Week 12 - What will happen next? Super Spreader Events (SSEs)

Most previous blogs have largely relied on published work, but in order to cover

the immense number of papers on Covid-19 this blog includes papers that have

not been accepted for publication but are sponsored by Wellcome Open research

 

SSE’s can either apply to a cataclysmic event, with several people involved, or to an individual who has infected several people. The old idea, that single people passed infection on to single people, went out some time ago. We now have the 20/80 model, where 20% of the population are potential superspreaders, and they spread the virus to people who were near them at the time of the SSE. So, an SSE at a religious service will affect individuals who were at the same service, at a football match the new cases will be among those who were at that match, and so on. The new cases will be just as infectious as anyone else who is positive for the virus.

 

A recent example of an SSE

When 61 people met for a choir practice in a church in Washington, on 10 March, everything seemed normal. For 2.5 hours the choristers sang, snacked on cookies and oranges, and sang some more. But one of them had been suffering for 3 days from what felt like a cold but turned out to be COVID-19. In the following weeks, 53 choir members got sick, three were hospitalized, and two died. The extra cases here will be others who were at that concert. Clusters have also occurred aboard ships and at nursing homes, meatpacking plants, ski resorts, churches, restaurants, hospitals, and prisons. Sometimes a single person infects dozens of people, whereas other clusters unfold across several generations of spread, in multiple venues.

Where do important SSEs occur?

 

An article by John Kay (April 29 @ Quillette com) investigates 54 SSEs in 28 countries. The largest group of 19 consist of parties at which alcohol was served; a group of 9 were religious services where people sing (many religions, a Christian example being an open door prayer meeting in Mulhouse, France causing 2,500 cases); a group of 6 were face to face business meetings;  a group of 5 were at funerals; while another group of 5 were in European ski resorts. An example from West Australia of a meeting where singing occurred is interesting because the organisers had spaced the singers out. If they had been merely chatting, instead of singing, no one might have become sick; A group of 4 SSEs were at meat processing plants, where the high levels of noise from machinery oblige people to shout to make themselves heard.  A final group of 3 SSEs were at mass sports spectacles, where fans scatter saliva over others as excitement mounts. These SSEs happen in a wide range of environments, wherever people are close to each others faces, laughing, shouting, cheering, sobbing , singing, greeting or praying.

 

An example from a small town with an SSE, using a full range of measures, with the related SARS virus.

 

A paper by Streeck ea in a small German town that had recently experienced ‘carnival festivities’ accompanied by strict social distancing measures nevertheless experienced an SSE which

 caused a transient wave of infections. Of the 919 individuals surveyed 15.5% (CI: 12.3 -19.0%) were infected, 5 times higher

than the number of officially reported cases for this community (3.1%).  22.2% of all infected individuals were asymptomatic. Of the 7 deaths from the virus the infection fatality ratio (IFR) was 0.36% (CI 0.29-0.45%). (The IFR takes into account all individuals infected, not just those with a severe infection, as the case fatality rate (CFR) does). Given the high contagiousness of SARS-CoV-2, one would expect high rates of transmission. There was a relatively moderate increase of the secondary infection risk which depended size of each family (increase from 15.5% (baseline risk) to 43.6% for 2 people, 35.5% for 3 people, and 18.3% for 4 people, (p<0.001). In a 2 person unit where only one is without the virus, they can only relate to the virus positive person. This closeness is associated with a much greater risk of becoming infected. If in the larger group there is less closeness, this is associated with only a small increase in risk. The unexpectedly low risk has important implications for measures to contain the virus pandemic.

Restricting gatherings where superspreading is likely to occur will have a major impact on transmission.  However, superspreading events are poorly understood and difficult to study. In the Washington church above, other choristers will remember the person who turned out to be virus positive, and may therefore associate the fact that several others are now also positive. This may lead to distress and fear of stigma in those who are newly positive.

Most of the discussion around the spread of SARS-CoV-2 has concentrated on the reproduction number Ro, without social distancing, this reproduction number (R) may be about 3. But in real life, some people infect many others and others don’t spread the disease at all. The value of R is of course an average, but for the individuals who contribute to the average, the most common number may be zero.

 

 

Characteristics of individual patients who superspread

Some people shed far more virus, and for a longer period of time than others, perhaps because of differences in their immune system or the distribution of virus receptors in their body. A study of healthy people in 2019 showed some breathe out many more particles than others when they talk (the volume at which they speak explained some of the variation). Singing may release more virus than speaking, which could help explain the choir outbreaks. People’s behaviour also plays a role. Having many social contacts or not washing your hands makes you more likely to pass on the virus.

We are closest to understanding where COVID-19 clusters are likely to occur. There is a much higher risk in enclosed spaces than outside. A Japanese study found that the risk of infection indoors is almost 19 times higher than outdoors. It has been noted that although ‘Zumba classes’ have been connected to outbreaks, Pilates classes (which are not as intense) have not. Maybe slow, gentle breathing is not a risk factor, but heavy, deep, or rapid breathing and shouting is.

