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CDC EXECUTIVE                                                                                  CDC EXECUTIVE
 SUMMARY                                                                                           SUMMARY







                                               the G614 variant spreads more quickly   What is CDC doing to track emerging
                                               than viruses without the mutation.   variants of SARS-CoV-2?

 Centers for Disease Control                 •  Ability to cause either milder or more se-  launched the National SARS-CoV-2 Strain
                                                                                   In November 2020, CDC officially
                                               vere disease in humans. There is no evi-
                                               dence that VOC 202012/01 produces   Surveillance (NS3) program to increase the
 Implications of the Emerging SARS-CoV-2 Variant VOC 202012/01   more severe illness than other SARS-CoV-  number and representativeness of viruses un-
                                               2 variants.                       dergoing characterization. When fully imple-

 Updated December 22, 2020                                                       mented in January 2021, each state will send
                                             •  Ability to evade detection by specific diag-
                                                                                 CDC at least 10 samples biweekly for se-
                                               nostic tests. Most commercial polymerase
                                                                                 quencing and further characterization. In ad-
                                               chain reaction (PCR) tests have multiple
                                                                                 dition, CDC’s COVID-19 response is
                                               targets to detect the virus, such that even
                                                                                 actively seeking samples of interest, such as
        they are “non-synonymous”), but this amino   if a mutation impacts one of the targets,
 Executive summary   Why has this variant been in the    the United Kingdom and the United States,   samples associated with animal infection

 A new variant strain of SARS-CoV-2 that   news recently?   as well as the high prevalence of this variant   acid substitution does not impact the pro-  the other PCR targets will still work.   and, in the future, samples from vaccine-
        tein’s function.
 contains a series of mutations has been de-  Since November 2020, a variant strain of   among current UK infections, increase the   •  Decreased susceptibility to therapeutic   breakthrough infections. Data from these ef-
          VOC 202012/01 has 14 non-synonymous
 scribed in the United Kingdom (UK) and   SARS-CoV-2 has become prevalent in the   likelihood of importation. Given the small   agents such as monoclonal antibodies.   forts are continuously analyzed at CDC, and

        (amino acid [AA] altering) mutations, 6 syn-
 become highly prevalent in London and   southeast of England, reportedly accounting   fraction of US infections that have been se-  •  Ability to evade vaccine-induced immu-  genomic data are rapidly uploaded to public
        onymous (non-AA altering), and 3 deletions,
 southeast England. Based on these muta-  for 60% of recent infections in London. This   quenced, the variant could already be in the   nity. FDA-authorized vaccines are “poly-  databases for use by researchers, public health
        notably including,
 tions, this variant strain has been predicted   variant has a mutation in the receptor bind-  United States without having been detected.      clonal,” producing antibodies that target   agencies, and industry. To coordinate US se-
 to potentially be more rapidly transmissible   ing domain (RBD) of the spike protein at po-     •  69/70 deletion: this double deletion has   several parts of the spike protein. The virus   quencing efforts outside of CDC, since early
 than other circulating strains of SARS-CoV-  sition 501, where amino acid asparagine (N)   What do we know already about    occurred spontaneously many times, and   would likely need to accumulate multiple   in the pandemic, CDC has led a national
 2. Although a variant may predominate in a   has been replaced with tyrosine (Y). The   variants containing N501Y?   likely leads to a change in the shape of (i.e.,   mutations in the spike protein to evade im-  coalition of laboratories sequencing SARS-
 geographic area, that fact alone does not   shorthand for this mutation is N501Y, some-  Prior work on variants with N501Y sug-  a conformational change in) the spike pro-  munity induced by vaccines or by natural   CoV-2 (SPHERES). The SPHERES coali-
 mean that the variant is more infectious. Sci-  times noted as S:N501Y to specify that it is   gests they may bind more tightly to the   tein.   infection.   tion consists of more than 160 institutions,

