The unusual Lambda variant is rapidly spreading in South America. Here’s what we know.

Its mutations help it dodge the immune system. Researchers are scrambling to figure out if it is more dangerous or transmissible than Delta.

A coronavirus variant known as Lambda, which has largely slid under the radar for the past nine months, is now causing almost all new infections in Peru.

Lambda (also known as C.37) was first detected in Peru in August 2020 and has spread to 29 countries, many in Latin America. And, since January 20, 2021, 668 Lambda infections have been reported in the United States. In Peru, Lambda is now responsible for more than 90 percent of new COVID-19 cases, a steep rise from less than 0.5 percent in December. The country has already suffered the world’s worst mortality due to COVID-19; the disease has killed about 0.54 percent of the population.

The Lambda variant likely caused the high number of infections during the second wave between the end of March and April, Peruvian Minister of Health Óscar Ugarte said in a news conference. In neighboring Chile, where the primary vaccine is China’s CoronaVac, Lambda accounts for 31 percent of sequenced cases in the last 60 days. The high case numbers are occurring even though 58.6 percent of Chile’s population is fully vaccinated and another 10 percent has received a single dose. The poor efficacy of the vaccine maybe partly to blame. A study by the University of Chile found that a single dose of the CoronaVac vaccine was only 3 percent effective, but that rose to 56.5 percent after both doses.

“Why Chile is getting such high infection rates is perplexing, and it’s likely due to several factors. Because of their high vaccination coverage, the restrictions were relaxed a little too soon, and that could have led to [a] rise in cases,” says Pablo Tsukayama, a microbiologist at Universidad Peruana Cayetano Heredia in Lima, Peru. It was Tsukayama who first spotted the Lambda variant after routinely sequencing the samples deposited between January and March 2021. “But it is also possible that the main variants in circulation, Gamma and Lambda, have some immune escape properties that lead to reduced protection from vaccines.”

The possibility that Lambda might be able to dodge the immune system led the World Health Organization to designate it as a Variant of Interest (VOI) on June 14. WHO categorizes a virus as a VOI when genetic changes in the virus are so significant that they may affect its transmissibility, disease severity, immune escape, diagnosis or therapy; and it spreads rapidly through a community.

While Latin America has only eight percent of the world’s population, it makes up more than 20 percent of global coronavirus cases and 32 percent of COVID-19 deaths worldwide. Although the region is still reporting more than half of the deaths registered globally, only one in 10 Latin Americans have been fully vaccinated. In countries such as Honduras and Guatemala, the number is less than 1 percent.

“I think we are about to see another critical situation in the next few weeks in Latin America,” says Alfonso Rodriguez-Morales, an epidemiologist and vice president of the Colombian Association of Infectious Diseases. That is because in some countries the vaccination programs still have not fully vaccinated more than 5 to 10 percent of their populations “and that is very critical.”

Why it is hard to detect variants? 

The Lambda variant remained undetected for many months because it was frequently mistaken for Gamma—the variant first identified in Brazil and also known as P.1.

Due to limited resources, the Peruvian National Institute of Health uses a fast and affordable method  based on the changes in the virus’s ORF1ab gene. That method cannot distinguish Beta and Gamma variants from Lambda. To sort the Lambda variant from others requires genetic sequencing, a costly and time-consuming process.

“We have very limited capacity in the region to conduct genomics surveillance, so estimating full prevalence of Lambda is difficult. Why any variant becomes dominant is not easy to predict. So, it is important that we ramp sequencing capacity in all places, not just in the United States and Europe,” says Tsukayama.

What has changed in Lambda?

The Lambda variant is very unusual because of the way its spike protein is altered compared to other variants. It has mutations at 14 positions including a long stretch of seven amino acids which has been deleted from a region of the spike protein called the N-terminal domain or NTD. Beyond these, Lambda also has mutations in the ORF1abgene that are found in other variants of concern: Alpha, Beta, and Gamma.

The ORF1ab gene encodes a large protein, parts of which help the coronavirus replicate and suppress the human immune response. Because of its importance, scientists are already developing antiviral therapies to target ORF1ab proteins.

