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1. Determinants of protection against SARS-CoV-2 Omicron BA.1 and Delta infections in fully vaccinated outpatients.

Author

Roy A, Saade C, Josset L, Clément B, Morfin F, Destras G, Valette M, Icard V, Billaud G, Oblette A, Debombourg M, Garrigou C, Brengel-Pesce K, Generenaz L, Saker K, Hernu R, Pozzetto B, Lina B, Trabaud MA, Trouillet-Assant S, and Bal A

Subjects
Humans, Outpatients, SARS-CoV-2, Interferon-gamma, Immunoglobulin G, Antibodies, Viral, COVID-19 prevention & control, Hepatitis D
Abstract

We aimed to evaluate the association between the humoral and cellular immune responses and symptomatic SARS-CoV-2 infection with Delta or Omicron BA.1 variants in fully vaccinated outpatients. Anti-receptor binding domain (RBD) IgG levels and interferon-gamma (IFN-γ) release were evaluated at PCR-diagnosis of SARS-CoV-2 in 636 samples from negative and positive patients during Delta and Omicron BA.1 periods. Median levels of anti-RBD IgG in positive patients were significantly lower than in negative patients for both variants (p < 0.05). The frequency of Omicron BA.1 infection in patients with anti-RBD IgG concentrations ≥1000 binding antibody units (BAU)/mL was 51.0% and decreased to 34.4% in patients with concentrations ≥3000 BAU/mL. For Delta infection, the frequency of infection was significantly lower when applying the same anti-RBD IgG thresholds (13.3% and 5.3% respectively, p < 0.05). In addition, individuals in the hybrid immunity group had a 4.5 times lower risk of Delta infection compared to the homologous vaccination group (aOR = 0.22, 95% CI: [0.05-0.64]. No significant decrease in the risk of Omicron BA.1 infection was observed in the hybrid group compared to the homologous group, but the risk decreased within the hybrid group as anti-RBD IgG titers increased (aOR = 0.08, 95% CI: [0.01-0.41], p = 0.008). IFN-γ release post-SARS-CoV-2 peptide stimulation was not different between samples from patients infected (either with Delta or Omicron BA.1 variant) or not (p > 0.05). Our results show that high circulating levels of anti-RBD IgG and hybrid immunity were independently associated with a lower risk of symptomatic SARS-CoV-2 infection in outpatients with differences according to the infecting variant (www.clinicaltrials.gov; ID NCT05060939)., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Published
2023
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2. SARS-CoV-2 N-Antigen Quantification in Respiratory Tract, Plasma and Urine: Kinetics and Association with RT-qPCR Results.

Author

Parraud D, Maucotel AL, Bouscambert M, Morfin F, Bitker L, Chidiac C, De Castro N, Frobert E, Gaymard A, and On Behalf Of The French Covid Cohort Study Group

Subjects
Humans, SARS-CoV-2 genetics, Kinetics, Respiratory System, RNA, Viral genetics, Sensitivity and Specificity, COVID-19 diagnosis, Blood Group Antigens
Abstract

Qualitative SARS-CoV-2 antigen assays based on immunochromatography are useful for mass diagnosis of COVID-19, even though their sensitivity is poor in comparison with RT-PCR assays. In addition, quantitative assays could improve antigenic test performance and allow testing with different specimens. Using quantitative assays, we tested 26 patients for viral RNA and N-antigen in respiratory samples, plasma and urine. This allowed us to compare the kinetics between the three compartments and to compare RNA and antigen concentrations in each. Our results showed the presence of N-antigen in respiratory (15/15, 100%), plasma (26/59, 44%) and urine (14/54, 28.9%) samples, whereas RNA was only detected in respiratory (15/15, 100%) and plasma (12/60, 20%) samples. We detected N-antigen in urine and plasma samples until the day 9 and day 13 post-inclusion, respectively. The antigen concentration was found to correlate with RNA levels in respiratory ( p < 0.001) and plasma samples ( p < 0.001). Finally, urinary antigen levels correlated with plasma levels ( p < 0.001). Urine N-antigen detection could be part of the strategy for the late diagnosis and prognostic evaluation of COVID-19, given the ease and painlessness of sampling and the duration of antigen excretion in this biological compartment.

Published
2023
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3. Application of a forecasting model to mitigate the consequences of unexpected RSV surge: Experience from the post-COVID-19 2021/22 winter season in a major metropolitan centre, Lyon, France.

Author

Casalegno JS, Bents S, Paget J, Gillet Y, Ploin D, Javouhey E, Lina B, Morfin F, Grenfell BT, and Baker RE

Subjects
Child, Humans, Infant, Seasons, France epidemiology, Respiratory Syncytial Virus Infections epidemiology, Respiratory Syncytial Virus Infections prevention & control, COVID-19 epidemiology, Respiratory Syncytial Virus, Human
Abstract

Background: The emergence of COVID-19 triggered the massive implementation of non-pharmaceutical interventions (NPI) which impacted the circulation of respiratory syncytial virus (RSV) during the 2020/2021 season., Methods: A time-series susceptible-infected-recovered (TSIR) model was used early September 2021 to forecast the implications of this disruption on the future 2021/2022 RSV epidemic in Lyon urban population., Results: When compared to observed hospital-confirmed cases, the model successfully captured the early start, peak timing, and end of the 2021/2022 RSV epidemic. These simulations, added to other streams of surveillance data, shared and discussed among the local field experts were of great value to mitigate the consequences of this atypical RSV outbreak on our hospital paediatric department., Conclusions: TSIR model, fitted to local hospital data covering large urban areas, can produce plausible post-COVID-19 RSV simulations. Collaborations between modellers and hospital management (who are both model users and data providers) should be encouraged in order to validate the use of dynamical models to timely allocate hospital resources to the future RSV epidemics., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

Published
2023
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4. Rapid and reliable inactivation protocols for the diagnostics of emerging viruses: The example of SARS-CoV-2 and monkeypox virus.

