Publications by authors named "Bruno Lina"

210 Publications

SARS-CoV-2 viral dynamics in non-human primates.

PLoS Comput Biol 2021 03 17;17(3):e1008785. Epub 2021 Mar 17.

Université de Paris, IAME, INSERM, Paris, France.

Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large burst size (>104 virus) and a within-host reproductive basic number of approximately 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly lost with a half-life of 9 hours, with no significant association between cytokine elevation and clearance, leading to a median time to viral clearance of 10 days, consistent with observations in mild human infections. Given these parameter estimates, we predict that a prophylactic treatment blocking 90% of viral production or viral infection could prevent viral growth. In conclusion, our results provide estimates of SARS-CoV-2 viral kinetic parameters in an experimental model of mild infection and they provide means to assess the efficacy of future antiviral treatments.
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http://dx.doi.org/10.1371/journal.pcbi.1008785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007039PMC
March 2021

Early assessment of diffusion and possible expansion of SARS-CoV-2 Lineage 20I/501Y.V1 (B.1.1.7, variant of concern 202012/01) in France, January to March 2021.

Euro Surveill 2021 03;26(9)

These senior authors contributed equally.

The emergence of SARS-CoV-2 variant 20I/501Y.V1 (VOC-202012/1 or GR/501Y.V1) is concerning given its increased transmissibility. We reanalysed 11,916 PCR-positive tests (41% of all positive tests) performed on 7-8 January 2021 in France. The prevalence of 20I/501Y.V1 was 3.3% among positive tests nationwide and 6.9% in the Paris region. Analysing the recent rise in the prevalence of 20I/501Y.V1, we estimate that, in the French context, 20I/501Y.V1 is 52-69% more transmissible than the previously circulating lineages, depending on modelling assumptions.
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.9.2100133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934223PMC
March 2021

Immune evasion means we need a new COVID-19 social contract.

Lancet Public Health 2021 04 18;6(4):e199-e200. Epub 2021 Feb 18.

Inserm 1219, University of Bordeaux, Bordeaux, France.

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http://dx.doi.org/10.1016/S2468-2667(21)00036-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891047PMC
April 2021

SARS-CoV-2 variants and ending the COVID-19 pandemic.

Lancet 2021 03 11;397(10278):952-954. Epub 2021 Feb 11.

Usher Institute of Population Health Sciences and Informatics, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK.

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http://dx.doi.org/10.1016/S0140-6736(21)00370-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906631PMC
March 2021

It's time to change the recommendations on COVID-19 and human milk donations.

Acta Paediatr 2021 May 9;110(5):1405-1406. Epub 2021 Feb 9.

Hospices Civils de Lyon Virology Lab, Institute of Infectious Agents, National Reference Center for Viral Respiratory Infections, Croix Rousse University Hospital, Lyon, France.

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http://dx.doi.org/10.1111/apa.15782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014273PMC
May 2021

Impact of the lockdown on the burden of COVID-19 in outpatient care in France, spring 2020.

Infect Dis (Lond) 2021 05 29;53(5):376-381. Epub 2021 Jan 29.

Sorbonne Université, INSERM, Institut Pierre Louis d'épidémiologie et de Santé publique (IPLESP), Paris, France.

Background: To limit the spread of SARS-CoV-2 several countries implemented measures to reduce the number of contacts such as a national lockdown. We estimated the impact of the first lockdown on the burden of COVID-19 in the community in France.

Methods: Physicians participating in the French Sentinelles network reported the number of patients with an acute respiratory infection (ARI) seen in consultation and performed nasopharyngeal swabs in a sample of these patients (first patient of the week). The swabs were tested by RT-PCR for the presence of SARS-CoV-2. Clinical and virological data were combined to estimate ARI incidence attributable to SARS-CoV-2 from 17 March to 10 May 2020.

