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1.
Emerg Microbes Infect ; 11(1): 2423-2432, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2028961

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.


Subject(s)
COVID-19 , Viral Vaccines , Humans , SARS-CoV-2/genetics , Virus Shedding , Antibodies, Viral , Immunoglobulin G , Antibodies, Neutralizing
2.
Viruses ; 14(8)2022 07 29.
Article in English | MEDLINE | ID: covidwho-1969505

ABSTRACT

Whole-genome sequencing has become an essential tool for real-time genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide. The handling of raw next-generation sequencing (NGS) data is a major challenge for sequencing laboratories. We developed an easy-to-use web-based application (EPISEQ SARS-CoV-2) to analyse SARS-CoV-2 NGS data generated on common sequencing platforms using a variety of commercially available reagents. This application performs in one click a quality check, a reference-based genome assembly, and the analysis of the generated consensus sequence as to coverage of the reference genome, mutation screening and variant identification according to the up-to-date Nextstrain clade and Pango lineage. In this study, we validated the EPISEQ SARS-CoV-2 pipeline against a reference pipeline and compared the performance of NGS data generated by different sequencing protocols using EPISEQ SARS-CoV-2. We showed a strong agreement in SARS-CoV-2 clade and lineage identification (>99%) and in spike mutation detection (>99%) between EPISEQ SARS-CoV-2 and the reference pipeline. The comparison of several sequencing approaches using EPISEQ SARS-CoV-2 revealed 100% concordance in clade and lineage classification. It also uncovered reagent-related sequencing issues with a potential impact on SARS-CoV-2 mutation reporting. Altogether, EPISEQ SARS-CoV-2 allows an easy, rapid and reliable analysis of raw NGS data to support the sequencing efforts of laboratories with limited bioinformatics capacity and those willing to accelerate genomic surveillance of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Genome, Viral , High-Throughput Nucleotide Sequencing/methods , Humans , Mutation , SARS-CoV-2/genetics
3.
Bastard, Paul, Vazquez, Sara, Liu, Jamin, Laurie, Matthew T.; Wang, Chung Yu, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Zamecnik, Colin, Philippot, Quentin, Rosain, Jérémie, Catherinot, Emilie, Willmore, Andrew, Mitchell, Anthea M.; Bair, Rebecca, Garçon, Pierre, Kenney, Heather, Fekkar, Arnaud, Salagianni, Maria, Poulakou, Garyphallia, Siouti, Eleni, Sahanic, Sabina, Tancevski, Ivan, Weiss, Günter, Nagl, Laurenz, Manry, Jérémy, Duvlis, Sotirija, Arroyo-Sánchez, Daniel, Paz Artal, Estela, Rubio, Luis, Perani, Cristiano, Bezzi, Michela, Sottini, Alessandra, Quaresima, Virginia, Roussel, Lucie, Vinh, Donald C.; Reyes, Luis Felipe, Garzaro, Margaux, Hatipoglu, Nevin, Boutboul, David, Tandjaoui-Lambiotte, Yacine, Borghesi, Alessandro, Aliberti, Anna, Cassaniti, Irene, Venet, Fabienne, Monneret, Guillaume, Halwani, Rabih, Sharif-Askari, Narjes Saheb, Danielson, Jeffrey, Burrel, Sonia, Morbieu, Caroline, Stepanovskyy, Yurii, Bondarenko, Anastasia, Volokha, Alla, Boyarchuk, Oksana, Gagro, Alenka, Neuville, Mathilde, Neven, Bénédicte, Keles, Sevgi, Hernu, Romain, Bal, Antonin, Novelli, Antonio, Novelli, Giuseppe, Saker, Kahina, Ailioaie, Oana, Antolí, Arnau, Jeziorski, Eric, Rocamora-Blanch, Gemma, Teixeira, Carla, Delaunay, Clarisse, Lhuillier, Marine, Le Turnier, Paul, Zhang, Yu, Mahevas, Matthieu, Pan-Hammarström, Qiang, Abolhassani, Hassan, Bompoil, Thierry, Dorgham, Karim, consortium, Covid Hge, French, Covid study group, consortium, Comet, Gorochov, Guy, Laouenan, Cédric, Rodríguez-Gallego, Carlos, Ng, Lisa F. P.; Renia, Laurent, Pujol, Aurora, Belot, Alexandre, Raffi, François, Allende, Luis M.; Martinez-Picado, Javier, Ozcelik, Tayfun, Keles, Sevgi, Imberti, Luisa, Notarangelo, Luigi D.; Troya, Jesus, Solanich, Xavier, Zhang, Shen-Ying, Puel, Anne, Wilson, Michael R.; Trouillet-Assant, Sophie, Abel, Laurent, Jouanguy, Emmanuelle, Ye, Chun Jimmie, Cobat, Aurélie, Thompson, Leslie M.; Andreakos, Evangelos, Zhang, Qian, Anderson, Mark S.; Casanova, Jean-Laurent, DeRisi, Joseph L..
Science immunology ; 2022.
Article in English | EuropePMC | ID: covidwho-1918542

