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Coronavirus treatments: What we have learned so far about Covid-19




Dr Jane Greatorex has had a varied career. She is currently senior tutor at Lucy Cavendish College in Cambridge and has previously worked in Sierra Leone on the Ebola outbreak and for Public Health England during the swine flu epidemic, as well as streamlining and improving HIV diagnostic services at Addenbrooke’s Hospital.

She maintains an active research interest in the influenza virus, most recently working on the shedding and survival of H1N1v, or swine flu.

We asked her what has been learnt so far about SARS-CoV-2 – the virus that causes the Covid-19 infection – and discussed the search for a vaccine and the treatments that are showing promise. But there was only one place to start.

Dr Jane Greatorex
Dr Jane Greatorex

We all know Donald Trump's suggestion of injecting people with disinfectant was highly dangerous. What did you make of the comments?

The problem is the way Mr Trump speaks, he sounds so sure about these things. We laugh, but I think we are wrong to do so. If you look in the American media people already think you can gargle with Dettol; and there has been an increase in deaths by poisoning because they don’t use these products sensibly.

I do fear for people's lives. I think I'm not alone in that. There's been a lot in the press from medics and scientists. No one believes he was being sarcastic. He didn't attempt to explain how dangerous his comments were if taken literally and if anything that makes things worse. He needs to say ‘Don’t drink or inject bleach or any disinfectant'. In fact disinfectants are only meant to work on the surface of things. If someone injected themselves with bleach, they would just die. It's not going to end well.

The messaging has been appalling in America. It’s astonishing that people honestly think it is OK to stop lockdown.

The pictures of the beaches make me want to weep. I’m really proud that mostly here people have stuck to lockdown, there are a few exceptions but nothing like Florida beaches or people protesting in their thousands. It will be very sad to see what happens there.

Should we all wear a mask?

The public thinks something is being hidden from them (with the information about masks). Why aren't they allowing us to have face masks? Well there aren't enough clinical grade ones to go around. Pure and simple. Hospital face masks are for professionals because they are getting large doses of virus directly in their faces. If you have to turn a patient over in hospital you may be handling somebody who is hooching out the virus. It is very different from walking down the street. The reason now we are saying you could make a face mask and start to wear one is as we get to the plateau of cases - and we are not there yet but we are reaching a horrible, but level, amount - you are less likely to meet someone on the street who could infect you.

You, on the other hand, could be the vector who passes on the virus; you could be the asymptomatic carrier and a mask could help prevent you spreading it. You want to make sure you are still socially distant from people at this stage, but eventually you will be able to get your haircut, for instance. One way to do that and to make sure infections continue to drop will be to make sure no one who is asymptomatic is spreading the virus and you do that by getting everyone to wear a face mask when they are likely to be in close proximity to others. As long as we are socially distant and washing our hands we are not putting ourselves at risk. But the government could explain more clearly why these measures are happening now. It's not that we are just finding stuff out, we are in a new stage.

Coronavirus treatments: what might work and what definitely won't
Coronavirus treatments: what might work and what definitely won't

Why can’t I get a test when other countries are doing them?

Everyone is using different tests. What’s out there is a slew of commercial assays (tests) and in-house developed ones, some of which are not validated in the same way as we validate in clinical laboratories in this country. So when you have a new assay, or test, you have to compare it to a gold standard. But when you have a new pathogen there is no gold standard test so you have to go with what is the best thing out there. Initially that was the assay published by the Chinese who were investigating the outbreak in Wuhan. If people have come up with better assays, how do you prove it is better without a recognised standard.

Everyone goes, well they had assays in China straight away. Well they were using patient samples as controls. Before the outbreak spread here, we didn't have a purified stock grown in the laboratory of maintained virus to say this is the standard virus. And you need to have that and then what you need is for everybody around the world, or at least in a single country, to be using the same standard so you know everyone is comparing their tests against the same thing. So, in this country that is what we have done. The National Institute of Biological Samples and Controls has produced those standards and they make them available to all the labs and everybody developing the assays can get hold of those standards so you know when you design an assay you are designing it to the same standards as everyone else in the country.

Part of the “problem” is we do things properly here. We did race out and try and buy all the commercial assays that were being produced because some companies jumped straight on the bandwagon, but some of them just didn't work.

So there’s an issue around trying to compare tests between countries and even within some countries. In China, possibly, where somebody tested positive then negative then positive again, it could have been due to the different tests used. However it does appear the virus does something odd around the way it replicates and the way you can detect it and not detect it during an infection.

What is the process for developing an antibody test for a new virus?

The analogy is when we first diagnose HIV in a patient. We get a patient who appears to be ill, they are running a temperature, they have risk factors and we think maybe this could be HIV. Perhaps we know the partner or some medical history that leads us to believe they may have HIV. So we do something called a dual test.

We look for the antigen, which is the virus genome, but we also look for the antibodies. That’s because early in the virus infection, the virus is going into the body and into the cells and it's not producing virus particles at first but the body is responding to it so we look for an early antibody response and we look for the antigen itself. The patient may be antibody positive at first but not virus positive.

The issue we have on antibody testing is it is quite hard to develop because you need to have a good stock of antigen and know that you have the purified standard virus and be able to design a test that detects antibodies. Developing a test is not instant. The problem is everybody thinks you can have a test instantly because you say, ‘Oh look, here’s a novel pathogen because we have sequenced it’.

But when we were studying HIV it took years for people to agree it was the virus causing the disease. It’s not always straightforward to make that jump. In this instance with SARS-CoV-2 it was. These people had pneumonia and we knew we were looking for a respiratory pathogen.