Author

Quéromès G, Frobert E, Bouscambert-Duchamp M, Oblette A, Valette M, Billaud G, Escuret V, Lina B, Morfin F, and Gaymard A

Subjects
Animals, Chlorocebus aethiops, Humans, Monkeypox virus, Virus Inactivation, Vero Cells, COVID-19 Testing, SARS-CoV-2, COVID-19 diagnosis
Abstract

The emergence and sustained transmission of novel pathogens are exerting an increasing demand on the diagnostics sector worldwide, as seen with the ongoing severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic and the more recent public health concern of monkeypox virus (MPXV) since May 2022. Appropriate and reliable viral inactivation measures are needed to ensure the safety of personnel handling these infectious samples. In the present study, seven commercialized diagnosis buffers, heat (56°C and 60°C), and sodium dodecyl sulfate detergent (2.0%, 1.0%, and 0.5% final concentrations) were tested against infectious SARS-CoV-2 and MPXV culture isolates on Vero cell culture. Cytopathic effects were observed up to 7 days postinoculation and viral load evolution was measured by semiquantitative polymerase chain reaction. The World Health Organization recommends an infectious titer reduction of at least 4 log 10 . As such, the data show efficacious SARS-CoV-2 inactivation by all investigated methods, with >6.0 log 10 reduction. MPXV inactivation was also validated with all investigated methods with 6.9 log 10 reductions, although some commercial buffers required a longer incubation period to yield complete inactivation. These results are valuable for facilities, notably those without biosafety level-3 capabilities, that need to implement rapid and reliable protocols common against both SARS-CoV-2 and MPXV., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Published
2023
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5. Dynamics of viral shedding during ancestral or Omicron BA.1 SARS-CoV-2 infection and enhancement of pre-existing immunity during breakthrough infections.

Author

Saade C, Brengel-Pesce K, Gaymard A, Trabaud MA, Destras G, Oriol G, Cheynet V, Debombourg M, Mokdad B, Billaud G, Oblette A, Créhalet H, Giannoli JM, Garrigou C, Generenaz L, Compagnon C, Boibieux A, Lina B, Morfin F, Pozzetto B, Josset L, Trouillet-Assant S, and Bal A

Subjects
Humans, SARS-CoV-2 genetics, Virus Shedding, Antibodies, Viral, Immunoglobulin G, Antibodies, Neutralizing, COVID-19, Viral Vaccines
Abstract

Omicron variant is circulating in the presence of a globally acquired immunity unlike the ancestral SARS-CoV-2 isolate. Herein, we investigated the normalized viral load dynamics and viral culture status in 44 fully vaccinated healthcare workers (HCWs) infected with the Omicron BA.1 variant. Viral load dynamics of 38 unvaccinated HCWs infected with the 20A variant during the first pandemic wave was also studied. We then explored the impact of Omicron infection on pre-existing immunity assessing anti-RBD IgG levels, neutralizing antibody titres against 19A, Delta and Omicron isolates, as well as IFN-γ release following cell stimulation with SARS-CoV-2 peptides. We reported that two weeks after diagnosis a greater proportion of HCWs infected with 20A (78.9%, 15/19) than with Omicron BA.1 (44.7%, 17/38; p = 0.02) were still positive by RT-qPCR. We found that Omicron breakthrough infections led to an overall enhancement of vaccine-induced humoral and cellular immunity as soon as a median [interquartile range] of 8 [7-9] days post symptom onset. Among samples with similar high viral loads, non-culturable samples exhibited higher neutralizing antibody titres and anti-RBD IgG levels than culturable samples. Additionally, Omicron infection led to an enhancement of antibodies neutralization capacity against other SARS-CoV-2 isolates. Taken together, the results suggest that Omicron BA.1 vaccine breakthrough infection is associated with a faster viral clearance than that of the ancestral SARS-CoV-2, in addition this new variant leads to a rapid enhancement of the humoral response against multiple SARS-CoV-2 variants, and of the cellular response.

Published
2022
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6. Detection and prevalence of SARS-CoV-2 co-infections during the Omicron variant circulation in France.

Author

Bal A, Simon B, Destras G, Chalvignac R, Semanas Q, Oblette A, Quéromès G, Fanget R, Regue H, Morfin F, Valette M, Lina B, and Josset L

Subjects
Humans, SARS-CoV-2 genetics, Prevalence, COVID-19 diagnosis, COVID-19 epidemiology, Coinfection epidemiology
Abstract

From December 2021-February 2022, an intense and unprecedented co-circulation of SARS-CoV-2 variants with high genetic diversity raised the question of possible co-infections between variants and how to detect them. Using 11 mixes of Delta:Omicron isolates at different ratios, we evaluated the performance of 4 different sets of primers used for whole-genome sequencing and developed an unbiased bioinformatics method for the detection of co-infections involving genetically distinct SARS-CoV-2 lineages. Applied on 21,387 samples collected between December 6, 2021 to February 27, 2022 from random genomic surveillance in France, we detected 53 co-infections between different lineages. The prevalence of Delta and Omicron (BA.1) co-infections and Omicron lineages BA.1 and BA.2 co-infections were estimated at 0.18% and 0.26%, respectively. Among 6,242 hospitalized patients, the intensive care unit (ICU) admission rates were 1.64%, 4.81% and 15.38% in Omicron, Delta and Delta/Omicron patients, respectively. No BA.1/BA.2 co-infections were reported among ICU admitted patients. Among the 53 co-infected patients, a total of 21 patients (39.6%) were not vaccinated. Although SARS-CoV-2 co-infections were rare in this study, their proper detection is crucial to evaluate their clinical impact and the risk of the emergence of potential recombinants., (© 2022. The Author(s).)

Published
2022
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7. SARS-CoV-2 rapid test versus RT-qPCR on noninvasive respiratory self-samples during a city mass testing campaign.

Author

Gagnaire J, Bonjean P, Verot E, Boulamail B, Labetoulle R, Gonzalo S, Hilliquin D, Pillet S, Michaud P, Brebion A, Morfin F, Goff JL, Pelissier C, Bourlet T, Group AS, Chauvin F, Berthelot P, Botelho-Nevers E, and Pozzetto B

Subjects
COVID-19 Testing, Clinical Laboratory Techniques, Humans, RNA, Viral analysis, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, COVID-19 diagnosis, SARS-CoV-2 genetics
Abstract

Competing Interests: Conflict of Interest None declared.

Published
2022
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8. SARS-CoV-2 Omicron Variant, Lineage BA.1, Is Associated with Lower Viral Load in Nasopharyngeal Samples Compared to Delta Variant.

