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
On April 14, 32 cases of infection with the 20C / 655Y (B.1.616) variant were confirmed (29 in Brittany, three in other regions). All cases have a direct or indirect link with the enhanced surveillance zone by Brittany. The majority of the cases relies on the transmissions within the hospital clusters in the zone.
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, whether in Brittany or elsewhere. Epidemiological investigations are continuing to characterize the episode and monitor the spread of this variant.
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
This Thursday, a 26th case of the Breton variant was confirmed at the Guingamp hospital center. The spread of this new form of covid-19 seems to be limited to Trégor. To date, 12 patients have died from it. Frail, elderly and / or people with co-morbidities.
However, it is impossible to conclude that there is a higher mortality caused by this variant compared to the others. The problem lies in the difficulty of detecting this mutant which often nestles deep in the respiratory system, rendering conventional nasopharyngeal PCR tests negative. “We have a surveillance bias. We have the results where we are able to find the virus. That is to say in the hospital, in people intubated in intensive care, for whom we can perform effective deep samples,” explains Alain Le Tertre, head of the Brittany unit of Public Health France.
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.
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.
“Professor Arnaud Fontanet, member of the scientific council, indicated Tuesday morning on on BFMTV that a ninth case of this Breton variant had been confirmed. According to our information, it could be a contamination spotted at the Pitié-Salpêtrière hospital in Paris, linked to the Lannion hospital center.”
Which territories are under surveillance?
In Brittany, five agglomerations are placed under surveillance (Morlaix, Lannion, Guingamp-Paimpol, Leff Armor and Saint-Brieuc). “In these areas, more extensive samples can be taken, in addition to the classic PCR, to try to identify this variant”, informs Stéphane Mulliez, director general of the Brittany regional health agency.
Will the measures announced be enough to curb the epidemic in France? We are already close to 100% saturation in intensive care. Whatever happens, we have two to three weeks before us before the measures taken have an effect on the intensive care admissions, during which the English variant will complete occupying the space.
Should we be afraid of the Breton mutant? It worries us as it is more difficult to detect by nasopharyngeal swab and can therefore go unnoticed. This makes the detection and isolation of patients difficult. Investigations are in progress by sequencing and by serology to estimate the extent of its diffusion. But it is too early to determine the magnitude and severity associated with it.
Interview with Epidemiologist Arnaud Fontanet, member of the French scientific council, in Le Journal de Dimanche
A new variant (derived from Clade 20C) has been detected in the context of a cluster at the Lannion hospital center, in the Côtes d’Armor. …several patients presenting typical symptoms suggesting an infection by SARS-CoV-2 but a negative RT-PCR test result on nasopharyngeal samples and for whom the diagnosis could be made by serology or by performing RT-PCR on deep respiratory samples.
Where was the “Breton variant” discovered?
The alert was given after the Breton SARS-CoV-2 mutation was detected in a cluster that formed at the Lannion hospital center , in Côtes-d’Armor, in early March. Of the 79 cases of contamination, eight people were carriers of this variant. These eight people died. For now, there is nothing to link their death to the variant.
French Health Department Press Release – 15th March 2021 “Following the identification by sequencing, in Brittany, of a new variant (derived from Clade 20C), the health authorities put in place the necessary monitoring and support measures.”
French Health Department Annex 1 – 15th March 2021 “Definition of SARS-CoV-2 (COVID-19) infection and action to be taken concerning a new variant detected in Brittany (variant of clade 20C) “
French Health Department Annex 2 – 15th March 2021 “Population diagnostic strategy concerning a new variant of clade 20C detected in Brittany“
French Health Department Annex 3 – 15th March 2021 “Diagnostic strategy for active case finding in hospitals concerning a new variant of clade 20C detected in Brittany”
1- Identify cases in hospitals in connection with the cluster of new variant of the 20C clade detected in Brittany and to objectify the impact of circulation of the 20C clade variant in these establishments.
2- Identify the cases of infection by the new variant of clade 20C among the patients hospitalized on national territory who fall within the definition of case as defined in the document “Definition of cases of infection with SARS- CoV-2 (COVID-19) and what to do about a new variant detected in Brittany (variant of clade 20C) ”.
3- Explore the sites and the kinetics of viral excretion for the 20C variant