The Centers for Disease Control and Prevention on Tuesday expanded an order to require a negative coronavirus test from international airline passengers as the U.S. faces a worsening outbreak.

The order, which goes into effect on Jan. 26, came after the Trump administration last month began requiring negative test results from U.K. travelers in an effort to contain the more transmissible coronavirus variant detected in the region.

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Despite that order, the variant has since been discovered in the U.S. The new, expanded order comes after another variant has been detected in Japan.

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“Variants of the SARS-CoV-2 virus continue to emerge in countries around the world, and there is evidence of increased transmissibility of some of these variants,” the CDC said in a statement announcing the order. “With the US already in surge status, the testing requirement for air passengers will help slow the spread of the virus as we work to vaccinate the American public.”

The order requires air passengers to get tested within the three days before their flight and provide documentation of the result to the airline. Alternatively, they could provide “documentation of having recovered from COVID-19.” U.S. travelers coming back to the country are also required to follow the order.

The CDC recommends travelers get tested again three to five days after their arrival and stay home for one week after their trip.

The order also comes as the U.S. coronavirus outbreak reaches a level never seen before, with over 22.7 million cases and nearly 380,000 deaths.

In an effort to combat the pandemic, federal officials on Tuesday announced they would release all vaccine doses instead of holding back the second shot.

Why do viruses mutate?

Viruses are prone to mutations. Indeed, all genetic material, including that of humans, can mutate when mistakes occur during replication.

A mutation of a virus occurs when there is a change in its genetic sequence. This creates variation and drives virus evolution.

Mutations lead to changes in the proteins that are encoded in the viral genetic code. These changes can either be advantageous, harmful, or neutral.

How many mutations does it take to produce a new strain of the virus? This is not easy to answer, in part because scientists disagree about the definition of the word “strain.”

In general, if a virus has enough mutations to make its biology significantly different, it may be a considered new strain. This means that it may respond differently to vaccines or treatments, or it may infect a different species or transmit in a different way.

But if the biology of the virus broadly remains the same, despite the mutations, the term “variant” may be more scientifically accurate.

Since the start of the pandemic, there has been much discussion about SARS-CoV-2 mutations and what implications they may have.

SARS-CoV-2, like many other coronaviruses, has an enzyme that proofreads its genetic code during replication, reducing the rate of mutations.

While the novel coronavirus has a relatively stable genome, compared with other types of virus, it does mutate sometimes, and scientists have closely monitored these changes.

One of the most widely talked about mutations has resulted in the D614G variant. This causes a change in the spike protein, which interacts with the ACE2 receptor on human cells to facilitate viral entry.

Specifically, an amino acid in the spike protein at position 614 is changed from aspartic acid to glycine.

Research by Dr. Bette Korber, from the Los Alamos National Laboratory, in New Mexico, and colleagues suggests that this change allows the variant to infect people more easily.

The D614G variant has become the predominant variant of SARS-CoV-2 worldwide, the research shows.

The team’s data indicate that people with the D614G variant of the virus may have higher levels of viral RNA than people with the original variant. But no evidence indicates that this causes more severe COVID-19.

Still, not all scientists agree with this group’s interpretation. Referring to the paper, Dr. Nathan Grubaugh, from the Yale School of Public Health, in New Haven, CT, and colleagues commented that more research is needed to support the idea that this variant is indeed more transmissible.

While researchers continue to study the differences between the D and G variants, the world has turned its focus toward B.1.1.7 and how it may shape the course of the pandemic.

B.1.1.7 and the founder effect

The B.1.1.7 variant has 23 mutations. Six cause no change in the amino acid sequence of the virus. Of the remaining 17 mutations, eight affect the spike protein.

The N501Y change, which involves a switch from asparagine to tyrosine at position 501, is located in the receptor-binding domain of the spike protein. This is a crucial section, as it interacts directly with the ACE2 receptor.

Another mutation in the RNA that encodes the spike protein allows researchers to detect this variant in polymerase chain reaction (PCR) test samples. This is because the mutation lies in one of the targeted areas that many diagnostic PCR tests use.

These tests also use other targets, usually a combination of at least two. Scientists can look for PCR tests that are negative for the spike sequence but positive for the other targets. This would indicate that the person has the B.1.1.7 variant of the SARS-CoV-2 virus.