A recent study by Braun, Loyal et al. has demonstrated the presence of S-reactive CD4+ T cells in 83% of COVID-19 patients. This study is the first to directly measure reactive T cell responses providing critical tools for large scale testing.  T cells critically indicate that the virus has caused a therapeutic response in the person exposed to the virus.

How should we measure ‘k’, the likelihood of an SSE?

Most people do not transmit, and that’s why in addition to R, scientists use a value called the dispersion factor (k), which describes how much a disease clusters. The lower k is, the more transmission comes from a small number of people. Adam Kucharski and others have estimated that k for COVID-19 is as low as 0.1. and concluded that probably about 10% of the population of covid-19 positive lead to 80% of the spread.

That could explain some puzzling aspects of this pandemic, including why the virus did not take off around the world sooner after it emerged in China, and why some very early cases elsewhere - such as one in France in late December 2019, apparently failed to ignite a wider outbreak. If k is really 0.1, Kucharski argues that most chains of infection die out by themselves and SARS-CoV-2 needs to be introduced undetected into a new country at least four times to have an even chance of establishing itself. If the Chinese epidemic was a big fire that sent sparks flying around the world, most of the sparks simply fizzled out.

Timing also plays a role. Emerging evidence suggests COVID-19 patients are most infectious for a short period of time. Entering a high-risk setting in that period may touch off a superspreading event, Kucharski and others say “two days later, that person could behave in the same way and you wouldn’t see the same outcome”.

Countries that have beaten back the virus to low levels need to be especially vigilant for superspreading events, because they can easily undo hard-won gains. After South Korea relaxed social distancing rules in early May, a man who later tested positive for COVID-19 visited several clubs in Seoul; public health officials scrambled to identify thousands of potential contacts and have already found 170 new cases. Privacy is another concern. Untangling the links between patients can reveal who was at the origin of a cluster or expose information about people’s private lives. Some clubs involved in the new South Korean cluster were gay venues, which resulted in an antigay backlash and made contact tracing harder.

If public health workers knew where clusters are likely to happen, they could try to prevent them and avoid shutting down broad swaths of society, Kucharski and others say lockdowns are an incredibly blunt tool, you’re basically saying: “we don’t know enough about where transmission is happening to be able to target it, so we’re just going to target all of it”.

But studying large COVID-19 clusters is harder than it seems. Many countries have not collected the kind of detailed contact tracing data needed. And the shutdowns have been so effective that they also robbed researchers of a chance to study superspreading events.

The research is also prone to bias. People are more likely to remember attending a basketball game than, say, getting a haircut. A phenomenon called recall bias that may make clusters seem bigger than they are. Clusters that have an interesting social angle—such as prison outbreaks—may get more media coverage and thus jump out to researchers, while others remain hidden. Clusters of mostly asymptomatic infections may be missed altogether.

If the idea of a negative binomial expansion makes your mind derail, you should probably close your eyes and hope for the best, as there are important limitations to these papers. Otherwise go to Endo 2020,   (available from the author) or to Zhang et al. 2020.

References: Braun J, Loyal L. ea Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors. doi: https://doi.org/10.1101/2020.04.17.20061440 Endo A, Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China.  Wellcome Open Res 2020, 5:67. Kucharski A. Russel TW ea. Early dynamics of transmission and control of COVID-19: a mathematical modelling study. The Lancet Infectious Diseases doi: 10.1016/S1473-3099(20)30144-4Kupferschmidt K   Why do some COVID-19 patients infect many others, whereas most don’t spread the virus at all?  May 19 for Science supported by the Pulitzer Center. Streeck H, Schulte B  Infection fatality rate of SARS-CoV-2 infection in a German community with a super-spreading event.  Institute of Virology, University of Bonn, Germany, for Science 2020, supported by the Pulitzer Center. Zhang Y, Ye Z, Lord D Estimating the dispersion parameter of the negative binomial expansion. Science 2020 supported by the Pulitzer Center.

Well, what have we learned?

If it turns out that there have recently been many new SSEs, we should be exceedingly worried about those where social distancing rules were ignored, since in an SSE these are our only protection. Excitable people form crowds and chant slogans – these are likely to lead to SSEs, and many cases among those attending the event. In both the USA and the UK, there have recently been large gatherings of people following the murder by the police of George Floyd. These have been large gatherings of angry people who have not observed social distancing, with much shouting. It is now highly likely that in both the UK and the USA, there will be SSE’s causing a steep rise in prevalence, and further lockdowns in both countries are also likely. The only ray of hope is that these demonstrations all took place in the open air. The way ahead is extremely threatening, and there has been no mention of SSEs by politicians in the news media in either country.

 

David Goldberg

7^th June

86 days served (that was meant to be the lot!) Lockdown stretching endlessly into the future, unless a really effective vaccine is invented!