Author

Sentis C, Billaud G, Bal A, Frobert E, Bouscambert M, Destras G, Josset L, Lina B, Morfin F, Gaymard A, and The Covid-Diagnosis Hcl Study Group

Subjects
Humans, Nasopharynx, Viral Load, COVID-19, SARS-CoV-2 genetics
Abstract

Objectives: High viral load in upper respiratory tract specimens observed for Delta cases might contribute to its increased infectivity compared to the other variant. However, it is not yet documented if the Omicron variant's enhanced infectivity is also related to a higher viral load. Our aim was to determine if the Omicron variant's spread is also related to higher viral loads compared to the Delta variant., Methods: Nasopharyngeal swabs, 129 (Omicron) and 85 (Delta), from Health Care Workers were collected during December 2021 at the University Hospital of Lyon, France. Cycle threshold (Ct) for the RdRp target of cobas ® 6800 SARS-CoV-2 assay was used as a proxy to evaluate SARS-CoV-2 viral load. Variant identification was performed using a screening panel and confirmed by whole genome sequencing., Results: Herein, we showed that the RT-PCR Ct values in Health Care Workers sampled within 5 days after symptom onset were significantly higher for Omicron cases than Delta cases (21.7 for Delta variant and 23.8 for Omicron variant, p = 0.008). This difference was also observed regarding patient with complete vaccination., Conclusions: This result supports the studies showing that the increased transmissibility of Omicron is related to other mechanisms than higher virus excretion.

Published
2022
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9. Live virus neutralization testing in convalescent patients and subjects vaccinated against 19A, 20B, 20I/501Y.V1 and 20H/501Y.V2 isolates of SARS-CoV-2.

Author

Saade C, Gonzalez C, Bal A, Valette M, Saker K, Lina B, Josset L, Trabaud MA, Thiery G, Botelho-Nevers E, Paul S, Verhoeven P, Bourlet T, Pillet S, Morfin F, Trouillet-Assant S, Pozzetto B, and On Behalf Of Covid-Ser Study Group

Subjects
COVID-19 prevention & control, COVID-19 virology, COVID-19 Vaccines administration & dosage, COVID-19 Vaccines genetics, Humans, Neutralization Tests, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 immunology, COVID-19 Vaccines immunology, SARS-CoV-2 immunology
Abstract

SARS-CoV-2 mutations appeared recently and can lead to conformational changes in the spike protein and probably induce modifications in antigenicity. We assessed the neutralizing capacity of antibodies to prevent cell infection, using a live virus neutralization test with different strains [19A (initial one), 20B (B.1.1.241 lineage), 20I/501Y.V1 (B.1.1.7 lineage), and 20H/501Y.V2 (B.1.351 lineage)] in serum samples collected from different populations: two-dose vaccinated COVID-19-naive healthcare workers (HCWs; Pfizer-BioNTech BNT161b2), 6-months post mild COVID-19 HCWs, and critical COVID-19 patients. No significant difference was observed between the 20B and 19A isolates for HCWs with mild COVID-19 and critical patients. However, a significant decrease in neutralization ability was found for 20I/501Y.V1 in comparison with 19A isolate for critical patients and HCWs 6-months post infection. Concerning 20H/501Y.V2, all populations had a significant reduction in neutralizing antibody titers in comparison with the 19A isolate. Interestingly, a significant difference in neutralization capacity was observed for vaccinated HCWs between the two variants but not in the convalescent groups.

Published
2021
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10. Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France.

Author

Quéromès G, Destras G, Bal A, Regue H, Burfin G, Brun S, Fanget R, Morfin F, Valette M, Trouillet-Assant S, Lina B, Frobert E, and Josset L

Subjects
Adult, Aged, Aged, 80 and over, Base Sequence, COVID-19 immunology, COVID-19 virology, Cross Infection epidemiology, Cross Infection immunology, Cytokines immunology, Female, Frameshift Mutation, France epidemiology, Hospitalization, Humans, Immunity, Inflammation, Male, Phylogeny, Sequence Deletion, Viral Proteins immunology, COVID-19 epidemiology, Cross Infection virology, Genetic Variation, Genome, Viral, SARS-CoV-2 genetics, Viral Proteins genetics
Abstract

During routine molecular surveillance of SARS-CoV-2 performed at the National Reference Center of Respiratory Viruses (Lyon, France) ( n = 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. In vitro 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 CCL2/MCP1 , PTX3 , and TNFα , 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.

Published
2021
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11. Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs.

Author

Lopez J, Mommert M, Mouton W, Pizzorno A, Brengel-Pesce K, Mezidi M, Villard M, Lina B, Richard JC, Fassier JB, Cheynet V, Padey B, Duliere V, Julien T, Paul S, Bastard P, Belot A, Bal A, Casanova JL, Rosa-Calatrava M, Morfin F, Walzer T, and Trouillet-Assant S

Subjects
Adult, Aged, Animals, Antiviral Agents immunology, Antiviral Agents pharmacology, Autoantibodies blood, COVID-19 blood, COVID-19 virology, Chlorocebus aethiops, Female, Humans, Interferon Type I pharmacology, Longitudinal Studies, Male, Middle Aged, Nasal Cavity immunology, Nasal Cavity virology, Prospective Studies, SARS-CoV-2 physiology, Vero Cells, Viral Load drug effects, Viral Load immunology, Virus Replication drug effects, Virus Replication immunology, Autoantibodies immunology, COVID-19 immunology, Interferon Type I immunology, SARS-CoV-2 immunology
Abstract

IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3-dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α2 levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection., Competing Interests: Disclosures: M. Mommert, W. Mouton, K. Brengel-Pesce, A. Bal, and V. Cheynet reported personal fees from bioMérieux during the conduct of the study and personal fees from bioMérieux outside the submitted work. M. Mommert, K. Brengel-Pesce, and S. Trouillet-Assant have a patent to FR2107421 pending. A. Pizzorno, B. Padey, and M. Rosa-Calatrava reported a patent to FR 20/02351 (Therapeutic treatments against SARS-CoV-2) pending. S. Trouillet-Assant and J.-B. Fassier reported non-financial support from bioMérieux during the conduct of the study and non-financial support from bioMérieux outside the submitted work. No other disclosures were reported., (© 2021 Lopez et al.)

Published
2021
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12. Clinical and laboratory characteristics of symptomatic healthcare workers with suspected COVID-19: a prospective cohort study.