Results: The incidence of ARI attributable to COVID-19 decreased after the second week of the lockdown period from 142 (95%CI [101; 183]) to 41 (95%CI [21; 60]) per 100,000 population. A decrease was observed in all areas in metropolitan France. The youngest age groups (<15-years-old) were least affected with a cumulated incidence estimated to 14 per 100,000 population during the study period.

Conclusions: The data collected in primary care suggests that the first lockdown implemented in France during spring 2020 significantly reduced the incidence of acute respiratory infections including COVID-19 in France and limited the geographic spread of SARS-CoV-2.
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http://dx.doi.org/10.1080/23744235.2021.1880024DOI Listing
May 2021

Factors associated with admission to intensive care units in COVID-19 patients in Lyon-France.

PLoS One 2021 27;16(1):e0243709. Epub 2021 Jan 27.

Service Hygiène, Epidémiologie, Infectiovigilance et Prévention, Centre Hospitalier Edouard Herriot, Hospices Civils de Lyon, Lyon, France.

Introduction: A new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analysing clinical presentation on admission and the determinants associated with admission in intensive care units (ICUs) in hospitalized COVID-19 patients.

Patients And Methods: In this prospective hospital-based study, socio-demographic, clinical and biological characteristics, on admission, of adult COVID-19 hospitalized patients presenting from the community for their first admission were prospectively collected and analysed. Characteristics of patients hospitalized in medical ward to those admitted in ICU were compared using Mann-Whitney and Chi-square or Fisher exact test when appropriate. Univariate logistic regression was first used to identify variables on admission that were associated with the outcome i.e. admission to an ICU versus total hospital stay in a medical ward. Forward selection was then applied beginning with sex, age and temperature in the multivariable logistic regression model.

Results: Of the 412 patients included, 325 were discharged and 87 died in hospital. Multivariable regression showed increasing odds of ICU hospitalization with temperature (OR, 1.56 [95% CI, 1.06-2.28] per degree Celsius increase), oxygen saturation <90% (OR, 12.45 [95% CI, 5.27-29.4]), abnormal lung auscultation on admission (OR, 3.58 [95% CI, 1.58-8.11]), elevated level of CRP (OR, 2.7 [95% CI, 1.29-5.66for CRP>100mg/L vs CRP<10mg/L). and monocytopenia (OR, 3.28 [95% CI, 1.4-7.68]) were also associated with increasing odds of ICU hospitalization. Older patients were less likely to be hospitalized in ICU (OR, 0.17 [95%CI, 0.05-0.51].

Conclusions: Age and delay between onset of symptoms and hospital admission were associated with the risk of hospitalisation in ICU. Age being a fixed variable, interventions that shorten this delay would improve the prognosis of Covid-19 patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243709PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840037PMC
February 2021

Two-step strategy for the identification of SARS-CoV-2 variant of concern 202012/01 and other variants with spike deletion H69-V70, France, August to December 2020.

Euro Surveill 2021 01;26(3)

The members of the COVID-Diagnosis HCL Study Group are listed below.

We report the strategy leading to the first detection of variant of concern 202012/01 (VOC) in France (21 December 2020). First, the spike (S) deletion H69-V70 (ΔH69/ΔV70), identified in certain SARS-CoV-2 variants including VOC, is screened for. This deletion is associated with a S-gene target failure (SGTF) in the three-target RT-PCR assay (TaqPath kit). Subsequently, SGTF samples are whole genome sequenced. This approach revealed mutations co-occurring with ΔH69/ΔV70 including S:N501Y in the VOC.
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.3.2100008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848679PMC
January 2021

Estimation of influenza-attributable burden in primary care from season 2014/2015 to 2018/2019, France.

Eur J Clin Microbiol Infect Dis 2021 Jan 20. Epub 2021 Jan 20.

Sorbonne Université, INSERM, Institut Pierre Louis d'épidémiologie et de Santé publique (IPLESP UMRS 1136), Paris, France.

