Should We Be Concerned About the Lambda Variant?

Yet another SARS-CoV-2 variant is making headlines, but experts reassure that early evidence suggests it can’t substantially evade vaccines — though it does have potential to become a variant of concern, one expert said.

The Lambda (C.37) variant, first identified in Peru in December 2020, now accounts for the majority of infections there, and is on the rise in other South American countries, including Argentina, Ecuador, Chile, and Brazil.

The World Health Organization named it a “variant of interest” — not yet the more severe “variant of concern” — on June 14, “based on evidence of continued emergence and suspected phenotypic implications.” The U.K. followed suit on June 23, “based on global spread and a novel combination of mutations.” (Lambda is not currently listed at all on the CDC’s variant tracker.)

Peru has been struggling with a high rate of COVID-19 infections, with a current 7-day average of 4,000 cases per day. That’s raised eyebrows among experts who’ve discovered that Lambda has an unusual combination of mutations that may make it more transmissible.

Nathaniel Landau, PhD, a virologist at NYU Grossman School of Medicine, and colleagues reported the novel mutations in a preprint in BioRxiv, highlighting two in the receptor binding domain of the spike protein (L452Q and F490S), as well as a novel deletion (del246-252) and novel mutations (G75V and T76I) in the N-terminal domain of spike. It also has other known spike mutations, D614G and T859N.

The novel mutations in spike may contribute to increased transmissibility, and could result in greater reinfection rates or reduced vaccine efficacy, the researchers reported. Their analysis showed that Pfizer serum samples were about 3-fold more resistant to neutralization, and Moderna samples were about 2.3-fold more resistant. Convalescent plasma was about 3.3-fold more resistant, while Regeneron’s monoclonal antibody combination had no loss of antibody titer, the group said.

“The typical titer for someone who is vaccinated is 1:2,000,” Landau told MedPage Today. “You can take that down to 1:500 and it will still kill the virus. … Natural infection titers tend to be 1:200, on average, and that’s still protective.”

“We’ve done this for Alpha, Beta, Gamma, Delta, and now Lambda,” Landau added. “The results we see are very similar for all these variants. We’re primarily looking at the mRNA vaccines, and vaccine-elicited antibodies do a good job of neutralizing all the variants.”

Landau said his team is also examining the impact of these variants on adenoviral vector vaccines and will publish results in the near future.

The team attributed the resistance to the new L452Q and F490S mutations — particularly the former, which appears to increase the spike protein’s affinity for the ACE2 receptor. The similar L452R mutation seen in other variants was a “primary contributor to the increased transmissibility of the Alpha, Beta, and Delta variants,” the researchers wrote. “The findings suggest that L452Q, like L452R in the Delta variant, increases virus affinity for ACE2, likely contributing to increased transmissibility.”

“That amino acid mutation in Delta is what causes the virus to become more transmissible and give some resistance to vaccine-elicited antibodies,” Landau said of the 452 mutation. “But even with a 4-fold reduction in titers, the vaccine is producing an antibody response that’s more than sufficient.”

A preprint study from Chile published in MedRxiv similarly found that Lambda was associated with a 3.05-fold reduction in neutralization for the CoronaVac vaccine compared with wild type virus.

The evidence does suggest that Lambda could become a variant of concern, Landau said.

The U.K. is closely watching Lambda, calling for further studies to better understand any implications for counter measures and vaccine efficacy. There were only six cases of Lambda in the U.K. between Feb. 23 and June 7, according to Public Health England. Five of those had a history of travel overseas, and in one case travel status was unknown. No deaths were reported.

As of June 24, there had been 1,845 sequences of the Lambda variant reported to GISAID, which were contributed by about two dozen countries, including the U.S., which contributed 525 cases, Public Health England reported.

Peter Hotez, MD, PhD, of Baylor College of Medicine in Houston, tweeted that the BioRxiv paper suggests the “good news is that mRNA vaccines still look good” — but this serves as a reminder to “accelerate vaccinating the Southern Hemisphere, Latin America, Africa, [Southeast] Asia ASAP.”

“We’re playing with fire,” Hotez tweeted.