Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 27, Number 5—May 2021
Research Letter

Novel SARS-CoV-2 Variant Derived from Clade 19B, France

Slim FouratiComments to Author , Jean-Winoc Decousser, Souraya Khouider, Melissa N’Debi, Vanessa Demontant, Elisabeth Trawinski, Aurélie Gourgeon, Christine Gangloff, Grégory Destras, Antonin Bal, Laurence Josset, Alexandre Soulier, Yannick Costa, Guillaume Gricourt, Bruno Lina, Raphaël Lepeule, Jean-Michel Pawlotsky, and Christophe Rodriguez
Author affiliations: Institut Mondor de Recherche Biomédicale, Université Paris-Est, Créteil, France; (S. Fourati, S. Khouider, A. Gourgeon, A. Soulier, J.-M. Pawlotsky, C. Rodriguez); Hôpital Henri Mondor, Créteil (J.-W. Decousser, M. N’Debi, V. Demontant, E. Trawinski, G. Gricourt, R. Lepeule, C. Rodriguez); Hôpital Albert Chenevier, Créteil (C. Gangloff); Université de Lyon, France (G. Destras, A. Bal, L. Josset, B. Lina); Grand Hôpital de l’Est Francilien, Jossigny, France (Y. Costa)

Cite This Article

Abstract

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.

During fall 2020, new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, some of which have become variants of concern, progressively replaced the original strains in regions where they were first identified. We report a new SARS-CoV-2 variant of interest derived from clade 19B (tentatively named HMN.19B variant, or Henri Mondor variant) that is actively circulating in France.

On January 21, 2021, a hospital administrative assistant receiving long-term treatment with anti–tumor necrosis factor-α (adalimumab) for ankylosing spondylitis sought treatment for headache, fatigue, and rhinitis suggestive of coronavirus disease (COVID-19). SARS-CoV-2 RNA was confirmed by reverse transcription PCR (RT-PCR). Her partner (household contact), along with 2 nurses from the same occupational health unit sharing their locker room with the administrative assistant, sought treatment for symptoms suggestive of COVID-19 during January 21–23. Virus was confirmed in all instances by RT-PCR.

The slightly immunocompromised administrative assistant and her immunocompetent partner reported a history of symptomatic COVID-19 infection in early October 2020, confirmed in both cases by a positive RT-PCR result. However, both patients tested negative for SARS-CoV-2 protein N antibodies in January 2021. One of the 2 infected nurses had received a first dose of COVID-19 vaccine (Pfizer-BioNTech, https://www.pfizer.com) 11 days before her positive RT-PCR result. All 4 patients experienced mild COVID-19 and did not require hospitalization.

Figure

Phylogenetic tree built with sequences from the 33 patients infected with the new HMN.19B or Henri Mondor variant and from 1,537 SARS-CoV-2–infected patients in France sampled during January 18–February 23, 2021, sequenced in 9 successive series. Phylogeny was performed after full-length genome alignment with Muscle 3.8.31 (maximum-likelihood model general time-reversible plus invariant sites model, 1,000 bootstrap replicates) by means of IQ-Tree 1.3.11.1 and iTOL. The HMN.19B (Henri Mondor) variant cluster is considerably different from all the others, with a 99% bootstrap value. HMN.19B sequences are colored according to the geographic origin of the patients: red, greater Paris area (IDF or HMN); blue, southeast France (ARA); green, southwest France (NAQ). *Original cluster in an occupational health unit; **cluster in the hematology department of our institution. Amino-acid substitutions and deletions detected in all sequences are described in the orange box. ARA, Auvergne-Rhône-Alpes; HMN, Henri Mondor; IDF, Ile-de-France; NAQ, Nouvelle-Aquitaine.

Figure. Phylogenetic tree built with sequences from the 33 patients infected with the new HMN.19B or Henri Mondor variant and from 1,537 SARS-CoV-2–infected patients in France sampled during January 18–February 23,...

