Quantitative Biology

A compartmental epidemic model is proposed to predict the Covid-19 virus spread. It considers: both detected and undetected infected populations, medical quarantine and social sequestration, release from sequestration, plus possible reinfection. The coefficients in the model are evaluated by fitting to empirical data for eight US states: Arizona, California, Florida, Illinois, Louisiana, New Jersey, New York State, and Texas. Together these states make up 43% of the US population; some of these states appear to have handled their initial outbreaks well, while others appear to be emerging hotspots. The evolution of Covid-19 is fairly similar among the states: variations in contact and recovery rates remain below 5%; however, not surprisingly, variations are larger in death rate, reinfection rate, stay-at-home effect, and release rate from sequestration. The results reveal that outbreaks may have been well underway in several states before first detected and that California might have seen more than one influx of the pandemic. Our projections based on the current situation indicate that Covid-19 will become endemic, spreading for more than two years. Should states fully relax stay-at-home orders, most states may experience a secondary peak in 2021. If lockdowns had been kept in place, the number of Covid-19 deaths so far could have been significantly lower in most states that opened up. Additionally, our model predicts that decreasing contact rate by 10%, or increasing testing by approximately 15%, or doubling lockdown compliance (from the current ∼ 15% to ∼ 30%) will eradicate infections in the state of Texas within a year. Extending our fits for all of the US states, we predict about 11 million total infections (including undetected), 8 million cumulative confirmed cases, and 630,000 cumulative deaths by November 1, 2020.

Following the highly restrictive measures adopted by many countries for combating the current pandemic, the number of individuals infected by SARS-CoV-2 and the associated number of deaths is steadily decreasing. This fact, together with the impossibility of maintaining the lockdown indefinitely, raises the crucial question of whether it is possible to design an exit strategy based on quantitative analysis. Guided by rigorous mathematical results, we show that this is indeed possible: we present a robust numerical algorithm which can compute the cumulative number of deaths that will occur as a result of increasing the number of contacts by a given multiple, using as input only the most reliable of all data available during the lockdown, namely the cumulative number of deaths.

Recent analysis of early COVID-19 data from China showed that the number of confirmed cases followed a subexponential power-law increase, with a growth exponent of around 2.2 [B.\,F.~Maier, D.~Brockmann, {\it Science} {\bf 368}, 742 (2020)]. The power-law behavior was attributed to a combination of effective containment and mitigation measures employed as well as behavioral changes by the population. In this work, we report a random walk Monte Carlo simulation study of proximity-based infection spread. Control interventions such as lockdown measures and mobility restrictions are incorporated in the simulations through a single parameter, the size of each step in the random walk process. The step size l is taken to be a multiple of ⟨r⟩ , which is the average separation between individuals. Three temporal growth regimes (quadratic, intermediate power-law and exponential) are shown to emerge naturally from our simulations. For l=⟨r⟩ , we get intermediate power-law growth exponents that are in general agreement with available data from China. On the other hand, we obtain a quadratic growth for smaller step sizes l≲⟨r⟩/2 , while for large l the growth is found to be exponential. %Together with available data, these results suggest that the early containment of the disease within China was close to optimal. We further performed a comparative case study of early fatality data (under varying levels of lockdown conditions) from three other countries, India, Brazil and South Africa. We show that reasonable agreement with these data can be obtained by incorporating small-world-like connections in our simulations.

A reaction-diffusion model was developed describing the spread of the COVID-19 virus considering the mean daily movement of susceptible, exposed and asymptomatic individuals. The model was calibrated using data on the confirmed infection and death from France as well as their initial spatial distribution. First, the system of partial differential equations is studied, then the basic reproduction number, R0 is derived. Second, numerical simulations, based on a combination of level-set and finite differences, shown the spatial spread of COVID-19 from March 16 to June 16. Finally, scenarios of unlockdown are compared according to variation of distancing, or partially spatial lockdown.

We introduce a deterministic model that partitions the total population into the susceptible, infected, quarantined, and those traced after exposure, the recovered and the deceased. We hypothesize 'accessible population for transmission of the disease' to be a small fraction of the total population, for instance when interventions are in force. This hypothesis, together with the structure of the set of coupled nonlinear ordinary differential equations for the populations, allows us to decouple the equations into just two equations. This further reduces to a logistic type of equation for the total infected population. The equation can be solved analytically and therefore allows for a clear interpretation of the growth and inhibiting factors in terms of the parameters in the full model. The validity of the 'accessible population' hypothesis and the efficacy of the reduced logistic model is demonstrated by the ease of fitting the United Kingdom data for the cumulative infected and daily new infected cases. The model can also be used to forecast further progression of the disease. In an effort to find optimized parameter values compatible with the United Kingdom coronavirus data, we first determine the relative importance of the various transition rates participating in the original model. Using this we show that the original model equations provide a very good fit with the United Kingdom data for the cumulative number of infections and the daily new cases. The fact that the model calculated daily new cases exhibits a turning point, suggests the beginning of a slow-down in the spread of infections. However, since the rate of slowing down beyond the turning point is small, the cumulative number of infections is likely to saturate to about 3.52× 10 5 around late July, provided the lock-down conditions continue to prevail.