ABSTRACT

Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals;however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population. Type I IFN auto-Abs are found in 20% of hypoxemic, mRNA vaccinated COVID-19 patients despite SARS-CoV-2 neutralizing antibodies. Description

4.
Clin Microbiol Infect ; 28(11): 1503.e5-1503.e8, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1914264

ABSTRACT

OBJECTIVES: To describe Delta/Omicron SARS-CoV-2 variants co-infection detection and confirmation during the fifth wave of COVID-19 pandemics in France in 7 immunocompetent and epidemiologically unrelated patients. METHODS: Since December 2021, the surveillance of Delta/Omicron SARS-CoV-2 variants of concern (VOC) circulation was performed through prospective screening of positive-samples using single nucleotide polymorphism (SNP) PCR assays targeting SARS-CoV-2 S-gene mutations K417N (Omicron specific) and L452R (Delta specific). Samples showing unexpected mutational profiles were further submitted to whole genome sequencing (WGS) using three different primer sets. RESULTS: Between weeks 49-2021 and 02-2022, SARS-CoV-2 genome was detected in 3831 respiratory samples, of which 3237 (84.5%) were screened for VOC specific SNPs. Unexpected mutation profiles suggesting a dual Delta/Omicron population were observed in 7 nasopharyngeal samples (0.2%). These co-infections were confirmed by WGS. For 2 patients, the sequence analyses of longitudinal samples collected 7 to 11 days apart showed that Delta or Omicron can outcompete the other variant during dual infection. Additionally, for one of these samples, a recombination event between Delta and Omicron was detected. CONCLUSIONS: This work demonstrates that SARS-CoV-2 Delta/Omicron co-infections are not rare in high virus co-circulation periods. Moreover, co-infections can further lead to genetic recombination which may generate new chimeric variants with unpredictable epidemic or pathogenic properties that could represent a serious health threat.


Subject(s)
COVID-19 , Coinfection , Humans , SARS-CoV-2/genetics , Coinfection/epidemiology , Prospective Studies , COVID-19/epidemiology , Sequence Analysis
8.
Viruses ; 14(5)2022 04 28.
Article in English | MEDLINE | ID: covidwho-1820408

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Nasopharynx , SARS-CoV-2/genetics , Viral Load
9.
J Clin Virol ; 152: 105169, 2022 07.
Article in English | MEDLINE | ID: covidwho-1804471

ABSTRACT

The virus neutralization test (VNT) is the reference for the assessment of the functional ability of neutralizing antibodies (NAb) to block SARS-CoV-2 entry into cells. New competitive immunoassays measuring antibodies preventing interaction between the spike protein and its cellular receptor are proposed as surrogate VNT (sVNT). We tested three commercial sVNT (a qualitative immunochromatographic test and two quantitative immunoassays named YHLO and TECO) together with a conventional anti-spike IgG assay (bioMérieux) in comparison with an in-house plaque reduction neutralization test (PRNT50) using the original 19A strain and different variants of concern (VOC), on a panel of 306 sera from naturally-infected or vaccinated patients. The qualitative test was rapidly discarded because of poor sensitivity and specificity. Areas under the curve of YHLO and TECO assays were, respectively, 85.83 and 84.07 (p-value >0.05) using a positivity threshold of 20 for PRNT50, and 95.63 and 90.35 (p-value =0.02) using a threshold of 80. However, the performances of YHLO and bioMérieux were very close for both thresholds, demonstrating the absence of added value of sVNT compared to a conventional assay for the evaluation of the presence of NAb in seropositive subjects. In addition, the PRNT50 assay showed a reduction of NAb titers towards different VOC in comparison to the 19A strain that could not be appreciated by the commercial tests. Despite the good correlation between the anti-spike antibody titer and the titer of NAb by PRNT50, our results highlight the difficulty to distinguish true NAb among the anti-RBD antibodies with commercial user-friendly immunoassays.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/diagnosis , Humans , Neutralization Tests/methods
10.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331250