Full-length genome sequencing revealed that the 4 cluster members were infected with a new phylogenetic variant stemming from clade 19B, tentatively called HMN.19B variant or Henri Mondor variant (Appendix). Compared with the reference sequence (GenBank accession no. NC_045512.2) from the international GISAID database (https://www.gisaid.org), variant HMN.19B carries 25 nt substitutions, with a high ratio of nonsynonymous (n = 18) to synonymous (n = 7) mutations, 2 deletions, and a high number of amino acid substitutions within the spike protein (n = 8) at key positions: spike substitutions in comparison with other recently emerged variants (Table) and all mutations (Figure).

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 (Figure). These patients were 1 prison administration staff member from northeast of the Paris area, tested February 9 during a prison screening campaign; 3 epidemiologically related subjects from a cluster in the hematology department of our hospital (an asymptomatic nursing student tested February 12, his mentor nurse tested February 14, and a hospitalized patient tested February 15); and 8 epidemiologically unrelated cases found positive for SARS-CoV-2 RNA during February 3–23 in different hospitals in the greater Paris area (GISAID identification numbers in Appendix Table).

During the same period, the National Reference Center for Respiratory Viral Infections (Lyon, France) identified 17 additional patients infected with closely related viruses, which carried >7 similar substitutions in spike (some were lacking Q677H in spike [Figure]). Three patients were from the greater Paris area, 10 from southeastern France, and 4 from southwestern France (Figure).

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 (2; Yang et al., unpub. data, https://doi.org/10.1101/2020.12.29.42469).

New variants with several spike mutations (20I/501Y.V1) have been associated with increased transmissibility. Whether HMN.19B will be less susceptible to protection by natural, therapeutic, or vaccine-induced immune responses remains to be determined. Several of its spike substitutions (N501Y, L452R, and H655Y) have been shown to require higher levels of neutralizing antibodies to be controlled, both in vitro and in vivo (3,4; Liu et al., unpub. data, https://doi.org/10.1101/2020.11.06.372037).

In conclusion, we report a new SARS-CoV-2 variant circulating in France. Our results emphasize the need for careful molecular surveillance of SARS-CoV-2 evolution to track emergence of any new variant of interest with potential epidemiologic or pathophysiologic consequences.

Dr. Fourati is a researcher at University of East Paris, Créteil, France. He is also a clinical virologist in the Department of Microbiology, Henri Mondor Hospital, Créteil, France. His primary research interests include viral evolution and adaptation, and viral hepatitis and respiratory viruses including SARS CoV-2.

Top

Acknowledgment

We thank Martine Valette and Quentin Semanas for their help and commitment.

Top

References

  1. Korber  B, Fischer  WM, Gnanakaran  S, Yoon  H, Theiler  J, Abfalterer  W, et al.; Sheffield COVID-19 Genomics Group. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell. 2020;182:812827.e19. DOIPubMed
  2. Weisblum  Y, Schmidt  F, Zhang  F, DaSilva  J, Poston  D, Lorenzi  JC, et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. eLife. 2020;9:e61312. DOIPubMed
  3. Choi  B, Choudhary  MC, Regan  J, Sparks  JA, Padera  RF, Qiu  X, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med. 2020;383:22913. DOIPubMed
  4. Baum  A, Fulton  BO, Wloga  E, Copin  R, Pascal  KE, Russo  V, et al. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science. 2020;369:10148. DOIPubMed

Top

Figure
Table

Top

Cite This Article

DOI: 10.3201/eid2705.210324

Original Publication Date: March 30, 2021

Table of Contents – Volume 27, Number 5—May 2021

Comments

Please use the form below to submit correspondence to the authors or contact them at the following address:

Slim Fourati, Virology Department, Henri Mondor Hospital, 51 Av. du Maréchal de Lattre de Tassigny, 94010 Créteil, France

Send To

10000 character(s) remaining.

Top

Page created: March 16, 2021
Page updated: April 22, 2021
Page reviewed: April 22, 2021
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external