 entists are working to learn more about this   in the spike protein. This variant carries many   human angiotensin-converting enzyme 2   •  P681H: near the S1/S2 furin cleavage site,      including academic centers, industry, non-
 variant to better understand how easily it   other mutations, including a double deletion   (ACE2) receptor. It is unknown whether   a site with high variability in coron-  Among these possibilities, the last—the   governmental organizations, and public
 might be transmitted and whether currently   (positions 69 and 70).   that tighter binding, if true, translates into   aviruses. This mutation has also emerged   ability to evade vaccine-induced immunity—  health agencies. Of the approximately
 authorized vaccines will protect people      any significant epidemiological or clinical   spontaneously multiple times.   would likely be the most concerning because   275,000 full-genome sequences currently in
 against it. At this time, there is no evidence   Why has this variant emerged    differences. In one laboratory study of trans-     once a large proportion of the population is   public databases, 51,000 are from the United
 that this variant causes more severe illness or   in the UK?   mission of the virus between ferrets, this mu-  •  ORF8 stop codon (Q27stop): This muta-  vaccinated, there will be immune pressure   States. (The UK currently has the most se-
 increased risk of death. Information regard-  We do not know. By chance alone, viral   tation (and one other) spontaneously arose   tion is not in the spike protein but in a dif-  that could favor and accelerate emergence of   quences, with 125,000).
 ing the virologic, epidemiologic, and clinical   variants often emerge or disappear, and   in the ferrets during the experiment. The sig-  ferent gene (in open reading frame 8), the   such variants by selecting for “escape mu-
 characteristics of the variant are rapidly   that may be the case here. Alternatively, it   nificance of this observation remains to be   function of which is unknown. Similar   tants.” There is no evidence that this is occur-  Last Updated Dec. 22, 2020
 emerging. CDC, in collaboration with other   may be emerging because it is better fit to   elucidated. VOC 202012/01 so far has no   mutations have occurred in the past. In   ring, and most experts believe escape mutants   Content source: National Center for Im-
 public health agencies, is monitoring the sit-  spread in humans. This rapid change from   known association with animals or animal   Singapore, one strain with this type of mu-  are unlikely to emerge because of the nature   munization and Respiratory Diseases
 uation closely. CDC will communicate new   being a rare strain to becoming a common   contact.   tation emerged and disappeared.   of the virus.   (NCIRD), Division of Viral Diseases
 information as it becomes available.   strain has concerned scientists in the UK,
    who are urgently evaluating the characteris-  What about the other mutations in    What implications could the    Is this new variant related to the newly
 Does this variant have a name?   tics of the variant strain and of the illness that   this variant of SARS-CoV-2?   emergence of new variants have?   emergent variant in South Africa?
 At present, the variant is referred to as   it causes.   SARS-CoV-2 mutates regularly, acquiring   Among the potential consequences of   On December 18, 2020, the South African
 “SARS-CoV-2 VOC 202012/01” (i.e., the      about one new mutation in its genome every   these mutations are the following:   government announced that it had also seen
 first variant of concern from 2020, December),   Have we seen this variant in    two weeks. Many mutations are silent (i.e.,   •  Ability to spread more quickly in hu-  the emergence of a new strain in a scenario
 or “B.1.1.7.” The press often uses the terms   the United States?   cause no change in the structure of the pro-  mans. There is already evidence that one   similar to that in the UK. The South African
 “variant,” “strain,” “lineage,” and “mutant” in-  The VOC 202012/01 variant has not been   teins they encode) because they produce a   mutation, D614G, has this property to   variant also has the N501Y mutation and
 terchangeably. For the time being in the con-  identified through sequencing efforts in the   three-letter codon that translates to the same   spread more quickly. In the lab, G614 vari-  several other mutations but emerged com-
 text of this variant, the first three of these terms   United States, although viruses have only   amino acid (i.e., they are “synonymous”).   ants propagate more quickly in human res-  pletely independently of the UK strain and
 are generally being used interchangeably by the   been sequenced from about 51,000 of the 17   Other mutations may change the codon in a   piratory epithelial cells, out-competing   is not related to it.
 scientific community as well.   million US cases. Ongoing travel between   way that leads to an amino acid change (i.e.,   D614 viruses. There also is evidence that



  30     SAN ANTONIO MEDICINE  • January 2021                                                Visit us at www.bcms.org     31
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