Role of SARS-CoV-2 mutations in the evolution of the COVID-19 pandemic.

OBJECTIVES: The SARS-CoV-2 pandemic and large-scale genomic surveillance provided an exceptional opportunity to analyze mutations that appeared over three years in viral genomes. Here we studied mutations and their epidemic consequences for SARS-CoV-2 genomes from our center. METHODS: We analyzed 61,397 SARS-CoV-2 genomes we sequenced from respiratory samples for genomic surveillance. Mutations frequencies were calculated using Nextclade, Microsoft Excel, and an in-house Python script. RESULTS: A total of 22,225 nucleotide mutations were identified, 220 (1.0%) being each at the root of ≥836 genomes, classifying mutations as 'hyperfertile'. Two seeded the European pandemic: P323L in RNA polymerase, associated with an increased mutation rate, and D614G in spike that improved fitness. Most 'hyperfertile' mutations occurred in areas not predicted with increased virulence. Their mean number was 8±6 (0-22) per 1000 nucleotides per gene. They were 3.7-times more frequent in accessory than informational genes (13.8 versus 3.7/1000 nucleotides). Particularly, they were 4.1-times more frequent in ORF8 than in the RNA polymerase gene. Interestingly, stop codons were present in 97 positions, almost only in accessory genes, including ORF8 (21/100 codons). CONCLUSIONS: most 'hyperfertile' mutations did not predict emergence of a new epidemic, and some were stop codons indicating the existence of so-named 'non-virulence' genes.

Fascia Ecosystem: A Step Forward in Sleep Engineering and Research.

Millions suffer from sleep disorders, and sleep clinics and research institutions seek improved sleep study methods. This paper proposes the Fascia Ecosystem for Sleep Engineering to improve traditional sleep studies. The Fascia Sleep Mask is more comfortable and accessible than overnight stays at a sleep center, and the Fascia Portal and Fascia Hub allow for home-based sleep studies with real-time intervention and data analysis capabilities.A study of 10 sleep experts found that the Fascia Portal is easy to access, navigate, and use, with 44.4% finding it very easy to access, 33.3% very easy to navigate, and 60% very easy to get used to. Most experts found the Fascia Portal reliable and easy to use.Moreover, the study analyzed physiological signals during various states of sleep and wakefulness in two subjects. The results demonstrated that the Fascia dataset captured higher amplitude spindles in N2 sleep (72.20 V and 109.87 V in frontal and parietal regions, respectively) and higher peak-to-peak amplitude slow waves in N3 sleep (93.51 V) compared to benchmark datasets. Fascia produced stronger and more consistent EOG signals during REM sleep, indicating its potential to improve sleep disorder diagnosis and treatment by providing a deeper understanding of sleep patterns.

From viral democratic genomes to viral wild bunch of quasispecies.

The tremendous majority of RNA genomes from pathogenic viruses analyzed and deposited in databases are consensus or "democratic" genomes. They represent the genomes most frequently found in the clinical samples of patients but do not account for the huge genetic diversity of coexisting genomes, which is better described as quasispecies. A viral quasispecies is defined as the dynamic distribution of nonidentical but closely related mutants, variants, recombinant, or reassortant viral genomes. Viral quasispecies have collective behavior and dynamics and are the subject of internal interactions that comprise interference, complementation, or cooperation. In the setting of SARS-CoV-2 infection, intrahost SARS-CoV-2 genetic diversity was recently notably reported for immunocompromised, chronically infected patients, for patients treated with monoclonal antibodies targeting the viral spike protein, and for different body compartments of a single patient. A question that deserves attention is whether such diversity is generated postinfection from a clonal genome in response to selection pressure or is already present at the time of infection as a quasispecies. In the present review, we summarize the data supporting that hosts are infected by a "wild bunch" of viruses rather than by multiple virions sharing the same genome. Each virion in the "wild bunch" may have different virulence and tissue tropisms. As the number of viruses replicated during host infections is huge, a viral quasispecies at any time of infection is wide and is also influenced by host-specific selection pressure after infection, which accounts for the difficulty in deciphering and predicting the appearance of more fit variants and the evolution of epidemics of novel RNA viruses.

Old World Medieval Treponema pallidum Complex Treponematosis: A Case Report.

