COVID-19 Variants

Over the last few months, we have been expanding our vocabulary related to the pandemic – variants, genome sequencing, genomic surveillance, are all new ‘trendy’ words that we have heard about in the news.

Variants, variations in the virus’ RNA, are a major preoccupation for scientists and health authorities globally as it seems that they are spreading faster than the ‘original’ identified virus. To better understand what variants are let’s start by taking a closer look at what a virus is.

A virus is a submicroscopic infectious agent that only replicates inside the living cells of an organism. SARS-CoV-2 is a single-stranded RNA-enveloped virus.  Its RNA components are adenine, uracil, cytosine, and guanine.  These bases pair in a specific way: AU (adenine-uracil) or GC (guanine-cytosine) to form a strand of RNA.  During the intracellular life cycle, coronaviruses use the genetic material of the host cell to express and replicate their genomic RNA to produce full-length copies that are incorporated into newly produced viral particles.[1]

What is a COVID-19 variant and how do they arise?  

Over time, virus change and adapt to their environment.  Mutations of viruses produce variants.  This process occurs in all viruses.  It is not a process that is unique to COVID-19 virus.  Like all single-stranded RNA viruses, COVID-19 has a single RNA strand made of a specific RNA sequence.   This sequence was previously identified from the originating virus. Scientists were able to read the genetic sequence, identify and tag the virus as COVID-19, which proved to be a different virus than previously identified Corona viruses, like for example, the Corona Virus that caused the SARS out break in 2002.

As the pandemic progressed, scientists continued to examine the RNA sequence of the COVID-19 viruses extracted from a sample of infected people.  Eventually, differences in the genetic sequences were noted at the AU and GC base pairs. These mutated genetic sequences came from samples collected in England, South Africa, and Brazil.

To understand a viral variant, let us imagine a book as an analogy.  One scientist wrote the original version of the book and he gave copies of that book to all the scientists in the world.  The book represents the virus, and the pages represent the genomic sequence of these different COVID-19 variants.  All scientists are reading the same book, it is just like they are decoding the sequence of the virus.   All their books have the same number of pages, chapters and paragraphs all organised the same way.  However, the differences, that represent the viral variants would be represented by typos in certain sentences in a paragraph on any given page. These typos are indicative of a variant – a sort of different edition of the book. These variants affect how a virus evolves and becomes better at entering cells to reproduce.

Figure 1: Simple example of an RNA mutation

It is very difficult to spot these genomic differences; only experienced and competent laboratory specialists with highly specialized equipment are capable of discriminating between the different strands of viruses – this is referred to as genomic sequencing. Sequencing decodes the virus from beginning to end, the entire genetic code from start to finish is mapped out. Decoding the COVID-19 virus represents reading its RNA sequence one base pair at a time. Genomic sequencing is far more expensive and time-consuming than running a PCR test to check for viral presence in a patient sample.

How did we find COVID-19 variants?

The increase in the number of positive cases in England, South Africa, and Brazil lead to the observation that the infection rate was higher in these countries versus others. The scientific community recognized this increase in infection rate as something to pay attention to, as they were expecting that COVID-19 would mutate and give rise to new variants based on past experience with similar viruses.  By comparing samples taken from infected patients in these three countries and comparing them with the genomic signature of the known and wide-spread COVID-19 strand, scientists discovered that the genomic sequence was different. Each of these three variants showed distinctive differences in their RNA sequence.

Currently, there are three well-defined SARS-CoV-2 variants of concern that are circulating globally and appear to make the virus more transmissible[2]:

  • the B1.1.7 variant originating in the United Kingdom,
  • the B.1.351 variant originating in South Africa, and
  • the P.1 variant originating in Brazil.

