The 2019 novel coronavirus (COVID-19) has now escaped China and taken a firm grip on the rest of the world, with Italy in a complete lockdown, most of Europe shuttered and the UK and the US spaffing their response up a wall. A few weeks ago I wrote a short post assessing the case fatality rate of the disease and assessing whether it is a global threat, and I think now is time to write an update on the virus. In this post I will address the mortality rate, some ways of looking at the total disease burden, discuss its infectiousness, and talk about what might be coming if we don’t get a grip on this. In the past few weeks I have been working with Chinese collaborators on this virus so I am going to take the unusual step of referencing some of my meat life work, though as always I won’t name collaborators, so as to avoid their names being associated with a blog that sometimes involves human sacrifice.

As always, what COVID-19 is doing can be understood in terms of infectious disease epidemiology and the mathematics that underlies it, but only to the extent that we have good quality data. Fortunately we now do have some decent data, so we can begin to make some strong judgments – and the conclusions we will draw are not pretty.

How deadly is this disease?

The deadliness of an infectious disease can be assessed in terms of its case fatality ratio (CFR), which is the proportion of affected cases who die. In my last post I estimated the CFR for COVID-19 to be about 0.4% (uncertainty range 0.22 – 1.7%), and suggested it was between 2 and 10 times as deadly as influenza. The official CFR in China has hovered around 2%, but we know that many mild cases were not diagnosed, and the true CFR must be lower. Since then, however, the Diamond Princess cruise ship hove into view, was quarantined off Yokohama, and carefully monitored. This is a very serendipitous event (for those not on the ship, obviously) since it means we have a complete case record – every case on that ship was diagnosed, symptomatic or not. On that ship we saw 700 people infected and 7 deaths, so a CFR of 1%. I used a simple Bayesian method to use that confirmed mortality rate, updated by the deaths in China, to estimate the under reporting rate in China to be at least 50%, work which is currently available as a preprint at the WHO’s COVID-19 preprint archive. I think a decent estimate of the under reporting rate is 90%, indicating that there are 10 times as many cases as are being reported, and the true CFR is therefore 10 times lower. That puts the CFR in China at 0.2%, or probably twice as deadly as the seasonal flu. However, we also have data from South Korea, where an extensive testing regime was put in place, that suggests a CFR more in the range of 1%.

It’s worth noting that the CFR depends on the age distribution of affected people, and the age distribution in the cruise ship was skewed to very old. This suggests that in a younger population the CFR would be lower. There is also likely to be a differential rate of underreporting, with probably a lower percentage of children being reported than elderly people. It is noteworthy that only 1% of confirmed cases in China were children, which is very different to influenza. As quarantine measures get harsher and health systems struggle, it is likely that people will choose to risk not reporting their virus, and this will lead to over estimates of mortality and underestimates of total cases. But it certainly appears this disease is at least twice as dangerous as influenza.

CFRs also seem to be very different in the west, where testing coverage has been poor in some countries. Today California reported 675 cases and 16 deaths, 2.5 times the CFR rate on the Diamond Princess in probably a younger population. Until countries like the US and UK expand their testing, we won’t know exactly how bad it is in those countries but we should expect a large number of infected people to die.

On the internet and in some opinion pieces, and from the mouths of some conservative politicians, you will hear people say that it “only” kills 1% of people and so you don’t need to worry too much. This is highly misleading, because it does not take into account that in a normal year less than 1% of the population dies, and a disease that kills 1% of people will double your nation’s total death rate if it is allowed to spread uncontrolled. It is important to understand what the background risk is before you assess small numbers as “low risk”!

What is the burden of the disease?

The CFR tells you how likely an affected person is to die, but an important question is what is the burden of the disease? Burden means the total number of patients who need to be hospitalized, and the final mortality rate as a proportion of the population. While the CFR tells us what to expect for those infected, estimates of burden tell us what society can expect this disease to do.