Influenza viruses cause seasonal epidemics whose intensity varies according to the circulating virus type and subtype. We aim to estimate influenza-like illness (ILI) incidence attributable to influenza viruses in France from October 2014 to May 2019. Physicians participating in the French Sentinelles network reported the number of patients with ILI seen in consultation and performed nasopharyngeal swabs in a sample of these patients. The swabs were tested by RT-PCR for the presence of influenza viruses. These clinical and virological data were combined to estimate ILI incidence attributable to influenza viruses by subtypes and age groups. Influenza incidence rates over seasons ranged from 1.9 (95% CI, 1.9; 2.0) to 3.4% (95% CI, 3.2; 3.6) of the population. Each season, more than half of ILI cases were attributable to influenza. Children under 15 years were the most affected, with influenza incidence rates ranging from 3.0 (95% CI, 2.8;3.3) to 5.7% (95% CI, 5.3;6.1). Co-circulation of several (sub)types of influenza viruses was observed each year, except in 2016/2017 where A(H3N2) viruses accounted for 98.0% of the influenza cases. Weekly ILI incidences attributable to each influenza virus (sub)type were mostly synchronized with ILI incidence, except in 2014/2015 and 2017/2018, where incidence attributable to type B viruses peaked few weeks later. The burden of medically attended influenza among patients with ILI is significant in France, varying considerably across years and age groups. These results show the importance of influenza surveillance in primary care combining clinical and virological data.
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http://dx.doi.org/10.1007/s10096-021-04161-1DOI Listing
January 2021

Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralization and commercial assays.

Clin Microbiol Infect 2021 Jan 13. Epub 2021 Jan 13.

Laboratoire de Virologie, Institut des Agents Infectieux, Laboratoire Associé Au Centre National de Référence des Virus des Infections Respiratoires, Hospices Civils de Lyon, Lyon, France; CIRI, Centre International de Recherche en Infectiologie, Team VirPath, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France. Electronic address:

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http://dx.doi.org/10.1016/j.cmi.2021.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803622PMC
January 2021

Impact of mass testing during an epidemic rebound of SARS-CoV-2: a modelling study using the example of France.

Euro Surveill 2021 01;26(1)

Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, UMR2000, CNRS, Paris, France.

We used a mathematical model to evaluate the impact of mass testing in the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Under optimistic assumptions, one round of mass testing may reduce daily infections by up to 20-30%. Consequently, very frequent testing would be required to control a quickly growing epidemic if other control measures were to be relaxed. Mass testing is most relevant when epidemic growth remains limited through a combination of interventions.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.26.1.2001978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791601PMC
January 2021

Evaluation of high-throughput SARS-CoV-2 serological assays in a longitudinal cohort of patients with mild COVID-19: clinical sensitivity, specificity and association with virus neutralization test.

Clin Chem 2021 Jan 5. Epub 2021 Jan 5.

CIRI, Centre International de Recherche en Infectiologie, Team VirPath, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007, Lyon, France.

Background: The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild patients with COVID-19.

Methods: 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The clinical sensitivity (determined weekly) of nine commercial serological assays were evaluated. Clinical specificity was assessed using 69 pre-pandemic sera. Correlation, agreement and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at 2 neutralizing antibody titers.

Results: The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The clinical specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0-68.1) for bioMérieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1-48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7-89.7), 90.3 (78.1-96.1) and 96.8% (86.8-99.3) for Siemens, bioMérieux IgG and DiaSorin, respectively. None of commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC<0.76).

Conclusions: Although some assays show a better agreement with VNT than others, the present findings emphasize that commercialized serological tests including those targeting the RBD cannot substitute a VNT for the assessment of functional antibody response.
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http://dx.doi.org/10.1093/clinchem/hvaa336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929008PMC
January 2021

Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France.

Emerg Microbes Infect 2021 Dec;10(1):167-177

CIRI, Centre International de Recherche en Infectiologie, Team VirPatH, Lyon, Fracne.

