A new SARS-CoV-2 variant poorly detected by RT-PCR on nasopharyngeal samples, with high lethality (preprint)

Background: 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 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. Findings: From 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): 28day mortality 15/34 (44%) with B.1.616, vs. 5/32 (16%) for VOC, P=0.036. Interpretation: 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.

Role of non-aerosols activities in the transmission of SARS-Cov-2 infection among health care workers. (preprint)

Abstract Background. Since 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. Methods. We 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. Findings. Among 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. Interpretation. Main 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.

Prevalence and Characteristics of Persistent Symptoms After Non-Severe COVID-19: A Prospective Cohort Study (preprint)

We performed a prospective cohort study of 311 outpatients with non-severe COVID-19 (187 women, median age 39 years). Of the 214 (68.8%) who completed the 6-week follow-up questionnaire, 115 (53.7%) had recovered. Others mostly reported dyspnea (n=86, 40.2%), weight loss (n=83, 38.8%), sleep disorders (n=68, 31.8%), and anxiety (n=56, 26.2%). Of those who developed ageusia and anosmia, these symptoms were still present at week 6 in, respectively, 11/111 (9.9%), and 19/114 (16.7%). Chest CT scan and lung function tests found no explanation in the most disabled patients (n=23). This study confirms the high prevalence of persistent symptoms after non-severe COVID-19.

Neurological manifestations associated with COVID-19: a nationwide registry (preprint)

Background: The 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. Methods: We 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. Results: We 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%). Conclusion: Neurological 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.