household crowding and increased environmental ultraviolet radiation. In addition, the epidemiological state was found to constitute a significant indicator of the forecast reliability horizon, spanning from as low as few days to more than four weeks. Embedding the model in an ensemble framework may extend the predictability horizon. Therefore, it may contribute to the accuracy of health risk assessment and inform public health decision making of more efficient control measures.