A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study

Pierre Fillâtre; Marie-José Dufour; Sylvie Behillil; Rémi Vatan; Pascale Reusse; Alice Gabellec; Nicolas Velmans; Catherine Montagne; Sophie Geffroy Du Coudret; Edith Droumaguet; Véronique Merour; Vincent Enouf; Rodolphe Buzelé; Marion Valence; Elena Guillotel; Bertrand Gagnière; Artem Baidaliuk; Anna Zhukova; Mathieu Tourdjman; Vincent Thibault; Claire Grolhier; Charlotte Pronier; François-Xavier Lescure; Etienne Simon-Loriere; Dominique Costagliola; Sylvie Van Der Werf; Pierre Tattevin; Nicolas Massart

doi:10.1016/j.cmi.2021.09.035

A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study

Clin Microbiol Infect. 2022 Feb;28(2):298.e9-298.e15. doi: 10.1016/j.cmi.2021.09.035. Epub 2021 Oct 7.

Authors

Pierre Fillâtre¹, Marie-José Dufour², Sylvie Behillil³, Rémi Vatan⁴, Pascale Reusse⁵, Alice Gabellec⁵, Nicolas Velmans⁶, Catherine Montagne⁷, Sophie Geffroy Du Coudret⁸, Edith Droumaguet⁹, Véronique Merour¹⁰, Vincent Enouf¹¹, Rodolphe Buzelé¹², Marion Valence¹², Elena Guillotel¹³, Bertrand Gagnière¹⁴, Artem Baidaliuk¹⁵, Anna Zhukova¹⁶, Mathieu Tourdjman¹⁷, Vincent Thibault¹⁸, Claire Grolhier¹⁸, Charlotte Pronier¹⁸, François-Xavier Lescure¹⁹, Etienne Simon-Loriere¹⁵, Dominique Costagliola²⁰, Sylvie Van Der Werf³, Pierre Tattevin²¹, Nicolas Massart²²

Affiliations

¹ Service de Réanimation Polyvalente, CH de Saint-Brieuc, 10 rue Marcel Proust, 22000, Saint-Brieuc, France. Electronic address: pierre.fillatre@armorsante.bzh.
² Service de Biologie Médicale, CH de Lannion, Centre Hospitalier Pierre-le-Damany, 22303, Lannion, France.
³ National Reference Centre for Respiratory Viruses, Molecular Genetics of RNA Viruses, CNRS-UMR 3569, University of Paris, Institut Pasteur, Paris, France.
⁴ Service de Médecine Interne, CH de Lannion, Centre Hospitalier Pierre-le-Damany, 22303, Lannion, France; Service de Maladies Infectieuses, CH de Saint-Brieuc, 10 rue Marcel Proust, 22000, Saint-Brieuc, France.
⁵ Service de Gériatrie, CH de Lannion, Centre Hospitalier Pierre-le-Damany, 22303, Lannion, France.
⁶ Service de Médecine Interne, CH de Lannion, Centre Hospitalier Pierre-le-Damany, 22303, Lannion, France.
⁷ Service d'Imagerie Médicale, CH de Lannion, Centre Hospitalier Pierre-le-Damany, 22303, Lannion, France.
⁸ Service de Pneumologie, CH de Lannion, Centre Hospitalier Pierre-le-Damany, 22303, Lannion, France.
⁹ Département d'Informatique Médicale, CH de Lannion, Centre Hospitalier Pierre-le-Damany, 22303, Lannion, France.
¹⁰ Plateforme de Surveillance Continue, CH de Lannion, Centre Hospitalier Pierre-le-Damany, 22303, Lannion, France.
¹¹ National Reference Centre for Respiratory Viruses, Molecular Genetics of RNA Viruses, CNRS-UMR 3569, University of Paris, Institut Pasteur, Paris, France; Mutualized Platform of Microbiology, Pasteur International Bioresources Network, Institut Pasteur, Paris, France.
¹² Service de Maladies Infectieuses, CH de Saint-Brieuc, 10 rue Marcel Proust, 22000, Saint-Brieuc, France.
¹³ Service de Biologie Médicale, CH de Saint-Brieuc, 10, rue Marcel Proust, 22000, Saint-Brieuc, France.
¹⁴ Santé Publique France, French National Public Health Agency, Cellule Bretagne, Rennes, France.
¹⁵ Evolutionary Genomics of RNA Viruses, Institut Pasteur, Paris, France.
¹⁶ Unité Bioinformatique Evolutive & Hub de Bioinformatique et Biostatistique-Département Biologie Computationnelle, USR3756 (C3BI/DBC), Institut Pasteur, Paris, France.
¹⁷ Santé Publique France, The French Public Health Agency, Saint-Maurice, France.
¹⁸ Service de Virologie, CHU de Rennes, 2, rue Henri le Guilloux, 35000, Rennes, France.
¹⁹ Department of Infectious and Tropical Diseases, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France; Infections Antimicrobials Modelling Evolution (IAME), UMR 1137, University of Paris, Paris, France.
²⁰ Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (IPLESP), Paris, France.
²¹ Service de Maladie Infectieuse et de Réanimation Médicale, CHU de Rennes, 2, rue Henri le Guilloux, 35000, Rennes, France.
²² Service de Réanimation Polyvalente, CH de Saint-Brieuc, 10 rue Marcel Proust, 22000, Saint-Brieuc, France.

Abstract

Objectives: In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant.

Methods: Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown.

Results: From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006).

Conclusion: We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.

Keywords: COVID-19; Coronavirus infections/epidemiology; Coronavirus infections/virology; SARS-CoV-2 variants; Severity of illness index.

Publication types

Observational Study

MeSH terms

COVID-19* / epidemiology
COVID-19* / virology
France / epidemiology
Humans
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
SARS-CoV-2*

Supplementary concepts

SARS-CoV-2 variants