During routine molecular surveillance of SARS-CoV-2 performed at the National Reference Center of Respiratory Viruses (Lyon, France) ( = 229 sequences collected February-April 2020), two frameshifting deletions were detected in the open reading frame 6, at the same position (27267). While a 26-nucleotide deletion variant (D26) was only found in one nasopharyngeal sample in March 2020, the 34-nucleotide deletion (D34) was found within a single geriatric hospital unit in 5/9 patients and one health care worker in April 2020. Phylogeny analysis strongly suggested a nosocomial transmission of D34, with potential fecal transmission, as also identified in a stool sample. No difference in disease severity was observed between patients hospitalized in the geriatric unit infected with WT or D34. D26 and D34 characterization revealed comparable replication kinetics with the wild-type (WT), but differential host immune responses. While interferon-stimulated genes were similarly upregulated after infection with WT and ORF6 variants, the latter specifically induced overexpression of 9 genes coding for inflammatory cytokines in the NF-kB pathway, including , , and , for which high plasma levels have been associated with severe COVID-19. Our findings emphasize the need to monitor the occurrence of ORF6 deletions and assess their impact on the host immune response.
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http://dx.doi.org/10.1080/22221751.2021.1872351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850418PMC
December 2021

Transcriptional Profiling of Immune and Inflammatory Responses in the Context of SARS-CoV-2 Fungal Superinfection in a Human Airway Epithelial Model.

Microorganisms 2020 Dec 11;8(12). Epub 2020 Dec 11.

CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France.

An increasing amount of evidence indicates a relatively high prevalence of superinfections associated with coronavirus disease 2019 (COVID-19), including invasive aspergillosis, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection, we determine and compare the host transcriptional response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) versus superinfection, using a model of reconstituted human airway epithelium. Our analyses reveal that both simple infection and superinfection induce strong deregulation of core components of innate immune and inflammatory responses, with a stronger response to superinfection in the bronchial epithelial model compared to its nasal counterpart. Our results also highlight unique transcriptional footprints of SARS-CoV-2 superinfection, such as an imbalanced type I/type III IFN, and an induction of several monocyte and neutrophil associated chemokines, that could be useful for the understanding of -associated COVID-19 and also the management of severe forms of aspergillosis in this specific context.
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http://dx.doi.org/10.3390/microorganisms8121974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764715PMC
December 2020

Evaluation of NGS-based approaches for SARS-CoV-2 whole genome characterisation.

Virus Evol 2020 Jul 5;6(2):veaa075. Epub 2020 Oct 5.

Laboratoire de Virologie, Institut des Agents Infectieux (IAI), Hospices Civils de Lyon, Groupement Hospitalier Nord, Lyon cedex 4, France.

Since the beginning of the COVID-19 outbreak, SARS-CoV-2 whole-genome sequencing (WGS) has been performed at unprecedented rate worldwide with the use of very diverse Next-Generation Sequencing (NGS) methods. Herein, we compare the performance of four NGS-based approaches for SARS-CoV-2 WGS. Twenty-four clinical respiratory samples with a large scale of Ct values (from 10.7 to 33.9) were sequenced with four methods. Three used Illumina sequencing: an in-house metagenomic NGS (mNGS) protocol and two newly commercialised kits including a hybridisation capture method developed by Illumina (DNA Prep with Enrichment kit and Respiratory Virus Oligo Panel, RVOP), and an amplicon sequencing method developed by Paragon Genomics (CleanPlex SARS-CoV-2 kit). We also evaluated the widely used amplicon sequencing protocol developed by ARTIC Network and combined with Oxford Nanopore Technologies (ONT) sequencing. All four methods yielded near-complete genomes (>99%) for high viral loads samples ( = 8), with mNGS and RVOP producing the most complete genomes. For mid viral loads (Ct 20-25), amplicon-based enrichment methods led to genome coverage >99 per cent for all samples while 1/8 sample sequenced with RVOP and 2/8 samples sequenced with mNGS had a genome coverage below 99 per cent. For low viral loads (Ct ≥25), amplicon-based enrichment methods were the most sensitive techniques. All methods were highly concordant in terms of identity in complete consensus sequence. Just one mismatch in three samples was observed in CleanPlex the other methods, due to the dedicated bioinformatics pipeline setting a high threshold to call SNP compared to reference sequence. Importantly, all methods correctly identified a newly observed 34nt-deletion in ORF6 but required specific bioinformatic validation for RVOP. Finally, as a major warning for targeted techniques, a loss of coverage in any given region of the genome should alert to a potential rearrangement or a SNP in primer-annealing or probe-hybridizing regions and would require further validation using unbiased metagenomic sequencing.
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http://dx.doi.org/10.1093/ve/veaa075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665770PMC
July 2020

