Delta 4+ variant: Complete vaccine escape & enhanced infectivity with Pfizer vaccine

“Here we suggest an evolutionary pathway by which the Delta variant could achieve complete escape from vaccine-induced immunity”.   Although Pfizer-BioNTech BNT162b2-immune sera neutralized the Delta variant, when four common mutations were introduced into the receptor binding domain (RBD) of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity.

Unique mutations in the Delta NTD were involved in the enhanced infectivity by the BNT162b2-immune sera. Sera of mice immunized by Delta spike, but not wild-type spike, consistently neutralized the Delta 4+ variant without enhancing infectivity.

The 4 key mutations inserted were K417N, N439K, E484K and N501Y.

 

Preprint: The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines 

 

 

Public Health England releases detailed vaccine breakthrough information

 

So what is Plan B if the vaccines fail?

 

 

280 cases of Delta variant with N501Y, some with E484K too

Delta + Alpha + Beta + Gamma recombinant variant found in Turkey.

 

 

 

 

Image by Elliot Alderson from Pixabay

Preprint: Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2

In this study, we reported the emergence and spread of the novel B.1.621 lineage of SARS-CoV-2, a new VOI with the insertion 146N and several amino acid substitutions in the Spike protein (T95I,Y144T, Y145S, R346K, E484K, N501Y and P681H). Although B.1.621 does not meet all of the VOC classification criteria so far, the set of mutations gathered the Spike protein could confer a synergistic impact on attributes such as reduction of vaccine-induced protection from severe disease, increased transmission and disease severity

Medrxiv preprint: Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2
 

Belgium: 7 fully vaccinated care home residents die after contracting B.1.621 variant first found in Colombia

 

 

Image by gustavo9917 from Pixabay

Preprint: Persistent #coronavirus infection and intra-host evolution in association with advanced HIV infection

“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.”

Preprint: Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV
infection

 

 

Photo by National Cancer Institute on Unsplash

France: 46 cases of B.1.1.7 with E484Q mutation in Bordeaux #coronavirus outbreak of VOC 20I/484Q

The French city of Bordeaux is to fast-track vaccinations for residents in one neighbourhood, opening access the jab for all adults after nearly 50 people tested positive for a “very rare” variant of Covid-19.  Labelled VOC 20I/484Q, the strain is related to the British variant B.1.1.7 but with an additional mutation E484Q. The variant has already been identified on a national level in France but it has reportedly been very rare until now.  At least 46 people have been infected with the variant in Bordeaux, with mass testing launched on Friday to track down further cases.

“There has never been a cluster like that in the general population,” said Professor Patrick Dehail of the The National Reference Center in Lyon

Lexpress.fr report

 

UPDATE 1: There’s nothing in the latest Epidemiological Update from French Health Department about 20I/E484Q, but 20I/E484K gets a mention:

Le VOC 20I/484K, identifié pour la première fois en Grande-Bretagne suite à l’acquisition par le VOC 20I/501Y.V1 de la mutation E484K, était peu détecté en France jusqu’à la mi-mars. Une transmission communautaire a été rapportée depuis début avril dans plusieurs régions : Bretagne (en particulier à Brest), Ile-de-France et Hauts-de-France. Toutefois, le variant 20I/484K restait très nettement minoritaire par rapport au variant 20I/501Y. Dans les autres régions, aucune évolution notable dans les détections de cas du variant 20I/E484K n’a été observée et le nombre de cas restait faible.

 

UPDATE 2: The European CDC, which still lists all B.1.617 sub-lineages as Variants of Interest (VOI), not Variants of Concern (VOC), shows the E484Q mutation appears in both B.1.617.1 and B.1.617.3, but NOT B.1.617.2

 

More….