First, let us establish a simple baseline: Japan, with 120 million people, experiences 1 million deaths a year. This is the burden of mortality in a peaceful, well-functioning society with a standard pattern of infectious disease and an elderly population. We can apply this approximately to other countries to see what is going on, on the safe assumption that any estimates we get will be conservative estimates because Japan has one of the highest mortality rates in the world[1]. Consider Wuhan, population 12 million. It should expect 100,000 deaths a year, or about 8,000 a month. Over two months it experienced about 3000 COVID-19 deaths, when it should have seen about 15,000 deaths normally. So the virus caused about 20% excess mortality. This is a very large excess mortality. Now consider Italy, which has seen 3500 deaths in about one month. Italy has a population of 60 million so should see 500,000 deaths a year, or about 40,000 a month. So it has seen about 10% excess mortality. However, those 3500 deaths have been clustered in just the Northern region, which likely only has a population similar to Wuhan – so more likely it has seen 40% excess mortality. That is a very high burden, which is reflected in obituaries in the affected towns.

Reports are also beginning to spread on both social media and in the news about the impact on hospitals in Italy and the US. In particular in Northern Italy, doctors are having to make very hard decisions about access to equipment, with new guidance likening the situation to medical decisions made after disasters. Something like 5% of affected people in Wuhan needed to be admitted to intensive care, and it appears that the symptoms of COVID-19 last longer than influenza. It also appears that mortality rates are high, and there are already predictions that Italy will run out of intensive care facilities rapidly. The situation in northern Italy is probably exacerbated by the age of the population and the rapid growth of the disease there, but it shows that there is a lot of potential for this virus to rapidly overwhelm health systems, and when it does you can expect mortality rates to sky-rocket.

This is why the UK government talked about “flattening the curve”, because even if the same total number of people are affected, the more slowly they are affected the less risk that the care system breaks down. This is particularly true in systems like the US, where hospitals maintain lean operating structures, or the UK where the health system has been stripped of all its resources by years of Tory mismanagement.

Who does it affect?

The first Chinese study of the epidemiology of this disease suggested that the mortality rate increases steeply, from 0% in children to 15% in the very elderly. It also suggested that only a very small number of confirmed cases are young people, but this is likely due to underreporting. This excellent medium post uses data from an Italian media report to compare the age distribution of cases in Italy with those in South Korea, and shows that in South Korea 30% of cases were in people aged 20-29, versus just 4% in Italy. This discrepancy arises because South Korea did extensive population-level testing, while Italy is just doing testing in severe cases (or was, at the time the report was written). Most of those young people will experience COVID-19 as a simple influenza-like illness, rather than the devastating respiratory disease that affects elderly people, and if we standardize the Chinese CFR to this Korean population we would likely see it drop from 2% to 1%, as the Koreans are experiencing. This South Korean age distribution contains some important information:

  • The disease does not seem to affect children much, and doesn’t harm them, which is good
  • Young people aged 20-39 are likely to be very efficient carriers and spreaders of the disease
  • Elderly people are at lower risk of getting the disease than younger people but for them it is very dangerous

This makes very clear the importance of social distancing and lockdowns for preventing the spread of the disease. Those young people will be spreading it to each other and their family members, while not feeling that it is very bad. If you saturate that young population with messages that people are overreacting and that there is not a serious risk and that “only” the elderly and the sick will die, you will spread this disease very effectively to their parents and grandparents – who will die.

It’s worth noting that a small proportion of those young people do experience severe symptoms and require hospitalization and ventilation. In health workers in China there was a death rate among health workers of about 0.2%, and we could probably take that as the likely CFR in young people with good access to care. If the disease spreads fast enough and overwhelms health systems, we can expect to see not insignificant mortality in people aged 20-39, as their access to intensive care breaks down. This is especially likely in populations with high prevalence of asthma (Australia) or diabetes (the US and the UK) or smoking (Italy, and some parts of eastern Europe). So it is not at this stage a good idea for young people to be complacent about their own risk, and if you have any sense of social solidarity you should be being very careful about the risk you pose to others.