Virology, epidemiology, immunology and vaccine development of SARS-CoV-2, update after nine months of pandemic.

Biologicals 2021 Jan 19;69:76-82. Epub 2020 Nov 19.

International Alliance for Biological Standardization - IABS, Geneva, Switzerland. Electronic address:

This International Alliance for Biological Standardization COVID-19 webinar was organized to provide an update on the virology, epidemiology and immunology of, and the vaccine development for SARS-CoV-2, none months after COVID-19 was declared a public health emergency of international concern. It brought together a broad range of international stakeholders, including academia, regulators, funders and industry, with a considerable delegation from low- and middle-income countries.
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http://dx.doi.org/10.1016/j.biologicals.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676373PMC
January 2021

Description of an influenza outbreak in a French university hospital and risk factors of nosocomial influenza.

Eur J Clin Microbiol Infect Dis 2021 Apr 15;40(4):879-884. Epub 2020 Oct 15.

Infection control unit, CHU Grenoble Alpes, Grenoble, France.

Our objective was to evaluate risk factors of nosocomial influenza (NI) in an university hospital during the 2015/2016 influenza season. All hospitalized patients with influenza-like illness associated with laboratory confirmation by polymerase chain reaction were included in a prospective observational study. We identified 44 cases (19%) of NI among the 233 cases of influenza: 38/178 (21%) in adults and 6/55 (11%) in children. Among adults, hospitalization in a double or multi-occupancy room was independently associated with NI (adjusted Odds Ratio, 3.42; 95% CI, 1.29-9.08; p = 0.013). The results of the study underline the importance of single room to prevent NI.
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http://dx.doi.org/10.1007/s10096-020-04070-9DOI Listing
April 2021

COVID-19: France grapples with the pragmatics of isolation.

Lancet Public Health 2020 11 10;5(11):e573-e574. Epub 2020 Oct 10.

National Ethical Consultative Committee for Life Sciences and Health, Paris, France.

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http://dx.doi.org/10.1016/S2468-2667(20)30235-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547370PMC
November 2020

Comparison of Nucleic Acid Extraction Methods for a Viral Metagenomics Analysis of Respiratory Viruses.

Microorganisms 2020 Oct 6;8(10). Epub 2020 Oct 6.

Laboratoire de Virologie, Institut des Agents Infectieux (IAI), Hospices Civils de Lyon, Groupement Hospitalier Nord, F-69004 Lyon, France.

Viral metagenomics next-generation sequencing (mNGS) is increasingly being used to characterize the human virome. The impact of viral nucleic extraction on virome profiling has been poorly studied. Here, we aimed to compare the sensitivity and sample and reagent contamination of three extraction methods used for viral mNGS: two automated platforms (eMAG; MagNA Pure 24, MP24) and the manual QIAamp Viral RNA Mini Kit (QIAamp). Clinical respiratory samples (positive for Respiratory Syncytial Virus or Herpes Simplex Virus), one mock sample (including five viruses isolated from respiratory samples), and a no-template control (NTC) were extracted and processed through an mNGS workflow. QIAamp yielded a lower proportion of viral reads for both clinical and mock samples. The sample cross-contamination was higher when using MP24, with up to 36.09% of the viral reads mapping to mock viruses in the NTC (vs. 1.53% and 1.45% for eMAG and QIAamp, respectively). The highest number of viral reads mapping to bacteriophages in the NTC was found with QIAamp, suggesting reagent contamination. Our results highlight the importance of the extraction method choice for accurate virome characterization.
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http://dx.doi.org/10.3390/microorganisms8101539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601816PMC
October 2020

