CDC, WHO Establish New Threat Levels for COVID-19 Variants

The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have established new criteria to classify variants of SARS-CoV-2, the virus that causes COVID-19.

The criteria are meant to clarify how much is known about recent changes to the circulating viruses. The levels also help convey risk. 

The new designations are “variant of interest”; “variant of concern”; and “variant of high consequence.” 

• A variant of interest has caused discrete clusters of infections in the United States or in other countries, or seems to be driving a surge in cases. It also has gene changes that suggest it might be more contagious or that may help it to escape immunity conferred by natural infection or vaccination. Therapeutics and tests may not work as well against it. The CDC is watching three of these.

• A variant of concern has been proven through scientific research to be more contagious or to cause more severe disease. It may also reduce the effectiveness of therapeutics and vaccines. People who have previously had COVID-19 may become reinfected by the new strain. The CDC is tracking five of these.

• A variant of high consequence causes more severe disease and greater numbers of hospitalizations. It has also been shown to defeat medical countermeasures, such as vaccines, antiviral drugs, and monoclonal antibodies. So far, none of the variants meets this definition.

In following the new criteria, the CDC said it was casting a wide net when designating variants of interest, but would require stronger evidence before it would name a variant of concern.

“CDC is aligned with the WHO approach in that the threshold for designating a variant of interest should be relatively low in order to monitor potentially important variants; however, the threshold for designating a variant of concern should be high in order to focus resources on the variants with the highest public health implications,” according to a CDC spokesperson.

Previously, variants have been classified by the CDC, but that’s about to change slightly. Going forward, final decisions on which variants are important to pay attention to will be made by the CDC in consultation with the new SARS Interagency Group on variants, which comprises experts from the National Institutes of Health (NIH), the Food and Drug Administration, the Department of Defense, the Biomedical Advanced Research and Development Authority, and the Department of Agriculture.

The task force is urgently needed, said Michael Diamond, MD, PhD, associate director of the Center for Human Immunology and Immunotherapy Programs at Washington University School of Medicine in St. Louis.

The CDC has been hit in recent years by budget cuts and political interference, and doesn’t currently have the muscle needed to respond as quickly or robustly as it needs to, according to scientists familiar with the effort.

“There needs to be some superstructure to deal with this,” said Diamond, who is involved in the effort through a working group at the NIH. Diamond said that 50 to 100 scientists have joined some of the calls he’s participated in.

“We need to do this because we need to be able to coordinate surveillance with in vitro testing, with animal-based testing with industry to be able to access their therapeutics, their vaccines, and to be able to provide feedback and retest them over time. This can’t be done just by ad hoc academic collaboration or even one agency,” he said.

“Let’s say the CDC says, oh we identified a variant that’s emerging in Iowa at high frequency. Well, CDC does not have the facilities to quickly and nimbly test whether that variant actually is meaningful or not,” Diamond said.

“So we need to figure that out. This needs to then initiate a pipeline of experiments that would be done through academic, government, and non-government agencies, whereby we could test that variant, generate recombinant pseudoviruses, generate recombinant viruses, and generate recombinant spike proteins,” Diamond said.

The animal experiments would help to evaluate whether it increases infection rates or lessens the effect of vaccines or drugs. If it does, decisions would be made about “how are we going to respond in the context of modifying existing drugs or therapeutics or vaccines?” Diamond said.

The government would then coordinate with pharmaceutical companies.

Tracking Emergent Variants

Beyond the new CDC/WHO designations, Public Health England, the United Kingdom’s counterpart to the CDC, is using an additional classification for “variants under investigation.” Variants under investigation are newly identified and are the subject of ongoing studies, but scientists don’t yet know anything about their significance to public health.

On Tuesday, Public Health England announced that it was investigating the emerging P3 variant, which was first detected in the Philippines.

On Monday, researchers in Colombia published a preprint study describing a new variant of B.1.111 with mutations on its spike protein at L249S and E484K. Those two mutations have helped other viruses escape antibodies created by the body in response to both vaccines and natural infection. 

Public Health France also announced on Tuesday a new cluster of cases connected to a hospital in the Brittany region caused by a new variant in clade 20C. The French variant has nine mutations on its spike protein, and wasn’t detected through PCR testing, suggesting that the changes keep it from being detected by those tests.

Keeping Variants in Perspective

When a virus mutates, or acquires a change to its genetic code, this creates a variant. It’s merely a version of the virus that is different from the virus that created it. Variants arise frequently, and usually are not harmful to humans. Occasionally, a change or group of changes will help one version of the virus outcompete other variants. It might reproduce more quickly, for example, or develop a different or more efficient way to infect cells. Sometimes a change will tweak its structure just enough so the antibodies our immune system makes can’t latch onto it. 

When that happens, more disease, and more severe disease, can follow. Drugs and vaccines may need to be altered by pharmaceutical companies to keep up.

Variants of Concern

So far, the CDC is tracking five variants of concern: the B.1.1.7 variant, first identified in the United Kingdom; the P.1 variant, first detected in Japan and Brazil; the B.1.351 variant, first reported in South Africa; and the B.1.427 and B.1.429 variants, which have been spreading in California. 

Surveillance of these variants is currently limited. The United States is doing relatively little genomic surveillance of the virus compared with other countries, like the United Kingdom.

The B.1.1.7 variant is at least 50% more contagious than the older versions of the virus. It has caused major COVID-19 surges in the United Kingdom, Israel, and Europe. As of March 16, the CDC says 4686 cases have been detected in the United States, and span all 50 states.

Labs have detected 142 cases of the B.1.351 variant. These come from 25 states. There have been at least 27 cases of the P.1 variant in at least 12 states. Studies have shown that the current vaccines are less effective against these two variants. They are also not as vulnerable to some of the monoclonal antibody therapies that have been developed. Like B.1.1.7, B.1.351 appears to be about 50% more contagious.

The B.1.427 and B.1.429 variants appear to be about 20% more contagious than earlier versions of the virus. They may also slightly reduce the effectiveness of vaccines and therapeutics. The immunity generated by the vaccines is so strong, though, that this reduction isn’t expected to keep them from being effective at preventing infections or reducing transmission of the virus.

Sources

Michael Diamond, MD, PhD, associate director, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, Missouri

CDC, SARS-CoV2 Variants, updated March 16, 2021

WHO, Weekly Epidemiological Report, February 25, 2021

WHO, Weekly Epidemiological Report, March 16, 2021

Public Health England, Variants of Concern or Under Investigation, Updated March 15, 2021

Créditos: Comité científico Covid