It used to be my job developing assays and it would take about 18 months to develop an assay. You have to validate them with a minimum number of positive samples that are from patients who were symptomatic, test against samples from patients infected with different viruses to check for false positives, and then test the sensitivity (smallest detectable amount of virus) of the assay. It's not a quick thing to do it properly. The government has not explained this well. I don’t think I have ever seen the head of Public Health England on TV at all either, Duncan Selbie. He hasn’t raised his head above the parapet and it would be nice to see him defend the people who are trying to do this testing.

I think the public would rather hear a clear answer on testing and PPE and the fact we need to do more studies on transmissibility and we are still not sure what is an infectious dose of this virus we need to know that.

How can we limit the spread of Covid-19? (33642947)
How can we limit the spread of Covid-19? (33642947)

What will studies look at next?

We need to ask things like how do you catch the virus if you are healthy and you have not been near anyone sick. Actually we don’t know the answer to that. It's possible that asymptomatic shedders shed more than we realise and there is something different about their bodies. We need to find those asymptomatic people for lots of reasons, not merely because they cope with it themselves and don’t become ill. We need to know what's different about them. The problem is all those studies take so long because you have to find all those people.

Should I wash my shopping?

I think it does no harm. If you walk around the shops you might take things off the shelf to read them. I’m diabetic so I read packets for calories. I pick an item up and put it back down again. I try not to now. When I come home from shopping I do wipe down the packaging, I do wash fruit and vegetables. I would suggest people should do that anyway. If you are going to eat an apple without taking the skin off please wash it. I would wash it in very dilute warm soapy water.

How long do people who have recovered remain immune?

We don't know. It's way too early to say that. It is utterly different from a cold. Colds are caused by a whole range of viruses. In a winter you may have a cold due to a rhinovirus, or the four different coronaviruses that are out there normally that cause perfectly normal winter colds. They are all different and if you are infected by one it doesn’t give you any cross protection from another.

What trials are looking promising?

I don’t know specifics, but most of the drug trials are not turning out well at the moment. There was some hope over antiretrovirals but that was no good. There was some hope over the antimalarial drugs, but that was no good. I think there are another number of things in the fire and it’s gone a bit quiet. That could imply things are going well and they want to keep quiet about it. The scientific press tends to say as quickly as possible if things are not looking good.

With vaccine trials you have to test on healthy volunteers. First you make sure it doesn’t kill you if you inject it then they have to give it to people who can be challenged with a virus and whether they will actually use Sars Coronavirus 2, I don’t know.

Why is the BCG vaccine being tested?.

For more than a decade we have known the BCG is not a brilliant vaccine against pulmonary tuberculosis - it has about 50-60 percent efficacy. I had the BCG as a child and I had a booster before I went and worked in Dhaka, where TB is prevalent.

I was setting up a laboratory attached to the hospital and caught TB there from my colleagues even though I’d had a booster.

I didn’t realise because I thought the vaccine had protected me. About two years after that I went to America and had my lungs x rayed and they found I had latent TB. So I became interested in the BCG and why it doesn't work and we actually stopped using it because it wasn’t particularly effective. But what we do know is that it is effective against other pathogens. It affects the innate immune system that sends in the white blood cells when you get a cut, for instance. The natural killer cells are the first line of defence against the virus before your immune system has the chance to produce specific T cells and specific B cells. It seems the BCG might help this process. We know in hospitals it can help with some viral pathogens. I think there is evidence from one of the Chinese studies that people who have had the BCG vaccine seem to do better.

When can we relax again after the pandemic?

We need to remember if the virus does die down over the summer it will be back. It is in circulation with all the other respiratory viruses. Yes there will be herd immunity and a higher level of people who are immune but there are always people who didn’t meet it because we shielded them. And there are always new people. The hope is we can create a vaccine.

Could there be a vaccine by September?

There might be one developed but to grow it, to quality control it and to the roll it out that's a bit difficult. The problem with the flu vaccine is you have to grow it in eggs and that’s why its hard to make enough flu vaccine year on year and we don't roll it out to the entire population. With coronavirus at least you can grow it in tissue culture. Even so, I don’t know if it can be available that soon.

Several drugs already in use for other conditions are being tested to see if they can treat Covid-19
Several drugs already in use for other conditions are being tested to see if they can treat Covid-19

Will there be another wave of infections from the virus?

I think the British public is amazing. They understand why they are doing this lockdown and clearly the number of cases has levelled off instead of having a massive spike of deaths.

That didn't happen and won’t so long as they think hard about social distancing until at least the end of the year.

I don't mean social isolation because, we do have to get back to work. I will be having meetings about the college in the next few days. We will need to buy in, for every building, wall mounted hand sanitizer units like in a hospital setting. That will immediately start reducing infection. Students may not be having parties at least until Christmas because we don't want those large social gatherings.

We need to space offices out a bit more. If you wake up with a temperature you should work from home and not shed your virus onto everyone. I hope we will be back in September but we will have to show we have thought everything through to make sure everyone is safe. There is a way out of lockdown eventually but it will require effort and communication and a lot of research, this is unprecedented.

Should children go back to school?

We will carefully watch what happens in other countries China is sending some years back so that will be our best source of information. It will likely be like what we have seen with other respiratory infections. We will have to be careful. They are not all the same but with swine flu a second peak coincided with the kids going back to school. At the moment I don’t think there have been good studies looking at kids. Most of the work has been around hospital patients and few of those are children. It would be nice to have some studies like the best of the school ones for swine flu.

The children have all learned to handwash now and they know about self isolating.

Read more

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