Lambda COVID-19 variant and its ‘unusual mutations’: What we know so far

The World Health Organisation (WHO) classified it as a ‘Variant of Interest’ on June 14, 2021 after the variant has “exploded” in certain Latin American countries. It's now spread to nearly 30 countries around the world. The agency noted in a report that the Lambda variant accounts for 81% of the cases detected since April 2021 in Peru based on genome sequencing data available.

What's the extent of Lambda's reach so far?

Lambda has so far been detected in genome samples from at least 29 countries.

With Lambda, why is genome sequencing a challenge?

Advances in genome sequencing have greatly helped in the global surveillance of genetic mutations in the SARS-CoV-2. The cost of each sequence has also come down significantly. But the science, though established and available, is constrained by economics. The bulk of SARS-CoV-2 genome surveillance data come from rich countries. In particular, since there aren’t many genetic sequencing facilities in Latin America, it is difficult to ascertain how much of the current outbreak there is driven by the Lambda strain.

As of May 2021, Prof. Tsukayama said South America has generated 20,000 genomes — about 1.2% of the total in GISAID server, and just 1% of total cases in the continent. This limited surveillance also greatly limits the ability of scientists to detect variants.

Where are Lambda cases reported?

GISAID data show that Lambda has been detected in the following countries/territories:

What makes Lambda different from other variants?

Scientists have reported a “unique pattern of mutations” in Lambda’s spike protein. This “exo-protein” on the SARS-CoV-2 viral surface is the coronavirus’ “key” used to infect human cells, especially in the lungs.

Prof. Tsukayama, a molecular biologist in Peru's Cayetano Heredia University in Lima, reported that Lambda (C.37) has 19 “non-synonymous” mutations in its genome (which generate a change in the amino acid sequence). Seven of these occur in the Spike protein, the main antigen of the virus. 

Following amino acid mutations are so far recorded — in Lambda’s spike protein code alone: G75V, T761, Δ246-252, L452Q, F490S, D614G and T859N. That’s according to a study published by Sally Robertson on June 27, 2021. Robertson stated that the "Lambda lineage of SARS-CoV-2 has potential to become variant of concern".

Why are scientists concerned?

Experts have been intrigued by at least one mutation — called L452Q, similar to the L452R mutation — believed to be behind the high infectiousness of the Delta variant. Mutations L452Q and F490S both map to the Spike protein’s receptor-binding domain (RBD), according to Robertson’s study.

While L452Q is almost exclusive to Lambda (C.37), L452R is also present in Delta and Variants of Interest (VOI) Epsilon and Kappa — and is associated with increased affinity for the ACE2 receptor. F490S has been associated with reduced in-vitro susceptibility to antibody neutralisation. Meaning it is able to withstand antibodies generated either by vaccination or a previous infection.

The WHO, also states that “Lambda has been associated with substantive rates of community transmission, with rising prevalence over time concurrent with increased COVID-19 incidence, in multiple countries."

What’s the evidence of Lambda's high transmissibility?

C.37 (renamed by WHO as Lambda on May 31, 2021) first caught the attention of clinicians in December. “We had 200 lambda infections in December,” said Tsukayama. “It accounted for just one in every 200 samples. By the end of March, it made up half of all samples taken in Lima. Now, three months later, we are looking at more than 80% of all infections nationwide. Lambda has become the dominant variant in Peru in a very short period of time.”

Lambda’s high transmissibility had helped it spread so quickly in Peru, Tsukayama said: “With 187,000 dead and the highest mortality rates in the world, we are the country that has struggled most when it comes to the coronavirus. Therefore, it is probably no wonder that the new variant has gotten its start here.”

Also, a new pre-print study — based on tests on samples from healthcare workers in Chile — suggests that the Lambda variant is more infectious than both the Alpha (B.1.1.7, first detected in the UK) or the Gamma (P.1, first detected in Brazil) variants.

Does Lambda cause more severe COVID than other variants?

Scientists currently differ on the answer to this question. “At the moment, there’s no evidence to suggest it’s more aggressive than other variants. It’s possible that it has a higher rate of contagion, but more work needs to be done on it,” Jairo Mendez Rico, an adviser on emerging viral diseases at the Pan-American Health Organisation, told the Financial Times.

What are the Lambda symptoms?

Symptoms that are associated with other variants of coronavirus — fever, loss of smell and taste, among others — are likely to be associated with Lambda variant as well, according to the UK’s National Health Service.

Is Lambda recorded in India?

India has not recorded any Lambda variant cases. The subcontinent has seen a surge in Delta and Delta Plus variant cases. Maharashtra recently recorded the first death due to infection from the Delta Plus variant of COVID-19.

Is Lambda more “aggressive” variant?

It’s not clear at this point, say experts. It doesn’t follow that the 7 mutations seen in Lambda’s Spike protein (which allows it to bind more strongly with the human ACE2 receptor, and gives it more infectivity) — would make it more dangerous and fatal, compared to other strains, especially the four variants of concern (Alpha, Beta, Gamma and Delta).

“One reason why it is hard to make sense of the threat from Lambda, using computational and lab data, is that it has rather an unusual set of mutations, compared with other variants,” Jeff Barrett, director of the COVID-19 Genomics Initiative at the Wellcome Sanger Institute in the UK, told FT.

Lambda has not raised concern of the WHO. “So far we have seen no indication that the lambda variant is more aggressive,” the WHO virologist Jairo Mendez-Rico told DW. “It is possible that it may exhibit higher infection rates, but we don't yet have enough reliable data to compare it to gamma or delta.”

How many SARS-CoV-2 variants are being tracked by experts?

WHO epidemiologist Dr Maria Van Kerkhove said the agency is monitoring more than 50 different Covid variants, but not all become enough of a public health threat to make the WHO’s formal watchlist.

The lambda variant has multiple mutations in the spike protein that could have an impact on its transmissibility, but more studies are needed to fully understand the mutations, Dr Kerkhove told a July 2 briefing. She explained the current characterisation of Lambda as a "variant of interest" (as opposed to being classified as "variant of concern"), and cited the challenges posed by limited viral genome sequencing (watch WHO video below from 53:15) “We are limited in our understanding of virus evolution because of sequencing that is happening around the world. The amount of genetic sequencing has increased substantially over time…and there are over 2 million full genome sequences that had been shared through GISAID, for example, but we need geographic representation of the viruses and the sequencing of those viruses around the world.”

So much more needs to be done, she said, to build the capacity of different countries and continents to boost surveillance and testing and in overall public health to deal with the present coronavirus pandemic and potential pathogens.

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