COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022.

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Influenza vaccine effectiveness in Europe: Results from the 2022-2023 VEBIS (Vaccine Effectiveness, Burden and Impact Studies) primary care multicentre study.

Background: Influenza A(H3N2) viruses dominated early in the 2022-2023 influenza season in Europe, followed by higher circulation of influenza A(H1N1)pdm09 and B viruses. The VEBIS primary care network estimated the influenza vaccine effectiveness (VE) using a multicentre test-negative study. Materials and Methods: Primary care practitioners collected information and specimens from patients consulting with acute respiratory infection. We measured VE against any influenza, influenza (sub)type and clade, by age group, by influenza vaccine target group and by time since vaccination, using logistic regression. Results: We included 38 058 patients, of which 3786 were influenza A(H3N2), 1548 influenza A(H1N1)pdm09 and 3275 influenza B cases. Against influenza A(H3N2), VE was 36% (95% CI: 25-45) among all ages and ranged between 30% and 52% by age group and target group. VE against influenza A(H3N2) clade 2b was 38% (95% CI: 25-49). Overall, VE against influenza A(H1N1)pdm09 was 46% (95% CI: 35-56) and ranged between 29% and 59% by age group and target group. VE against influenza A(H1N1)pdm09 clade 5a.2a was 56% (95% CI: 46-65) and 79% (95% CI: 64-88) against clade 5a.2a.1. VE against influenza B was 76% (95% CI: 70-81); overall, 84%, 72% and 71% were among 0-14-year-olds, 15-64-year-olds and those in the influenza vaccination target group, respectively. VE against influenza B with a position 197 mutation of the hemagglutinin (HA) gene was 79% (95% CI: 73-85) and 90% (95% CI: 85-94) without this mutation. Conclusion: The 2022-2023 end-of-season results from the VEBIS network at primary care level showed high VE among children and against influenza B, with lower VE against influenza A(H1N1)pdm09 and A(H3N2).

Seasonal and inter-seasonal RSV activity in the European Region during the COVID-19 pandemic from autumn 2020 to summer 2022.

Background: The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in early 2020 and subsequent implementation of public health and social measures (PHSM) disrupted the epidemiology of respiratory viruses. This work describes the epidemiology of respiratory syncytial virus (RSV) observed during two winter seasons (weeks 40-20) and inter-seasonal periods (weeks 21-39) during the pandemic between October 2020 and September 2022. Methods: Using data submitted to The European Surveillance System (TESSy) by countries or territories in the World Health Organization (WHO) European Region between weeks 40/2020 and 39/2022, we aggregated country-specific weekly RSV counts of sentinel, non-sentinel and Severe Acute Respiratory Infection (SARI) surveillance specimens and calculated percentage positivity. Results for both 2020/21 and 2021/22 seasons and inter-seasons were compared with pre-pandemic 2016/17 to 2019/20 seasons and inter-seasons. Results: Although more specimens were tested than in pre-COVID-19 pandemic seasons, very few RSV detections were reported during the 2020/21 season in all surveillance systems. During the 2021 inter-season, a gradual increase in detections was observed in all systems. In 2021/22, all systems saw early peaks of RSV infection, and during the 2022 inter-seasonal period, patterns of detections were closer to those seen before the COVID-19 pandemic. Conclusion: RSV surveillance continued throughout the COVID-19 pandemic, with an initial reduction in transmission, followed by very high and out-of-season RSV circulation (summer 2021) and then an early start of the 2021/22 season. As of the 2022/23 season, RSV circulation had not yet normalised.

Investigations into SARS-CoV-2 and other coronaviruses on mink farms in France late in the first year of the COVID-19 pandemic.