BACKGROUND: Introduction of 1 Treponema pallidum complex pathogen in naive European populations following the return of Christopher Columbus' troops from Central America in 1493 is a central dogma in venereology. METHODS: Among skeletal elements from the seventh or eighth century uncovered in Roquevaire, France, individual RS-1003 femur macroscopically suspected of having an infectious disease was investigated by means of paleoautoimmunohistochemistry, direct metagenomics, and paleoserology, along with 1 control femur from an apparently healthy individual (R-1003) and experimental negative controls. RESULTS: RS-1003 femur showed infectious bone; paleoautoimmunohistochemistry of the lesions led to microscopic detection of a T. pallidum complex pathogen. Phylogenetic analyses comprising 71 T. pallidum complex-specific reads covering 2.37% of the T. pallidum subsp. pallidum reference genome sequence revealed an ancestral T. pallidum complex pathogen in the lesion. Paleoserology detecting T. pallidum-specific antigens confirmed positive serological findings in individual RS-1003. Individual R-1003 and the negative controls remained negative. CONCLUSIONS: This case, predating by 8 centuries previous detections of T. pallidum complex treponematosis in Europe, indicated that European populations were not naive to these pathogens before the 1493 introduction of a Central American T. pallidum complex pathogen overwhelming the T. pallidum ones previously circulating in the Old World. These data break a century-old dogma in medical microbiology.

Identification and Characterization of an HtrA Sheddase Produced by Coxiella burnetii.

Having previously shown that soluble E-cadherin (sE-cad) is found in sera of Q fever patients and that infection of BeWo cells by C. burnetii leads to modulation of the E-cad/ß-cat pathway, our purpose was to identify which sheddase(s) might catalyze the cleavage of E-cad. Here, we searched for a direct mechanism of cleavage initiated by the bacterium itself, assuming the possible synthesis of a sheddase encoded in the genome of C. burnetii or an indirect mechanism based on the activation of a human sheddase. Using a straightforward bioinformatics approach to scan the complete genomes of four laboratory strains of C. burnetii, we demonstrate that C. burnetii encodes a 451 amino acid sheddase (CbHtrA) belonging to the HtrA family that is differently expressed according to the bacterial virulence. An artificial CbHtrA gene (CoxbHtrA) was expressed, and the CoxbHtrA recombinant protein was found to have sheddase activity. We also found evidence that the C. burnetii infection triggers an over-induction of the human HuHtrA gene expression. Finally, we demonstrate that cleavage of E-cad by CoxbHtrA on macrophages-THP-1 cells leads to an M2 polarization of the target cells and the induction of their secretion of IL-10, which "disarms" the target cells and improves C. burnetii replication. Taken together, these results demonstrate that the genome of C. burnetii encodes a functional HtrA sheddase and establishes a link between the HtrA sheddase-induced cleavage of E-cad, the M2 polarization of the target cells and their secretion of IL-10, and the intracellular replication of C. burnetii.

Tracking Mycoviruses in Public RNAseq Datasets of Malassezia: Three Original Totiviruses Revealed.

Mycoviruses are viruses that selectively infect and multiply in fungal cells. Malassezia is the most abundant fungus on human skin and is associated with a variety of conditions, including atopic eczema, atopic dermatitis, dandruff, folliculitis, pityriasis versicolor, and seborrheic dermatitis. Here, we conducted mycovirome studies on 194 public transcriptomes of Malassezia (2,568,212,042 paired-end reads) screened against all available viral proteins. Transcriptomic data were assembled de novo resulting in 1,170,715 contigs and 2,995,306 open reading frames (ORFs) that were subsequently tracked for potential viral sequences. Eighty-eight virus-associated ORFs were detected in 68 contigs from 28 Sequence Read Archive (SRA) samples. Seventy-five and thirteen ORFs were retrieved from transcriptomes of Malassezia globosa and Malassezia restricta, respectively. Phylogenetic reconstructions revealed three new mycoviruses belonging to the Totivirus genus and named Malassezia globosa-associated-totivirus 1 (MgaTV1); Malassezia restricta-associated-totivirus 1 (MraTV1) and Malassezia restricta-associated-totivirus 2 (MraTV2). These viral candidates extend our understanding of the diversity and taxonomy of mycoviruses as well as their co-evolution with their fungal hosts. These results reflected the unexpected diversity of mycoviruses hidden in public databases. In conclusion, this study sheds light on the discovery of novel mycoviruses and opens the door to study their impact on disease caused by the host fungus Malassezia and globally, their implication in clinical skin disorders.

