“Here we present a case of prolonged infection of greater than 6 months with shedding of high titer SARS-CoV-2 in an individual with advanced HIV and antiretroviral treatment failure. …Through whole genome sequencing at multiple time-points, we demonstrate the early emergence of the E484K substitution associated with escape from neutralizing antibodies, followed by other escape mutations and the N501Y substitution found in most variants of concern.”
Well that escalated quickly. It took just a little over one month to do it, but B.1.617.2 is now just hours away from outcompeting B.1.1.7 (aka the UK or Kent variant) on a national scale in Great Britain.
Let’s not forget that B.1.1.7 virtually conquered the globe after being discovered in Britain in September 2020. B117 Infections started to climb rapidly in Britain in December 2020, and it became the dominant sars-cov-2 variant in many countries across the globe shortly thereafter. Now, barely 5 months later, it is being dethroned by a variant that carries neither of the signature sars-cov-2 mutations that were of such concern in the existing VOC’s – E484K and N501Y.
This is the same B.1.617.2 / B.1.1.7 chart for India:
UPDATE 24th May 2021:
“Here we report the discovery of 24 recent B.1.1.482 pango lineage SARS-CoV-2 viruses in South Yorkshire that have acquired approximately 23 additional mutations when compared to the majority of other samples of this lineage. Nine of these additional mutations are found in the spike gene and six represent changes which are found in variants of interest and concern across the world and/or associated with reduced antibody binding (T95I, G142D, △144, N439K, E484K, P681H). Similar mutation profiles were also seen in B.1.1.482 samples from other regions in the UK. We recommended the monitoring of samples of this lineage which is now designated AV.1.”
Virological.org – Detection of Spike Mutations; D80G, T95I, G142D, △144, N439K, E484K, P681H, I1130V, and D1139H, in B.1.1.482 Lineage (AV.1) Samples from South Yorkshire, UK (UK Variant under investigation VUI-21MAY-01)
“Last month, Gytis Dudas was tracking a concerning new coronavirus variant that had triggered an outbreak of COVID-19 in his native Lithuania and appeared sporadically elsewhere in Europe and in the United States. Exploring an international database of coronavirus genomes, Dudas found a crucial clue: One sample of the new variant came from a person who had recently flown to France from Cameroon. A collaborator, Guy Baele of KU Leuven, soon identified six more sequences from people in Europe who had traveled in Cameroon. But then their quest to pinpoint the variant’s origins hit a wall: Cameroon had uploaded a total of only 48 genomes to the global sequence repository, called GISAID. None included the variant”
B.1.620 is also listed as a Variant of Interest by the ECDC:
“In this study we have presented evidence that a SARS-CoV-2 lineage designated B.1.620, ﬁrst detected in Europe in late February, is associated with Central Africa, where it appears to circulate at very high prevalence, and has been introduced into Europe and the US on multiple occasions. A fair number of known B.1.620 genomes that were sequenced in Europe stem from travel-related cases returning from Cameroon, suggesting that it is likely to be the immediate source of this lineage.”
VOC amino acid changes lineage B.1.620 shares most in common with:
B.1.1.7 (ORF1a: SGF3675/3677Δ, S:Y144Δ, S: HV69/70Δ, S: P681H, and S: D1118H)
P.1 (ORF1a: SGF3675/3677Δ, S:P26S, S:E484K, S: T1027I) and
B.1.351 (ORF1a: SGF3675/3677Δ, S: E484K, S: LLA241/243Δ)
MedrXiv preprint – Travel-driven emergence and spread of SARS-CoV-2 lineage B.1.620 with multiple VOC-like mutations and deletions in Europe
In consultation with the WHO SARS-CoV-2 Virus Evolution Working Group, WHO has determined that viruses within the lineage B.1.617 have been characterized as a VOC. B.1.617 contains three sub-lineages, which differ by few but potentially relevant mutations in the spike protein as well as prevalence of detection globally.
As of 11 May, over 4500 sequences have been uploaded to GISAID and assigned to B.1.617 from 44 countries in all six WHO regions, and WHO has received reports of detections from five additional countries. Though there may be important differences among the three sublineages, currently available evidence is too limited for VOI/VOC characterization by sublineage.
Future delineation of sublineages as VOIs/VOCs may be possible as our understanding by sublineage and relative importance of their epidemiology increases. At the present time, WHO has designated B.1.617 as a VOC based on early evidence of phenotypic impacts compared to other circulating virus variants, namely:
- B.1.617 sublineages appear to have higher rates of transmission, including observed rapid increases in prevalence in multiple countries (moderate evidence available for B.1.617.1 and B.1.617.2), and
- Preliminary evidence suggests potential reduced effectiveness of Bamlanivimab, a monoclonal antibody used for COVID-19 treatment, and potentially slightly reduced susceptibility to neutralisation antibodies (limited evidence available for B.1.617.1).
