Loss of smell, or anosmia, is one of the earliest and most commonly reported symptoms of COVID-19. Scientists from the Institut Pasteur, the CNRS, Inserm, Université de Paris and the Paris Public Hospital Network (AP-HP) determined the mechanisms involved in the loss of smell in patients infected with SARS-CoV-2 at different stages of the disease. They discovered that SARS-CoV-2 infects sensory neurons and causes persistent epithelial and olfactory nervous system inflammation. Furthermore, in some patients with persistent clinical signs, anosmia is associated with prolonged epithelial and olfactory nervous system inflammation and lasting presence of the virus in the olfactory epithelium.
This study unexpectedly demonstrates that nasopharyngeal swabs may test negative by standard RT-qPCR even if the virus is still present at the back of the nasal cavities, in the olfactory epithelium.
Research paper – COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters
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
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).
“Last month, Gytis Dudas was tracking a concerning new coronavirus variant that had triggered an outbreak of COVID-19 in his native Lithuania and appeared sporadically elsewhere in Europe and in the United States. Exploring an international database of coronavirus genomes, Dudas found a crucial clue: One sample of the new variant came from a person who had recently flown to France from Cameroon. A collaborator, Guy Baele of KU Leuven, soon identified six more sequences from people in Europe who had traveled in Cameroon. But then their quest to pinpoint the variant’s origins hit a wall: Cameroon had uploaded a total of only 48 genomes to the global sequence repository, called GISAID. None included the variant”
B.1.620 is also listed as a Variant of Interest by the ECDC:
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.
The 19B / 501Y Henri Mondor variant (lineage A.27) has been detected in France since January 2021 infrequently but overall stable, with fluctuations from one week to the next: it represented 1% of sequences interpretable in the Flash # 6 survey (03/30/2021) versus 0.2% in the Flash # 5 survey (03/16/2021). In week 13, 18 detections of this variant were reported by the EMERGEN consortium. The clusters of large size that have been detected in connection with this variant have been closed to date, although strings of intrafamily transmission continue to be detected, particularly in the PACA region.
However, several points of attention should be noted and justify continuing the reinforced surveillance of this variant. First of all, it was detected in several large clusters, affecting school establishments, care (including hospitals, SSR and nursing homes) or military, especially in Ile-de-France (hospital and intra-family clusters), Pays de la Loire (3 clusters mainly affecting school establishments and military), Brittany (1 cluster in nursing homes in Morbihan) and Nouvelle-Aquitaine (6 clusters affecting healthcare establishments in Dordogne).
Maintaining sporadic detection of this variant on the national territory indicates a community transmission with low noise. At this point it seems less competitive than VOC 20I / 501Y.V1, since its prevalence remains much lower than the latter, including in geographic areas where it appears to have disseminated more extensively than nationally during of the 1st quarter of 2021 (Dordogne and Ile-de-France in particular).
In addition, three cases considered to be probable reinfections were identified 9 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 a significant impact on its transmissibility or an increased severity of the infection caused by this variant compared to the reference viral strains or variants of concern.
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.
Nine new cases of atypical thrombosis (clots) and two cases of coagulation disorders associated with AstraZeneca’s Covid-19 vaccine, with four additional deaths, occurred in France between April 2 and April 8, according to French health authorities. The nine new cases of rare thrombosis concern people who present “a profile different from that” of the cases declared previously, notes the ANSM. The age of the patients is “higher”: “It is about four women and five men, older (average age of 62 years) who presented more digestive thromboses.
Marie-Antoinette Sevestre-Pietri, French Society of Vascular Medicine President: “”In the long term, it will probably be necessary to do without adenovirus vaccines”
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
According to Me Étienne Boittin, family lawyer, the 42yr old man, who died in Pleumeur-Bodou (Côtes-d’Armor), was vaccinated on March 13 and died on March 22. “He was in good health, he had a medical reason which was sufficient to vaccinate him but which was unrelated to the thrombosis which was fatal to him”, declared Me Boittin. “I have three cases of death resulting from a thrombosis for which one wonders about the link between the thrombosis and the injection of AstraZeneca”, he added.
Image by Ash_Crow, CC BY-SA 3.0 http://creativecommons.org/licenses/by-sa/3.0/, via Wikimedia Commons
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.