Comparison of eight commercial, high-throughput, automated or ELISA assays detecting SARS-CoV-2 IgG or total antibody.

J Clin Virol 2020 11 7;132:104613. Epub 2020 Sep 7.

Laboratoire de Virologie, Institut des Agents Infectieux, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France; Centre National de Référence des Virus des Infections respiratoires (dont la grippe), Hospices Civils de Lyon, Lyon, France; Université Lyon 1, Faculté de Médecine Lyon Est, CIRI, Inserm U1111 CNRS UMR5308, Virpath, Lyon, France.

Background: Many commercial assays, of different designs, detecting SARS-CoV-2-specific antibodies exist but with little experience with them.

Objectives: The aim of this study was to compare the performance of assays detecting IgG or total antibodies to N or S antigens, validated for routine use in France, with samples from subjects with more or less severe SARS-CoV-2 infection.

Methods: Eight assays were used: Abbott Architect, DiaSorin Liaison®, bioMérieux Vidas®, Roche Elecsys Cobas®, Siemens Atellica®, BioRad Platelia ELISA, Epitope Diagnostics ELISA, and Wantai ELISA. The tested population included 86 samples from 40 hospitalized subjects and 28 outpatients at different time from symptom onset.

Results: The positivity rate varied depending on the assay but was greater for all assays in hospitalized than non-hospitalized patients. Despite a good correlation between the assays, discrepancies occurred, without a systematic origin, even for samples taken more than 20 days after symptom onset. These discrepancies were linked to low antibody levels in pauci-symptomatic patients.

Conclusion: Whichever assay is chosen, a false negative result may need to be ruled out with another test in a risk situation.
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http://dx.doi.org/10.1016/j.jcv.2020.104613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476603PMC
November 2020

Analytical Performances of the Panther Fusion System for the Detection of Respiratory Viruses in the French National Reference Centre of Lyon, France.

Microorganisms 2020 Sep 7;8(9). Epub 2020 Sep 7.

Laboratoire de Virologie, Hospices Civils de Lyon, Institut des Agents Infectieux, Centre National de Référence des virus des infections respiratoires (dont la Grippe), Hôpital de la Croix-Rousse, 103 grande rue de la Croix-Rousse, CEDEX 04, 69317 Lyon, France.

Respiratory infection are mainly caused by viral pathogens. During the 2017-2018 epidemic season, Panther Fusion Respiratory kits (Influenza virus A&B (FluA&B), respiratory syncytial virus (RSV), adenovirus (ADV), metapneumovirus (MPV), rhinovirus (RV), parainfluenzae virus (PIV), were compared to the Respiratory MultiWells System r-gene. Respiratory clinical specimens were tested retrospectively ( = 268) and prospectively ( = 463). Analytical performances were determined (sensitivity -Sep-, specificity -Spe- and κ) considering concordances of ≥2 molecular testing specific to each viral target (discrepant results were verified at the National Reference Centres for Enteroviruses or Respiratory viruses, Lyon, France). After retrospective (and prospective) testing, Sep, Spe, and κ were 100% (97.7%), 100% (99%) and 100% (94%) for FluA: 100% (95.5%), 100% (99.3%) and 100% (94%) for FluB, and 100% (88.5%), 100% (98.7%) and 100% (89%) for RSV; 82.1% (41.7%), 100% (99.5%) and 86% (54%) for ADV; 94.7% (73.7%), 96.1% (98.0%) and 91% (65%) for MPV; 96.1% (94.6%), 90.2% (98.5%) and 86% (91%) for HRV; and 90% (72.7%), 100% (99.3%) and 91% (72%), respectively, for PIV. Analytical performances were above 85% for all viruses except for ADV, MPV and PIV, confirming the analytical performance of the Panther Fusion system, a high throughput system with reduced turn-around-time, when compared to non-automated systems.
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http://dx.doi.org/10.3390/microorganisms8091371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563737PMC
September 2020

Coronavirus disease 2019 attack rate in HIV-infected patients and in preexposure prophylaxis users.

