There’s plenty of coverage in the UK press today about a so-called “Nepal Variant” of Sars-CoV-2. But what is the “Nepal Variant”? Does it exist? The quick answer is no, it doesn’t exist.
Nepal has seen a huge rise the Delta variant B.1.617.2 recently due to its proximity to India, but then Britain has also seen a huge increase in the B16172 Delta variant too. No asian newspapers have mentioned a “Nepal Variant” recently.
In fact, the ONLY place we can find mention of a “Nepal Variant” is in the UK newspapers today:
And all this, just three days after the WHO agreed to rename Sars-CoV-2 variants to avoid stigmatisaton. The UK press is awash with stories about a new “Nepal Variant”, stigmatising a country that is presumably too small and too busy fighting Covid-19 to respond.
** UPDATE 3rd June 2021: “The World Health Organisation has said it is “not aware” of any variant of concern detected in Nepal. It comes after reports that Portugal may be dropped from the green list amid fears a new variant is spreading there.”
** Update 2: We note that all three of the above mentioned newspapers have now changed their copy and removed any mention of a “Nepal Variant” although the original URL’s are still in use.
“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.”
Lubango central hospital in Angola is under pressure due to the growing number of patients, reporting the possible collapse of the system. In the Angolan province of Huíla, local health authorities are concerned with the increase in deaths and cases of Covid-19, especially since the beginning of May. The province recorded 14 deaths in the last seven days, an average of two a day, in addition to an increase in hospitalizations for serious and critical cases at the central hospital in Lubango.
In view of the worsening situation and the fear of collapse in the health system, local health authorities are reiterating calls to the population to redouble preventive measures and announced the opening of four new Covid-19 patient care centers in the municipalities of Chibia , Kuvango, Jamba and Cacula and thus try to stop the wear and tear in the largest hospital in the region.
Uganda was the first country on the continent to confirm the presence of the B.1.617 variant first identified in India late last year.
This variant has now been reported in Kenya, Morocco, Algeria, South Africa, Botswana, Angola, DR Congo, Nigeria, Uganda, Zambia and Zimbabwe.
Image by Erik Cleves Kristensen – View of Luanda, Angola, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=2048784
More amazing work by Prof. Christina Pagel in deciphering the latest Public Health England data dumps for B16172. It’s well worth reading the whole thread! The UK’s laissez faire attitude to border control and quarantine enforcement means that, after B.1.1.7, Britain is, once again, about to export a highly dangerous Sars-Cov-2 VOC worldwide.
LONG THREAD on B.1.617.2 & latest PHE data covering:
1) latest tech report on B.1.617.2 (aka "India" variant)
2) vaccine efficacy against B.1.617.2
3) consequences for roadmap
4) avoidability… or not.
— Prof. Christina Pagel (@chrischirp) May 23, 2021
110 direct flights from India have landed at UK airports since the country was added to the red list, amid rising concerns about the Indian Covid variant, LBC can reveal. @BenKentish has the exclusive. pic.twitter.com/MonEVVLJ0M
— LBC (@LBC) May 18, 2021
'Around 80 flights to Spain are expected to take off every day this week' but the country remains on the UK's amber list.
— Good Morning Britain (@GMB) May 24, 2021
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
B.1.617 cases as of 16th May 2021 as per Wikipedia
And yes, we KNOW it’s because there is far more sequencing done in the UK than in India. The Brits should be proud of their world-class genome sequencing effort. They have been at the bleeding edge of the fight against this pandemic since day one.
UPDATE 17th May 2021: Wikipedia updated to show new figures:
Eleven out of 18 positive patients were vaccinated, at least 6 are infected with the B.1.617 variant.
AT A GLANCE: The #COVID19 cluster at Singapore’s Changi Airport T3 has grown to 18, with 6 patients testing preliminarily positive for the B1617 variant https://t.co/x5GLRB5m3Z pic.twitter.com/DUwce0tdk9
— CNA (@ChannelNewsAsia) May 12, 2021
The number of confirmed UK cases of the Covid variant first detected in India has almost doubled in four days, Health Secretary Matt Hancock said, as experts warned it could become the dominant type of the virus imminently. Speaking on the day indoor hospitality and other venues were allowed to reopen, Hancock told MPs that 2,323 cases of the variant known as B.1.617.2 had been confirmed, up from 1,313 on Thursday, with 483 of those in the outbreaks in Bolton and Blackburn.
This does not look good…..
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
According to the Covid-19 genomics UK consortium database, in sequences up to 11th May, there have been 1,604 instances of B.1.617.2, making it the second most common variant in the UK. Public Health England have designated B.1.617.2 a “variant of concern”, acknowledging it appears to be at least as transmissible as the dominant so-called Kent variant in the UK.
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”.