Trajectories of COVID-19: A longitudinal analysis of many nations and subnational regions.

The COVID-19 pandemic is the first to be rapidly and sequentially measured by nation-wide PCR community testing for the presence of the viral RNA at a global scale. We take advantage of the novel "natural experiment" where diverse nations and major subnational regions implemented various policies including social distancing and vaccination at different times with different levels of stringency and adherence. Initially, case numbers expand exponentially with doubling times of ~1-2 weeks. In the nations where interventions were not implemented or perhaps lees effectual, case numbers increased exponentially but then stabilized around 102-to-103 new infections (per km2 built-up area per day). Dynamics under effective interventions were perturbed and infections decayed to low levels. They rebounded concomitantly with the lifting of social distancing policies or pharmaceutical efficacy decline, converging on a stable equilibrium setpoint. Here we deploy a mathematical model which captures this V-shape behavior, incorporating a direct measure of intervention efficacy. Importantly, it allows the derivation of a maximal estimate for the basic reproductive number Ro (mean 1.6-1.8). We were able to test this approach by comparing the approximated "herd immunity" to the vaccination coverage observed that corresponded to rapid declines in community infections during 2021. The estimates reported here agree with the observed phenomena. Moreover, the decay (0.4-0.5) and rebound rates (0.2-0.3) were similar throughout the pandemic and among all the nations and regions studied. Finally, a longitudinal analysis comparing multiple national and regional results provides insights on the underlying epidemiology of SARS-CoV-2 and intervention efficacy, as well as evidence for the existence of an endemic steady state of COVID-19.

Moore's Law revisited through Intel chip density.

Gordon Moore famously observed that the number of transistors in state-of-the-art integrated circuits (units per chip) increases exponentially, doubling every 12-24 months. Analysts have debated whether simple exponential growth describes the dynamics of computer processor evolution. We note that the increase encompasses two related phenomena, integration of larger numbers of transistors and transistor miniaturization. Growth in the number of transistors per unit area, or chip density, allows examination of the evolution with a single measure. Density of Intel processors between 1959 and 2013 are consistent with a biphasic sigmoidal curve with characteristic times of 9.5 years. During each stage, transistor density increased at least tenfold within approximately six years, followed by at least three years with negligible growth rates. The six waves of transistor density increase account for and give insight into the underlying processes driving advances in processor manufacturing and point to future limits that might be overcome.

Mathematical modeling of viral kinetics under immune control during primary HIV-1 infection.

Primary human immunodeficiency virus (HIV) infection is characterized by an initial exponential increase of viral load in peripheral blood reaching a peak, followed by a rapid decline to the viral setpoint. Although the target-cell-limited model can account for part of the viral kinetics observed early in infection [Phillips, 1996. Reduction of HIV concentration during acute infection: independence from a specific immune response. Science 271 (5248), 497-499], it frequently predicts highly oscillatory kinetics after peak viremia, which is not typically observed in clinical data. Furthermore, the target-cell-limited model is unable to predict long-term viral kinetics, unless a delayed immune effect is assumed [Stafford et al., 2000. Modeling plasma virus concentration during primary HIV infection. J. Theor. Biol. 203 (3), 285-301]. We show here that extending the target-cell-limited model, by implementing a saturation term for HIV-infected cell loss dependent upon infected cell levels, is able to reproduce the diverse observed viral kinetic patterns without the assumption of a delayed immune response. Our results suggest that the immune response may have significant effect on the control of the virus during primary infection and may support experimental observations that an anti-HIV immune response is already functional during peak viremia.