COVID-19: A Virologist’s Perspective

The Verse’s Lois Cowie talks to Dr Sarah Pitt about the science of past coronaviruses and how they compare to COVID-19.

At the time of writing, COVID-19 has infected 640,000 people globally, resulting in 30,000 deaths (1). In the UK there have been 19,522 positive results out of total 127,737 tests carried out. 1,228 people have died (2). The government has introduced measures to prevent the spread of the virus including requiring people to remain in their houses except for essential shopping, to go to work if they cannot work from home and once daily for exercise. For more information on this, please visit https://www.gov.uk/government/publications/full-guidance-on-staying-at-home-and-away-from-others/full-guidance-on-staying-at-home-and-away-from-others.

The uncertainty of the situation combined with being in a lockdown can be really stressful. There are resources at the bottom of this article to help people who are finding this all a bit much.

On 18th March, I spoke with Dr Sarah Pitt for some insight into the science surrounding COVID-19. Dr Pitt did her undergraduate degree in microbiology at the University of Bristol before going on to train as a hospital diagnostic virologist at the Hammersmith Hospital in London. She worked in virology for the NHS for nearly 20 years before moving into lecturing 15 years ago. Now, Dr Pitt lectures at the University of Brighton and is the chief examiner in virology for the UK for the Institute of Biomedical Science. Like many academics and retired NHS workers, Dr Pitt will be returning to an NHS diagnostic virology lab in response to the COVID-19 outbreak.

(Responses edited for length and clarity. Literature references for further reading added by the writer.)

What is a Coronavirus, and how is COVID-19 different from SARS-CoV and MERS-CoV?

Coronavirus is a type of virus and there are 1000s of known coronaviruses. There are a lot in animals and most of the ones we know about are found in bats. In humans, there are seven known coronaviruses. There are two which are well-established causes of common cold [rather than the rhinoviruses] which are probably responsible for about 25% of colds. There are two more that have been recognised in a very small number of cases, again not necessarily associated with a really serious disease, but also not involved in outbreaks, just a few sporadic cases.

Then in 2002, a new coronavirus emerged in China which was SARS-CoV (severe acute respiratory syndrome Coronavirus) and that affected a lot of people mostly in China, Hong Kong and Asia and was confined there. The outbreak went on for about a year and eventually burned itself out. Most people who got infected with SARS-CoV showed symptoms and showed them quite early on, so although it was very worrying and people did die, and people were very ill, it was easier to contain it because we could tell who had it. When they sequenced SARS-CoV virus and compared it with all other known coronaviruses, they found that it had quite a lot of homology with bat coronaviruses, and they also found similar viruses in civet cats. 

Evolutionarily what seems to have happened is the bat virus mutated, got into the civet cat, and then got into humans that way, so although it’s a bat coronavirus, it’s gone through an intermediate animal. That kind of event happens quite a lot – there’s a report in the literature of an outbreak of coronavirus in pigs in 2017 (3), where again it was a bad coronavirus that just killed a lot of piglets in china so it didn’t really get into the news. Bat coronaviruses mutating and getting into other animals is more common than we think, but obviously, it only gets into humans very occasionally.

The next one that turned up in 2012 is the middle eastern respiratory syndrome coronavirus (MERS-CoV). It’s a very serious disease and most people who get infected get very severe symptoms and the chances of dying from MERS-CoV is 34%, but because of that, it does tend to get contained. Most of the cases that we’ve seen since 2012 have been in Saudi Arabia, and there have been a few other cases outside there. SARS-CoV-1 went away; MERS-CoV hasn’t really gone away but it’s under control. When the sequencing was done, the intermediate animal for MERS-CoV is camels – but it is a bat coronavirus. It’s gone from bats, mutated, got into camels and from the camels, it’s got into humans.

This new coronavirus was originally called COVID-19 (corona virus identified in 2019) and emerged in china. They sequenced the virus really quickly because we can do that sort of thing much faster than we could 20 years ago, and again they found a very strong relationship between this virus and a bat corona virus, but also it’s really closely related to the original SARS-CoV-1 from 2002, and so they’ve actually called it SARS-CoV-2. The International Committee on Taxonomy of Viruses has designated (and the World Health Organisation have accepted) the disease as COVID-19 and the virus as SARS-CoV-2.