The seven amino acids deleted from the NTD belong to an NTD supersite where the spike is attacked by many of the body’s potent antibodies. Many variants, including Alpha, Beta, and Gamma also harbor mutations within this zone, suggesting that this region is important for the evolution of the virus. “NTD is not crucial for carrying out important functions of the virus and thus, it is easy for the virus to mutate and still remain viable, so as to evade the existing antibody response,” explains Shee-Mei Lok, an infectious disease scientist at National University of Singapore.

The anti-NTD antibodies made naturally in the body may block subsequent viruses from entering the cell even after it has attached with the ACE2 receptor on the cell’s surface, which is why vaccine developers are focusing on it.

Among other mutations of Lambda is a unique one at location 452 which is also mutated in other highly transmissive variants: Delta, Delta Plus, Epsilon, and Kappa. While Lambda’s L452Q mutation has never been seen before in a variant, scientists predict that mutations at the 452 position boost the ability of SARS-CoV-2 to infect a cell.

The 452 position occurs in the part of the spike protein that interacts directly with the ACE2 receptor protein found on the lung and other human cells, and that interaction allows it to enter the body. “The 452 position is recognized by many neutralizing antibodies. Mutations at this site could result in decreased binding and thus less protection by certain vaccines in certain people, those with marginal responses to start with,” says Michael Diamond, an immunologist at Washington University School of Medicine.

Evgeni Sokurenko, a microbiologist at University of Washington, has shown that a single mutation at this position could have set off the recent rapid expansion of COVID-19 variants. A similar mutation—L452R—in the Epsilon variant causes high infectiousness, enhances the virus’s capacity to grow, and reduces the neutralizing activity of many antibodies.

In a study not yet peer reviewed, Nathaniel Landau, a microbiologist at the NYU Grossman School of Medicine, has shown that a lab-made Lambda-like virus was twice as infectious as the early SARS-CoV-2 variant, due only to the L452Q. Other mutations found in Lambda had no significant effect on infectivity. Another study not yet peer reviewed also confirms that Lambda is likely more infectious than Gamma and Alpha.

What do we know about vaccines and Lambda?

There are very few studies on Lambda, but preliminary results suggest that current vaccines are still effective but perhaps less than against the original virus.

“We believe that, at least for the mRNA vaccines—Moderna and Pfizer, that those vaccines will protect very well against Lambda, in the same way that they protect against the Delta virus. Even though some of the antibody no longer works against the variants, it's still enough that they will fight the virus and get rid of it pretty well,” assures Landau who led one study.

Another study, also not yet peer reviewed, shows that Lambda can escape the neutralizing antibodies produced by the WHO approved, China-developed CoronaVac vaccine, although lead author Ricardo Soto Rifo, a virologist at the Institute of Biomedical Sciences, Santiago, Chile, clarified, “We still don't have evidence to say that Lambda is more transmissible, we don't have evidence to say that Lambda is responsible for vaccine breakthrough, we don't have evidence to state that Lambda is responsible for more severe disease or whether Lambda is responsible for death.”

Two doses of CoronaVac, an inactivated virus vaccine which is the available vaccine in many Latin American countries, is considered less effective than the mRNA vaccines, but is still good in protecting against severe disease and death.

Despite some skepticism around the efficacy of CoronaVac against new variants, everyone should get vaccinated by whatever authorized vaccine is available in their region, says Herbert Virgin, an immunologist, a member of the National Academy of Sciences, and chief scientific officer of Vir Biotechnology. “If you don't vaccinate … the virus will evolve,” adds Virgin.

Although worrying about a new variant like Lambda gaining ground in a faraway country might seem excessive, it is important to stay vigilant and follow precautionary measures. “Lambda isn't scarier than the Delta virus. The key is, that they're both highly transmissible viruses. But if you get the vaccine, you're most likely going to be protected,” Landau advises. “And the rate of infection with these viruses is going to go down in areas where people get the vaccine.”

Editor's note: This article originally misstated Alfonso Rodriguez-Morales' title. He is an epidemiologist and vice president of the Colombian Association of Infectious Diseases.

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