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

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

OBJECTIVES: In early January 2021, an outbreak of nosocomial cases of COVID-19 emerged in Western France, with RT-PCR tests repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole genome sequencing (WGS) revealed a new variant, currently defining a novel SARS-CoV-2 lineage: B.1.616. In March, WHO classified this variant as ‘under investigation’ (VUI). We analyzed 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 inpatients with either: i) positive SARS-CoV-2 RT-PCR on a respiratory sample; ii) seroconversion with anti-SARS-CoV-2 IgG/IgM; iii) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as either: i) B.1.616; ii) variant of concern (VOC); iii) unknown. RESULTS: From January 1(st) to March 24(th), 2021, 114 patients fulfilled 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], vs 73 years IQR [67-82], P<0.05) and their first RT-PCR tests were rarely positive (6/39, 15% vs 31/32, 97%, P<0.05). 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, vs. 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, poorly detected by RT-PCR on nasopharyngeal samples, with high lethality.