Updated: Apr 5
Written and recorded by Yidan Gao, edited by LisaMichelle Pecaro
Listen to the corresponding podcast episode at: tinyurl.com/VariantCast
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April of 2021 is just around the corner. One year ago, governments around the globe requested a total of almost 4 million people to stay home and prepare for month-long lockdowns, to slow the spread of COVID-19. During the year of 2020, many significant advances have been made in understanding virology, deciphering the SARS-CoV-2 genome, exhorting mask wearing and developing vaccines. But just as we are working strenuously to combat the virus, SARS-CoV-2 quietly mutates and presents as several new variants that can better infect humans and evade the immune system.
There are several known strains of SARS-CoV-2 that have caught public attention and are circulating globally.
In chronological order:
As early as March 2020, the D614G mutant first emerged in Europe.
In July 2020, researchers at the University of California San Francisco identified 2 new strains, B.1.427/B.1.429, circulating in Los Angeles, CA.
Early in October 2020, B.1.351, was reported in South Africa.
On December 14, 2020, a new B.1.1.7 variant was reported in the United Kingdom (UK), but the Public Health authorities of England suspected that this variant emerged as early as September 2020.
In early January 2021, the P.1 variant was detected during a routine screening of Brazilian travelers arriving in Japan.
The above figure was created by Yidan Gao.
This podcast follows the ordered timeline of variant detection.
Let’s start from the first variant, the D614G variant was thoroughly described in one of our previous blogs. Here are some refreshers on this strain. D614G refers to a point mutation at amino acid residue 614 from aspartic acid (D) to glycine (G), occurring in the spike protein of SARS-CoV-2. The spike protein, as described in our previous blogs, is a popular target for mutation. This change in amino acid sequence changes the protein structure and interactions with its receptor, leading to an increase in binding affinity. Binding affinity refers to the strength of interaction between one protein, in this case, the spike protein, and its binding partner, the ACE2 protein, which is a receptor found on host cells. We will see this theme of increased binding affinity arise multiple times in our discussion.
B.1.427 and B.1.429 were two coronavirus strains found predominantly in the state of California last July. Mutations in B.1.427 include two point mutations of the spike protein at residues 452 and 614, respectively. Two extra mutant residues of the spike were found in B.1.429 at residues 12 and 152. The Centers for Disease Control & Prevention (CDC) recently listed B.1.427/429 as variants of concern, together with B.1.1.7, B.1.351 and P.1, due to an approximately 20% enhancement of transmissibility. This increase in contagiousness is likely associated with these point mutations, which help the virus to evade the immune system by escaping antibody binding.
Three month later in October, B.1.351 was recognized in South Africa and spread to the US in late January 2021. According to the CDC, there have not been any reports on the correlation of B.1.351 with increased disease severity. However, the fact that this variant has many more mutations poses some concern for scientists in predicting vaccine efficacy. Specifically, the point mutation of the spike protein at the 484th residue, which changes glutamic acid (E) to lysine (K), might render the variant moderately resistant to monoclonal antibodies during therapeutic applications, according to Weisblum et al.
Two months later, B.1.1.7 silently emerged from the UK. It was recognized by the public in mid-December and soon spread to the US at the end of December 2020. Epidemiologists reported that the new variant has a greater transmissibility. The variant’s behavior confirmed this, because it became the dominant strain in the US only 3 months after arriving. In B.1.1.7 specifically, 3 main mutations are concerning. Two of them involve point mutations that change amino acids at residue 501 and 681. The other mutation involves a deletion of the 69th and 70th amino acids in the spike protein stalk. Synergy of these mutations increases the receptor binding affinity of the SARS-CoV-2 spike to ACE2, on host epithelial cells. The emergence of this viral strain led to numerous investigations on its association with mortality. In their matched cohort study, Challen et al. followed 54,000 SARS-CoV-2 positive patients from October 1st, 2020 to January 29th, 2021 and measured death within 28 days after a positive COVID test. The probability of mortality was enhanced from 2.5 (previous circulating variants) to 4.1 (B.1.1.7) per 1,000 detected cases. For more information about B.1.1.7, you are welcome to access one of our previous blogs here.
The P.1 variant originated in Brazil and spread to the US around the same time as B.1.351. The highlight for this viral strain is that it largely infected Manaus, a city in Brazil that had already experienced a round of COVID infections in October 2020. Opposed to what is commonly expected, in some patients, first exposure to SARS-CoV-2 did not convey secondary protection to future exposure with the P.1 strain. The fact that some citizens in Manaus were infected again suggests that mutations on the P.1 variant allowed it to evade the neutralizing effect of the antibodies generated through first exposure.
B.1.526 is not listed on the CDC official site as one of the ‘Variants of Concern’ as of March. 26, 2021. But B.1.526 is making its way up to be one of the most common variants circulating in New York and New Jersey. Government officials in New Jersey paused re-opening plans in order to prevent social gathering and community transmission. This new variant contains mutations in the spike protein, similar to previous strains, including those that are associated with potential antibody resistance. Still, a lot remains unknown about this specific viral strain.
The descriptions above cover the majority of the prevalent variants as of March 27, 2021. For more updates about variant information, you may visit the CDC’s website, which lists all of the identified variants that we may or may not touch on. Although some viral variants pose concerns that they may partially evade immunity generated by vaccines, the approved COVID vaccines still elicit broad immune response, which will likely resist the majority of evasion associated with mutations on variants. Vaccine modification and development are also in the works to combat these new variants. The World Health Organization urges the public to get vaccinated if they are eligible. Lastly, even though the virus mutates and may render some therapeutic interventions or vaccines less effective, preventative measures, such as wearing a mask and social distancing, are still powerful tools to keep ourselves and our community safe.
Results from ongoing research and the current understanding of COVID-19 are constantly evolving. This post contains information that was last updated on March 27, 2021.