Wednesday, April 08, 2020

CDC EID Journal: High Contagiousness & Rapid Spread of SARS-CoV-2


R0  (pronounced R-naught) or
Basic Reproduction Number

#15,181

The yardstick by which disease transmissibility is measured is its R0 (pronounced R-naught) or Basic Reproductive Number. Essentially, the number of new cases in a susceptible population likely to arise from a single infection.
In the simplest of terms, with an R0  below 1.0, a virus (as an outbreak) begins to sputter and dies out. Above 1.0, and an outbreak can have `legs’.
Calculating the R0 is notoriously difficult, particularly since much hinges upon the existence and subtle differences between viral strains, the accuracy of surveillance and reporting, `seasonality’, and individual host responses to the virus (i.e. number of `super spreaders’).
Perhaps most importantly, the R0  can also be changed by the actions we take as a society to prevent the spread of the virus. Interventions, like social distancing, handwashing, isolating the sick, and even quarantines can reduce a sky-high R0  - at least for some diseases - to something far more manageable.  
We are seeing evidence of that in Italy, China, and a number of other countries which have imposed strong mitigation measures against COVID-19.  A result that, frankly, three months ago few would have predicted. 

Early in China's outbreak, we saw a number of attempts to quantify the R0 of the novel coronavirus (see here,  here, here, and here).  Most put that number between 2.5 and 4.0, all considerably higher than seasonal influenza. 
Yesterday the CDC's EID Journal published a new analysis, from scientists at Los Alamos, which calculates the early R0 in Wuhan, China at an even higher rate ( 5.7 (95% CI 3.8–8.9)) than previously estimated.
Despite these lofty pre-mitigation estimates, the authors point out that the `. . .  spread of the virus can be contained with early and appropriate measures'.

I've only reproduced the abstract and the discussion below. Follow the link to read the study in its entirety.

Volume 26, Number 7—July 2020
Research
High Contagiousness and Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2

Steven Sanche1, Yen Ting Lin1, Chonggang Xu, Ethan Romero-Severson, Nick Hengartner, and Ruian Ke
Author affiliations: Los Alamos National Laboratory, Los Alamos, New Mexico, USA
Abstract
Severe acute respiratory syndrome coronavirus 2 is the causative agent of the 2019 novel coronavirus disease pandemic. Initial estimates of the early dynamics of the outbreak in Wuhan, China, suggested a doubling time of the number of infected persons of 6–7 days and a basic reproductive number (R0) of 2.2–2.7. 
We collected extensive individual case reports across China and estimated key epidemiologic parameters, including the incubation period. We then designed 2 mathematical modeling approaches to infer the outbreak dynamics in Wuhan by using high-resolution domestic travel and infection data. 
Results show that the doubling time early in the epidemic in Wuhan was 2.3–3.3 days. Assuming a serial interval of 6–9 days, we calculated a median R0  value of 5.7 (95% CI 3.8–8.9). We further show that active surveillance, contact tracing, quarantine, and early strong social distancing efforts are needed to stop transmission of the virus.
(SNIP)
Discussion
In this study, we estimated several basic epidemiologic parameters, including the incubation period (4.2 days), a time dependent duration from symptom onset to hospitalization (changing from 5.5 days in early January to 1.5 days in late January outside Hubei Province), and the time from symptom onset to death (16.1 days).
By using 2 distinct approaches, we estimated the growth rate of the early outbreak in Wuhan to be 0.21–0.30 per day (a doubling time of 2.3–3.3 days), suggesting a much faster rate of spread than initially measured. This finding would have important implications for forecasting epidemic trajectories and the effect on healthcare systems as well as for evaluating the effectiveness of intervention strategies.
We found R0  is likely to be 5.7 given our current state of knowledge, with a broad 95% CI (3.8–8.9). Among many factors, the lack of awareness of this new pathogen and the Lunar New Year travel and gathering in early and mid-January 2020 might or might not play a role in the high R0. A recent study based on structural analysis of the virus particles suggests SARS-CoV-2 has a much higher affinity to the receptor needed for cell entry than the 2003 SARS virus (21), providing a molecular basis for the high infectiousness of SARS-CoV-2.
How contagious SARS-CoV-2 is in other countries remains to be seen. Given the rapid rate of spread as seen in current outbreaks in Europe, we need to be aware of the difficulty of controlling SARS-CoV-2 once it establishes sustained human-to-human transmission in a new population (20). 
Our results suggest that a combination of control measures, including early and active surveillance, quarantine, and especially strong social distancing efforts, are needed to slow down or stop the spread of the virus.
If these measures are not implemented early and strongly, the virus has the potential to spread rapidly and infect a large fraction of the population, overwhelming healthcare systems. Fortunately, the decline in newly confirmed cases in China and South Korea in March 2020 and the stably low incidences in Taiwan, Hong Kong, and Singapore strongly suggest that the spread of the virus can be contained with early and appropriate measures. 
Dr. Sanche is a postdoctoral research associate at Los Alamos National Laboratory, Los Alamos, New Mexico, USA. His primary research interest lies in complex disease dynamics inferred from data science and mathematical modeling. Dr. Lin is also a postdoctoral research associate at Los Alamos National Laboratory. His primary research interest lies in applied stochastic processes, biological physics, statistical inference, and computational system biology.