ABSTRACT

In Dec 2021-Feb 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 we developed an unbiased bioinformatics method which can detect all co-infections irrespective of the SARS-CoV-2 lineages involved. Applied on 21,387 samples collected between weeks 49-2021 and 08-2022 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. 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.

11.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329746

ABSTRACT

We report evidence of Delta/Omicron SARS-CoV-2 co-infections during the fifth wave of COVID-19 pandemics in France for 7 immunocompetent and epidemiologically unrelated patients. These co-infections were detected by PCR assays targeting SARS-CoV-2 S-gene mutations K417N and L452R and confirmed by whole genome sequencing which allowed the proportion estimation of each subpopulation. For 2 patients, the analyses of longitudinal samples collected 7 to 11 days apart showed that Delta or Omicron can outcompete the other variant during dual infection.

13.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327361

ABSTRACT

High viral load in upper respiratory tract specimens observed for Delta cases may contributed to its increased infectivity compared to the Alpha variant. Herein, we showed that the RT-PCR Ct values in Health Care Workers sampled within five days after symptom onset were significantly higher for Omicron cases than Delta cases (+2.84 Ct, p=0.008). This result comfort the studies showing that the increased transmissibility of Omicron is related to other mechanisms than higher virus excretion.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319836

ABSTRACT

Quantifying the effectiveness of large-scale non-pharmaceutical interventions (NPIs) against COVID-19 is critical to adapting responses against future waves of the pandemic. Most studies of NPIs thus far have relied on epidemiological data. Here, we report the impact of NPIs on the evolution of SARS-CoV-2, taking the perspective of the virus. We examined how variations through time and space of SARS-CoV-2 genomic divergence rates, which reflect variations of the epidemic reproduction number Rt, can be explained by NPIs and combinations thereof. Based on the analysis of 5,198 SARS-CoV-2 genomes from 57 countries along with a detailed chronology of 9 non-pharmaceutical interventions during the early epidemic phase up to May 2020, we find that home containment (35% Rt reduction) and education lockdown (26%) had the strongest predicted effectiveness. To estimate the cumulative effect of NPIs, we modelled the probability of reducing Rt below 1, which is required to stop the epidemic, for various intervention combinations and initial Rt values. In these models, no intervention implemented alone was sufficient to stop the epidemic for Rt’s above 2 and all interventions combined were required for Rt’s above 3. Our approach can help inform decisions on the minimal set of NPIs required to control the epidemic depending on the current Rt value.