Author

Bal A, Brengel-Pesce K, Gaymard A, Quéromès G, Guibert N, Frobert E, Bouscambert M, Trabaud MA, Allantaz-Frager F, Oriol G, Cheynet V, d'Aubarede C, Massardier-Pilonchery A, Buisson M, Lupo J, Pozzetto B, Poignard P, Lina B, Fassier JB, Morfin F, and Trouillet-Assant S

Subjects
Adult, Aged, Aged, 80 and over, COVID-19 epidemiology, COVID-19 Nucleic Acid Testing, COVID-19 Serological Testing, Female, Humans, Male, Middle Aged, Prospective Studies, Viral Load, Young Adult, COVID-19 diagnosis, Health Personnel, SARS-CoV-2 isolation & purification
Abstract

A comprehensive clinical and microbiological assessments of COVID-19 in front-line healthcare workers (HCWs) is needed. Between April 10th and May 28th, 2020, 319 HCWs with acute illness were reviewed. In addition to SARS-CoV-2 RT-PCR screening, a multiplex molecular panel was used for testing other respiratory pathogens. For SARS-CoV-2 positive HCWs, the normalized viral load, viral culture, and virus neutralization assays were performed weekly. For SARS-CoV-2 negative HCWs, SARS-CoV-2 serological testing was performed one month after inclusion. Among the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; 65/67 (97.0%) developed mild form of COVID-19. Other respiratory pathogens were found in 6/66 (9.1%) SARS-CoV-2 positive and 47/241 (19.5%) SARS-Cov-2 negative HCWs (p = 0.07). The proportion of HCWs with a viral load > 5.0 log 10  cp/mL (Ct value < 25) was less than 15% at 8 days after symptom onset; 12% of HCWs were positive after 40 days (Ct > 37). More than 90% of cultivable virus had a viral load > 4.5 log 10  cp/mL (Ct < 26) and were collected within 10 days after symptom onset. Among negative HCWs, 6/190 (3.2%) seroconverted. Our data suggest that the determination of viral load can be used for appreciating the infectiousness of infected HCWs. These data could be helpful for facilitating their return to work., (© 2021. The Author(s).)

Published
2021
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13. 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.

Author

Gaymard A, Bosetti P, Feri A, Destras G, Enouf V, Andronico A, Burrel S, Behillil S, Sauvage C, Bal A, Morfin F, Van Der Werf S, Josset L, Blanquart F, Coignard B, Cauchemez S, and Lina B

Subjects
France epidemiology, Humans, Paris, COVID-19 epidemiology, SARS-CoV-2
Abstract

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.

Published
2021
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14. 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.

Author

Bal A, Destras G, Gaymard A, Stefic K, Marlet J, Eymieux S, Regue H, Semanas Q, d'Aubarede C, Billaud G, Laurent F, Gonzalez C, Mekki Y, Valette M, Bouscambert M, Gaudy-Graffin C, Lina B, Morfin F, and Josset L

Subjects
France epidemiology, Humans, Base Sequence, COVID-19 epidemiology, Genome, Viral, SARS-CoV-2 genetics, Sequence Deletion genetics, Spike Glycoprotein, Coronavirus genetics
Abstract

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.

Published
2021
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16. Six-month antibody response to SARS-CoV-2 in healthcare workers assessed by virus neutralization and commercial assays

Author

Fascia Pascal, Adnot Jérôme, Fontaine Juliette, Massardier-Pilonchéry Amélie, Boibieux André, Josset Laurence, Nicolas Guibert, Oria Fatima, Nazare Julie-Anne, Chiarello Pierre, Samperiz Audrey, Antonin Bal, Prudent Mélanie, Simon Chantal, Dulce Alfaiate, Fassier Jean-Baptiste, Florence Morfin-Sherpa, Constance d'Aubarede, Brunel-Dalmas Florence, Lahousse Matthieu, Pitiot Virginie, Trabaud Mary-Anne, Gaillot-Durand Lucie, Bal Antonin, Lina Bruno, Trouillet-Assant Sophie, Gueyffier François, Perry Marielle, Gillet Myriam, Adèle Paul, Jean-Baptiste Fassier, Valette Martine, Bourgeois Gaëlle, Lozano Hélène, Kahina Saker, Alfaiate Dulce, Morfin Florence, Mary-Anne Trabaud, Rabilloud Muriel, Schlienger Isabelle, Narbey David, Durupt François, Makhloufi Djamila, Bruno Pozzetto, Paul Adèle, Caire Eurydice, Bergeret Alain, Godinot Matthieu, Escuret Vanessa, Bonnet Florent, Moll Frédéric, Guibert Nicolas, Gaymard Alexandre, Cotte Laurent, Sophie Trouillet-Assant, Muriel Rabilloud, Virginie Pitiot, Amélie Massardier-Pilonchery, Milon Marie-Paule, Charbotel Barbara, Carole Langlois-Jacques, Bruno Lina, Hospices Civils de Lyon (HCL), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Université de Lyon, Institut des Agents Infectieux [Lyon] (IAI), Service de médecine et santé au travail, hospices civils de Lyon, Laboratoire de virologie, Physiopathologie et biothérapies des infections muqueuses (GIMAP), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)

Subjects
Male, Time Factors, Antibodies, Viral, Neutralization, MEDECINE, Health personnel, 0302 clinical medicine, SANTE, SARS-COV2, Medicine, 030212 general & internal medicine, Letter to the Editor, 0303 health sciences, biology, PERSONNEL DE SANTE, virus diseases, General Medicine, Middle Aged, University hospital, TRAVAIL, 3. Good health, Titer, Infectious Diseases, Female, Antibody, Serological assays, ANTICORPS, Adult, Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Health Personnel, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), education, GESTION DU PERSONNEL, Virus Neutralization, Virus, 03 medical and health sciences, Neutralization Tests, Seroprevalence, Humans, Healthcare workers, Virus neutralisation assay, 030304 developmental biology, SARS-CoV-2, business.industry, COVID-19, Antibodies, Neutralizing, Virology, Antibody response, biology.protein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

We conducted a prospective study in healthcare workers (n=296) of the University Hospital of Lyon, France. Serum samples (n=296) collected six months after disease onset were tested using three commercial assays: the Wantai Ab assay detecting total antibodies against the receptor binding domain (RBD) of the S protein, the bioMerieux Vidas assay detecting IgG to the RBD and the Abbott Architect assay detecting IgG to the N protein. The neutralising antibody (NAb) titre was also determined for all samples with a virus neutralisation assay (VNA) using live virus. The positivity rate was 100% with the Wantai assay, 84.8% with the bioMerieux assay and 55.4% with the Abbott assay. Only 51% of HCWs were positive for the presence of NAb. Less than 10 % of HCWs had a NAb titre greater than 80. At a neutralising titre of 80, the area under the curves [IC 95%] was 0.71 [0.62-0.81], 0.75 [0.65-0.85] and 0.95 [0.92-0.97] for Wantai, Abbott and Vidas respectively. The data presented herein suggest that commercial assays detecting antibodies against the N protein must not be used in long-term seroprevalence surveys while the Wantai assay could be useful for this purpose. VNA should remain the gold standard to assess the protective antibody response, but some commercial assays could be used as first-line screening of long-term presence of NAb.

