COVID Q & A – The Virus

COVID Q & A

Naturally Speaking’s blog series on COVID-19: scientifically-informed, data-driven answers to your burning questions about the coronavirus pandemic

The virus causing the pandemic: SARS-CoV-2

This post about the virus comes in two flavours:

  1. Short and sweet – bite size summary
  2. Hungry for more? Look no further! This version includes a bit more detail and links to further resources.

If we don’t answer all your most pressing questions, please feel free to post them in the Comments section below – we’ll do our best to respond. We’ll also aim to provide any updates as advice and knowledge evolves.

Q. What kind of virus is causing COVID-19?

A. The virus causing COVID-19 belongs to a large family of viruses, known as coronaviruses, which infect a range of mammals and birds. In humans, there are four seasonal coronaviruses that circulate widely, generally causing mild illness; these account for around 15% of common colds. In recent years, coronaviruses that normally infect animals have caused a few more serious disease outbreaks in people. The virus associated with an outbreak of severe acute respiratory syndrome in 2002-2004 was identified as a coronavirus and named the SARS coronavirus (SARS-CoV). Another novel coronavirus, known as Middle East Respiratory Syndrome-related coronavirus (MERS-CoV), has caused intermittent outbreaks of serious disease since 2012. The COVID-19 virus has been identified as the seventh coronavirus to infect humans. Genetically, it is related to the virus that caused the earlier SARS outbreak (sharing around 80% of their genetic material) and so has been named SARS coronavirus 2 or SARS-CoV-2.

Q. What does this virus look like?

A. The COVID-19 virus is roughly spherical in shape and is coated with spikes of protein. Coronaviruses are named for their distinctive appearance whereby the spikes cause the virus to resemble a solar corona (corona is Latin for crown) when viewed under a powerful microscope. Laid out side by side, 10,000 of these viruses would only span around a single millimetre. The spike proteins allow the virus to bind to and infect host cells. However, these same spike proteins are also the part of the virus ‘seen’ by the immune system and so may be important for vaccine development. Below the spikes is a layer of fatty (lipid) membrane; this membrane can be disrupted by soap and alcohol gels which is why handwashing is an important part of disease control. Within this spherical membrane is the virus’ genetic material, or genome. While humans have a DNA genome consisting of over 3 billion base pairs, the SARS-CoV-2 virus has an RNA genome with just under 30 thousand nucleotides – small compared to ours, but actually pretty big for an RNA virus genome.

Q. Where did the COVID-19 virus come from?

A. We can be very confident that the COVID-19 virus originally comes from an animal source, although it is now spreading from person to person. Bats and pangolins (scaly ant-eaters) have both been suggested as possible sources. However, so far no virus found in animals is similar enough to be the direct ancestor of the virus in humans and the exact origins of this outbreak remain unknown.

Diseases that are transmitted from animals to humans are known as ‘zoonoses’. Other recent coronavirus outbreaks are also thought to have zoonotic origins, with bats representing the main reservoir from which the virus has been transmitted to humans via another intermediate host. For instance, the 2003 SARS coronavirus is believed to have jumped to humans from bats via the civet cat, since some coronaviruses isolated from civet cats have been almost identical to the SARS coronavirus (sharing 99.8% of their genome). Finding nearly identical viruses in a suspected host species is taken as strong evidence of that species being the source. In order to pin-point the likely source, however, many samples need to be taken and sequenced, which can take a long time (and a certain degree of luck!).

The closest known relative to the COVID-19 virus comes from a bat sampled in 2013 in the Chinese province of Yunnan, and shares around 96% of the genome. Related viruses have also been recovered from illegally smuggled pangolins in China. While these pangolin viruses are a little less similar to the COVID-19 virus (~91% similar), interestingly, of all the coronaviruses found to date, these pangolin viruses are the most similar in the receptor-binding domain of the spike protein, the part of the virus responsible for recognising our cells and initiating infection.  

It has been suggested in the news that the virus originally escaped from a lab or was genetically engineered and intentionally released, but there is no evidence for this based on the genetic material of the COVID-19 virus. Genetic, serological and epidemiological data are all consistently pointing to a start of the outbreak in November/December 2019 in China.