15.
O'Toole, Áine, Hill, Verity, Pybus, Oliver, Watts, Alexander, Bogoch, Issac, Khan, Kamran, Messina, Jane, Tegally, Houriiyah, Lessells, Richard, Giandhari, Jennifer, Pillay, Sureshnee, Tumedi, Kefentse Arnold, Nyepetsi, Gape, Kebabonye, Malebogo, Matsheka, Maitshwarelo, Mine, Madisa, Tokajian, Sima, Hassan, Hamad, Salloum, Tamara, Merhi, Georgi, Koweyes, Jad, Geoghegan, Jemma, de Ligt, Joep, Ren, Xiaoyun, Storey, Matthew, Freed, Nikki, Pattabiraman, Chitra, Prasad, Pramada, Desai, Anita, Vasanthapuram, Ravi, Schulz, Thomas, Steinbrück, Lars, Stadler, Tanja, Parisi, Antonio, Bianco, Angelica, García de Viedma, Darío, Buenestado-Serrano, Sergio, Borges, Vítor, Isidro, Joana, Duarte, Sílvia, Gomes, João Paulo, Zuckerman, Neta, Mandelboim, Michal, Mor, Orna, Seemann, Torsten, Arnott, Alicia, Draper, Jenny, Gall, Mailie, Rawlinson, William, Deveson, Ira, Schlebusch, Sanmarié, McMahon, Jamie, Leong, Lex, Lim, Chuan Kok, Chironna, Maria, Loconsole, Daniela, Bal, Antonin, Josset, Laurence, Holmes, Edward, St. George, Kirsten, Lasek-Nesselquist, Erica, Sikkema, Reina, Oude Munnink, Bas, Koopmans, Marion, Brytting, Mia, Sudha rani, V.; Pavani, S.; Smura, Teemu, Heim, Albert, Kurkela, Satu, Umair, Massab, Salman, Muhammad, Bartolini, Barbara, Rueca, Martina, Drosten, Christian, Wolff, Thorsten, Silander, Olin, Eggink, Dirk, Reusken, Chantal, Vennema, Harry, Park, Aekyung, Carrington, Christine, Sahadeo, Nikita, Carr, Michael, Gonzalez, Gabo, de Oliveira, Tulio, Faria, Nuno, Rambaut, Andrew, Kraemer, Moritz, The, Covid-Genomics U. K. consortium, Network for Genomic Surveillance in South, Africa, Brazil, U. K. Cadde Genomic Network, Swiss Viollier Sequencing, Consortium, Diego, Search Alliance San, National Virus Reference, Laboratory, Seq, Covid Spain, Danish Covid-19 Genome, Consortium, Communicable Diseases Genomic, Network, Dutch National, Sars-CoV-surveillance program, Division of Emerging Infectious, Diseases.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318194

ABSTRACT

Late in 2020, two genetically-distinct clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations of biological concern were reported, one in the United Kingdom and one in South Africa. Using a combination of data from routine surveillance, genomic sequencing and international travel we track the international dispersal of lineages B.1.1.7 and B.1.351 (variant 501Y-V2). We account for potential biases in genomic surveillance efforts by including passenger volumes from location of where the lineage was first reported, London and South Africa respectively. Using the software tool grinch (global report investigating novel coronavirus haplotypes), we track the international spread of lineages of concern with automated daily reports, Further, we have built a custom tracking website (cov-lineages.org/global_report.html) which hosts this daily report and will continue to include novel SARS-CoV-2 lineages of concern as they are detected.

16.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316368

ABSTRACT

Introduction: End stage kidney disease (ESKD) and cancer have been identified as risk factors for severe and fatal cases of COVID-19, making vaccination in these patients a priority. Patients suffering from ESKD have a significantly weaker response to common vaccines than general population. However, humoral and cellular immune responses after two doses of RNA-based vaccine BNT162b2 (Pfizer–BioNTech) have been poorly explored in this vulnerable population.Case presentationA 69-year-old male patient was followed for ESKD and myeloma. He developed a severe SARS-CoV-2 pneumonia twenty days after two doses of BNT162b2 vaccine. Whole genome sequencing found that the virus belonged to the 20I/501Y.V1 clade. A serology draws eight days after the 2 nd vaccine dose showed positive RBD IgG without neutralizing activity. A serum specimen sampled thirty days after the onset of SARS-CoV-2 infection showed seroconversion against both RBD and N antigens. This specimen was shown to exhibit a frank neutralizing activity. The QuantiFERON® SARS-CoV-2 (Qiagen) showed a positive specific cellular response although the QuantiFERON monitor displayed a weak cellular response. ConclusionsImpaired immunity due to renal failure probably explain the severe pneumonia despite vaccination. The fact that the patient developpe a neutralizing activity and a cellular response after a third stimulation by infection may suggest to systemically administrate a third dose of vaccine in ESKD patients.