Infection and Persistence of Coxiella burnetii Clinical Isolate in the Placental Environment.

Infection by Coxiella burnetii, the etiological agent of Q fever, poses the risk of causing severe obstetrical complications in pregnant women. C. burnetii is known for its placental tropism based on animal models of infection. The Nine Mile strain has been mostly used to study C. burnetii pathogenicity but the contribution of human isolates to C. burnetii pathogenicity is poorly understood. In this study, we compared five C. burnetii isolates from human placentas with C. burnetii strains including Nine Mile (NM) as reference. Comparative genomic analysis revealed that the Cb122 isolate was distinct from other placental isolates and the C. burnetii NM strain with a set of unique genes involved in energy generation and a type 1 secretion system. The infection of Balb/C mice with the Cb122 isolate showed higher virulence than that of NM or other placental isolates. We evaluated the pathogenicity of the Cb122 isolate by in vitro and ex vivo experiments. As C. burnetii is known to infect and survive within macrophages, we isolated monocytes and placental macrophages from healthy donors and infected them with the Cb122 isolate and the reference strain. We showed that bacteria from the Cb122 isolate were less internalized by monocyte-derived macrophages (MDM) than NM bacteria but the reference strain and the Cb122 isolate were similarly internalized by placental macrophages. The Cb122 isolate and the reference strain survived similarly in the two macrophage types. While the Cb122 isolate and the NM strain stimulated a poorly inflammatory program in MDM, they elicited an inflammatory program in placenta macrophages. We also reported that the Cb122 isolate and NM strain were internalized by trophoblastic cell lines and primary trophoblasts without specific replicative profiles. Placental explants were then infected with the Cb122 isolate and the NM strain. The bacteria from the Cb122 isolate were enriched in the chorionic villous foetal side. It is likely that the Cb122 isolate exhibited increased virulence in the multicellular environment provided by explants. Taken together, these results showed that the placental isolate of C. burnetii exhibits a specific infectious profile but its pathogenic role is not as high as the host immune response in pregnant women.

The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule.

The nature and dynamics of mutations associated with the emergence, spread, and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant ("Marseille-4") for 10 months since its onset in July 2020. Here, we analyzed and classified into subvariants and lineages 7453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1 ± 1.4 months, during which 4.1 ± 2.6 mutations accumulated. Growth rate was 0.079 ± 0.045, varying from 0.010 to 0.173. Most of the lineages exhibited a bell-shaped distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marseille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in SARS-CoV-2 of mink and in the Alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.

Bartonella quintana Transmitted by Head Lice: An Outbreak of Trench Fever in Senegal.

BACKGROUND: Louse-borne trench fever caused by Bartonella quintana is a neglected public health concern, known to be transmitted from body louse feces via scratching. No viable B. quintana have ever been isolated from head lice before; therefore, their role as a vector is still poorly understood. METHODS: In Senegal, the implementation of a permanent local surveillance system in a point-of-care laboratory (POC) allows the monitoring of emerging diseases. Here we used culture as well as molecular and genomic approaches to document an outbreak of trench fever associated with head lice in the village of Ndiop. Head lice and blood samples were collected from febrile patients between November 2010 and April 2015. Genomes of 2 isolated strains of B. quintana were sequenced and analyzed. RESULTS: A total of 2289 blood samples were collected in the 2010-2015 period. From 2010-2013, B. quintana DNA was detected by polymerase chain reaction (PCR) in 0.25% (4/1580). In 2014, 228 blood samples were collected, along with 161 head lice from 5 individuals. B. quintana DNA was detected in 4.4% (10/228) of blood samples, and in lice specimens collected from febrile patients (61.7%, 50/81) and non-febrile patients (61.4%, 43/70). Two B. quintana strains were isolated from blood and head lice from 2 different patients. Genomic sequence analysis showed 99.98% overall similarity between both strains. CONCLUSIONS: The presence of live B. quintana in head lice, and the genetic identity of strains from patients' blood and head lice during a localized outbreak in Senegal, supports the evidence of head lice vectorial capacity.

Is it time to switch to a formulation other than the live attenuated poliovirus vaccine to prevent poliomyelitis?