“Scientists have now studied this situation with these variants and have found that they do tend to spread faster, they’re more transmissible or more infectious.  For example, the B1.1.7 variant (United Kingdom variant) showed 22 coding changes across the whole virus genome, and this is the cause of concern throughout the scientific community. However, so far, these variants do not seem to cause more severe illness or a higher death rate or any sort of different clinical manifestations.” [3],[4]

The impact of these variants on human health is still under investigation.  On February 3rd, 2021, researchers at the London School of Hygiene & Tropical Medicine (LSHTM) released an analysis of some of the data, suggesting that the risk of dying is around 35% higher for people who are confirmed to be infected with the new variant.[5]  Other studies originating from the UK suggest that more data is needed before stating that these variants, especially the UK variant, would be more deadly than the original COVID-19 virus.

More studies are needed to understand the situation’s landscape and assess the difference in mortality rates between the different COVID-19 variants.  It is also imperative that the worldwide effort to trace and limit the spread of these variants intensifies and extends to more countries.

By following the trail of these variants as they appear in patients across different regions, we can determine where that variant originated and combined it with that person’s travel history when it was introduced into the region. This is crucial to distinguish between infections arising from travel versus community spread. Tracing the virus and its mutations also provides health authorities with critical information towards recommendations regarding outbreak control and where to direct resources.

There is still a lot of discussion about mutations and how more contagious and deadly the mutated viruses are by now.  However, it’s important to note that not all mutations are always favourable for the virus. 

What is preoccupying for the scientific community are the successful mutations of the virus.  It is important to understand that these mutations are just a series of trials and errors from the virus’ multiplication process likely, at random, and the most adapted will survive and multiply. The race is now on to try to identify and understand the variants to prepare more efficient vaccines to stop the propagation of more resistant variants.

PCR vs Genomic sequencing 

A PCR test will confirm the presence of the virus, but it will not be able to discriminate between the different variants. Polymerase Chain Reaction (PCR) uses the original COVID-19 RNA to identify the presence of the virus. Our mobile RT-qPCR solution performance is not affected by the COVID-19 variants that have been identified thus far. Our customers can contribute to help identifying any potential variants by ensuring that all their positive tests are being sent to the local health authorities responsible for COVID testing and genomic sequencing for variants.

A continuous effort

The study of SARS-CoV-2 whole-genome sequencing (WGS) data has led to many important findings of this pathogen. But we will need more sequence data from samples from all over the world to come up with effective approaches to control and prevent COVID-19 infections, especially from mutated forms of the virus. Scientists from across the globe are collaborating to generate and share this invaluable information and apply it to disease diagnosis and control efforts. 

There is a strong possibility that other variants will appear and maintaining focus and efforts on sequencing will help prepare against vaccines and treatment resistance.

In Canada, reducing the impact of novel SARS-CoV-2 variants is a critical focus of the global COVID-19 response. Genome Canada, through its leadership of the Canadian COVID Genomics Network (CanCOGeN), is part of an integrated national effort to rapidly identify, understand, and track the distribution of these variants in Canada.

The latest travel restrictions and mandatory testing when people are back in Canada from travelling abroad will certainly help in tracking those variants.  These measures may not please many travellers, but they are playing a crucial role in identifying potential variants entering our countries, most of the time by travellers showing no symptoms.

On-site COVID-19 testing and detection programs using qPCR solutions should review their screening and testing strategies to ensure compliance with the latest requirements from their local Health Authority. This will also help to ensure a strategy is in place to account for the currently identified variants. 

Through a new Government of Canada Variants of Concern Strategy, CanCOGeN is working with the Public Health Agency of Canada’s (PHAC) National Microbiology Laboratory, Health Canada, Canadian Institutes of Health Research (CIHR), and other provincial and territorial partners to quickly scale up genomic sequencing and research efforts to detect new variants, increase real-time data sharing capacities, and inform appropriate public health responses.

This is the reason why possible positive samples must be analysed to identified variants, the probable origin, thus having a better proactive response to start contact tracing.

Together, we can make a difference!

[1] Wu, Katherine J.,  Smithsonian Magazine, 15 April 2020.

[2] Genome Canada, February 12, 2020

[3] Dr. Wendt Barclay, head of the department of infectious disease at Imperial College London, December 22, 2020.

[4] Dr. Soumya Swaminathan, WHO, January 8, 2021

[5] Davies, N. et al. Preprint at medRxiv (2021).