BY MERLIN CROSSLEY

If someone sneezes on you at close range – you’ll collect the whole sneeze. But if you jump back, doubling the distance, you’ll won’t collect half the sneeze, you’ll only get a quarter. That’s the “inverse square rule”. In reality, sneezing works in three dimensions, not two, so you’ll receive even fewer droplets.

So physical distancing is important. We know it’s important for society, but it is also personally important. One of the big questions scientists are asking now is: why do some people get so much sicker than others?

One answer to this question may be – dose.

If you step back, if you wash your hands, you’ll receive less virus. This means that your immune system will have a better chance of beating the virus before it multiplies out of control inside you and causes serious disease.

Part of the reason that so many doctors died in the SARS epidemic, and that medical workers are dying in Italy, is probably related to the dose of virus they are encountering.

You will have heard of other discussions about why some people are getting sicker than others. In general, older people get sicker. No one knows why but we all hypothesis that a combination of weaknesses that develop with age causes the greater mortality. It is also known that pre-existing chronic diseases are associated with more severe symptoms, and as we age we tend to develop chronic conditions, like heart disease, diabetes, cancer, and other less well defined impairments.

But you have also probably heard that some younger people – strong, fit, and otherwise healthy people – are getting very sick, whereas others don’t get sick at all. Why?

Part of the answer might relate to past exposure to pre-existing corona viruses. There are four common human corona viruses, in addition to SARS-CoV-2 that causes COVID-19, and the other serious viruses that cause SARS and MERS. The four common ones have odd names – 229E, NL63, OC43, and HKU1 and cause common colds. One hypothesis about why some people get severe disease, and others don’t, is that people who have recently had a cold caused by one of these, may have some immunity to the new virus.

Alternatively, the opposite may be true. It is complicated but there are some viruses that cause a more severe disease the second time, and work on immunisation for SARS ran into that problem some time back. I won’t expand on this here, but it is one of the reasons that any vaccine, like all existing vaccines to infectious diseases, will have to be carefully tested for safety and is unlikely to be available quickly.

Another interesting hypothesis is that the virus may find it easier to get into and survive in some people than others – because we are all different, we have slightly different genes that make slightly different proteins. We know that the virus binds to a protein on cell surfaces, called ACE2, to get into cells. It could be that susceptible people have slightly different ACE2 and the virus binds better. Furthermore, we all have slightly different immune systems and researchers are sequencing immune system genes to look for correlations between variants and severity of symptoms. Interestingly, it is sometimes those with the strongest immune response, who do worse, because the body overreacts and that causes damage.

As more and more genomic information becomes available it should be possible to expand these studies beyond just one or two key immune system genes to looking at the whole genome. That would not only help us to identify who is most at risk, it may also help us understand what other things the virus affects and how to block the impacts.

While all this work is going on other angles are being tackled. In a previous blog I wrote about the importance of diagnostic tests. One biotech company is now talking about a machine that can test 50,000 samples in 5 minutes. Of course, people still have to collect the samples and put them in the machine, so it is not as instant as it sounds, but testing is getting better. This is hugely important.

There are also new tests for anti-bodies to identify who has been exposed to and recovered from the virus. In Britain there is talk of making these available to people at home. It is suggested that perhaps 40% of people may be asymptomatic and won’t even know they have had the virus. We will soon find out whether this is accurate. It is possible that these people could be safe to return to work across society.

I think scaled up testing is feasible and is going to be a big player as this epidemic unfolds. It is not going to be easy to eradicate this virus, given asymptomatic spread, and recent reports that the virus can infect cats, but broader testing will help us buy more time for vaccine development.

Finally, new treatments are emerging. The first one is beautifully simple. You just take the blood of someone who has recovered, purify the anti-bodies and inject them into the new patient to help them neutralise the virus. It’s like an anti-serum. Early reports suggest this therapy is helping in some hospitals in the US. In the future it should be possible to manufacture the right anti-bodies at scale.

It is just two weeks since I wrote a blog about buying time to allow strategies like these to be developed. I am still optimistic. Given time the science will deliver.

But it is not just the science. The underlying science related to viruses has been there for a while and scientists continue to pose and answer specific questions like those above, but it is the biotech industry that is scaling up tests, it is the transport industry that is distributing the equipment, it is the health care industry that is in the front line treating patients and collecting the data, and cleaners everywhere work around the clock to sanitise surfaces, and there are many others.

Scientists dig deep and ask questions, but it takes a broad team to deliver and implement solutions, and it takes everyone in our community to keep buying time by physical distancing. work from home if you can, keep safe, and keep your distance.

Merlin Crossley is  a molecular biologist and DVC Academic  at UNSW

The Crossley Lab blog appears in CMM Friday


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