17.
J Clin Microbiol ; 60(1): e0174621, 2022 01 19.
Article in English | MEDLINE | ID: covidwho-1637201

ABSTRACT

With the availability of vaccines, commercial assays detecting anti-severe acute respiratory syndrome coronavirus-2 antibodies (Ab) evolved toward quantitative assays directed to the spike glycoprotein or its receptor binding domain (RBD). The main objective of the present study was to compare the Ab titers obtained with quantitative commercial binding Ab assays, after one dose (convalescent individuals) or two doses (naive individuals) of vaccine, in health care workers (HCW). Antibody titers were measured in 255 sera (from 150 HCW) with five quantitative immunoassays (Abbott RBD IgG II quant, bioMérieux RBD IgG, DiaSorin Trimeric spike IgG, Siemens Healthineers RBD IgG, Wantai RBD IgG). One qualitative total antibody anti-RBD detection assay (Wantai) was used to detect previous infection before vaccination. The results are presented in binding Ab units (BAU)/mL after application, when possible, of a conversion factor provided by the manufacturers and established from a World Health Organization internal standard. There was a 100% seroconversion with all assays evaluated after two doses of vaccine. With assays allowing BAU/mL correction, Ab titers were correlated (Pearson correlation coefficient, ρ, range: 0.85-0.94). The titer differences varied by a mean of 10.6% between Siemens and bioMérieux assays to 60.9% between Abbott and DiaSorin assays. These results underline the importance of BAU conversion for the comparison of Ab titer obtained with the different quantitative assays. However, significant differences persist, notably, between kits detecting Ab against the different antigens. A true standardization of the assays would be to include the International Standard in the calibration of each assay to express the results in IU/mL.


Subject(s)
COVID-19 , Antibodies, Viral , Health Personnel , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination
18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296527

ABSTRACT

Herein, we describe the characteristics of vaccine breakthrough infections (VBI) in fully vaccinated individuals according to five vaccine strategies during the Delta wave in France. Inclusion criterion was a positive test at least 2 weeks after a full vaccine schedule: homologous vaccination with Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273);heterologous vaccination with Astrazeneca and Pfizer-BioNTech (ChadOx1/BNT162b2);single-dose vaccines Johnson & Johnson (Ad26.COV2.S) or Astrazeneca (ChadOx1). A total of 1630 VBI from patients fully vaccinated between February and July were included in this study. SARS-CoV-2 sequencing performed for 1366 samples showed that the delta variant represented 94.1% (1286/1366). Delta-VBI were mainly symptomatic (mild symptoms) with no difference according to the vaccine strategy (p=0.362). The median RT-PCR Ct values at diagnosis were significantly different between symptomatic and asymptomatic cases only for BNT162b2 group (17.7 (15.07, 20.51) vs 19.00 (16.00, 23.00), p=0.004). Up to 50% of VBI was classified as early-VBI (infected less than one month after full immunization) for BNT162b2, mRNA-1273, ChadOx1, and J Ad26.COV2.S. People aged 14-49 yo were overrepresented in early VBI compared to non-early VBI for BNT162b2 and mRNA-1273 (73.92% vs 37.87% for BNT162b2 and 77.78% vs 46.67 % for mRNA-1273, p<0.05). Our data emphasize a high prevalence of Delta-VBI occurring only one month after full immunization in young patients that might be related to relaxation of barrier gestures.

19.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294824

ABSTRACT

Background SARS-CoV-2 mutations appeared recently and can lead to conformational changes in the spike protein and probably induce modifications in antigenicity. In this study, we wanted to assess the neutralizing capacity of antibodies to prevent cell infection, using a live virus neutralisation test. Methods Sera samples were collected from different populations: two-dose vaccinated COVID-19-naïve healthcare workers (HCWs;Pfizer-BioNTech BNT161b2), 6-months post mild COVID-19 HCWs, and critical COVID-19 patients. We tested various clades such as 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). Results 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 neutralisation 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 neutralising antibody titres in comparison with the 19A isolate. Interestingly, a significant difference in neutralisation capacity was observed for vaccinated HCWs between the two variants whereas it was not significant for the convalescent groups. Conclusion Neutralisation capacity was slightly reduced for critical patients and HCWs 6-months post infection. No neutralisation escape could be feared concerning the two variants of concern in both populations. The reduced neutralising response observed towards the 20H/501Y.V2 in comparison with the 19A and 20I/501Y.V1 isolates in fully immunized subjects with the BNT162b2 vaccine is a striking finding of the study.

20.
Nature ; 600(7890): 701-706, 2021 12.
Article in English | MEDLINE | ID: covidwho-1483135

ABSTRACT

Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine1,2, European health authorities recommended that patients under the age of 55 years who received one dose of ChAdOx1-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals.


Subject(s)
/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , /immunology , SARS-CoV-2/immunology , Vaccination/statistics & numerical data , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Female , France/epidemiology , Hospitals, University , Humans , Immunologic Memory/immunology , Incidence , Male , /immunology , Middle Aged , Spike Glycoprotein, Coronavirus/immunology
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