A variant twist and an undue strain

Just as safe and effective vaccines against Covid-19 rolled out to great fanfare, SARS-CoV-2 once again showed it had another ace up its sleeve. A new variant, variously termed the UK variant, B117 or VUI 122020/01, was spreading rapidly in the UK. Preliminary indirect evidence suggested that this variant possessed a 70 percent increased infectivity over the currently circulating viruses. As more countries reported this UK variant, many governments started to block travel from affected countries in hopes of keeping it out or at least slowing down its spread. At midnight on Dec. 24, the Philippines stopped entry of travelers from the UK, except for returning Filipino citizens. This was quickly followed by restriction of travel from countries reporting the new variant.

What exactly is a variant? How is it different from a strain? What are its implications on the deadliness of the disease and, more important, will the medications and vaccines still work? How do we stop the variant from entering our country, and how do we stop the virus from producing more variants?

Viruses naturally acquire mutations in their genetic material in the course of their evolution. Most mutations are harmless to the virus, and some mutations are harmful to the virus. Occasionally, the virus gets lucky and chance favors mutations that enable it to better invade a host. If the virus survives and multiplies, these mutations give rise to variants. These variants can be traced back through viral lineages. The dates these mutations arose can be catalogued and read to create a molecular clock. The original virus and the subsequent variants form a virus family tree.

A strain is an immunologically distinct type of virus within a viral species. Strains are bigger groups than variants when classifying viruses. Differences between strains are bigger than differences between variants. If strains were dog breeds (Chihuahuas for example), variants are differences within the dog breed (a dark brown Chihuahua versus a light brown Chihuahua).

There is only one strain of SARS-CoV-2. This is the strain that causes Covid-19, which emerged from China in December 2019. Other known coronavirus strains are SARS-CoV, which caused Severe Acute Respiratory Syndrome (SARS) in 2003, and MERS-CoV, which caused Middle Eastern Respiratory Syndrome (MERS) in 2012. There are other coronavirus strains that cause upper respiratory infections that are not as deadly as the previous three.

This one strain of SARS-CoV-2 has given rise to many variants as it spread throughout the world. Most variants do not exhibit any clinically apparent differences compared with the original virus. Some variants may be less virulent, meaning they cause milder disease. Some variants are less fit, meaning they are less likely to survive and be transmitted.

Viruses are built like color-coded Lego sets with instructions included. The genes or RNA sequences are the instructions for building the virus. Viruses are named according to their structure. In D614G, the letters D and G refer to amino acids. D is aspartic acid while G is glycine. 614 is the 614th codon of the spike protein.

A codon is a set of three nucleic acids that select for a specific amino acid, much the same way an instruction set dictates which color and size of Lego brick to use. D614G means that there was a mutation on the 614th codon of the spike protein that changed the amino acid being coded from aspartic acid (D) to glycine (G).

This mutation changes the structure of the spike protein, making it more stable and less prone to breaking. The virus then sticks to human cells more efficiently, resulting in an at least three times higher degree of infectiousness. Though it is more infectious, there is no evidence that the D614G variant is deadlier than the original virus. This D614G variant was the first SARS-CoV-2 variant to gain worldwide notoriety.

The D614G variant emerged in Europe around March 2020 and became the dominant variant worldwide in a few months. Laboratory experiments confirmed its increased infectivity. Patients infected with this variant shed higher amounts of the virus. As the Philippines was emerging from the lockdown in June, D614G entered the country likely from Filipino residents returning from Europe. The combination of increased mobility from easing of lockdown restrictions and a more infectious variant quickly produced a surge that nearly overwhelmed our healthcare system. Fortunately, the Philippines was able to adjust its response and eventually control the spike in cases. Based on current genetic sequences, D614G is now one of the most dominant variants in the Philippines.

The UK variant was first characterized in December 2020, but was already circulating in some parts of Great Britain a few months before. This variant, based on indirect evidence, may be up to 70 percent more infectious than other variants. It contains the D614G mutation, but it has additional mutations, including two important ones on the spike protein. These are the H69/V70 deletion and the N501Y mutation. These have also emerged in other variants worldwide. The fear is that if this virus variant spreads farther worldwide, the number of new infections can spiral out of control. This is why many countries have been shutting their borders while scaling up their facilities and attempting to slow down any kind of surge.

Since the number of mutations compared with overall viral genetic material is still low, the UK variant is not yet expected to be less susceptible to the currently available vaccines. Though subsequent SARS-CoV-2 variants may eventually render current vaccines less effective, this will be a gradual process. With proper monitoring, scientists can keep track of vaccine efficacy and tweak the vaccines to retain potency against newly emerging variants.

In the meantime, there are two ways to prevent variants from spreading. First is to continue using the usual minimum health standards of mask, face shield, and physical distancing. The new variant is still transmitted the same way, and these measures will still work. Second is to keep the number of infections low, since each new infection is a new opportunity for the virus to mutate.

Monitoring of SARS-CoV-2 variants is accomplished by genetic sequencing of virus isolates. A good surveillance system is needed to periodically assess whether the UK strain is present and spreading in a country. The Research Institute for Tropical Medicine, the Philippine Genome Center, and the University of the Philippines National Institutes of Health have the technical skills and equipment to do whole genome sequencing of SARS-CoV-2 to detect specific variants. These institutions are currently sequencing viral isolates from October and November to check if the UK variant has already entered our country. Viral isolates from travelers with specific risk for the UK variant will be sequenced as well. For now, there is no evidence that the UK variant is here, but it may just be a matter of time before it eventually enters. Delaying the UK variant’s entry will buy time to prepare the healthcare system and avoid coinciding with an expected surge in cases due to the holidays.

After everything the nation has survived, the challenge of this new variant can be met. The June surge was controlled with everyone’s cooperation. Advanced information is available this time, and a better job of anticipating and controlling the expected increase in cases can be done. The vaccines will arrive soon, but in the meantime playing it safe is the name of the game. It’s a new year, and the battle continues.