In this paper we propose a regime separation for the analysis of Covid19 on Romania combined with mathematical models of SIR and SIRD. The main regimes we study are, the free spread of the virus, the quarantine and partial relaxation and the last one is the relaxation regime. The main model we use is SIR which is a classical model, but because we can not fully trust the numbers of infected or recovered we base our analysis on the number of deceased people which is more reliable. To actually deal with this we introduce a simple modification of the SIR model to account for the deceased separately. This in turn will be our base for fitting the parameters. The estimation of the parameters is done in two steps. The first one consists in training a neural network based on SIR models to detect the regime changes. Once this is done we fit the main parameters of the SIRD model using a grid search. At the end, we make some predictions on what the evolution will be in a timeframe of a month with the fitted parameters.

We present a simple technique to compare the development of the Covid-19 epidemic in different regions, based only on the time series of confirmed cases. Weekly new infections, taken for every day, are interpreted as infection potential of Covid-19. We derive a robust time-varying reproduction rate for the infection potential, including asymptomatic cases, which does not depend on death rate or testing intensity. It requires few assumptions and shows a more plausible time course than official reproduction rates in several countries.

SARS-CoV-2 has disrupted the life of billions of people around the world since the first outbreak was officially declared in China at the beginning of 2020. Yet, important questions such as how deadly it is or its degree of spread within different countries remain unanswered. In this work, we exploit the `universal' growth of the mortality rate with age observed in different countries since the beginning of their respective outbreaks, combined with the results of the antibody prevalence tests in the population of Spain, to unveil both unknowns. We validate these results with an analogous antibody rate survey in the canton of Geneva, Switzerland. We also argue that the official number of deaths over 70 years old is importantly underestimated in most of the countries, and we use the comparison between the official records with the number of deaths mentioning COVID-19 in the death certificates to quantify by how much. Using this information, we estimate the fatality infection ratio (IFR) for the different age segments and the fraction of the population infected in different countries assuming a uniform exposure to the virus in all age segments. We also give estimations for the non-uniform IFR using the sero-epidemiological results of Spain, showing a very similar growth of the fatality ratio with age. Only for Spain, we estimate the probability (if infected) of being identified as a case, being hospitalized or admitted in the intensive care units as function of age. In general, we observe a nearly exponential growth of the fatality ratio with age, which anticipates large differences in total IFR in countries with different demographic distributions, with numbers that range from 1.82\% in Italy, to 0.62\% in China or even 0.14\% in middle Africa.

Some bacteria and archaea possess an adaptive immune system that maintains a memory of past viral infections as DNA elements called spacers, stored in the CRISPR loci of their genomes. This memory is used to mount targeted responses against threats. However, cross-reactivity of CRISPR targeting mechanisms suggests that incorporation of foreign spacers can also lead to autoimmunity. We show that balancing antiviral defense against autoimmunity predicts a scaling law relating spacer length and CRISPR repertoire size. By analyzing a database of microbial CRISPR-Cas systems, we find that the predicted scaling law is realized empirically across prokaryotes, and arises through the proportionate use of different CRISPR types by species differing in the size of immune memory. In contrast, strains with nonfunctional CRISPR loci do not show this scaling. We also demonstrate that simple population-level selection mechanisms can generate the scaling, along with observed variations between strains of a given species.

Analysing and understanding the transmission and evolution of the COVID-19 pandemic is mandatory to be able to design the best social and medical policies, foresee their outcomes and deal with all the subsequent socio-economic effects. We address this important problem from a computational and machine learning perspective. More specifically, we want to statistically estimate all the relevant parameters for the new coronavirus COVID-19, such as the reproduction number, fatality rate or length of infectiousness period, based on Romanian patients, as well as be able to predict future outcomes. This endeavor is important, since it is well known that these factors vary across the globe, and might be dependent on many causes, including social, medical, age and genetic factors. We use a recently published improved version of SEIR, which is the classic, established model for infectious diseases. We want to infer all the parameters of the model, which govern the evolution of the pandemic in Romania, based on the only reliable, true measurement, which is the number of deaths. Once the model parameters are estimated, we are able to predict all the other relevant measures, such as the number of exposed and infectious people. To this end, we propose a self-supervised approach to train a deep convolutional network to guess the correct set of Modified-SEIR model parameters, given the observed number of daily fatalities. Then, we refine the solution with a stochastic coordinate descent approach. We compare our deep learning optimization scheme with the classic grid search approach and show great improvement in both computational time and prediction accuracy. We find an optimistic result in the case fatality rate for Romania which may be around 0.3% and we also demonstrate that our model is able to correctly predict the number of daily fatalities for up to three weeks in the future.