Published
2021
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17. Low levels of respiratory syncytial virus activity in Europe during the 2020/21 season: what can we expect in the coming summer and autumn/winter?

Author

van Summeren, Jojanneke, Meijer, Adam, Aspelund, Guðrún, Casalegno, Jean Sebastien, Erna, Guðrún, Hoang, Uy, Lina, Bruno, de Lusignan, Simon, Teirlinck, Anne C., Thors, Valtýr, Paget, John, Ouziel, Antoine, Tardy, Jean-claude, Gaucherand, Pascal, Massardier, Jerome, Polazzi, Stephanie, Duclos, Antoine, Benchaib, Mehdi, Cartier, Regine, Jourdain, Marine, Ottmann, Michelle, Kramer, Rolf, Fiorini, Sylvie, Rivat, Nathalie, Mekki, Yahia, Fort-Jacquier, Julie, Barral, Maud-Catherine, Noelie, Vey, Haesebaert, Julie, Horvat, Come, Vidoni, Leo, Reynes, Jean-Marc, Eleouet, Jean-Francois, Josset, Laurence, Receveur, Matthieu, Javouhey, Etienne, Ploin, Dominique, Valette, Martine, Fanget, Remi, Targe, Sandrine Couray, Myar-Dury, Anne-Florence, Doret-Dion, Muriel, Massoud, Mona, Masson, Elsa, Bard, Emilie, Queromes, Gregory, Vanhems, Phillipe, Claris, Olivier, Butin, Marine, Ader, Florence, Bin, Sylvie, Gaymard, Alexandre, Morfin, Florence, Gillet, Yves, Netherlands Institute for Health Services Research [Utrecht] (NIVEL), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Directorate of Health [Reykjavík], Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Landspitali National University Hospital of Iceland, University of Oxford [Oxford], Children’s Hospital [Reykjavik, Iceland], University of Iceland [Reykjavik], This study is performed as a side project of the RSV ComNet study. The aim of the RSV ComNet project is to measure the disease burden of RSV in children aged ≤5 years in primary care, and is funded by Sanofi Pasteur and AstraZeneca., VRS study group in Lyon: Antoine Ouziel, Jean-claude Tardy, Pascal Gaucherand, Jerome Massardier, Stephanie Polazzi, Antoine Duclos, Mehdi Benchaib, Regine Cartier, Marine Jourdain, Michelle Ottmann, Rolf Kramer, Sylvie Fiorini, Nathalie Rivat, Yahia Mekki, Julie Fort-Jacquier, Maud-Catherine Barral, Vey Noelie, Julie Haesebaert, Come Horvat, Leo Vidoni, Jean-Marc Reynes, Jean-Francois Eleouet, Laurence Josset, Matthieu Receveur, Etienne Javouhey, Dominique Ploin, Martine Valette, Remi Fanget, Sandrine Couray Targe, Anne-Florence Myar-Dury, Muriel Doret-Dion, Mona Massoud, Elsa Masson, Emilie Bard, Gregory Queromes, Phillipe Vanhems, Olivier Claris, Marine Butin, Florence Ader, Sylvie Bin, Alexandre Gaymard, Florence Morfin, Yves Gillet, and Lyon, VRS study group in

Subjects
Author's Correction, 0301 basic medicine, Veterinary medicine, viruses, Iceland, surveillance data, MESH: Respiratory Syncytial Virus, Human, Respiratory syncytial virus, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Epidemiology, MESH: COVID-19, 030212 general & internal medicine, Respiratory system, Child, virus diseases, RSV, respiratory system, MESH: Iceland, MESH: Infant, Europe, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, epidemiology, France, Seasons, Winter season, Rapid Communication, medicine.medical_specialty, 2019-20 coronavirus outbreak, Surveillance data, Coronavirus disease 2019 (COVID-19), COVID-19 pandemic, Respiratory Syncytial Virus Infections, Biology, Virus, 03 medical and health sciences, MESH: Respiratory Syncytial Virus Infections, Virology, medicine, Humans, MESH: SARS-CoV-2, MESH: Humans, SARS-CoV-2, Public Health, Environmental and Occupational Health, Small children, COVID-19, Infant, MESH: France, 030104 developmental biology, Respiratory Syncytial Virus, Human, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, MESH: Seasons
Abstract

International audience; Since the introduction of non-pharmacological interventions to control COVID-19, respiratory syncytial virus (RSV) activity in Europe has been limited. Surveillance data for 17 countries showed delayed RSV epidemics in France (≥ 12 w) and Iceland (≥ 4 w) during the 2020/21 season. RSV cases (predominantly small children) in France and Iceland were older compared with previous seasons. We hypothesise that future RSV epidemic(s) could start outside the usual autumn/winter season and be larger than expected. Year-round surveillance of RSV is of critical importance.

Published
2021
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18. 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

