Update on 2019_nCoV outbreak part 7

We live in fascinating times. Within a week R_0 has be become a fashionable topic to discuss at cocktail receptions, science has transitioned from old-fashioned hidden peer review to open review on preprint servers and China is doing the largest experiment in infection control ever. And since tonight we have a public health emergency of international concern (PHEIC).

I’m very impressed by the actions in China, so far. It looks as if they very rapidly (within a month) recognized a cluster among patients with severe pneumonia in which no pathogen was detected (which happens in about 50% of these patients). Then, within a month they identified the cause of these infections, sequenced it and found the receptor for the virus, and immediately shared all information.

They also must have realized around that time that they were dealing with something very transmissible, which was subsequently confirmed by the many R_0 estimates. I think most agree that R_0 is somewhere between 2 and 3, but what does that mean for infection control?

R_0 is determined in the very early phase of the epidemic, when all subjects are susceptible to infection and when preventive measures have not been started. In that phase the virus is transmitted in a certain network, in this case a city of 10 Million, in which many contacts occur that could lead to successful transmission. When the outbreak is recognized, many mechanisms start that reduce transmission. In hospitals protective measures are taken and outside hospitals people start changing their behaviour. For instance, they avoid public transport and mass gatherings and stay at home. From then on it is better to name R an effective R value, which is of course less than R_0. Infection control aims to bring the effective R value below 1, and keep it there. The latter is not to be underestimated: if the original behaviour is resumed at a time that the virus is still circulating, the epidemic may rapidly speed up again. As may happen if the virus escapes to another – unprepared – network.

How can we see whether R declines? Just look at the epidemic curve (from which R is derived). As long as the number of newly infected subjects per day increases, R is >1. So, we want to reach the downhill slope of the epidemic curve, as fast as possible.

How to do that? Every epidemic dies out if the number of susceptibles declines. That is when a large part of the population has become immune, either through vaccination, surviving the infection (with immunity), or protective therapy (not really immune, but similar effect). The proportion of the population needed in this category is around 60-70% with this R_0, which is unlikely to happen soon for this virus. This leaves classical measures to reduce transmission with at least 60-70%.

China has the laudable ambition to do this. For that they have quarantined millions, which is a daunting task. Imagine Ursula van der Leyen (chair of the European commission) quaratining London, Paris, Amsterdam and Madrid.

Within the fence almost all transmission must be stopped. How long will this take? Well, if all transmission (100%) is prevented as of tomorrow, new infections will occur for at least a week, due to the incubation period. If interruption is less effective, say 70%, it will take (much) longer. The effectiveness to stop transmission outside hospitals requires isolation of infectious persons during their infectious period, which might start before being symptomatic. So, it may take some time before the outbreak is controlled sufficiently to open the fences without risks of the epidemic starting all over again. Question is how long they can keep the gates closed.

So, let’s carefully follow the epidemic curves, and hope that they are accurate and not compromised by reduced case notification due to shortness in testing capacity or collapses of hospital systems, which may give a false-positive reassurance. If China succeeds in controlling this outbreak, their efforts could be placed next to the Chinese Wall, as another Wonder of the World.

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