UK: #coronavirus variant B.1.617.2 within hours of outcompeting B.1.1.7 in Britain

 

Image by Göran Waldt from Pixabay

UK: #coronavirus variant B.1.617.2 within hours of outcompeting B.1.1.7 in Britain

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:

 

Charts courtesy of outbreak.info

 

UPDATE 24th May 2021:

UK: PHE data shows B.1.617.2 now outcompetes B.1.1.7

 

OLDER POSTS:

India: The stunning rise of the B.1.617.2 [Delta] #coronavirus variant

 

UK: eleven vaccine breakthrough cases reported for B.1.617.2

UK SAGE: Lab studies suggest that the N501Y spike protein mutation increases binding to rat and mouse ACE2 leading to viral replication

A report issued by the UK government’s Scientific Advisory Group for Emergencies (SAGE) found the likelihood that a variant of concern (VOC) that has arisen in humans could infect a rodent and then spread among the animals is high. Researchers say lab evidence indicates that while rats and mice appear unable to contract the most common forms of coronavirus COVID-19, the N501Y spike protein mutation “has an increased affinity” for rodents.

The report said: “There is a plausible pathway for infection of rodents with new variants of concern from infected humans following contamination of an environment. “Experimental evidence has shown SARS-CoV-2 with N501Y has increased affinity for lab rodents and there is nothing to suggest the same would not be true for wild rodents.

SAGE: Coronavirus (COVID-19) response, 8 April 2021

 

 

Image by sipa from Pixabay

Brazil: rapid spread and high impact of the #coronavirus VOC P.1 in Sao Paulo – March 2021

Here, we show evidence of how fast the VOC P.1 has spread in the most populated city in South America – Sao Paulo.  From March 1st to March 15th, 427 nasopharyngeal samples were collected from 245 HP and 125 from HCW outpatients (25.5% and 23.2% of positivity rate, respectively). We then selected 60 samples with Ct value ≤ 30 (38 samples from HP, and 22 from HCW). All HCW presented only mild symptoms and did not need hospitalization.

Of the 60 selected samples, 52 whole genome sequences were generated (30 from HP and 22 from HCW) following the sequencing protocol using the Illumina MiSeq platform and the analysis pipeline described by Resende et al (8). The SARS-CoV-2 lineages were classified by the PANGO lineages nomenclature (9). Genome sequences generated have been deposited at the EpiCoV database on GISAID https://www.gisaid.org/) under accession numbers EPI_ISL_1464630 to EPI_ISL_1464677.

Of the 52 sequenced samples, 44 (84.4%) were identified as VOC P.1;  5 (9.2%) as VOI P.2; 1 (1,9%) as B.1.1.7, and 2 (3,8%) B.1.1.28.

The most notable variants circulating in the second wave, including B.1.1.7 (detected first in the United Kingdom) and B.1.1.351 (detected first in South Africa), and P.1, are related to an increase of transmissibility (2,10). Interestingly, the P.1 variant was first identified in the State of Amazonas, about 3,800 kilometers apart from São Paulo (5). It is evident that the P.1 variant prevailed during the first two weeks of March, showing a regular distribution among HP and HCW with no difference in terms of age, sex, vaccination, and outcome (Table). From the first to the second weeks of March, we observed a higher frequency of P.1 (78.6% and 91.7%, respectively). In this survey, only one sample from a HP was identified as VOC B.1.1.7. The other two samples were identified as B.1.1.28, a widely spread lineage during the first wave in Brazil.

There is a broad discussion about whether the available vaccines against SARS-CoV-2 will be less effective at preventing infection with the emerging variants (10). In this work, 14 samples (26.9%) of the 52 sequenced samples were from individuals that had received at least one dose of vaccine, ChAdOx1-S/nCoV-19 (n=2) or SINOVAC (n=26). Although they were vaccinated, they could not be considered immunized, regarding the days after vaccination.

Among the hospitalized patients, 19 (63%) were admitted to the intensive care unit, from which nine were discharged and ten died. Comparing the RT-PCR Ct values of all attended patients since the first wave, we did not observe any difference in the Ct mean values with those of P.1 (data not shown). May 2020 registered the peak of number of positive cases with a Ct mean of 23.6. Now, as of April 2021, we are facing a rise in the number of cases. However, the Ct mean was 24.9, which may indicate that the spread of P.1 does not contribute to an actual increase in the viral load.