Author

Gaymard, Alexandre, Bosetti, Paolo, Feri, Adeline, Destras, Gregory, Enouf, Vincent, Andronico, Alessio, Burrel, Sonia, Behillil, Sylvie, Sauvage, Claire, Bal, Antonin, Morfin, Florence, Van Der Werf, Sylvie, Josset, Laurence, Blanquart, François, Coignard, Bruno, Cauchemez, Simon, Lina, Bruno, Gault, Elyanne, Moreau, Frédérique, Brichler, Ségolène, Delagrèverie, Héloïse, Descamps, Diane, Charpentier, Charlotte, Rozenberg, Flore, L'Honneur, Anne-Sophie, Veyer, David, Bélec, Laurent, Fourati, Slim, Rodriguez, Christophe, Pawlotsky, Jean-Michel, Fourgeaud, Jacques, Abid, Hanène, Roque-Afonso, Anne-Marie, Fenaux, Honorine, Jary, Aude, Marot, Stéphane, Salmona, Maud, Chaix, Marie-Laure, Morand-Joubert, Laurence, Schnuriger, Aurélie, Juillet, Stéphanie Marque, Bargain, Pauline, Poggi, Cécile, Chollet, Lionel, Guillaume, Clémence, Guinard, Jérôme, Vallet, Sophie, Pilorgé, Léa, Schvoerer, Evelyne, Hartard, Cédric, Castelain, Sandrine, François, Catherine, Ducancelle, Alexandra, Lefeuvre, Caroline, Lepiller, Quentin, Marty-Quinternet, Solène, Bellecave, Pantxika, Tumiotto, Camille, Dina, Julia, Le Gouil, Meriadeg, Henquell, Cécile, Mirand, Audrey, Césaire, Raymond, de Rougemont, Alexis, Auvray, Christelle, Larrat, Sylvie, Némoz, Benjamin, Tinez, Claire, Guigon, Aurélie, Hantz, Sébastien, Rogez, Sylvie, Dos Santos, Georges, Perez, Pascale, Jost, Christelle, Montes, Brigitte, Foulongne, Vincent, Imbert, Berthe-Marie, Bressollette, Céline, Giordanengo, Valérie, Gonfrier, Géraldine, Garcia, Magali, Lévêque, Nicolas, Brodard, Véronique, Moret, Hélène, Thibault, Vincent, Maillard, Anne, Jaffar-Bandjee, Marie-Christine, Gueudin, Marie, Plantier, Jean-Christophe, Pozzetto, Bruno, Pillet, Sylvie, Fafi-Kremer, Samira, Solis, Morgane, Izopet, Jacques, Trémeaux, Pauline, Stefic, Karl, Handala, Lynda, Billaud, Geneviève, Frobert, Emilie, Mérens, Audrey, Bigaillon, Christine, Desroches, Marine, Thepenier, Cédric, Janvier, Frédéric, Otto, Marie-Pierre, Roquebert, Bénédicte, Haïm-Boukobza, Stéphanie, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Laboratoire de Virologie [CHU Amiens], CHU Amiens-Picardie, ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), We acknowledge financial support from Santé publique France (the French national public health agency), the French Ministry of health (Grant COVIDseq), the Consortium for the surveillance and research on emerging pathogens via microbial genomics (EMERGEN) coordinated by Santé publique France and ANRS Maladies Infectieuses Emergentes, the Investissement d’Avenir programme, the Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases programme (grant ANR-10-LABX-62-IBEID), the European Union’s Horizon 2020 research and in-novation programme under grants 101003589 (RECOVER). This work has been supported by the laboratories belonging to the ColVHB network*., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Gestionnaire, Hal Sorbonne Université, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Rapid European COVID-19 Emergency Response research - RECOVER - - H2020-SC1-PHE-CORONAVIRUS-20202020-02-14 - 2022-02-13 - 101003589 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris)

Subjects
Author's Correction, Paris, medicine.medical_specialty, 2019-20 coronavirus outbreak, Lineage (genetic), Coronavirus disease 2019 (COVID-19), Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viral infections, [SDV]Life Sciences [q-bio], Context (language use), Biology, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, Humans, MESH: COVID-19, MESH: SARS-CoV-2, 030212 general & internal medicine, 030304 developmental biology, COVID, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, SARS-CoV-2, MESH: Paris, Public Health, Environmental and Occupational Health, COVID-19, [SDV] Life Sciences [q-bio], MESH: France, 20I/501Y.V1, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, surveillance, France, mutation, Rapid Communication, Demography
Abstract

International audience; 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.

Published
2021
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19. 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

Author

Bal, Antonin, Destras, Gregory, Gaymard, Alexandre, Stefic, Karl, Marlet, Julien, Eymieux, Sébastien, Regue, Hadrien, Semanas, Quentin, d’Aubarede, Constance, Billaud, Geneviève, Laurent, Frédéric, Gonzalez, Claudia, Mekki, Yahia, Valette, Martine, Bouscambert, Maude, Gaudy-Graffin, Catherine, Lina, Bruno, Morfin, Florence, Josset, Laurence, Casalegno, Jean-Sébastien, Frobert, Emilie, Escuret, Vanessa, Icard, Vinca, Jeannoel, Marion, Milon, Marie-Paule, Ramière, Christophe, Scholtès, Caroline, Tardy, Jean-Claude, Trabaud, Mary-Anne, Schuffenecker, Isabelle, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), The members of the COVID-Diagnosis HCL Study Group : Jean-Sébastien Casalegno, Emilie Frobert, Vanessa Escuret, Vinca Icard, Marion Jeannoel, Marie-Paule Milon, Christophe Ramière, Caroline Scholtès, Jean-Claude Tardy, Mary-Anne Trabaud, Isabelle Schuffenecker, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Marlet, Julien, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Two step, spike protein, variants, deletion, Genome, Viral, Biology, spike protein, Genome, 03 medical and health sciences, COVID-19, whole genome sequencing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Humans, Spike (database), Base sequence, Sequence Deletion, whole genome sequencing, variants, Base Sequence, deletion, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, 030104 developmental biology, Spike Glycoprotein, Coronavirus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Identification (biology), France, Rapid Communication
Abstract

International audience; 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.

Published
2021
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20. Characteristics of the delayed respiratory syncytial virus epidemic, 2020/2021, Rhône Loire, France

Author

Casalegno, Jean-Sebastien, Ploin, Dominique, Cantais, Aymeric, Masson, Elsa, Bard, Emilie, Valette, Martine, Fanget, Remi, Targe, Sandrine Couray, Myar-Dury, Anne-Florence, Doret-Dion, Muriel, Massoud, Mona, Queromes, Gregory, Vanhems, Philippe, Claris, Olivier, Butin, Marine, Pillet, Sylvie, Ader, Florence, Bin, Sylvie, Gaymard, Alexandre, Lina, Bruno, Morfin, Florence, Javouhey, Etienne, Gillet, Yves, Ouziel, Antoine, Tardy, Jean-claude, Gaucherand, Pascal, Panetta, Luc, Massardier, Jerome, Polazzi, Stephanie, Duclos, Antoine, Benchaib, Mehdi, Cartier, Regine, Jourdain, Marine, Ottmann, Michelle, Kramer, Rolf, Fiorini, Sylvie, Rivat, Nathalie, Mekki, Yahia, Fort-Jacquier, Julie, Barral, Maud-Catherine, Noelie, Vey, Haesebaert, Julie, Horvat, Come, Vidoni, Leo, Reynes, Jean-Marc, Eleouet, Jean-Francois, Josset, Laurence, Receveur, Matthieu, Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Hôpital Edouard Herriot [CHU - HCL], Santé publique, épidémiologie et écologie évolutive des maladies infectieuses (PHE3ID), Pôle Information Médicale Evaluation Recherche (IMER), Hôpital de la Croix-Rousse [CHU - HCL], VRS study group in Lyon: Antoine Ouziel, Jean-claude Tardy, Pascal Gaucherand, Luc Panetta, Jerome Massardier, Stephanie Polazzi, Antoine Duclos, Mehdi Benchaib, Regine Cartier, Marine Jourdain, Michelle Ottmann, Rolf Kramer, Sylvie Fiorini, Nathalie Rivat, Yahia Mekki, Julie Fort-Jacquier, Maud-Catherine Barral, Vey Noelie, Julie Haesebaert, Come Horvat, Leo Vidoni, Jean-Marc Reynes, Jean-Francois Eleouet, Laurence Josset, Matthieu Receveur, Reynes, Jean-Marc, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)

