New variants of SARS-CoV-2, the virus that causes Covid-19, seem to be emerging on a constant basis.
It's difficult to know what to think when you hear about them on the news. In December, the Alpha variant, then known as the UK variant, appeared. In recent weeks, it’s been all about the Delta variant.
Now, news stories are popping up about the Lambda variant. But it’s just one of a large number of variants that scientists are monitoring.
As that list continues to grow, how worried should we be?
The World Health Organization tracks SARS-CoV-2 variants with the help of officials and laboratories globally.
In Ireland, the Health Surveillance Protection Agency (HPSC) compiles reports on variants detected here, and contributes to the European Centre for Disease Prevention and Control (ECDC) efforts to monitor variants in the region.
New ones are detected almost daily.
The virus replicates millions of times within each infected person. As that happens, slight errors in the "photocopying" process occur, which are then compounded when replicated in others.
If these mutations, or a combination of them, confer an advantage to the virus, the variant can spread locally. Monitoring agencies, like the HPSC, ECDC, and eventually the WHO, will then become aware of it.
Those found to have genetic characteristics that may pose a risk to global health are categorised by the WHO as "Variants of Interest", or VOIs.
Variants are commonly listed and then removed from this category when more evidence emerges.
VOIs that go on to demonstrate clear evidence of increased transmissibility, disease severity, or an ability to undermine immunity are subsequently categorised as "Variants of Concern" (VOCs).
The HPSC and ECDC use the same categories. However, they conduct separate assessments based on the variants they consider relevant to their own areas.
"We characterise them through a series of consultations with our expert networks," said the WHO’s Covid-19 Technical Lead, Dr Maria Van Kerkhove, when asked recently about variants at a news conference.
"But we are limited in our understanding of the virus evolution by the amount of genetic sequencing which is occurring around the world."
The WHO currently lists four variants as of concern: Alpha, Beta, Gamma and Delta.
These were previously known as the UK, South African, Brazilian and Indian variants. In Ireland and Europe, the same four are considered VOCs.
Of these, clearly Delta is now of most concern to all. It’s on the way to becoming globally dominant.
"Any variant that is going to become dominant is, by definition, going to be fitter than the others," Dr Kim Roberts, the lead virologist in Trinity College Dublin, told Prime Time.
"It’ll either replicate faster, bind to cells faster, or be able to avoid the immunity response better, or a combination of those."
Four other variants are currently considered Variants of Interest by the WHO.
Lambda is the most recent addition to the WHO list, where it joins Eta, Iota and Kappa. If there's an emerging variant worth being concerned about, it should be listed there.
Lambda has made news headlines in recent days following a small number of detections in the UK. It was first detected in South America, where little genetic sequencing is done compared to Europe, North America and Asia.
So what’s known about the WHO variants of interest like Lambda? And how do they compare to the dominant variants of Alpha and, increasingly, Delta?
Eta was originally linked to cases in Nigeria. It came to media attention in Europe in February following a number of cases detected in the UK. Reports based on early scientific analysis said it may be more transmissible than previous variants. This followed the explosive emergence of the Alpha variant in the preceding two months.
However, Eta has not caused significant outbreaks in Europe in the meantime. Just 495 cases have since been reported in the UK. Here, there have been 72 cases.
Data uploaded to the variants tracking database GISAID indicate detections globally for Eta peaked in mid-March and have since consistently reduced. Since then, Alpha has become dominant.
Iota is associated with the New York region of the United States. It spread across parts of the US in early 2021. Just 11 cases have been detected in Ireland. Like the WHO, the HPSC considers it a variant of interest. However, the ECDC lists it at the lower concern level of "Variant Under Monitoring".
It carries two mutations that concern scientists. The early indications were it may have genetic characteristics that would help it to evade antibodies gained by people who'd been vaccinated, or recovered from a Covid-19 infection.
The Alpha variant appears to have been seeded in the New York area around the time Iota emerged. By mid-March, sequences for the region indicate the two variants were each making up 40% of cases.
Yet, by early May, 50% of cases sequenced were Alpha, and Iota had fallen to 20%. In the wider US, 70% of cases reported to GISAID were Alpha, with just 9% Iota.
Only a proportion of cases are ever sequenced each week, but from the data available, Alpha has squeezed out both Eta and Iota in places where each have been present.