Q. Can humans transmit the COVID-19 virus to animals?

A. Various animal species appear to have been infected with SARS-CoV-2 as a result of human-to-animal transmission, while the susceptibility of others has been assessed experimentally. It remains to be determined exactly how susceptible different species are, whether infected species will suffer illness, and whether there is a risk that onward transmission within these species will become established. 

Researchers would like to know which species are most susceptible to infection by SARS-CoV-2. This could not only shed light on the origin of the current pandemic, but in addition, this information could identify species at risk of being infected by humans, a risk both to these species themselves but also to humans if these species act as an animal reservoir seeding future outbreaks. In lab experiments, ferrets, hamsters, rhesus macaques, and fruit bats have been shown to be susceptible to the COVID-19 virus. Meanwhile, there are reports of human-to-animal transmission resulting in infections in various animals in contact with humans, including pet cats and dogs, tigers and lions in zoos, and farmed mink. There are reports of mink-to-mink transmission on infected farms in the Netherlands and emerging evidence of mink-to-human transmission

Most vertebrates have a version of ACE2, the receptor which the virus must recognize and bind to in order to kick-start an infection. Computational methods have been used to predict susceptibility across the animal kingdom by assessing how similar the structure of the version of ACE2 possessed by each species is to that of humans. This research has predicted various mammals including sheep, gorillas, and chimpanzees to be highly susceptible, while other species including rats, mice, and most non-mammals to be unlikely to be infected. It is also important to think ecologically: species that make more contacts with humans are more likely to be exposed to the virus, while species that live more socially may be at greater risk of supporting onward transmission, compared with more solitary species.

Q. Has the COVID-19 virus mutated, and if so, has this affected disease severity or the transmissibility of the virus?

A. Mutations are changes to the genetic code that arise naturally as viruses replicate – they are perfectly normal and most do not change the characteristics of the virus. Occasionally mutations may change virus traits such as pathogenicity or transmissibility; however, there is no clear evidence that genetic changes to the COVID-19 virus have altered characteristics of the virus during the outbreak.

As viruses replicate, mutations or mistakes in the copying of genetic material occur and these changes in the sequence gradually accumulate over time. Most mutations are either harmful for the virus, and consequently don’t get spread within the population, or they occur in parts of the genetic code that don’t have major impacts on the virus. Monitoring mutations in the genome of SARS-CoV-2 shows the virus is evolving at a rate of around 26 mutations per year – this compares with around 50 mutations per year for seasonal flu. Because mutations happen at a relatively steady speed over time, accumulated changes in the genetic material of the virus can be used to estimate the date at which the viral ancestor of the pandemic existed. Mutations can also help to track how the virus has spread; these changes are being tracked almost in real time using whole genome sequences from the viruses, which are being made publicly available so that scientists worldwide can monitor how the virus is evolving. These data can also help to understand how many independent introductions of the virus have occurred into an area, whether introductions continue to occur after certain interventions (like travel bans) have been implemented, or how long transmission has gone undetected in a particular area. 

Occasionally mutations occur that alter the characteristics or ‘phenotype’ of a virus – on rare occasions, mutations can influence a virus’ pathogenicity, transmissibility, or ability to infect a particular host. These mutations are subject to natural selection and changes in their frequency through time are how viruses evolve. Scientists are monitoring frequencies of mutations in the SARS-CoV-2 genome, looking for signals that might highlight mutations that are beneficial for the virus, and potentially important for disease severity, transmissibility, or vaccine effectiveness. Whether any mutations of this kind have occurred is hotly debated at present: there are some hints that a mutation to the viral spike protein called D614G may increase transmissibility of the virus by some mechanism, though other researchers disagree that the data can support this claim. To get a better idea of whether the mutation actually changes the virus in any meaningful way requires experimental studies, though if this mutation does affect the characteristics of the virus, it is probably only a small change. At present, there is no clear evidence for the emergence of distinct types in the evolution of SARS-CoV-2. There is certainly no evidence to suggest the emergence of strains with different characteristics that would cause problems for protection by a single vaccine, similar to those difficulties we face with seasonal flu vaccines.

Feature image is original artwork by PhD candidate Chiara Crestani, ©2020.

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