The latest Melbourne outbreak is believed to have begun when a traveller infected with the Kappa variant (B16171) returned to Australia.
“We’ve got to run this thing to ground otherwise people will die,” Victoria’s acting state Premier James Merlino said, adding they were dealing with a virus variant “quicker and more contagious than we have ever seen before”.
Thousands of close contacts have been identified and the list of venues visited by the 60 confirmed cases has grown to about 350.
“The spike (S) glycoprotein of the SARS-CoV-2 virus that emerged in 2019 contained a suboptimal furin cleavage site at the S1/S2 junction with the sequence 681 PRRAR/S 686. This cleavage site is required for efficient airway replication, transmission, and pathogenicity of the virus. …P681R significantly enhanced the ability of furin to cleave the peptide confirming that the arginine substitution is responsible for the enhanced cleavage of the B.1.617 S protein.
We speculate that enhanced S1/S2 cleavage seen in B.1.617 and B.1.1.7 [Alpha variant] (which contains P681H) may be contributing to the enhanced transmissibility of these SARS-CoV-2 variants.”
The Brazilian Society of Virology (SBV) yesterday, May 25, confirmed the identification of a new Brazilian coronavirus strain, denominated P4. According to the SBV, the variant has the L452R mutation in the S protein of SARS-CoV-2. According to the SBV, the new variant has been circulating in the region of the São Paulo cities of Mococa, Caconde, and Itapira (close to the border with Minas Gerais), and also in the region of Porto Ferreira .
The L452R mutation in the S protein of SARS-CoV-2 is found in all three sub-lineages of the Indian variant B.1.617 – B.1.617.1, B.1.617.2 and B.1.617.3. There is still no data on whether the new P.4 strain is more transmissible or more lethal than other strains.
The variant of the SARS-Cov-2 coronavirus was detected for the first time in a sample taken in the municipality of Mococa, which is located in the northeast of the state of Sao Paulo.
In addition to Mococa, coronavirus cases caused by the P.4 strain have been registered in municipalities such as Cesário Lange, Porto Ferreira, Santa Cruz das Palmeiras, Tambaú, Itirapina, Rio Claro, Araras, Sumaré, Caconde, Iperó, Capão Bonito , São Miguel Arcanjo, Itapetininga y Descalvado , all located in Sao Paulo.
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
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
British Columbia CDC: “Researchers are monitoring for specific sublineages of this variant, including B.1.617.1, 1.617.2, B.1.617.3 and B.1.617.4” (is this a typo?)
Scientists at the Indian National Institute of Virology (NIV), Pune, have found that both Covaxin and Covishield produce half as many antibodies against the B.1.617 variant of the novel coronavirus as against the ‘original’ B.1 variant.
The scientists conducted their studies with blood sera (plural of serum, the fluid part of the blood) obtained from people who had received either two doses of *Covaxin or two doses of *Covishield. They were motivated by the need to understand how the vaccines’ efficacies varied against infections due to newer strains of the virus. The B.1.617 variant – made up of three sub-lineages – is accounting for more cases in India. The UK recently elevated the B.1.617.2 sub-lineage as a ‘variant of concern’.
*Covaxin was developed by Indian pharmaceutical company Bharat Biotech in collaboration with the Indian Council of Medical Research
*Covishield is India’s version of the Oxford-AstraZeneca vaccine manufactured in Pune by the Serum Institute of India
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
Targeted testing is to start in Nottingham, UK for two weeks after a rise in cases of the Indian variant of Covid. Nottingham City Council said some cases had been found in shared, private accommodation in the city. It said not all cases related to travel and some were “thought to have been picked up via community transmission”. Public Health England, which elevated the Indian variant as a “variant of concern” last week, said it was monitoring them “extremely closely”.
A World Health Organization official said Monday it is reclassifying the Indian Sars-Cov-2 variant B.1.617 as a “variant of concern,” indicating that it’s become a global health threat. Maria Van Kerkhove, the WHO’s technical lead for Covid-19, said the agency will provide more details in its weekly situation report on the pandemic Tuesday but added that the variant, known as B.1.617, has been found in preliminary studies to spread more easily than the original virus and there is some evidence it may able to evade vaccines.
“as such we are classifying this as a variant of concern at the global level,” she said during a press conference. “Even though there is increased transmissibility demonstrated by some preliminary studies, we need much more information about this virus variant in this lineage in all of the sub lineages, so we need more sequencing, targeted sequencing to be done.”
Covid-19 deaths In India rose by more than 4,000 for a second consecutive day on Sunday (May 9) as calls for a nationwide lockdown to curb the spread of the virus mounted. India’s health ministry reported 4,092 fatalities over the past 24 hours, taking the overall death toll to 242,362. New cases rose by 403,738, just shy of the record and increasing the total since the start of the pandemic to 22.3 million.
An estimated 35,000–40,000 people were killed outright by the bombing at Nagasaki.
Early indications from an analysis of the growth of the B.1.617 variant of the Covid-19 virus has shown it to be at least twice as infectious as the UK variant and thrice as infectious as the variant behind last year’s Covid-19 wave.
Scientists involved in the whole genome sequencing as part of the Centre’s Covid-19 genomic surveillance exercise told The New Indian Express that this conclusion is based on the growth of this mutant, as compared to others, in districts where B.1.617 has been identified along with other variants in samples collected from infected individuals.
“We have been examining this data carefully and the way this lineage of virus, also called the double mutant, is growing as compared to others is remarkable,” said a senior scientist involved in the INSACOG project, a consortium of several institutions under the National Centre for Disease Control that carry out an extensive genomic surveillance. “For the public, what needs to be communicated very clearly is that there is a greater need to double mask and maintain social distancing as this virus is highly infectious.
** Update ** Tom Wenseleers: “Based on this data, the new variant from India has a very big transmission or growth advantage,” even over B.1.1.7, he says. “It’s kind of like the U.K. variant squared.”
The UK government is thought to have detected more than 40 clusters of the Indian Covid variant B.1.617 in the UK, and is on the verge of declaring it a “variant of concern”. The mutant strain is thought to be driving the massive surge of infections in India.
Professor Christina Pagel: [B.1.617] rapidly became dominant in India and, again the sequenced data there is sparse, but early modelling shows that it might well be more transmissible than our B.117 Kent strain. ‘What we have also seen in India is that B.1.617.2 is becoming the dominant subtype – exactly the same pattern we see here in the UK. ‘While this could reflect the situation in India through importation, the Sanger data tries to exclude travel related cases or surge testing and we still see the rise of B.1.617.2 in that’.
UPDATED 25th May 2021 – B.1.617.2 found in 100% of sequences from the last 15 days
** NOTE: B.1.617.2 carries the T478K mutation according to the European Centre for Disease Prevention and Control
See also Bioxriv preprint: Preliminary report on SARS-CoV-2 Spike mutation T478K