Viruses in the B.1.617 lineage were first reported in India in October 2020. The resurgence in COVID-19 cases and deaths in India has raised questions on the potential role of B.1.617 and other variants (e.g., B.1.1.7) in circulation. A recent risk assessment of the situation in India conducted by WHO found that resurgence and acceleration of COVID-19 transmission in India had several potential contributing factors, including increase in the proportion of cases of SARS-CoV-2 variants with potentially increased transmissibility; several religious and political mass gathering events which increased social mixing; and, under use of and reduced adherence to public health and social measures (PHSM). The exact contributions of these each of these factors on increased transmission in India are not well understood.
Approximately 0.1% of positive samples in India have been sequenced and uploaded to GISAID to identify SARS-CoV-2 variants. The prevalence of several VOCs including B.1.1.7 and B.1.612 sublineages increased concurrent to the surge in COVID-19 cases reported in India. While B.1.1.7 and B.1.612.1 variants have begun to wane in recent weeks, a marked increase in the proportion of viruses sequenced as B.1.612.2 has been observed over the same period. Since the identification of these variants through late April 2021, B.1.617.1 and B.1.617.2 accounted for 21% and 7% of sequenced samples from India, respectively.
A preliminary analyses conducted by WHO using sequences submitted to GISAID suggests that B.1.617.1 and B.1.617.2 have a substantially higher growth rate than other circulating variants in India, suggesting potential increased transmissibility compared. Too few sequences of B.1.617.3 have been detected to date to assess its relative transmissibility. Other studies suggest that the case numbers increased more rapidly during the most recent surge when variants B.1.1.7 and B.1.617 were circulating, compared to the first surge (June to October 2020).
A structural analysis of B.1.617 receptor binding domain (RBD) mutations (L452R and E484Q, along with P681R in the furin cleavage site) suggest that mutations in these variants may result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility, and possibly capacity to escape binding and neutralization by some monoclonal antibodies.
In a preliminary study on hamsters, infection with B.1.617.1 resulted in increased body weight loss, higher viral load in lungs and pronounced lung lesions as compared to B.1 variants (D614G).
Potential impacts of B.1.617 lineage on effectiveness of vaccines or therapeutics, or reinfection risks, remain uncertain. Preliminary laboratory studies awaiting peer review suggest a limited reduction in neutralisation by antibodies; however, real-world impacts may be limited. e One study found a seven-fold reduction in neutralization effectiveness against B.1.617.1 of antibodies generated by vaccination with Moderna – mRNA-1273 and Pfizer BioNTech-Comirnaty vaccines.
A second study also found a reduction in neutralization against virus carrying the E484Q mutation (contained in B.1.617.1 and B.1.617.3) for Pfizer BioNTech – Comirnaty vaccine, similar to that found with the E484K mutation.
A third study reviewing a limited sample of convalescent sera of COVID-19 cases (n=17) and sera from recipients of the Bharat – Covaxin vaccine (n=23) concluded that most neutralizing activity against B.1.617 was retained.
A fourth study reported an approximately three-fold decrease in neutralization activity by plasma from recipients of Pfizer BioNTech – Comirnaty vaccine (n=15) against B.1.617, and a limited two-fold decrease by convalescent sera from cases with severe COVID-19 (n=15). The same study showed that B.1.617.1 (with additional spike mutations R21T, and Q218H) mediates increased entry into certain human and intestinal cell lines, and was resistant to the monoclonal antibody Bamlanivimab; however, it was efficiently inhibited by Imdevimab and by a cocktail of Casirivimab and Imdevimab.
Outside of India, the United Kingdom has reported the largest number of cases sequenced as B.1.617 sub-lineages, and recently designated B.1.617.2 as a national variant of concern. This follows a recent steep increase in the number of cases sequenced as B.1.617 sublineages, and a national assessment that characterized B.1.617.2 as at least equivalent in terms of transmissibility as VOC B.1.1.7; however, they noted insufficient data to assess the potential for immune escape.
As of 5 May, the United Kingdom has reported 520 genomically confirmed B.1.617.2 cases (of which approximately two-thirds were domestically acquired), 261 confirmed B.1.617 cases (without further delineation), and nine confirmed B.1.617.3 cases.
Further robust studies into the phenotypic impacts of these variants, including impacts on epidemiological characteristics (transmissibility, severity, re-infection risk, etc.) and impact on countermeasures, are urgently needed.
WHO COVID-19 Weekly Epidemiological Update – Data as received by WHO from national authorities, as of 9 May 2021, 10 am CET
Examination of the SARS-CoV-2 sequences revealed that both patients were infected with variant viruses. Rapid identification of sequence variants by targeted PCR amplification showed that neither sequence precisely fit any known clade. Some of the substitutions in Patient 1 (T95I, del144, E484K, A570D, D614G, P681H, and D796H) were shared with B.1.526 (T95I, E484K, and D614G6), and three substitutions were shared with Patient 2 (in whom the variants T95I, G142V and del144, F220I, R190T, R237K, R246T, and D614G were detected). Whole viral genome sequencing revealed several additional substitutions, including D796H, present in a guanine–cytosine–rich region not identified by targeted PCR. These substitutions may decrease sensitivity to convalescent serum11 and may have some unique noncoding changes as compared with the clades first identified in Wuhan, the United Kingdom, and New York City.
