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

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.

Graphical abstract

Fig. 1

Phylogenetic analysis of the B.1.616 lineage of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characteristic non-synonymous substitutions. (A) Subsampled global phylogenetic maximum likelihood tree of SARS-CoV-2 with annotated Nextstrain clades next to the corresponding nodes and tips highlighted only for sequences from the Pangolin B.1.616 lineage. (B) Detailed view of the B1.616 lineage. In (A) and (B) branch lengths correspond to the number of nucleotide substitutions (shown below the tree) from the reference Wuhan-Hu-1 strain (NC_045512). (C) Nucleotide and amino-acid substitutions from the reference Wuhan-Hu-1 strain shared among the sequences from Lannion, France are represented as ticks along the SARS-CoV-2 genome and are annotated with text if non-synonymous. Light grey text annotated amino-acid substitutions are not unique to the Lannion (B1.616) lineage.

Fig. 2

Survival curves. VOC, variant of concern.