The VOI 20C / H655Y (lineage B.1.616) initially detected in Lannion, in Brittany, was classified as variant to follow on 03/14/2021. Among the mutations and deletions carried by this VOI, several are found in one or more VOCs and VOIs, and could lead to increased transmissibility (H655Y in particular), post-vaccination or post-infection immune escape or even lower efficacy monoclonal antibody treatments (Y144- deletion, D215G and V483A mutations).
However, according to analyzes carried out by the CNR using sera from vaccinated subjects, infected subjects, or antibodies monoclonal, the data available at this stage do not show significant escape of the variant 20C / 655Y on neutralization. As of 05/04/2021, 42 confirmed cases of infection with the 20C / 655Y variant have been reported in France, including 39 in Brittany and 3 in other regions in people linked to the zone of circulation of the virus in Brittany (made up of several urban communities around Lannion, Guingamp, Saint- Brieuc, Paimpol). Eighteen deaths (43%) were reported, mostly in the elderly (age median 84 years) or with co-morbidities.
The high lethality associated with this variant is probably related to a bias in the identification of cases in which this variant was detected, most often from deep samples (generally more serious), but additional investigations are carried out to characterize the impact of this variant in terms of severity. The majority of confirmed cases are related to transmission chains in healthcare establishments in this geographical area (CH de Guingamp, de Lannion, de Paimpol).
We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, characterized by poor detection by RT-PCR tests on nasopharyngeal samples despite typical clinical, radiological, and biological features of COVID-19. We also noted high case fatality rate in our sampled population. This work also highlights the difficulties to manage nosocomial cases when the gold-standard test fails to confirm the diagnosis. With constantly emerging new variants, one should remain attentive to any unusual clinical situation that could be linked to such emergence.
In our study, among patients with a positive RT-PCR assay in the B.1.616 group, the sensitivity of one, two, three, and four tests on nasopharyngeal samples were, respectively, 5/34 (15%), 13/34 (38%), 14/34 (45%), and 17/34 (55%). RT-PCR tests on sputum, or broncho-alveolar lavage (BAL), were positive in 8/34 (24%) B.1.616-related COVID-19 cases with previous negative nasopharyngeal RT-PCR tests.
As samples from the lower respiratory tract are more difficult to obtain in frail patients, the real extent of the B.1.616-related COVID-19 outbreak in our institution has probably been underestimated. A large surveillance study, with sequencing of a representative sample of 15% of all RT-PCR-positive COVID-19 cases during the study period found no community-acquired B.1.616-related COVID-19 (Flash study#5, SpF, Paris, France, unpublished data), but the low detection in standard sampling may have contributed to this result.”
MedrXiv preprint – A new SARS-CoV-2 variant poorly detected by RT-PCR on nasopharyngeal samples, with high lethality
As of April 28, 40 cases of infection with the 20C/655Y (B.1.616) variant have been confirmed (37 in Brittany, three in other regions). The diagnosis was made on a first positive RT-PCR from a sample nasopharyngeal in 13% of them, and from a deep sample in 68% of cases. All cases have a direct or indirect link with the enhanced surveillance zone in Brittany. The majority of cases are linked to transmissions within hospital clusters in the area. A few cases have been reported in link with a chain of transmission in the community but, to date, the monitoring indicators do not suggest a significant community diffusion of this variant in the population, whether in Brittany or elsewhere. Epidemiological investigations are continuing to characterize the episode and monitor the diffusion of this variant.
As of 04/21, 37 confirmed cases of infection with the 20C / 655Y [B.1.616] variant have been reported in France, including 34 in Brittany and 3 in other regions in people linked to the area of circulation of the virus in Brittany (made up of several urban communities around Lannion, Guingamp, Saint-Brieuc, Paimpol). The cases mainly occurred in elderly patients with co-morbidities. Sixteen deaths have been reported, mainly in the elderly (median age 84 years) or with comorbidities. The majority of confirmed cases are linked to chains of transmission in health facilities in this area.