How fast does it spread?

The speed at which an infectious disease spreads can be summarized by two numbers: the generation time and the basic reproduction number (R0). Generation time is the time it takes for symptoms to appear in a second case after infection by the first case, and the basic reproduction number is the number of additional cases that will be caused by one infection. For influenza the generation time is typically 2-4 days, while for COVID-19 it is probably 4-6 days. The basic reproduction number of influenza is between 1.3 – 1.5, while the initial estimates for COVID-19 were 2.5, meaning that each case of COVID-19 will affect 2.5 people. Unfortunately I think these early estimates were very wrong, and my own research suggests the number is more likely between 4 and 5. This means that each case will infect 4-5 other cases before it resolves. This is a very fast-spreading disease, much more effective at spreading than influenza, and this high R0 explains why it was able to suddenly explode in Italy and the US. A disease with an R0 over 2 is scary and requires special efforts to control.

Those early estimates of R0 at 2 to 2.5 had a significant negative impact on assessment of the global threat of this disease. I believe they led the scientific community to be slightly complacent, and to think that the disease would be relatively easy to contain and would not be as destructive as it has become. In my research our figures for projected infection numbers show clearly that these models with lower R0 simply cannot predict the future trend of the virus – they undershoot it significantly and fit the epidemic curve poorly. Sadly governments are still acting on the basis of these estimates: the UK government’s estimate that the disease will stop spreading once 60% of people are affected is based on an R0 of 2.5, when an R0 of 4 suggests 75% of people need to be infected. An early R0 estimate of 4 would have rung alarm bells throughout the world, and would have been much more consistent with the disaster we saw unfolding in Hubei. Fortunately the Chinese medical establishment were not so complacent, and worked hard to buy the world time to prepare for this virus’s escape. Sadly many western countries did not take advantage of that extra month, and are paying the price now as they see what this disease really is like.

Because this disease is so highly infectious, special measures are needed to contain it. For a mildly dangerous disease with an R0 of 1.3 (like influenza), vaccination of the very vulnerable and sensible social distancing among infected people is sufficient to contain it without major economic disruption. Above 2, however, things get dicey, and at 4 we need to consider major measures – social distancing, canceling mass gatherings, quarantining affected individuals and cities, and travel restrictions. This is everything that China did in the second month of the outbreak once they understood what they were dealing with, and is also the key to South Korea, Japan and Singapore’s success. Because some western governments did not take this seriously, they are now going to have to take extreme measures to stop this.

How many people will be infected?

The total proportion of the population that will be affected is called the final size of the epidemic, and there is an equation linking the final size to the basic reproduction number. This equation tells us that for influenza probably 40% of the population will be affected, but it also tells us that for epidemics with basic reproduction number over 2 basically the entire population will be affected. In the case of Japan that will mean 120 million people affected with a mortality rate of probably 0.4% (assuming the health care system handles such a ridiculous scenario), or about 500,000 deaths – 50% of the total number of deaths that occur in one year. The Great East Japan Earthquake and tsunami killed 16,000 people and was considered a major disaster. It’s also worth considering that those 500,000 deaths would probably occur over 3-4 months, so over the time period they would be equivalent to probably doubling or tripling the normal mortality rate. That is a catastrophe by any measure, and although at the end of the epidemic “only” half a percent of the population will be dead, the entire population will be traumatized by it.

For a virus of this epidemicity with this kind of fatality rate, we need to take extreme measures to control it, and we need to take it very seriously as soon as it arrives in our communities. This virus cannot be contained by business as usual.

Essential supplies ready

What’s going on in Japan?