The polioviruses (PVs) are mainly transmitted by direct contact with an infected person through the fecal-oral route and respiratory secretions (or more rarely via contaminated water or food) and have a primary tropism for the gut. After their replication in the gut, in rare cases (far less than 1% of the infected individuals), PVs can spread to the central nervous system leading to flaccid paralysis, which can result in respiratory paralysis and death. By the middle of the 20th century, every year the wild polioviruses (WPVs) are supposed to have killed or paralyzed over half a million people. The introduction of the oral poliovirus vaccines (OPVs) through mass vaccination campaigns (combined with better application of hygiene measures), was a success story which enabled the World Health Organization (WHO) to set the global eradication of poliomyelitis as an objective. However this strategy of viral eradication has its limits as the majority of poliomyelitis cases today arise in individuals infected with circulating vaccine-derived polioviruses (cVDPVs) which regain pathogenicity following reversion or recombination. In recent years (between January 2018 and May 2023), the WHO recorded 8.8 times more cases of polio which were linked to the attenuated OPV vaccines (3,442 polio cases after reversion or recombination events) than cases linked to a WPV (390 cases). Recent knowledge of the evolution of RNA viruses and the exchange of genetic material among biological entities of the intestinal microbiota, call for a reassessment of the polio eradication vaccine strategies.

SARS-CoV-2 quasi-species analysis from patients with persistent nasopharyngeal shedding.

At the time of a new and unprecedented viral pandemic, many questions are being asked about the genomic evolution of SARS-CoV-2 and the emergence of different variants, leading to therapeutic and immune evasion and survival of this genetically highly labile RNA virus. The nasopharyngeal persistence of infectious virus beyond 17 days proves its constant interaction with the human immune system and increases the intra-individual mutational possibilities. We performed a prospective high-throughput sequencing study (ARTIC Nanopore) of SARS-CoV-2 from so-called "persistent" patients, comparing them with a non-persistent population, and analyzing the quasi-species present in a single sample at time t. Global intra-individual variability in persistent patients was found to be higher than in controls (mean 5.3%, Standard deviation 0.9 versus 4.6% SD 0.3, respectively, p < 0.001). In the detailed analysis, we found a greater difference between persistent and non-persistent patients with non-severe COVID 19, and between the two groups infected with clade 20A. Furthermore, we found minority N501Y and P681H mutation clouds in all patients, with no significant differences found both groups. The question of the SARS-CoV-2 viral variants' genesis remains to be further investigated, with the need to prevent new viral propagations and their consequences, and quasi-species analysis could be an important key to watch out.

A 21L/BA.2-21K/BA.1 "MixOmicron" SARS-CoV-2 hybrid undetected by qPCR that screen for variant in routine diagnosis.

Among the multiple SARS-CoV-2 variants identified since summer 2020, several have co-circulated, creating opportunities for coinfections and potentially genetic recombinations that are common in coronaviruses. Viral recombinants are indeed beginning to be reported more frequently. Here, we describe a new SARS-CoV-2 recombinant genome that is mostly that of a Omicron 21L/BA.2 variant but with a 3' tip originating from a Omicron 21K/BA.1 variant. Two such genomes were obtained in our institute from adults sampled in February 2022 in university hospitals of Marseille, southern France, by next-generation sequencing carried out with the Illumina or Nanopore technologies. The recombination site was located between nucleotides 26,858-27,382. In the two genomic assemblies, mean sequencing depth at mutation-harboring positions was 271 and 1362 reads and mean prevalence of the majoritary nucleotide was 99.3 ± 2.2% and 98.8 ± 1.6%, respectively. Phylogeny generated trees with slightly different topologies according to whether genomes analyzed were depleted or not of the 3' tip. This 3' terminal end brought in the Omicron 21L/BA.2 genome a short transposable element of 41 nucleotides named S2m that is present in most SARS-CoV-2 except a few variants among which the Omicron 21L/BA.2 variant and may be involved in virulence. Importantly, this recombinant is not detected by currently used qPCR that screen for variants in routine diagnosis. The present observation emphasizes the need to survey closely the genetic pathways of SARS-CoV-2 variability by whole genome sequencing, and it could contribute to gain a better understanding of factors that lead to observed differences between epidemic potentials of the different variants.

Prevotella merdae sp. nov., a new bacterial species isolated from human faeces.