Two cases have also been reported in connection with a chain of transmission in the community but to date this variant does not seem to spread widely in the population. However, given the difficulties associated with the diagnosis from nasopharyngeal samples, it is possible that community cases have not been identified. Confirmed cases linked to clusters hospitals for which deep samples are taken would only be a fraction of the cases. The diagnosis of SARS-CoV-2 infection was not made on a first positive nasopharyngeal swab than for 3 (9%) cases. For the majority (22/33, 67%), the virological diagnosis by RT-PCR was made only to from a deep sample: sputum (15/22, 68%) or bronchoalveolar lavage (7/22, 32%). For 7 cases, virological diagnosis by RT-PCR required the taking of nasopharyngeal swabs iterative (median 3, min: 2 – max: 7) or stool (1 case).
At this stage, this VOI is characterized mainly by detection in the upper respiratory tract more difficult than for other viral strains of SARS-CoV-2 currently circulating in France. The origin of this phenomenon is not yet known with certainty, several hypotheses currently being investigated, including shorter and / or weaker viral shedding in the nasopharynx, or tropism increase of this variant for the lower respiratory system.
The difficulty in detecting cases of infection with this varying in nasopharyngeal swabs could result in decreased efficacy current control measures for the transmission of SARS-CoV-2, based on patient isolation having a positive diagnostic test and contact-tracing. In addition, the occurrence of several clusters shows the transmission potential of this variant. These two elements therefore encourage us to maintain vigilance vis-à-vis this VOI. Epidemiological investigations are continuing in order to describe the characteristics of the cases and follow the geographical spread of this variant.
French Health Department Document: Analyse de risque liée aux variants émergents de SARS-CoV-2 réalisée conjointement par le CNR des virus des infections respiratoires et Santé publique France
Forbes are carrying an interesting about the recently discovered coronavirus variant found in Tanzania, Africa in travellers arriving from Angola. The variant is from “From An Entirely New Branch Of SARS-CoV-2”, and carries Spike mutations E484K, P681H, T478R, Q957H, H655Y, D215G, D80Y. L210N, W258L, R246I. “An additional 18 amino acid changes occur in proteins outside the spike protein. These include 14 in the orf1ab proteins that specify the replication complex. “
“This is a remarkable illustration of convergent evolution,” say’s Forbes
Clade 20C variant that emerged in Brittany. A cluster of infections with a 20C clade variant (“20C / 655Y variant” or B.1.616), was detected in the Côtes d´Armor, with cases occurring between January and March 2021. The particularity associated with the cases confirmed infections with this variant is the possibility of presenting symptoms suggestive of COVID-19 with negative RT-PCR on usual nasopharyngeal swabs.
The virus is nevertheless detectable by the usual PCR techniques but seems to be found in a preferential in the lower airways. To date, it has not been shown that this variant would be more transmissible or lead to more severe forms. Reinforced surveillance has been put in place in the geographical area concerned in Brittany. A national case investigation protocol suggestive of infection with the 20C / 655Y variant has been disseminated to identify and describe the cases that may occur outside this geographic area. In case of suspicion of infection with this variant (investigation protocol available on the website of Public Health France), samples beyond the nasal sphere pharyngeal gland should be offered whenever possible to increase the sensitivity of the diagnosis by RT-PCR.
As of April 07, 25 cases of infection with the 20C / 655Y variant have been confirmed by the CNR (22 in Brittany, 3 in other regions). All cases have a direct or indirect link with the enhanced surveillance zone by Brittany. The majority of cases are linked to transmissions within hospital clusters in the area. A few cases have been reported in connection with a chain of transmission in the community but, to date, there are significant dissemination of this variant in the population has not been documented, either in Brittany or elsewhere. Epidemiological investigations are continuing to characterize the episode and monitor the spread of this variant.
French Public Health Document: COVID-19: epidemiological update of April 8, 2021
France’s “Breton variant”, B.1.616, was added to the WHO list of Variants of Interest this week. Key Spike mutations are listed as G142 deletion; D66H; Y144V; D215G; V483A; D614G; H655Y; G669S; Q949R; and N1187D
Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge.
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)
On Tuesday, the DGS sent a new protocol to ensure enhanced surveillance of cases of Sars-CoV-2 infection linked to the 20C / H655Y variant, several cases of which were identified in mid-March at the Lannion hospital center (Côtes-d’Armor). The last assessment given on Friday reported 13 confirmed cases (including one spotted in Ile-de-France) with 7 deaths.
The peculiarity of the confirmed cases is that the patients had symptoms suggestive of Covid-19 but an RT-PCR “weakly positive or even negative on the usual nasopharyngeal swabs”, recalls the DGS.
