Monitoring in Rio de Janeiro, Brazil, has identified a possible new Sars-Cov-2 lineage, originating from P.1.1.28, in the region of Barra Mansa and Porto Real, on the border with the State of São Paulo, and which has only now been called P5. This strain has, among others, two mutations in the Spike protein (E484Q and N501T) that may be associated with escape from the immune system and with virus transmissibility. The discovery was widely reported in newspaper and television news throughout the week.
The results also describe the descendant lineage of VOC gamma (P.1) which was named P.1.2. This strain was initially found in the northern region of the state and is now widespread in all regions of the state of Rio and other states. Monitoring data still show that the P.1 lineage continues to be the most frequent (78%) in the state, and the low frequency of VOC Alpha (B.1.1.7) and the decline of P.2 since November of the year past.
According to Ana Tereza Vasconcelos, from the National Laboratory for Scientific Computing (LNCC), real-time municipal monitoring carried out by Rio de Janeiro is extraordinary for Brazil, and is within the recommendations of the World Health Organization, which recommends 18 days as optimal interval between the release of new data. Of the 92 municipalities in Rio de Janeiro, 91 are already being monitored. From March to June 2021, more than 2,300 samples have already been sequenced and processed on the LNCC supercomputer Santos Dumont, an institution linked to the Ministry of Science, Technology and Innovation (MCTI). Only the municipality of Comendador Levi Gasparian has not yet collected samples.
The data are from patients with a confirmed diagnosis of SARS-CoV-2 infection monitored in reference centers and hospitals in the State of Rio de Janeiro. Reports are issued every 15 days with updated data from 380 samples sequenced in the period and which are immediately available on the website http://www.corona-omica.rj.lncc.br/#/ .
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 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?)
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
A small-scale study on 113 healthcare workers who had received at least one vaccine dose at a private hospital in Delhi found that 18 tested positive for Covid but all except one had mild symptoms. Of the 113 in the study, 107 had received the second dose of the vaccine.
Taken in percentage form, the study found that breakthrough infections — Covid infection in vaccinated individuals — occurred in 15.9 per cent (18 persons) of the vaccinated individuals and 95 per cent had mild symptoms. Of these, 17 incurred the infection after the second dose. According to the study, of the breakthrough infections in 18 persons, 17 incurred the infection after the second dose. These 17 had got their second dose after a mean of 34.8 days following the first jab.
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.”
Five residents of a care home in Borsbeek in Antwerp province have been infected with the so-called Indian variants of Covid-19, according to the Flemish Agency for Health and Care. One of those affected has died. All of the home’s residents have been fully vaccinated.
In three of the cases involved in the new outbreak, the Indian variant has been confirmed, and it is supposed the same goes for the other two. One has since died, and another is in hospital.
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
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.
Sujeet Singh, director of the Indian National Centre for Disease Control (NCDC), said that in Maharashtra, the B.1.617 variant was found in proportions of over 50% in many cities. Nearly 64 cases of the UK strain were found in Maharashtra, six cases of the South African strain, one of the Brazilian strain and 427 cases of the Indian double mutant variant. Over 1,770 samples were sequenced for variants in Maharashtra.
The Covid-19 surge in Delhi, however, seems to be driven mainly by the UK variant B.1.1.7. In Delhi, there are primarily two types of variants — B.1.617 and the UK strain — found in the genome sequenced samples, the NCDC director said. The B.1.617 variant of coronavirus is also known as the double mutant strain. The UK variant was found in 28% of samples in the second week of March. In the last week of the month, 50% of samples had this variant, Singh added.
West Bengal had 40 cases of the UK strain B.1.1.7, nine cases of the South African strain B.1.351 and 124 cases of the Indian double mutant B.1.617.
The National Institute of Virology (NIV), Pune, has shared data with laboratories in Maharashtra showing that of 361 Covid-19 samples taken in Maharashtra from January to March and genome sequenced, 61% or 220 had the double mutation E484Q and L452R, now classified as B.1.617 lineage.
On March 24, the Central government had announced the detection of a double mutant variant in “15-20% samples in Maharashtra” but did not link the variant with the second surge in the state.