Strain Marseille-P4119T was isolated from a faecal sample of a healthy 32-year-old faecal transplant donor. The bacterium was anaerobic, Gram-negative, rod-shaped, non-motile, and did not produce spores. We studied its phenotypic characteristics and sequenced its whole genome. The major fatty acids were C15:0anteiso and C15:0iso. The final genome assembly was 3912650 bp long with a 44.4 mol% G + C content, 3094 protein-coding genes and 74 RNA genes. Strain Marseille-P4119T exhibited a 97.10% 16S rRNA sequence identity and a 29.0% dDDH with Prevotella stercorea CB35T, OrthoANI values ranged from 68.5% with Prevotella enoeca to 77.4% with Prevotella stercorea, the phylogenetically closest bacterial species with standing in nomenclature. Based on the phylogenetic, phenotypic and genomic analyses, we propose the creation of the novel species Prevotella merdae sp. nov. The type strain is Marseille-P4119T ( = CSUR P4119T = CECT 9566T).

The Antibacterial Effect of Platelets on Escherichia coli Strains.

Platelets play an important role in defense against pathogens; however, the interaction between Escherichia coli and platelets has not been well described and detailed. Our goal was to study the interaction between platelets and selected strains of E. coli in order to evaluate the antibacterial effect of platelets and to assess bacterial effects on platelet activation. Washed platelets and supernatants of pre-activated platelets were incubated with five clinical colistin-resistant and five laboratory colistin-sensitive strains of E. coli in order to study bacterial growth. Platelet activation was measured with flow cytometry by evaluating CD62P expression. To identify the difference in strain behavior toward platelets, a pangenome analysis using Roary and O-antigen serotyping was carried out. Both whole platelets and the supernatant of activated platelets inhibited growth of three laboratory colistin-sensitive strains. In contrast, platelets promoted growth of the other strains. There was a negative correlation between platelet activation and bacterial growth. The Roary results showed no logical clustering to explain the mechanism of platelet resistance. The diversity of the responses might be due to strains of different types of O-antigen. Our results show a bidirectional interaction between platelets and E. coli whose expression is dependent on the bacterial strain involved.

Screening and Whole Genome Sequencing of SARS-CoV-2 Circulating During the First Three Waves of the COVID-19 Pandemic in Libreville and the Haut-Ogooué Province in Gabon.

Since the onset of the COVID-19 pandemic, the SARS-CoV-2 viral dynamics in Africa have been less documented than on other continents. In Gabon, a Central African country, a total number of 37,511 cases of COVID-19 and 281 deaths have been reported as of December 8, 2021. After the first COVID-19 case was reported on March 12, 2020, in the capital Libreville, the country experienced two successive waves. The first one, occurred in March 2020 to August 2020, and the second one in January 2021 to May 2021. The third wave began in September 2021 and ended in November 2021. In order to reduce the data gap regarding the dynamics of SARS-CoV-2 in Central Africa, we performed a retrospective genotyping study using 1,006 samples collected from COVID-19 patients in Gabon from 2020 to 2021. Using SARS-CoV-2 variant screening by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) and whole genome sequencing (WGS), we genotyped 809 SARS-CoV-2 samples through qRT-PCR and identified to generated 291 new genomes. It allowed us to describe specific mutations and changes in the SARS-CoV-2 variants in Gabon. The qRT-PCR screening of 809 positive samples from March 2020 to September 2021 showed that 119 SARS-CoV-2 samples (14.7%) were classified as VOC Alpha (Pangolin lineage B.1.1.7), one (0.1%) was a VOC Beta (B.1.351), and 198 (24.5 %) were VOC Delta (B.1.617.2), while 491 samples (60.7%) remained negative for the variants sought. The B1.1 variant was predominant during the first wave while the VOC Alpha dominated the second wave. The B1.617.2 Delta variant is currently the dominant variant of the third wave. Similarly, the analysis of the 291 genome sequences indicated that the dominant variant during the first wave was lineage B.1.1, while the dominant variants of the second wave were lineages B.1.1.7 (50.6%) and B.1.1.318 (36.4%). The third wave started with the circulation of the Delta variant (B.1.617). Finally, we compared these results to the SARS-CoV-2 sequences reported in other African, European, American and Asian countries. Sequences of Gabonese SARS-CoV-2 strains presented the highest similarities with those of France, Belgium and neighboring countries of Central Africa, as well as West Africa.