SARS-CoV-2 is very similar to SARS-CoV-1 in a lot of respects, genetically the viruses are very similar, but what we’ve seen is that it’s a less strong virus because a lot of people are getting quite mild symptoms and we don’t know for sure, but we think there’s a lot of people who are asymptomatic- and that’s how it’s spreading around so fast and so easily. People don’t necessarily get the symptoms after a day or two, which they do with SARS-CoV-1 and with MERS-CoV, and they may never get any serious symptoms- but they will be shedding virus so they can pass it onto other people.

SARS-CoV-1 was so severe and killed a lot of people and made a lot of people severely ill, but when that happens it upsets the equilibrium of both the virus ecology and the human ecology. Both the animal and the human don’t want this to be happening and the virus doesn’t want to be there, and the immune system overreacts to this brand new virus, and it’s catastrophic for both the virus and the host, because if the virus kills off its host too quickly, you’ve got nowhere else for new viruses to go, and that’s why SARS-CoV-1 went away. With COVID-19 I think two things might happen- it might just go away if we use really strict control measures and keep the infection rate down. But because it’s causing quite a lot of mild symptoms, it might join the other four common cold viruses, it might even mutate a bit more and become a bit less serious – we don’t know which way it’s going to go, of course.

Image from WHO

Do we need a vaccine?

Yes, I think we do, because what we are expecting is that a lot of people will get the illness and develop some sort of immunity, but what we do know from SARS-CoV-1 and common cold viruses is that the immunity doesn’t really last all that long. Even if you develop antibodies from the time of your infection, studies of people from SARS-CoV-1 show up to 10% have lost their antibodies within a year (4) so we’re not expecting natural immunity to protect everybody, so a vaccine is really needed. Even if it wasn’t a 100% fool-proof vaccine if it stopped people being in hospital on a ventilator that would be a good thing. That’s the principle of the seasonal flu vaccine; the idea is to stop you getting the serious consequences of the influenza not to stop you getting flu altogether. 

If we had a vaccine that could do that against coronavirus, I think that would be invaluable. Since SARS-CoV-1 everybody has been trying to develop a vaccine and they haven’t got very far, one of the reasons is that SARS-CoV-1 went away, so a lot of the funding dried up, but another reason is that it’s actually proved quite hard to do. Likewise, with antiviral drugs, they haven’t found anything that really worked against SARS-CoV-1 and that’s a bit of a problem.

What sort of steps are scientists having to take to develop a vaccine or repurpose antiviral drugs?

They have to develop a vaccine, apparently, there’s one or two in clinical trials but you have to make sure it actually works and also that it’s safe to give to people. There are three phases of clinical trials before something is allowed to be used, so we’re looking at the end of the year before a vaccine is available- even if they bypass some regulations. Antiviral drugs are probably a better bet, and I read this morning [18 Mar 20] that there are some drugs they were working on in Japan against flu, which might stop viral replication (5), which means you’re infectious for a shorter amount of time which is going to be good in controlling the spread of the virus, but it’s not necessarily going to be good for treating people who are very severely ill- which is what we really do need.

How much difference will it make when an antibody test is found?

If it was possible to get a robust antibody test that would be great, but the problem with the quick tests that you can do on the wards is that they’re not as good, not as sensitive and not as specific. Even the ones that we use routinely have a lot of quality control issues. It would help a bit but you’re not going to pick everybody up with one of those tests, and if you’re negative, you’d probably have to have the main lab test anyway. 

In terms of doing more testing, we’re going to have to rely on commercial kits based on the viral genome which is a standard method of detecting viruses. The next phase is going to be validating all these new kits and rolling out testing as it’s required. My colleagues in the hospital laboratory work really hard to do the testing and make sure it’s robust and accurate.

How reliable is the modelling (6) that the government are basing their predictions on?