AIDS 2020 10;34(12):1765-1770

Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France.

Objective: A new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) emerged in China during late 2019 and resulted in the coronavirus disease 2019 (COVID-19) pandemic which peaked in France in March-April 2020. Immunodeficiency, precariousness and promiscuity could increase the risk of COVID-19 in HIV-infected patients and in preexposure prophylaxis (PrEP) users. No epidemiological data are available in these two populations. We report COVID-19 attack rate in HIV-infected patients and in PrEP users in the Rhône department, France, and compared it with the general population.

Design: Retrospective analysis of a laboratory database.

Methods: COVID-19 testing strategy in France was centered on symptomatic infections, hospitalized patients and symptomatic healthcare workers while most asymptomatic cases were not confirmed. SARS-CoV-2 positivity rate on PCR assays and COVID-19 attack rate were determined in HIV-infected patients and in PrEP users. COVID-19 attack rate in the general population was estimated from health authorities' database and demographic data. A corrected attack rate taking into account the laboratory representativeness was calculated.

Results: From March to April 2020, 24 860 samples from 19 113 patients (HIV-infected 77, PrEP users 27, others 19 009) were assessed for SARS-CoV-2 PCR assay. The positivity rate appeared similar in HIV-infected patients (15.6%), in PrEP users (14.8%) and in other patients (19.1%). The crude/corrected COVID-19 attack rate appeared similar in HIV-infected patients (0.31/0.38%) and in PrEP users (0.38/0.42%), and of the same order as the estimated attack rate in the general population (0.24%).

Conclusion: The risk of symptomatic COVID-19 in France appeared similar in HIV-infected patients and in PrEP users compared with the general population.
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http://dx.doi.org/10.1097/QAD.0000000000002639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493781PMC
October 2020

Systematic SARS-CoV-2 screening in cerebrospinal fluid during the COVID-19 pandemic.

Lancet Microbe 2020 Aug 11;1(4):e149. Epub 2020 Jun 11.

Laboratoire de Virologie, Centre National de Référence France-Sud des Virus des Infections Respiratoires, Institut des Agents Infectieux, Hospices Civils de Lyon, Groupement Hospitalier Nord, 69004 Lyon, France.

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http://dx.doi.org/10.1016/S2666-5247(20)30066-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289579PMC
August 2020

Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia.

Cell Rep Med 2020 Jul;1(4):100059

CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Université de Lyon, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 69007 Lyon, France.

In the current COVID-19 pandemic effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.
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http://dx.doi.org/10.1016/j.xcrm.2020.100059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373044PMC
July 2020

Incidence of asymptomatic and symptomatic influenza among healthcare workers: a multicenter prospective cohort study.

Clin Infect Dis 2020 Aug 4. Epub 2020 Aug 4.

Service d'Hygiène, Epidémiologie, Infectiovigilance et Prévention, Hospices Civils de Lyon, Lyon.

Background: Influenza is an important cause of viral hospital-acquired infection involving patients, healthcare workers (HCW), and visitors. The frequency of asymptomatic influenza among HCW with possible subsequent transmission is poorly described. The objective is to determine the cumulative incidence of asymptomatic, pauci-symptomatic and symptomatic influenza among HCW.