Subjects
0301 basic medicine, Pediatrics, Epidemiology, pharmacological interventions, MESH: Hospitalization, MESH: Respiratory Syncytial Virus, Human, disease burden, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, 030212 general & internal medicine, Respiratory system, Child, Respiratory Tract Infections, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Respiratory tract infections, Incidence (epidemiology), RSV, MESH: Infant, Hospitalization, non-pharmacological interventions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, bronchiolitis, France, Rapid Communication, Adult, medicine.medical_specialty, Respiratory Syncytial Virus Infections, Virus, MESH: Respiratory Syncytial Virus Infections, 03 medical and health sciences, Virology, Lower respiratory tract infection, medicine, Humans, Epidemics, MESH: Epidemics, Disease burden, MESH: Humans, business.industry, SARS-CoV-2, Public Health, Environmental and Occupational Health, Outbreak, COVID-19, Infant, MESH: Adult, medicine.disease, MESH: France, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Bronchiolitis, Respiratory Syncytial Virus, Human, MESH: Respiratory Tract Infections, SARI, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

International audience; The Rhône-Loire metropolitan areas’ 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged > 3 months to 5 years increased, and cases among adults > 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.

Published
2021
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21. Cluster of Coronavirus Disease 2019 (COVID-19) in the French Alps, February 2020

Author

Danis, Kostas, Epaulard, Olivier, Bénet, Thomas, Gaymard, Alexandre, Campoy, Séphora, Botelho-Nevers, Elisabeth, Bouscambert-Duchamp, Maude, Spaccaferri, Guillaume, Ader, Florence, Mailles, Alexandra, Boudalaa, Zoubida, Tolsma, Violaine, Berra, Julien, Vaux, Sophie, Forestier, Emmanuel, Landelle, Caroline, Fougere, Erica, Thabuis, Alexandra, Berthelot, Philippe, Veil, Raphael, Levy-Bruhl, Daniel, Chidiac, Christian, Lina, Bruno, Coignard, Bruno, Saura, Christine, Brottet, Elise, Casamatta, Delphine, Gallien, Yves, George, Scarlett, Viriot, Delphine, Ait Belghiti, Fatima, Bernard-Stoecklin, Sibylle, Desenclos, Jean-Claude, Giese, Coralie, Ghislain, Didier, Gounon, Magali, Grangeret, Nathalie, Marie, Cécile, Morel, Bruno, Deher, Muriel, Ronnaux Baron, Anne-Sophie, Courbis, Geneviève, Ragozin, Nathalie, Wolska, Monika, Serange, Eric, Mercatello, Delphine, Aiouaz, Soraya, Valette, Martine, Frobert, Emilie, Josset, Laurence, Escuret, Vanessa, Morfin, Florence, Billaud, Geneviève, Blanc, Myriam, Arata-Bardet, Julie, Froidure, Marie, Le Maréchal, Marion, Pavese, Patricia, Pierre, Isabelle, Becker, Agathe, Chauvelot, Pierre, Conrad, Anne, Ferry, Tristan, Miailhes, Patrick, Perpoint, Thomas, Pouderoux, Cécile, Roux, Sandrine, Valour, Florent, Lutz, Marie-France, Pouvaret, Anne, Vitrat, Virginie, Maillet, Mylène, Janssen, Cécile, Piet, Emilie, Bosch, Alexie, Destrem, Anne-Laure, Isnard, Margaux, Challan-Belval, Thibault, Wackenheim, Chloe, Couturier, Alice, Gheno, Gael, Roupioz, Thierry, Lucet, Nicolas, Ayouni, Stéphane, Vincent, Mireille, de Epidemiología, Servicio, General de Salud Pública del Gover Balear, Dirección, Masserey Spicher, Virginie, Bourquin, Catherine, Stoll, Jeanine, Chaud, Pascal, and Mounayar, Anne-Laure

Subjects
Microbiology (medical), Pediatrics, medicine.medical_specialty, Attack rate, Pneumonia, Viral, coronavirus, Disease cluster, Asymptomatic, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, 030225 pediatrics, medicine, Major Article, Cluster Analysis, Humans, Serologic Tests, 030212 general & internal medicine, cluster, Index case, Pandemics, Aged, Retrospective Studies, Aged, 80 and over, Transmission (medicine), business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, Middle Aged, medicine.disease, infection, AcademicSubjects/MED00290, Infectious Diseases, Coinfection, Female, France, medicine.symptom, business, Coronavirus Infections, Viral load
Abstract

BackgroundOn 7 February 2020, French Health authorities were informed of a confirmed case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an Englishman infected in Singapore who had recently stayed in a chalet in the French Alps. We conducted an investigation to identify secondary cases and interrupt transmission.MethodsWe defined as a confirmed case a person linked to the chalet with a positive reverse-transcription polymerase chain reaction sample for SARS-CoV-2.ResultsThe index case stayed 4 days in the chalet with 10 English tourists and a family of 5 French residents; SARS-CoV-2 was detected in 5 individuals in France, 6 in England (including the index case), and 1 in Spain (overall attack rate in the chalet: 75%). One pediatric case, with picornavirus and influenza A coinfection, visited 3 different schools while symptomatic. One case was asymptomatic, with similar viral load as that of a symptomatic case. Seven days after the first cases were diagnosed, 1 tertiary case was detected in a symptomatic patient with from the chalet a positive endotracheal aspirate; all previous and concurrent nasopharyngeal specimens were negative. Additionally, 172 contacts were monitored; all contacts tested for SARS-CoV-2 (N = 73) were negative.ConclusionsThe occurrence in this cluster of 1 asymptomatic case with similar viral load as a symptomatic patient suggests transmission potential of asymptomatic individuals. The fact that an infected child did not transmit the disease despite close interactions within schools suggests potential different transmission dynamics in children. Finally, the dissociation between upper and lower respiratory tract results underscores the need for close monitoring of the clinical evolution of suspected cases of coronavirus disease 2019.