Sequential Appearance and Isolation of a SARS-CoV-2 Recombinant between Two Major SARS-CoV-2 Variants in a Chronically Infected Immunocompromised Patient.

Genetic recombination is a major evolutionary mechanism among RNA viruses, and it is common in coronaviruses, including those infecting humans. A few SARS-CoV-2 recombinants have been reported to date whose genome harbored combinations of mutations from different mutants or variants, but only a single patient's sample was analyzed, and the virus was not isolated. Here, we report the gradual emergence of a hybrid genome of B.1.160 and Alpha variants in a lymphoma patient chronically infected for 14 months, and we isolated the recombinant virus. The hybrid genome was obtained by next-generation sequencing, and the recombination sites were confirmed by PCR. This consisted of a parental B.1.160 backbone interspersed with two fragments, including the spike gene, from an Alpha variant. An analysis of seven sequential samples from the patient decoded the recombination steps, including the initial infection with a B.1.160 variant, then a concurrent infection with this variant and an Alpha variant, the generation of hybrid genomes, and eventually the emergence of a predominant recombinant virus isolated at the end of the patient's follow-up. This case exemplifies the recombination process of SARS-CoV-2 in real life, and it calls for intensifying the genomic surveillance in patients coinfected with different SARS-CoV-2 variants, and more generally with several RNA viruses, as this may lead to the appearance of new viruses.

Investigation of a COVID-19 outbreak on the Charles de Gaulle aircraft carrier, March to April 2020: a retrospective cohort study.

BackgroundSARS-CoV-2 emergence was a threat for armed forces. A COVID-19 outbreak occurred on the French aircraft carrier Charles de Gaulle from mid-March to mid-April 2020.AimTo understand how the virus was introduced, circulated then stopped circulation, risk factors for infection and severity, and effectiveness of preventive measures.MethodsWe considered the entire crew as a cohort and collected personal, clinical, biological, and epidemiological data. We performed viral genome sequencing and searched for SARS-CoV-2 in the environment.ResultsThe attack rate was 65% (1,148/1,767); 1,568 (89%) were included. The male:female ratio was 6.9, and median age was 29 years (IQR: 24-36). We examined four clinical profiles: asymptomatic (13.0%), non-specific symptomatic (8.1%), specific symptomatic (76.3%), and severe (i.e. requiring oxygen therapy, 2.6%). Active smoking was not associated with severe COVID-19; age and obesity were risk factors. The instantaneous reproduction rate (Rt) and viral sequencing suggested several introductions of the virus with 4 of 5 introduced strains from within France, with an acceleration of Rt when lifting preventive measures. Physical distancing prevented infection (adjusted OR: 0.55; 95% CI: 0.40-0.76). Transmission may have stopped when the proportion of infected personnel was large enough to prevent circulation (65%; 95% CI: 62-68).ConclusionNon-specific clinical pictures of COVID-19 delayed detection of the outbreak. The lack of an isolation ward made it difficult to manage transmission; the outbreak spread until a protective threshold was reached. Physical distancing was effective when applied. Early surveillance with adapted prevention measures should prevent such an outbreak.

Culture and identification of a "Deltamicron" SARS-CoV-2 in a three cases cluster in southern France.

Multiple SARS-CoV-2 variants have successively, or concomitantly spread worldwide since the summer of 2020. A few co-infections with different variants were reported and genetic recombinations, common among coronaviruses, were reported or suspected based on co-detection of signature mutations of different variants in a given genome. Here we report three infections in southern France with a Delta 21J_AY.4-Omicron 21K/BA.1 "Deltamicron" recombinant. The hybrid genome harbors signature mutations of the two lineages, supported by a mean sequencing depth of 1163-1421 reads and a mean nucleotide diversity of 0.1%-0.6%. It is composed of the near full-length spike gene (from codons 156-179) of an Omicron 21K/BA.1 variant in a Delta 21J/AY.4 lineage backbone. Importantly, we cultured an isolate of this recombinant and sequenced its genome. It was observed by scanning electron microscopy. As it is misidentified with current variant screening quantitative polymerase chain reaction (qPCR), we designed and implemented for routine diagnosis a specific duplex qPCR. Finally, structural analysis of the recombinant spike suggested its hybrid content could optimize viral binding to the host cell membrane. These findings prompt further studies of the virological, epidemiological, and clinical features of this recombinant.