If you were to think of variants as generations in a family tree, Kappa is a sibling to Delta. Both are mutations of the B1.617 variant, with Kappa being B1.617.1 and Delta being B1.617.2. In Ireland, there have been 158 Kappa cases sequenced.
The WHO categorised Kappa and Delta as variants of interest on the same day – 4 April 2021. In the meantime, Delta has spread to tens of countries. The ECDC says it’s likely Delta will account for 90% of cases in Europe by August.
Kappa is still being monitored as a variant of interest by all three agencies, but the growth in detections hasn’t been accelerating globally at anything like it has with Delta, according to the GISAID database.
Lambda was designated a variant of interest by the WHO as recently as 14 June, but was first detected in Peru in August 2020. There have been no detected cases here, and it is not listed as a VOI in the most recent report from the HPSC, which was published on 2 July. The ECDC considers it a "variant under monitoring".
Last month, Lambda made up 82% of analysed Peruvian cases. One-third of cases in Chile have also been attributed to it. However, capacity to analyse swabs for the presence of variants is limited in much of South America.
Therefore, the data on the prevalence of Lambda is incomplete. At least one case has been detected in 28 other countries. In Europe, 99 cases have been reported in Germany, and 55 in Spain.
Initial assessments of the Lambda mutations said they may cause the variant to spread faster, and potentially evade immunity gained through vaccines or prior infections.
Further research released by scientists at Universidad de Chile on 1 July indicates Lambda is likely to be more transmissible than the Alpha variant and the Gamma variant, which was first detected in Brazil. That research didn’t look at the Delta variant.
With Delta fast becoming globally dominant, Lambda would need an evolutionary advantage to displace it.
"It’ll take something more powerful than Delta to out-compete Delta, so if it doesn’t out-compete Delta, it’ll soon be almost irrelevant," said Dr Barry.
On Friday, Public Health England published a risk assessment on Lambda. "There is no evidence as yet of a country where it is outcompeting Delta," it said, "though careful monitoring of the epidemiology in Chile and Peru is required."
The Chilean scientists found the mutations present in Lambda also caused some "immune escape" from antibodies triggered by the Chinese CoronaVac vaccine used in Chile.
The CoronaVac vaccine works by injecting "inactivated" virus alongside an adjuvant to illicit an immune response. It’s decades-old vaccine technology that has proven safe and reliable, and remains in use in Tetanus and Hepatitis B vaccines.
Two doses of CoronaVac had been estimated to provide 51% efficacy against infection against early variants. This compares poorly against the approximately 80% protection conferred by just a single dose of an mRNA vaccine.
It’s therefore also unclear if Lambda would cause a concerning level of immune escape in Europe if it did become dominant, given the vaccines in use.
Delta has also been shown to evade some immunity gained through a single dose of some two-shot vaccines.
"Based on what we know so far about Lambda, I wouldn’t be getting too worried about it yet," said Dr Barry.
"But it’s one of these things that scientists will certainly keep an eye on."
The future of variants
"As we move forward, the number of variants of interest will increase, and there’s more things we’ll have to watch," said Dr Roberts. "But that’s what we live with all the time with flu."
Already, talk of "Delta-plus" has emerged, prompting headlines across the globe. Some scientists believe the mutations present give it the potential to be more transmissible than Delta, but there is little definitive evidence as yet.
Only 125 sequences of Delta-plus have been reported to GISAID, the earliest being linked to a case in March. In no single week since 1 May have more than 20 Delta-plus sequences been submitted to the database. Every week since mid-May, more than 15,000 Delta cases have been uploaded.
So far, the WHO has decided to consider Delta and Delta-plus as one and the same. The "plus" is a change, but isn’t enough to consider it separately.
The bigger fear in the longer term is a variant that significantly undermines immunity gained through vaccines.
It'd require the development of new doses, and likely prolong the pandemic globally. However, reinfections, or cases in people who've been vaccinated against the current strains are generally considered by scientists as likely to be less severe.
"We have to accept viruses are changing," said Dr Roberts. "The more virus that is out there, the more mutation is likely. It’s all about probability."
"From a virologist’s perspective, it is just going to keep on going, but hopefully – hopefully soon – most people can just start ignoring it."