Published
2020
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22. Evaluation of NGS-based approaches for SARS-CoV-2 whole genome characterisation.

Author

Charre, Caroline, Ginevra, Christophe, Sabatier, Marina, Regue, Hadrien, Destras, Grégory, Brun, Solenne, Burfin, Gwendolyne, Scholtes, Caroline, Morfin, Florence, Valette, Martine, Lina, Bruno, Bal, Antonin, and Josset, Laurence

Subjects
SARS-CoV-2, METAGENOMICS, SINGLE nucleotide polymorphisms, DNA sequencing, COVID-19 pandemic
Abstract

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 (n  = 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 vs 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. [ABSTRACT FROM AUTHOR]

Published
2020
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23. Publisher Correction: Clinical and laboratory characteristics of symptomatic healthcare workers with suspected COVID-19: a prospective cohort study.

Author

Bal, Antonin, Brengel-Pesce, Karen, Gaymard, Alexandre, Quéromès, Grégory, Guibert, Nicolas, Frobert, Emilie, Bouscambert, Maude, Trabaud, Mary-Anne, Allantaz-Frager, Florence, Oriol, Guy, Cheynet, Valérie, d'Aubarede, Constance, Massardier-Pilonchery, Amélie, Buisson, Marlyse, Lupo, Julien, Pozzetto, Bruno, Poignard, Pascal, Lina, Bruno, Fassier, Jean-Baptiste, and Morfin, Florence

Subjects
MEDICAL personnel, COVID-19, PUBLISHING, COHORT analysis, LONGITUDINAL method, PATHOLOGICAL laboratories
Abstract

In addition, in the Introduction, "To improve the clinical management of SARS-CoV-2 infection in HCWs, a virological investigation including quantitative RT-PCR, viral culture, as well as the determination of neutralizing antibodytiters over the course of the disease is needed." now reads: "To improve the clinical management of SARS-CoV-2 infection in HCWs, a virological investigation including quantitative RT-PCR, viral culture, as well as the determination of neutralizing antibody titers over the course of the disease is needed." Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-93828-y, published online 22 July 2021 The original version of this Article contained an error in the spelling of the author Emilie Frobert which was incorrectly given as Emile Frobert. [Extracted from the article]

Published
2021
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24. Performance Assessment of SARS-CoV-2 PCR Assays Developed by WHO Referral Laboratories.

Author

Etievant, Sibyle, Bal, Antonin, Escuret, Vanessa, Brengel-Pesce, Karen, Bouscambert, Maude, Cheynet, Valérie, Generenaz, Laurence, Oriol, Guy, Destras, Gregory, Billaud, Geneviève, Josset, Laurence, Frobert, Emilie, Morfin, Florence, and Gaymard, Alexandre

Subjects
SARS-CoV-2, COVID-19 pandemic, COVID-19
Abstract

A reliable diagnostic assay is crucial to early detect new COVID-19 cases and limit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Since the onset of the COVID-19 pandemic, the World Health Organization has published several diagnostic molecular approaches developed by referral laboratories, including Charité (Germany), HKU (Hong Kong), China CDC (China), US CDC (United States), and Institut Pasteur, Paris (France). We aimed to compare the sensitivity and specificity of these different RT-PCR assays using SARS-CoV-2 cell culture supernatants and clinical respiratory samples. Overall, the different RT-PCR assays performed well for SARS-CoV-2 detection and were all specific except the N Charité (Germany), and N2 US CDC (United States) assays. RdRp Institut Pasteur (IP2, IP4), N China CDC, and N1 US CDC were found to be the most sensitive assays. The data presented herein are of prime importance to facilitate the equipment choice of diagnostic laboratories, as well as for the development of marketed tests. [ABSTRACT FROM AUTHOR]

Published
2020
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25. Assessment of serological techniques for screening patients for COVID-19 (COVID-SER): a prospective, multicentric study

Author

Trouillet-Assant, Sophie, Albert Vega, Chloe, Bal, Antonin, Nazare, Julie Anne, Fascia, Pascal, Paul, Adèle, Massardier-Pilonchery, Amélie, d Aubarede, Constance, Guibert, Nicolas, Pitiot, Virginie, Lahousse, Matthieu, Boibieux, André, Makhloufi, Djamila, Simon, Chantal, Rabilloud, Muriel, Trabaud, Mary Anne, Gueyffier, François, Fassier, Jean-Baptiste, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), HCL Groupement Hospitalier Nord [Lyon], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hôpital Henry Gabrielle [CHU - HCL], Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Hôpital Edouard Herriot [CHU - HCL], Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de LyonFondation des Hospices Civils de Lyon, COVID-SER study group: Jérôme Adnot, Dulce Alfaiate, Antonin Bal, Alain Bergeret, André Boibieux, Florent Bonnet, Gaëlle Bourgeois, Florence Brunel-Dalmas, Eurydice Caire, Barbara Charbotel, Pierre Chiarello, Laurent Cotte, Constance d'Aubarede, François Durupt, Escuret Vanessa, Fascia Pascal, Fassier Jean-Baptiste, Fontaine Juliette, Gaillot-Durand Lucie, Gaymard Alexandre, Gillet Myriam, Godinot Matthieu, Gueyffier François, Guibert Nicolas, Josset Laurence, Lahousse Matthieu, Lina Bruno, Lozano Hélène, Makhloufi Djamila, Massardier-Pilonchéry Amélie, Milon Marie-Paule, Moll Frédéric, Morfin Florence, Narbey David, Nazare Julie-Anne, Oria Fatima, Paul Adèle, Perry Marielle, Pitiot Virginie, Prudent Mélanie, Rabilloud Muriel, Samperiz Audrey, Schlienger Isabelle, Simon Chantal, Trabaud Mary-Anne, Trouillet-Assant Sophie, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CarMeN, laboratoire

Subjects
Male, SARS-CoV-2, public health, [SDV]Life Sciences [q-bio], COVID-19, General Medicine, Antibodies, Viral, diagnostic microbiology, [SDV] Life Sciences [q-bio], molecular diagnostics, Humans, Mass Screening, Female, Serologic Tests, Public Health, Prospective Studies, Pandemics
Abstract

International audience; INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated. METHODS AND ANALYSIS: We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04341142.

Published
2020
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