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Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21256690


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.

Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-21255922


BackgroundSince the emergence of SARS-CoV-2, health care workers (HCWs) have been on the front line in caring for COVID-19 patients. Better knowledge of risk factors for SARS-CoV-2 infection is crucial for the prevention of disease among this population. MethodsWe conducted a seroprevalence survey among HCWs in a French university hospital after the first wave (May-June 2020), based on a validated lateral flow immuno-assay test (LFIAT) for SARS-CoV-2. Demographic characteristics as well as data on the working characteristics of COVID-19 and non-COVID-19 wards and 23 care activities were systematically recorded. The effectiveness of protective equipment was also estimated, based on self-declaration of mask use. SARS-CoV-2 IgG status was modelled by multiple imputations approach, accounting for the performance of the test and data on serum validation ELISA immunoassay. FindingsAmong the 3,234 enrolled HCWs, the prevalence of SARS-CoV-2 IgG was 3.8%. Contact with relatives or HCWs who developed COVID-19 were risk factors for SARS-CoV-2 infection, but not contact with COVID-19 patients. In multivariate analyses, suboptimal use of protective equipment during naso-pharyngeal sampling, patient mobilisation, clinical and eye examination was associated with SARS-CoV-2 infection. In addition, patients washing and dressing and aerosol-generating procedures were risk factors for SARS-CoV-2 infection with or without self-declared appropriate use of protective equipment. InterpretationMain routes of transmission of SARS-CoV-2 IgG among HCWs were i) contact with relatives or HCWs with COVID-19, ii) close or prolonged contact with patients, iii) aerosol-generating procedures.

Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-20154260


BackgroundThe clinical description of the neurological manifestations in COVID-19 patients is still underway. This study aims to provide an overview of the spectrum, characteristics and outcomes of neurological manifestations associated with SARS-CoV-2 infection. MethodsWe conducted a nationwide, multicentric, retrospective study during the French COVID-19 epidemic in March-April 2020. All COVID-19 patients with de novo neurological manifestations were eligible. ResultsWe included 222 COVID-19 patients with neurological manifestations from 46 centers throughout the country. Median age was 65 years (IQR 53-72), and 136 patients (61.3%) were male. COVID-19 was severe or critical in almost half of the patients (102, 45.2%). The most common neurological diseases were COVID-19 associated encephalopathy (67/222, 30.2%), acute ischemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%), and Guillain-Barre Syndrome (15/222, 6.8%). Neurological manifestations appeared after first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19 associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barre Syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 MRI (70.7%). Brain MRI of encephalitis patients showed heterogeneous acute non vascular lesion in 14/21 patients (66.7%) with associated small ischemic lesion or microhemorrhages in 4 patients. Among patients with acute ischemic cerebrovascular syndrome, 13/57 (22.8%) had multi territory ischemic strokes, with large vessel thrombosis in 16/57 (28.1%). Cerebrospinal fluid was analyzed in 97 patients (43.7%), with pleocytosis in 18 patients (18.6%). A SARS-CoV-2 PCR was performed in 75 patients and was positive only in 2 encephalitis patients. Among patients with encephalitis, ten out of 21 (47.6%) fully recovered, 3 of whom received corticosteroids (CS). Less common neurological manifestations included isolated seizure (8/222, 3.6%), critical illness neuropathy (8/222, 3.6%), transient alteration of consciousness (5/222, 2.3%), intracranial hemorrhage (5/222, 2.3%), acute benign lymphocytic meningitis (3/222, 1.4%), cranial neuropathy (3/222, 1.4%), single acute demyelinating lesion (2/222, 0.9%), Tapia syndrome (2/222, 0.9%), cerebral venous thrombosis (1/222, 0.5%), sudden paraparesis (1/222, 0.5%), generalized myoclonus and cerebellar ataxia (1/222, 0.5%), bilateral fibular palsy (1/222, 0.5%) and isolated neurological symptoms (headache, anosmia, dizziness, sensitive or auditive symptoms, hiccups, 15/222, 6.8%). The median (IQR) follow-up of the 222 patients was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). ConclusionNeurological manifestations associated with COVID-19 mainly included CAE, AICS, encephalitis and GBS. Clinical spectrum and outcomes were broad and heterogeneous, suggesting different underlying pathogenic processes.

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