Written by Yidan Gao, edited by Edward Chen and 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 asked almost 4 billion people to stay home and prepare for month-long lockdowns to slow the spread of COVID-19. During 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 into 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, these strains are:
D614G: First emerged in Europe as early as March 2020.
B.1.427 and B.1.429: Circulating in Los Angeles, CA, were identified by researchers at UC San Francisco in July 2020.
B.1.351: Was reported in South Africa in early October 2020.
B.1.1.7: Was reported in the United Kingdom on December 14, 2020. However, the public health authorities in England suspected that this variant emerged as early as September 2020.
P.1: Was detected during a routine screening of Brazilian travelers arriving in Japan in early January 2021.
The above figure was created by Yidan Gao.
This podcast follows the ordered timeline of variant detection.
Let’s start with the first variant, the D614G variant, which was thoroughly described in one of our previous blogs. 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 increases its binding affinity with the receptor it uses to infect humans. 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 human 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 and 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 evade the immune system by escaping antibody recognition.
Three month later in October, B.1.351 was recognized in South Africa. This variant spread to the US in late January 2021. According to the CDC, there has not been any evidence of B.1.351 causing more disease. 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 residue 484, which changes glutamic acid (E) to lysine (K), might render the variant moderately resistant to monoclonal antibodies during therapeutic applications, according to a 2020 paper.
Two months later, B.1.1.7 silently emerged from the UK. This variant has been covered in one of our previous blogs. 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 greater transmissibility and it became the dominant strain in the US only 3 months after arriving. 3 specific mutations in the B.1.1.7 strain are most concerning. Two of them are point mutations that change the 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. These mutations increase the receptor binding affinity of the SARS-CoV-2 spike to the ACE2 receptor on host epithelial cells. The emergence of this viral strain led to numerous investigations on its association with mortality. In a matched cohort study, Challen et al. followed 54,000 COVID patients from October 1, 2020 to January 29, 2021 and measured death within 28 days after a positive COVID test. The mortality rate increased from 0.25% for previously existing variants to 0.41% for patients infected with the B.1.1.7 strain.
The P.1 variant originated in Brazil and spread to the US around the same time as B.1.351. This viral strain was widespread in Manaus, a city in Brazil. Because some Manaus residents were re-infected after recovery, the P.1 variant likely evades the neutralizing effect of antibodies generated after a first infection.
As of March 26, 2021, B.1.526 is not included on the CDC website among the ‘Variants of Concern’. However, B.1.526 is making its way up as one of the most common variants circulating in New York and New Jersey. Government officials in New Jersey paused reopening plans in order to prevent social gatherings 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.