COVID-19 Response Team Warns of Rise in Variants

The so-called U.K. variant continues to spread around the U.S., with cases identified in all but eight states, Biden administration officials said in a briefing on Wednesday.

There are now 1,277 cases of the B.1.17 variant in 42 states, including one case of the E484K escape mutation first identified in the U.K., which was previously seen on the so-called South African variant, which has been shown to impact certain COVID-19 treatments, such as convalescent plasma.

In addition, 19 cases of the B.1.351 (South African) variant were found in 10 states, and three cases of the P1 (Brazilian) variant were found in two states.

So far, there has been a paucity of data in peer-reviewed journals about whether current mRNA vaccines may hold up against variant strains, although two preliminary reports in the New England Journal of Medicine provided some insight. Philip Dormitzer, MD, PhD, of Pfizer Vaccine Research and Development in Pearl River, New York, and colleagues compared serum from participants in the Pfizer/BioNTech COVID-19 vaccine trial and found that neutralization of variant virus from the B.1.351 lineage was “weaker by approximately two-thirds.”

The researchers tested serum from 15 participants in the Pfizer/BioNTech COVID-19 vaccine trial, at 2-4 weeks after their second dose against variant strains, including a variant with mutations at three amino acid sites, including E484K, and a strain with mutations found in the B.1.351 strain.

Compared with a U.S. wild-type strain, data showed “poorer neutralization” of variants with the full set of B.1.351 spike mutations.

Limitations to the data included that it did not examine each mutation individually and did not examine “the potential for mutations to alter neutralization by affecting spike function rather than antigenicity.” The authors said it is “unclear” what effect this type of reduction in neutralization would have on vaccine-elicited protection from the B.1.351 variant.

A second preliminary report in NEJM from Darin Edwards, PhD, of Moderna in Cambridge, Massachusetts, and colleagues examined specimens from participants in Moderna’s phase I COVID-19 vaccine trial against “pseudoviruses.”

The team found no significant effect on neutralization against the strain comparable to the B.1.1.7 variant, but did find a significant decline in neutralizing antibody titers against the strain comparable to the B.1.351 variant and “a subset of its mutations affecting the [receptor-binding domain].”

“Protection against the B.1.351 variant conferred by the [Moderna] vaccine remains to be determined,” Edwards and co-authors wrote.

At the briefing, CDC Director Rochelle Walensky, MD, said that while COVID-19 cases and hospitalizations continue to move in the right direction in the U.S., “the continued spread of variants that are more transmissible could jeopardize the progress we have made in the last month if we let our guard down.”

“I know these variants are concerning, especially as we’re seeing signs of progress. I’m talking about them today because I am concerned too,” she added.

Melanie Firestone, PhD, of the CDC, and colleagues, detailed eight cases of the B.1.1.7 variant in Minnesota from December 2020 to January 2021 in an early edition of the Morbidity and Mortality Weekly Report.

However, Firestone and colleagues noted that there was no clear pattern to the cases, as individuals had a range of domestic and international travel history, symptoms, and even age.

While the first case of the B.1.1.7 variant was reported in the U.K. in December, researchers in the Minnesota Department of Health examined 30 SARS-CoV-2 specimens from Minnesota residents dating as early as November 1. The team specifically analyzed those with S-gene target failure, a proxy initially identified by British researchers to distinguish variant cases.

The investigators found six of eight variant cases using S-gene target failure, and two sequenced through CDC’s national surveillance system, from Dec. 18, 2020 to Jan. 11, 2021. Cases ranged in age from 15 to 41.

Three had a history of international travel during the 14 days prior to illness onset, including two to West Africa and one to the Dominican Republic, and three traveled to California. One individual tested positive for SARS-CoV-2 while in California.

Interestingly, while the three cases from California were genetically distinct from the other sequences, two specimens from international travelers “did not have sequences similar to those identified in Minnesota.”

Five individuals reported COVID-19 symptoms, while two were asymptomatic. No individuals traveled to the U.K. in the 14 days prior to illness onset.

The investigators noted that CDC modeling estimates that variant B.1.1.7 will become the dominant COVID-19 strain in the U.S. in March, and recent research in the U.K. suggests the variant is not only more transmissible, but also results in more COVID-19 hospitalizations and deaths.

At the briefing, Walensky stressed that non-pharmaceutical interventions can combat the spread of these variants, and emphasized the importance of vaccination.

“Fewer cases means fewer opportunities for the variant to spread and fewer opportunities for new variants to emerge,” she noted.

Anthony Fauci, MD, NIAID director and a member of the White House COVID-19 Response Team, also highlighted the latest research regarding the increasingly concerning question of whether vaccination actually prevents transmission of coronavirus.

Both Moderna and Pfizer are studying whether there is a difference in the viral load in the nasopharynx between a person who gets vaccinated and then has a breakthrough infection compared with an unvaccinated person who has an asymptomatic infection, Fauci said.

In the meantime, other recent studies on that question are “pointing into a very favorable direction,” and will need to be confirmed by additional studies, he stressed.

The underlying question around COVID-19 transmission and vaccines is whether there is in fact a relationship between viral load and transmissibility. This relationship has been consistently demonstrated through studies in diseases like HIV, using measurements of viral load in the blood, that determine the likelihood of transmitting the virus to a sexual partner, Fauci explained.

“The lower the viral load, the less likelihood of transmissibility. The higher the viral load, the higher the likelihood of transmissibility,” he said.

Of course in COVID-19, the viral load is measured in the nasopharynx, he noted, before launching into an explanation of two studies: one from Spain and another from Israel, on this very issue.

The study from Spain, published in The Lancet on Feb. 2, found after analyzing 282 clusters of infections, a direct correlation between viral load and the efficiency of transmission, similar to what had previously been found in HIV.

“In other words, higher viral load, good transmissibility, lower viral load, very poor transmissibility,” Fauci said.

And the Israeli study, a preprint published Feb. 8 in medRxiv, built on the assumption that decreased viral load will lead to decreased transmission. Researchers in this study compared the viral load in those who had been vaccinated and caught COVID-19 with those who had not been vaccinated but also caught the virus.

After tracking breakthrough infections in people who were vaccinated and comparing them with people who had been infected but not vaccinated, the researchers found a “markedly diminished viral load” in the subjects who were vaccinated but had experienced a breakthrough infection.

It’s worth noting that the number of vaccinations in Israel is “way up there,” Fauci said. Israel has administered 78 doses per 100 people, whereas the U.S. has administered 17.8 doses per 100 people.

And as has been reported in the media, he added, “Israel has a remarkable diminution in cases associated with the efficiency of their vaccine.”

The study out of Israel is just one example of the data “starting to point to the fact that vaccine is important not only for the health of the individual to protect them against infection and disease including the variants that Dr. Walensky has mentioned … but it also has very important implications from a public health standpoint for interfering and diminishing the dynamics of the outbreak,” Fauci said.

“So the bottom line message … is when your turn to get vaccinated comes up, get vaccinated,” he said. “It’s not only good for you and your family and your community, it will have a very important impact on the dynamics of the outbreak in our country.”