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.
The so-called double mutant coronavirus found in Maharashtra, India may be becoming the most prevalent among all mutant variants in India, genome sequencing data submitted by Indian scientists to a global database indicates, according to a recent analysis that takes into account when they were detected. The double mutant virus – now classified as B.1.617 – was the most common in the samples sequenced in the 60 days prior to April 2 at 24%.
The variant was first detected on October 5 and was relatively obscure till it began popping up on increasing number of samples January onwards, the India situation report on outbreak.info showed. On April 1, it accounted for 80% of all analysed genome sequences of mutant variants sent by India to the global repository GISAID.
Prof Paul Hunter, professor in medicine at the University of East Anglia, told the Guardian that the arrival of the India variant was potentially worrying. He said: “These two escape mutations working together could be a lot more problematic than the South African and Brazilian variants which have only got one escape mutation. “It might be even less controlled by vaccine than the Brazilian and South African variants.”
The variant featured two “escape mutations” – E484Q and L452R – that “are causing people to be concerned. “There’s laboratory evidence that both of these are escape mutations. Basically, applying what we know about other human coronaviruses would suggest that this is going to be even less controlled by vaccine. But we don’t know that for certain at the moment”
Maharashtra, which has been witnessing a surge in the cases of the coronavirus disease, recorded 63,294 infections on Sunday, taking the tally to 3,407,245, the state’s health department bulletin showed. The state also recorded 394 related fatalities, which took the death toll to 57,987. The case fatality rate is currently at 1.79%. According to India Today 20% of Covid cases in Maharashtra of new double variant B.1.617
The ‘double mutant’ virus that scientists had flagged last month as having a bearing on the spread of the pandemic in India, has a formal scientific classification: B.1.617. The variant is common in India and has a couple of defining mutations, E484Q and L425R, that enable them to become more infectious as well as evade antibodies. Though these mutations have individually been found in several other coronavirus variants, the presence of both these mutations together have been first found in some coronavirus genomes from India.
“This is a homegrown variant and widely exported internationally,” said a scientist involved in the sequencing studies but who declined to be identified.
Scientists have examined the Nextstrain and GISAID databases and found that the L452R mutation is present in more than 400 SARS-CoV-2 genomes isolated from over 20 countries. This indicates a strong positive selection for L452R mutation.
The scientists identified L452R amino acid substitution in the spike region as the dominant mutation in specimens collected since November 2020. Specifically, they observed that two independent SARS-CoV-2 variants (CAL.20C and CAL.20A) containing spike L452R mutation emerged recently in the state of California. Of these variants, CAL.20C (clade 20C; lineage B.1.429) is considered to be the predominant variant in California since November 2020. However, the CAL.20A variant (clade 20A; lineage B.1.232) identified in this study has emerged much more recently than CAL.20C and is primarily circulating in California. Based on the phylogenetic analysis, the scientists indicated that L452R mutation is the primary driving force behind the emergence of both variants. Such an increase in L452R mutation frequency in recent SARS-CoV-2 variants directly indicates its crucial involvement in viral adaptive evolution due to positive selection.
Interestingly, they found CAL.20A variant from a gorilla at the San Diego Zoo, which contains two additional mutations in the non-structural protein 2 (NSP2).
In contrast to CAL.20C, no massive clonal expansion was observed for CAL.20A. According to the study findings, CAL.20C contains two additional spike mutations along with L452R, which are missing in CAL.20A. The scientists believe that these additional mutations may be responsible for increasing the adaptive benefits of L452R, and because of this reason, CAL.20A could not achieve the same expansion rate as CAL.20C.
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)
We report a novel severe acute respiratory syndrome coronavirus 2 variant derived from clade 19B (HMN.19B variant or Henri Mondor variant). This variant is characterized by the presence of 18 amino acid substitutions, including 7–8 substitutions in the spike protein and 2 deletions. These variants actively circulate in different regions of France.
We identified a new, previously undescribed variant of SARS-CoV-2 (HMN.19B or Henri Mondor variant) within a cluster of hospital staff in Paris. This variant stems from an older SARS CoV-2 clade, 19B, which emerged in late 2019 but have been rarely detected since early 2020, overtaken by clades 20A, 20B, and 20C, which harbor the D614G substitution believed to improve viral transmission (1). The HMN.19B variant is characterized by the presence of 2 deletions and 18 amino acid substitutions over the entire sequence, including 8 substitutions within the spike protein, some of which are common with other recently described variants, a finding in keeping with the ongoing evolutionary convergence of SARS-CoV-2 variants. The acquisition of spike substitutions, including N501Y and L452R, has been suggested to enhance the interaction of spike with the angiotensin-converting enzyme 2 viral receptor. The resulting substantial fitness acquisition could explain the reappearance of clade 19B
In the 4 weeks after its first detection, our laboratory, which maintains 1 of the 4 national SARS CoV-2 sequencing surveillance platforms in France, found the HMN.19B variant in 12 patients from the greater Paris area
“The analysis of samples from Maharashtra has revealed that compared to December 2020, there has been an increase in the fraction of samples with the E484Q and L452R mutations. Such mutations confer immune escape and increased infectivity. These mutations have been found in about 15-20% of samples and do not match any previously catalogued VOCs. These have been categorized as VOCs but require the same epidemiological and public health response of “increased testing, comprehensive tracking of close contacts, prompt isolation of positive cases & contacts as well as treatment as per National Treatment Protocol” by the States/UTs.
From Kerala 2032 samples (from all 14 districts) have been sequenced. The N440K variant that is associated with immune escape has been found in 123 samples from 11 districts. This variant was earlier found in 33% of samples from Andhra Pradesh, and in 53 of 104 samples from Telangana. This variant has also been reported from 16 other countries including UK, Denmark, Singapore, Japan and Australia. As of now these can be at best said to be variant under investigation.”
Two variants of the SARS-CoV-2 coronavirus that causes covid-19 have combined their genomes to form a heavily mutated hybrid version of the virus. The “recombination” event was discovered in a virus sample in California, provoking warnings that we may be poised to enter a new phase of the pandemic.
The hybrid virus is the result of recombination of the highly transmissible B.1.1.7 variant discovered in the UK and the B.1.429 variant that originated in California and which may be responsible for a recent wave of cases in Los Angeles because it carries a mutation making it resistant to some antibodies.
The implications of the finding aren’t yet clear because very little is known about the recombinant’s biology. However, it does carry a mutation from B.1.1.7, called Δ69/70, which makes the UK virus more transmissible, and another from B.1.429, called L452R, which can confer resistance to antibodies.
The CAL.20C variant accounts for nearly half of COVID-19 cases in Southern California and about a third of cases in the state based on an analysis of viral genomes posted to a global database called GISAID.
What’s more, the researchers found that by the end of January, the variant had spread to 19 other states, up from five states in November 2020. It has also spread beyond the U.S. to six other countries — Australia, Denmark, Israel, New Zealand, Singapore and the United Kingdom.
“We detected a novel strain descended from cluster 20C and defined by five mutations (ORF1a: I4205V, ORF1b:D1183Y, S: S13I;W152C;L452R)(Figure 1). This strain, CAL.20C, was first observed in July 2020 in 1/1230 samples from LA county and not detected in Southern California again until October. Since then, this strain’s prevalence has increased absolutely and relatively in Southern California, where by December it accounted for 24% of all samples (Figure 2A) and 36.4% (66/181) of our local Los Angeles cohort.”