Method: A multicenter prospective cohort study was done in 5 French university hospitals, including 289 HCW during the 2016-2017 influenza season. HCW had 3 physical examinations (Time [T] 0, before epidemic onset; T.1, before epidemic peak; T.2, T.3 after epidemic peak). A blood sample was taken each time for influenza serology and a nasal swab was collected at T1 and T2 for influenza detection by PCR. Positive influenza was defined as either a positive influenza PCR, and/or virus-specific seroconversion against influenza A, the only circulating virus, with no vaccination record during follow-up. Symptoms were self-reported daily between T1 and T2. Cumulative incidence of influenza was stratified by clinical presentation per 100 HCW.

Findings: Of the 289 HCW included, 278 (96%) completed the entire follow-up. Overall, 62 HCW had evidence of influenza of whom 46·8% were asymptomatic, 41·9% were pauci-symptomatic, and 11·3% were symptomatic. Cumulative influenza incidence was 22·3% (95%CI:17·4%-27·2%). Cumulative incidence of asymptomatic influenza was 5·8% (95%CI: 3·3%-9·2%), 13·7% (95%CI:9·9%-18·2%) for pauci-symptomatic influenza, and 2·9% (95%CI:1·3%-5·5%) for symptomatic influenza.

Interpretation: Asymptomatic and pauci-symptomatic influenza were frequent among HCW, representing 47% and 42% of the influenza burden respectively. These findings highlight the importance of systematic implementation of infection control measures among HCW regardless of respiratory symptoms from preventing nosocomial transmission of influenza.

Trial Registration: clinicaltrials.gov identifier: NCT02868658.
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http://dx.doi.org/10.1093/cid/ciaa1109DOI Listing
August 2020

Human Respiratory Syncytial Virus-Induced Immune Signature of Infection Revealed by Transcriptome Analysis of Clinical Pediatric Nasopharyngeal Swab Samples.

J Infect Dis 2021 Mar;223(6):1052-1061

CIRI, Centre International de Recherche en Infectiologie (Team VirPath), Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, Lyon, France.

Human respiratory syncytial virus (HRSV) constitutes one the main causes of respiratory infection in neonates and infants worldwide. Transcriptome analysis of clinical samples using high-throughput technologies remains an important tool to better understand virus-host complex interactions in the real-life setting but also to identify new diagnosis/prognosis markers or therapeutics targets. A major challenge when exploiting clinical samples such as nasal swabs, washes, or bronchoalveolar lavages is the poor quantity and integrity of nucleic acids. In this study, we applied a tailored transcriptomics workflow to exploit nasal wash samples from children who tested positive for HRSV. Our analysis revealed a characteristic immune signature as a direct reflection of HRSV pathogenesis and highlighted putative biomarkers of interest such as IP-10, TMEM190, MCEMP1, and TIMM23.
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http://dx.doi.org/10.1093/infdis/jiaa468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006426PMC
March 2021

Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates.

Nature 2020 09 22;585(7826):584-587. Epub 2020 Jul 22.

Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, Fontenay-aux-Roses, France.

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic and no antiviral drug or vaccine is yet available for the treatment of this disease. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes COVID-19-worldwide but there is no definitive evidence that HCQ is effective for treating COVID-19. Here we evaluated the antiviral activity of HCQ both in vitro and in SARS-CoV-2-infected macaques. HCQ showed antiviral activity in African green monkey kidney cells (Vero E6) but not in a model of reconstituted human airway epithelium. In macaques, we tested different treatment strategies in comparison to a placebo treatment, before and after peak viral load, alone or in combination with azithromycin (AZTH). Neither HCQ nor the combination of HCQ and AZTH showed a significant effect on viral load in any of the analysed tissues. When the drug was used as a pre-exposure prophylaxis treatment, HCQ did not confer protection against infection with SARS-CoV-2. Our findings do not support the use of HCQ, either alone or in combination with AZTH, as an antiviral drug for the treatment of COVID-19 in humans.
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http://dx.doi.org/10.1038/s41586-020-2558-4DOI Listing
September 2020