The number of cases and deaths in Japan remains quite small, and there has been some discussion overseas that Japan’s response has been poor and it is hiding the true extent of the problem. I don’t think this is entirely correct. Japan introduced basic counter-measures early on, when China was struggling and well before other countries, including cancelling events, delaying the start of the school year, introducing screening at airports and testing at designated facilities, working from home and staggering commuter trips to reduce crowding on trains. For example, work events I was planning to attend were cancelled 2-3 weeks ago, and many meetings moved online back then. Japan has a long history of hygiene measures during winter, and influenza strategies are in place at most major companies to reduce infection risk. Most museums, aquariums and shopping malls have always had hand sanitizer at the entrance, and Japan has an excellent network of public toilets that make hand washing easy. Many Japanese have always maintained a practice of hand-washing and gargling upon returning home from any outside trip, and mask wearing is quite common. Japan’s health system also has a fair amount of excess capacity, so it is in a position to handle the initial cases, isolate them and manage them. This has meant that the growth of the epidemic was slow here and well contained, although it was a little out of control in Hokkaido, where the governor declared a state of emergency (now ended). It is true that many cases are not being tested – hospitals do not recommend mild cases to attend for treatment, but to stay home and self isolate, and it is likely that mild cases will not be tested – but this is not a cover-up situation, rather an attempt to ration tests (which are not being fully utilized at the moment). There are not yet reports of emergency rooms or hospitals being overwhelmed, and things are going quite smoothly. I expect at some point the government will need to introduce stricter laws, but because of that early intervention with basic measures the epidemic appears to be under control here.

My self-isolation plan was kind of forced on me at the end of February, because I dislocated my kneecap at kickboxing in a sadly age-related way, will probably require reconstruction surgery, and am spending a lot of time trapped at home as a result. Actually that was the day that everyone else was panic buying toilet paper and so I was stuck at home with a dwindling supply of the stuff until my friends stepped up. I think most people in Japan have reduced their social activities (probably not as much as me!), and are spending less time in gatherings and events (almost of all which are canceled now), and so through that reduction in contacts plus aggressive contact tracing, the disease is largely controlled here.

Is the world over-reacting?

No. You will have heard no doubt various conservatives on Fox news and in some print outlets complaining about how the world has over-reacted and we should all be just going to the pub, perhaps you’ve seen some Twitter bullshit where a MAGA person proudly declares that they ate out in a crowded restaurant and they’ll do whatever they want because Freedumb. Those people are stupid and you shouldn’t trust them. This virus spreads easily and kills easily, and if it gets a stranglehold on your health system it will be an order of magnitude more deadly than it is right now. If you live in a sensible country (i.e. not the UK or the USA) your government will have consulted with experts and developed a plan and you should follow their recommendations and guidelines, because they have a sense of what is coming down the pipeline and what you need to do to stop it. Do the minimum you are asked to do, and perhaps prepare for being asked to do more. Don’t panic buy, but if you feel like strict isolation is coming you should start laying in supplies. Trust your friends and neighbours to help you, and don’t assume your government is bullshitting you (unless you’re in the UK or the USA, obviously). This is serious, and needs to be taken seriously.

When HIV hit the world our need to wear a condom was presented to us as a self-preserving mechanism. If you choose to circumcise your baby boy you’re probably doing so as a service to future him, not to all the women or men he might spread STIs to. But this virus isn’t like HIV. Your responsibility here isn’t to yourself, it’s to the older, frailer and less healthy members of your community who are going to die – and die horribly, I might add, suffocating with a tube in their throat after days of awful, stifled struggle – if this disease is allowed to spread. We all need to work together to protect the more vulnerable members of our community, and if we don’t react now we will lose a lot of the older people we grew up with and love.

So let’s all hunker down and get rid of this virus together!

fn1: This is a weird and counter-intuitive aspect of demography. Japan has the longest life expectancy in the world’s healthiest population, and one of the world’s highest mortality rates. Iraq, in contrast, would see half as many deaths in a normal year (without American, ah, visitors). This is because healthy populations grow old, and then die in huge numbers.