Currently, cases have been confirmed outside of Brittany but all remain linked to Lannion. However, “in the absence of data concerning a possible increased transmissibility of this virus and / or a greater frequency of severe forms, this variant is at this stage classified as a variant to follow (VOI, variant of interest )”, indicates the DGS.
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
“We detected a new VOI in three incoming travelers from Tanzania who were tested together at the airport in mid-February. The three genomes from these passengers were almost identical and presented highly divergent sequences within the A lineage. The GISAID database contains nine other sequences reported to be sampled from cases involving travel from Tanzania, two of which are basal to the three sampled in Angola”
This new VOI, temporarily designated A.VOI.V2, has 31 amino acid substitutions (11 in spike) and three deletions (all in spike) (Figure 1C & 1D). The spike mutations include three substitutions in the receptor-binding domain (R346K, T478R and E484K); five substitutions and three deletions in the N-terminal domain, some of which are within the antigenic supersite (Y144?, R246M, SYL247-249? and W258L)4; and two substitutions adjacent to the S1/S2 cleavage site (H655Y and P681H). Several of these mutations are present in other VOCs/VOIs and are evolving under positive selection.
Variant de clade 20C ayant émergé en Bretagne
Un cluster d’infections par un variant de clade 20C (« variant 20C/H655Y »), a été détecté dans un hôpital des Côtes d’Armor, avec des cas survenus entre janvier et mars 2021. La particularité associée aux premiers cas confirmés d’infections à ce variant est la possibilité de présenter des symptômes évocateurs de la COVID-19 avec une RT-PCR faiblement positive, voire négative, sur les prélèvements naso-pharyngés habituels.
Le virus est néanmoins détectable par les techniques de PCR habituelles mais semble être retrouvé de manière préférentielle dans les voies aériennes basses. À ce jour, il n’est pas démontré que ce variant serait plus transmissible ni qu’il entraînerait de formes plus sévères, mais son émergence fait l’objet d’investigations et la situation est suivie sur le territoire via une surveillance spécifique. En cas de suspicion d’infection à ce variant (définition de cas et conduite à tenir, disponibles sur le site internet de Santé publique France), des prélèvements au-delà de la sphère naso-pharyngée chaque fois que possible doivent être proposés pour augmenter la sensibilité du diagnostic par RT-PCR. Selon les informations disponibles à ce jour, tous les cas confirmés du variant 20C/H655Y ont un lien épidémiologique direct ou indirect avec une commune des Côtes d’Armor et la diffusion du variant 20C/H655Y semble donc limitée actuellement à ce secteur géographique.
A cluster of infections by a 20C clade variant (“20C / H655Y variant”) was detected in a hospital in Côtes d’Armor, with cases occurring between January and March 2021. The particularity associated with the first confirmed cases of Infections with this variant is the possibility of presenting symptoms suggestive of COVID-19 with weakly positive or even negative RT-PCR on usual nasopharyngeal swabs. The virus is nevertheless detectable by the usual PCR techniques but seems to be found preferentially in the lower airways. To date, it has not been shown that this variant would be more transmissible or that it would lead to more severe forms, but its emergence is being investigated and the situation is being monitored in the territory via specific surveillance. In case of suspicion of infection with this variant (case definition and action to be taken, available on the website of Public Health France), samples beyond the nasopharyngeal sphere whenever possible should be proposed to increase the sensitivity of the diagnosis by RT-PCR. According to the information available to date, all the confirmed cases of the 20C / H655Y variant have a direct or indirect epidemiological link with a municipality in Côtes d’Armor and the spread of the 20C / H655Y variant therefore seems to be currently limited to this geographical area.
Public Health France has indicated that the Breton variant is limited to “a town in Côtes-d’Armor and the distribution of the 20C/H655Y variant therefore seems to be currently limited to this geographical area”. The geographical area is the city of Lannion.
Among the 13 confirmed cases, 11 come from the epidemic focus at the Lannion hospital center , another in the population (which is currently in strict confinement) and another in the Paris region, detected within the Pitié-Salpêtrière hospital.
Of these 13 confirmed cases, the ARS also confirms 7 deaths, including 5 contaminations with the Breton variant were detected by post-mortem samples. The remaining 6 are hospitalized. “Nothing indicates for the moment that this variant would be more contagious and more severe”, wishes to underline the ARS.