Medrixiv preprint

 

Image by Luciano Teixeira from Pixabay

1,039 cases of Brazilian #coronavirus variant P.1 reported in Canada

health-infobase.canada.ca

 

 

Brazilian #coronavirus variant P.1 now second most common variant in USA

“For the first time, however, the P.1 variant that originated in Brazil has taken the No. 2 spot. At least 434 people in the United States have been infected with the variant, which has devastated Brazil, with the largest number of cases found in Massachusetts, Illinois and Florida.”

 

 

Washington Post report

Chart courtesy of CDC

 

 

Detection of 54 cases of the P.1 variant in Massachusetts in less than a month

All three global VoCs (B.1.1.7, B.1.351, and P.1) have now been detected in MA. However, unlike B.1.1.7 and B.1.351, P.1 has shown a rapid rise in frequency in the few weeks following its first detection on March 16th, 2021.  Phylogenetic analysis of these 54 P.1 genomes from MA, alongside four additional P.1 genomes from neighbouring states (two from Connecticut (CT) and one each from Maine (ME) and Rhode Island (RI)) and 895 other global P.1 sequences from GISAID, 6 1 suggests at least six introductions of P.1 into MA and at least eight introductions of P.1 into the New England region, likely from both international and domestic sources.

Virological.org preprint  – Detection of a large cluster and multiple introductions of the P.1 SARS-CoV-2 Variant of Concern in Massachusetts

 

Image by David Mark from Pixabay

New SARS-CoV-2 #coronavirus lineage that shares mutations with known Variants of Concern (VOC) reported in 20 states across USA

We report a SARS-CoV-2 lineage that shares N501Y, P681H, and other mutations with known variants of concern, such as B.1.1.7. This lineage, which we refer to as B.1.x (COG-UK sometimes references similar samples as B.1.324.1), is present in at least 20 states across the USA and in at least six countries. However, a large deletion causes the sequence to be automatically rejected from repositories, suggesting that the frequency of this new lineage is underestimated using public data.

Recent dynamics based on 339 samples obtained in Santa Cruz County, CA, USA suggest that B.1.x may be increasing in frequency at a rate similar to that of B.1.1.7 in Southern California. At present the functional differences between this variant B.1.x and other circulating SARS-CoV-2 variants are unknown, and further studies on secondary attack rates, viral loads, immune evasion and/or disease severity are needed to determine if it poses a public health concern.

BiorXiv preprint:   A new SARS-CoV-2 lineage that shares mutations with known Variants of Concern is rejected by automated sequence repository quality control

Image by Jürgen Jester from Pixabay

France: #coronavirus VOI 19B/501Y, aka HMN.19B or Henri Mondor variant could be a reinfection risk

The VOI 19B ​​/ 501Y (lineage A.27) has been detected infrequently but regularly in France since January 2021. It represented 1.8% of the interpretable sequences during the Flash # 4 survey versus 0% during the Flash Inquiry # 3. In weeks 10 and 11, respectively 48 and 47 detections of this variant were reported by the 4 national sequencing platforms.

However, several points of attention should be note and justify continuing the reinforced surveillance of this variant. First, it was detected during several clusters, a priori all closed, affecting schools, healthcare (including centers hospitals, SSR and Ehpad) or military, with for some a high number of COVID-19 cases (more around sixty), particularly in Ile-de-France (2 hospital clusters and 8 intra-family clusters), Pays de la Loire (3 clusters), Brittany (1 cluster in Morbihan) and Nouvelle-Aquitaine (6 clusters in Dordogne).

Community transmission of this variant is suspected in at least two departments (Seine-et-Marne et Dordogne), and additional investigations are currently being carried out by the ARS concerned, in conjunction with SpF and CNR, to characterize this signal. In addition, three cases considered as probable re-infections were identified with confirmation of infection with this variant during the second episode, without it being possible to date to estimate the frequency of re-infections with this variant, nor to compare it with that of other viral strains circulating in France.

Data is still lacking at this stage on the clinical features of infection with this variant, but we did not detect a signal in favor of significant impact on its transmissibility or increased severity of infection caused by this variant. The strengthening of the surveillance of this variant should be able to more precisely document its characteristics, which will be noted to you when additional data becomes available.

French Health Department – Risk analysis related to emerging variants of SARS-COV-2  (PDF)

Image by Sue Harris from Pixabay