Although more detailed analysis of whole-genome sequencing from Patient 1 was undertaken, we could not conclude that the variant in this patient was a Pango lineage because it was only present in a single person.
Its closest links on the phylogenetic tree were the variant first identified in the United Kingdom (B.1.1.7) and the variant first identified in New York City (B.1.526), but with considerable differences. It will be of interest to determine whether this may have resulted from a recombination event between B.1.1.7 and B.1.526, as has been recently reported for recombination between the B.1.1.7 lineage and the “wild-type” lineage first identified in Wuhan. Alternatively, shared substitutions may be the result of convergent evolution.
Nepal’s daily coronavirus case is still closely tracking that of its neighbour India, Nepal may also be in need of assistance with medical supplies and equipment to alleviate suffering within the next 7 days.
“Nepal Health Ministry says situation unmanageable as hospitals run out of beds The country’s health system cracks as coronavirus cases surge, crossing the 5,000 mark.” Kathmandu Post Report
In this study, we conducted genetic surveillance and identified R.1 lineage harboring E484K mutation in RBD by whole genome sequencing. The R.1 lineage was observed in three patients and transmitted among relatives in Japan. To investigate the global distribution of R.1 lineage, we next collected registration data from the EpiCoV of GISAID database . As of March 5, 2021, a total of 305 samples of R.1 lineage had been registered from all over the world, with the majority spread in the USA (44%, 135/305) and Japan (28%, 84/305) (Figure 1A and Table 1). R.1 lineage was first reported in Texas, USA at the end of October 2020, and was found in Japan at the end of November 2020. The number of detected lineages has changed in a similar trend between the USA, Japan and other countries (Figure 1A), implying that SARS-CoV-2 R.1 lineage may have emerged in several regions at approximately the same time.
Examination of the SARS-CoV-2 sequences revealed that both patients were infected with variant viruses. Rapid identification of sequence variants by targeted PCR amplification showed that neither sequence precisely fit any known clade. Some of the substitutions in Patient 1 (T95I, del144, E484K, A570D, D614G, P681H, and D796H) were shared with B.1.526 (T95I, E484K, and D614G6), and three substitutions were shared with Patient 2 (in whom the variants T95I, G142V and del144, F220I, R190T, R237K, R246T, and D614G were detected).
NEJM article “Vaccine Breakthrough Infections with SARS-CoV-2 Variants”
A 39-year-old Brazilian man who died of COVID-19 last month was suffering from a second bout of the illness, researchers said on Tuesday, making it the country’s first confirmed death from coronavirus reinfection. Both episodes involved variants with the E484K mutation.
The man, from Campo Bom in the southern state of Rio Grande do Sul, had a history of chronic cardiovascular disease and diabetes. He first tested positive on November 30 but details about his symptoms – if any – are unclear. Genomic sequencing revealed the P.1 variant.
The patient fell ill a second time about 3 months later and tested positive on March 11, according to researchers at Feevale University. His initial symptoms were fatigue and respiratory distress, but his condition worsened and he was transferred to the ICU, where he was intubated and died on March 19.
Genomic sequencing of the sample from the second episode revealed the P.2 variant, which is classified as a Variant of Interest.
E484K has been found in a new Sars-Cov-2 variant labelled as B.1.618, which has been reported in West Bengal, India.
Data submitted from India to the global repository GISAID shows the B.1.618, at 12%, is the third most common variant sequenced in the last 60 days. The B.1.617, at 28%, is the most common among sequences, followed by B.1.1.7 (the UK variant), the India Mutation Report by Scripps Research showed, citing the GISAID data
“We were the first to identify two independent events of co-infection caused by the occurrence of B.1.1.28 (E484K) with either B.1.1.248 or B.1.91 lineages. Also, clustering analysis revealed the occurrence of a novel cluster of samples circulating in the state (named VUI-NP13L) characterized by 12 lineage-defining mutations.”
ScienceDirect.com preprint: Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co-infection events by two different lineages in Rio Grande do Sul, Brazil
Forbes are carrying an interesting about the recently discovered coronavirus variant found in Tanzania, Africa in travellers arriving from Angola. The variant is from “From An Entirely New Branch Of SARS-CoV-2”, and carries Spike mutations E484K, P681H, T478R, Q957H, H655Y, D215G, D80Y. L210N, W258L, R246I. “An additional 18 amino acid changes occur in proteins outside the spike protein. These include 14 in the orf1ab proteins that specify the replication complex. “
“This is a remarkable illustration of convergent evolution,” say’s Forbes