Unravelling the complexities of coronavirus: Q+A with Professor Sheena Cruickshank | 27 April 2020

Sheena Cruickshank is a Professor of Immunology in the Division of Infection, Immunity and Respiratory Medicine at the University of Manchester.

Whilst the world deals with the effects of the 2019 coronavirus outbreak, we have all experienced disruptions and changes to our daily lives. But how much do we really know about the coronavirus?

From the underlying science to the most promising treatment options and possible future impacts, Sheena answers our questions on the novel coronavirus and sheds light on the current global pandemic.

What are viruses and how do they differ from bacteria?

Viruses are made up of a core of genetic material, either DNA or RNA, surrounded by a protective coat called a capsid. They may have an additional protective layer (made of, for example, lipids) called the envelope. A key feature of a virus is that it is incapable of reproducing outside a host cell. This means that viruses invade cells and hijack cellular machinery in order to replicate – in essence, turning the cell into a virus-producing factory. Viruses are then shed from the cell, often by causing the cell to lyse or rupture. They can then infect other cells or be released back into the environment, for example when you cough.

Bacteria are single celled microbes with a very simple cell structure containing a single loop of DNA. Sometimes they have an extra structure called a plasmid that contains additional DNA, which may, for example, make the bacteria resistant to antibiotics. Bacteria reproduce by a process called binary fission whereby a parent cell divides into two identical daughter cells. These daughter cells are clones of the parent cell. Bacterial cell division can happen very quickly. In infections, some types of bacteria infect cells and divide within the infected cell whereas others will live outside cells.

Do all viruses share the same mechanism of replication? If so, why are some viruses are more deadly than others?

No, they don’t. Here is a good explainer: https://www.immunology.org/public-information/bitesized-immunology/pathogens-and-disease/virus-replication. There are lots of things that affect how deadly a virus is. For example, how well it survives outside a host can help it infect more hosts or how a virus is transmitted. Viruses that are spread by droplet transmission; from talking/coughing (e.g. cold viruses) or vomiting (e.g. norovirus) are very effective at transmitting between hosts. In comparison, viruses that require direct contact such as blood to blood transmission (e.g. hepatitis B) are much less infectious. A virus that has less stable genetic information or periods of latency may also be much harder for the immune system to get rid of. This is seen with the HIV infection which mutates quite regularly, or the chickenpox virus that is never eradicated and can reactivate years later as shingles infection.

What are coronaviruses and where do they originate from? 

Coronaviruses are a family of viruses and seven types are known to cause human disease. Many of these viruses are thought to originate in bats and be typical viral infections in those species.

How does the 2019 novel coronavirus differ from the virus causing influenza?

They are different families of viruses and there are several key differences between the infections the viruses cause.

  1. COVID seems to cause more deaths than flu even though quite a lot people seem to be asymptomatic.
  2. Influenza has a shorter time between infections and a patient having symptoms than COVID does.
  3. Flu can be spread to others in the first 3-5 days of illness and this is a major way it transmits.
  4. Children are quite vulnerable to the symptoms of flu and are often an important source of flu transmission, which is why there is interest in vaccinating school age children. We don’t know if children are spreading COVID in the same way as flu, but as far as we know they seem to be quite resistant to the symptoms of infection.

There is much more we need to learn about COVID infection.

What are the main therapeutic options that are being investigated to treat COVID-19?

The main approaches are therapies to control viral replication or drugs that affect the immune system. For many patients that get very bad symptoms, there is evidence that an overly exuberant immune system causes problems via what’s known as a cytokine storm. Cytokines are soluble proteins secreted from the body’s cells which can do many things including summon and switch on immune cells, fight disease and directly kill viruses. A potential problem with COVID-19 is that excessive levels of cytokines can overly activate immune cells which in turn, contribute to lung damage so the drugs investigated either block the cytokine storm or block the inflammation caused by having so many immune cells entering the lungs.

(This was written before research showed the benefits of dexamethasone in COVID-19 patients with severe disease (https://www.who.int/news-room/q-a-detail/q-a-dexamethasone-and-covid-19)).

What is plasma therapy? Do you view it as a promising treatment approach?

Plasma therapy is when you take blood plasma from patients that have recovered from an infection. The plasma could contain high levels of protective antibodies that may neutralise the infection and, if given as a treatment, could help shorten the duration or severity of infection. Antibodies are part of a protective immune response to infection and are made by specialised immune cells that are a type of B cell – a plasma cell. It takes time for someone to generate specific antibodies to any infection and this can mean the infection has time to make you very sick. However, antibodies are only part of the protective response to an infection and other specific immune cells called T cells are very important. We need to learn more about what these are doing in COVID-19.

Anti-malarial drugs have been suggested as another treatment option. What are these and do you think they could be successful?

There is no strong evidence that the anti-malarial drugs chloroquine and hydroxychloroquine can help COVID-19 infection and they are not the main focus of therapeutic efforts by the scientific community. Some countries have decided to recommend these drugs are they are safe, but organisations such as WHO and EU say the science does not support this decision: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30817-5/fulltext.

How fast can a virus acquire mutations? How does this affect vaccine development?

This varies from virus to virus, with some families of viruses being relatively stable.  Developing a vaccine is complex and involves identifying robust targets that our T and B cells can recognise. Some infections are hard to design vaccines for because they mutate, we don’t fully understand the immune response to the infection and/or we lack good lab models to study the infection. Vaccines are also very expensive to make and the process is lengthy, going through many stages of validation to ensure they provide good protection and are safe. It can take a good 18 months to develop a candidate through to full trials.

Why are Vitamin C, D, and Zinc particularly advertised as ‘immunity boosters’?

The phrase ‘immune boosters’ is a worrying one, as you don’t actually want an overactive immune response – if you do have an over exuberant response, it can be quite damaging as is evident in conditions like autoimmune disease. So more accurately, you want a good functioning immune response. A good balanced diet with plenty of vitamins is generally a good thing for our health, but by and large there is little evidence that any one vitamin is the wonder agent for your immune system. Some evidence suggests vitamin D can support the immune response to colds, but this may because many people are quite deficient in vitamin D.

How can we prepare in the future to better deal with inevitable pandemics?

There are many reasons why pandemics occur. Over-population can lead to a stress on natural resources as land is taken for food requirements. This can lead to loss of habitation for animals and may mean that there is greater contact between wild animals and humans, which increases the chance of zoonotic infections (infections that naturally occur in animals and are spread to humans) such as COVID occurring. We also saw with global travel how easy it was for an infection to be spread from country to country. Climate change also plays a huge role in infection transmission, and changes in habitat can change where infections can flourish – for example, mosquito borne diseases are found in many more areas now. Global cooperation and organisations such as WHO that monitor situations and provide advice and support are crucial in infection surveillance. Addressing the impacts of humans on our planet such as climate change is also really important. We also urgently need to think about food security: where we get food from, how it can be sustainable and how we can ensure quality is maintained to prevent infected food from entering our food chains.

This article was prepared by Jessica Brown on behalf of LIVE with Scientists.

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