The people at Imperial are really experienced at doing mathematical modelling. It’s probably as accurate and robust as it can be at the moment but there are so many things we just don’t know about this because it’s a brand-new virus. You compare it to what you expect a virus to do but this has already proven to behave differently from what everybody expected, so in terms of their suggestions to control the spread, they’re probably very good, but because it’s a brand new virus it’s unpredictable. It’s a pretty robust model and it’s the best that we’ve got at the moment.

Final Words?

The Chinese scientists published the sequence of the virus really early on in December, so all the top reference centres for virology across Europe all got together and developed a test which is based on detecting the viral genome. It’s quite a complicated test, and quite specialist equipment and specialist scientists which is one of the reasons why until now it’s only been done in reference laboratories. They’ve worked really hard and really effectively to get that up and running which is a good example of how these things work when scientists all get together.

Mental Health

The current situation can be stressful for many people especially students who are away from home and are concerned about their academic outcomes. Below is some advice from the World Health Organisation about coping with stress about coronavirus:

Advice from WHO (7)

Other helpful advice is available from the Mental Health Foundation at: https://www.mentalhealth.org.uk/publications/looking-after-your-mental-health-during-coronavirus-outbreak

And:

https://mentalhealth.org.uk/coronavirus/staying-at-home

Also, from the NHS:

https://www.nhs.uk/oneyou/every-mind-matters/coronavirus-covid-19-staying-at-home-tips/

COVID-19 is scary, but people like Dr Pitt are working incredibly hard to improve the testing, treatment and create vaccinations. Doctors, nurses, health care assistants, lab scientists, porters, cleaners and all the other amazing NHS staff are doing everything they can to help every patient in their care. The government has made big decisions that will protect all of us, so please adhere to the new rules – it won’t be like this forever!

References

1. World Health Organisation. Coronavirus disease (COVID-19) Pandemic. [Online] 25 03 2020. [Cited: 25 03 2020.] https://www.who.int/emergencies/diseases/novel-coronavirus-2019.

2. Public Health England. Number of coronavirus (COVID-19) cases and risk in the UK. Gov.uk. [Online] 25 03 2020. [Cited: 25 03 2020.] https://www.gov.uk/guidance/coronavirus-covid-19-information-for-the-public.

3. A New Bat-HKU2–like Coronavirus in Swine, China, 2017. Gong1, Lang, et al. 9, Guangzhou : Center for Disease Control, 2017, Energing Infectious Diseases, Vol. 23.

4. Duration of antibody responses after severe acute respiratory syndrome. L-P, Wu, et al. 10, s.l. : Center for Disease Control, 2007, Emerging Infectious Diseases , Vol. 13, pp. 1562-1564.

5. McCurry, Justin. Japanese flu drug ‘clearly effective’ in treating coronavirus, says China. The Guardian. [Online] 18 03 2020. [Cited: 25 03 2020.] https://www.theguardian.com/world/2020/mar/18/japanese-flu-drug-clearly-effective-in-treating-coronavirus-says-china.

6. Neil M Ferguson, Daniel Laydon, Gemma Nedjati-Gilani, Natsuko Imai, Kylie Ainslie, Marc Baguelin, et al. Impact of non-pharmaceutical interventions (NPIs) to reduce COVID19 mortality and healthcare demand. London : Imperial College COVID-19 Response Team, 2020.

7. World Health Organisation. Coping with stress during the 2019-nCoV outbreak. WHO International. [Online] 18 03 2020. https://www.who.int/docs/default-source/coronaviruse/coping-with-stress.pdf?sfvrsn=9845bc3a_2.

8. Public Health England. Guidance on social distancing for everyone in the UK and protecting older people and vulnerable adults. Gov.uk. [Online] 16 02 2020. https://www.gov.uk/government/publications/covid-19-guidance-on-social-distancing-and-for-vulnerable-people/guidance-on-social-distancing-for-everyone-in-the-uk-and-protecting-older-people-and-vulnerable-adults.

Featured image is also from the World Health Organization

Lois Cowie

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