ABSTRACT
BackgroundIn 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. MethodsClinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled patients with at least one of the following: 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 chest CT scan. Cases were categorized as either: i) B.1.616; ii) variant of concern (VOC); iii) unknown. FindingsFrom January 1st to March 24th, 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n=34), VOC (n=32), and unknown (n=48). B.1.616-related cases were older than VOC-related cases (81 years [73-88], vs 73 years [67-82], P<0.05) and their first RT-PCR tests were less often positive (5/34, 15% vs 31/32, 97%, P<0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.2 [1.3- 13.5], P=0.018), and increased lethality (logrank test P=0.01): 28-day mortality 15/34 (44%) with B.1.616, vs. 5/32 (16%) for VOC, P=0.036. InterpretationWe 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. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAmong the numerous SARS-CoV-2 variants described worldwide, only 3 are currently classified as Variant of Concern (VOC) by the WHO, since they are associated with either an increased risk in transmissibility, severity, or significant reduction in neutralization by antibodies: B.1.1.7, B.1.351 and P.1 (Pango lineage nomenclature). With the ongoing circulation of SARS-CoV-2 in many places worldwide, the emergence of new variants may reduce the efficacy of vaccines and jeopardize our prospects to control the pandemic. In early January 2021, an outbreak of cases highly suggestive of COVID-19 despite negative RT-PCR tests on repeated nasopharyngeal (NP) samples was reported in Western France, leading to several nosocomial clusters. Whole-genome sequencing (WGS) from lower respiratory tract samples identified a new lineage of SARS-CoV-2 virus, classified as B1.616. Consequently, the French public health agency (Sante publique France) and the WHO classified B.1.616 as variant under investigation (VUI). Added value of this studyOur observational study, conducted from January 1st to March 24th 2021 in the B.1.616 identified area, provides the first clinical and virological description of B.1.616-associated COVID-19. The 34 cases had clinical, biological and radiological findings in line with classical features of COVID-19, while RT-PCR tests on nasopharyngeal (NP) samples failed to detect SARS-CoV-2 in most patients. Indeed, this gold-standard test was positive in only 15% of the first tests in B.1.616-related COVID-19 patients. Of note, the diagnostic performance of RT-PCR tests was satisfactory on lower respiratory tract samples, suggesting that failure to detect B.1.616 on NP samples would be due to a viral load below the limit of detection in the upper respiratory tract, rather than to genomic mismatches between routine RT-PCR targets and this variant. In our cohort, B.1.616 was independently associated with worse clinical outcome, with high 28-day mortality (44%). Implications of all the available evidenceDiagnosis of B.1.616-related COVID-19 cases should not rely on RT-PCR tests on NP samples. In the epidemic area, strict infection control measures must be maintained as long as COVID-19 diagnosis is not ruled out, in order to limit nosocomial clusters and case fatality. Further studies are needed to confirm and investigate the association between genomic characteristics of B.1.616, and i) poor detection by RT-PCR tests on NP samples; ii) prognosis.
ABSTRACT
Although the global response to COVID-19 has not been entirely unified, the opportunity arises to assess the impact of regional public health interventions and to classify strategies according to their outcome. Analysis of genetic sequence data gathered over the course of the pandemic allows us to link the dynamics associated with networks of connected individuals with specific interventions. In this study, clusters of transmission were inferred from a phylogenetic tree representing the relationships of patient sequences sampled from December 30, 2019 to April 17, 2020. Metadata comprising sampling time and location were used to define the global behavior of transmission over this earlier sampling period, but also the involvement of individual regions in transmission cluster dynamics. Results demonstrate a positive impact of international travel restrictions and nationwide lockdowns on global cluster dynamics. However, residual, localized clusters displayed a wide range of estimated initial secondary infection rates, for which uniform public health interventions are unlikely to have sustainable effects. Our findings highlight the presence of so-called "super-spreaders", with the propensity to infect a larger-than-average number of people, in countries, such as the USA, for which additional mitigation efforts targeting events surrounding this type of spread are urgently needed to curb further dissemination of SARS-CoV-2.