Soon after the beginning of the COVID-19 pandemic in early 2020, the Betacoronavirus SARS-CoV-2 infection of several mink farms breeding American minks (Neovison vison) for fur was detected in various European countries. The risk of a new reservoir being formed and of a reverse zoonosis from minks quickly became a major concern. The aim of this study was to investigate the four French mink farms to see whether SARS-CoV-2 was circulating there in late 2020. The investigations took place during the slaughtering period, thus facilitating different types of sampling (swabs and blood). On one of the four mink farms, 96.6% of serum samples were positive when tested with a SARS-CoV-2 ELISA coated with purified N protein recombinant antigen, and 54 out of 162 (33%) pharyngo-tracheal swabs were positive by RT-qPCR. The genetic variability among 12 SARS-CoV-2 genomes sequenced from this farm indicated the co-circulation of several lineages at the time of sampling. All the SARS-CoV-2 genomes detected were nested within the 20A clade (Nextclade), together with SARS-CoV-2 genomes from humans sampled during the same period. The percentage of SARS-CoV-2 seropositivity by ELISA varied between 0.3 and 1.1% on the other three farms. Interestingly, among these three farms, 11 pharyngo-tracheal swabs and 3 fecal pools from two farms were positive by end-point RT-PCR for an Alphacoronavirus very similar to a mink coronavirus sequence observed on Danish farms in 2015. In addition, a mink Caliciviridae was identified on one of the two farms positive for Alphacoronavirus. The clinical impact of these inapparent viral infections is not known. The co-infection of SARS-CoV-2 with other viruses on mink farms could help explain the diversity of clinical symptoms noted on different infected farms in Europe. In addition, the co-circulation of an Alphacoronavirus and SARS-CoV-2 on a mink farm would potentially increase the risk of viral recombination between alpha and betacoronaviruses as already suggested in wild and domestic animals, as well as in humans.

One Health compartment analysis of ESBL-producing Escherichia coli reveals multiple transmission events in a rural area of Madagascar.

BACKGROUND: ESBL-producing Escherichia coli (ESBL-Ec) is considered a key indicator for antimicrobial resistance (AMR) epidemiological surveillance in animal, human and environment compartments. There is likelihood of ESBL-Ec animal-human transmission but proof of cross-compartment transmission is still unclear. OBJECTIVES: To characterize ESBL-Ec genetic similarity in various compartments (humans, animals and environment) from a rural area of Madagascar. METHODS: We collected ESBL-Ec isolates prospectively from humans, animals and the environment (water) between April and October 2018. These isolates were subject to WGS and analysed with cutting-edge phylogenomic methods to characterize population genetic structure and infer putative transmission events among compartments. RESULTS: Of the 1454 samples collected, 512 tested positive for ESBL-Ec. We successfully sequenced 510 samples, and a phylogenomic tree based on 179 365 SNPs was produced. Phylogenetic distances between and amongst compartments were indistinguishable, and 104 clusters of recent transmission events between compartments were highlighted. Amongst a large diversity of ESBL-Ec genotypes, no lineage host specificity was observed, indicating the regular occurrence of ESBL-Ec transfer among compartments in rural Madagascar. CONCLUSIONS: Our findings stress the importance of using a phylogenomic approach on ESBL-Ec samples in various putative compartments to obtain a clear baseline of AMR transmissions in rural settings, where one wants to identify risk factors associated with transmission or to measure the effect of 'One Health' interventions in low- and middle-income countries.

Emergence and evolution of the Omicron SARS-CoV-2 variant in the island of Martinique.

INTRODUCTION: We aimed to describe the epidemiological situation during the Omicron variant circulation in light of genomic surveillance data in Martinique, a territory with low vaccination rates. PATIENTS AND METHODS: We exploited COVID-19 national databases of virological tests, for the collection of hospital data and for the sequencing data from December 13, 2021 to July 11, 2022. RESULTS: Three prevailing sub-lineages of Omicron have been identified in Martinique (BA.1, BA.2, BA.5) during this period causing three distinct waves characterized by an increase in virological indicators compared to previous waves, with moderate severity in the first and last waves, caused by BA.1 and BA.5, respectively. CONCLUSION: The SARS-CoV-2 outbreak is still progressing in Martinique. Genomic surveillance system in this overseas territory must be continued for rapid detection of emerging variants/sub-lineages.

Investigations on SARS-CoV-2 and other coronaviruses in mink farms in France at the end of the first year of COVID-19 pandemic.

Soon after the beginning of the COVID-19 pandemic in early 2020, the Betacoronavirus SARS-CoV-2 infection of several mink farms breeding American minks ( Neovison vison ) for fur was detected in several countries of Europe. The risk of a new reservoir formation and of a reverse zoonosis from minks was then a major concern. The aim of this study was to investigate the four French mink farms for the circulation of SARS-CoV-2 at the end of 2020. The investigations took place during the slaughtering period thus facilitating different types of sampling (swabs and blood). In one of the four mink farms, 96.6% of serum samples were positive in SARS-CoV-2 ELISA coated with purified N protein recombinant antigen and 54 out of 162 (33%) pharyngo-tracheal swabs were positive by RT-qPCR. The genetic variability among 12 SARS-CoV-2 genomes sequenced in this farm indicated the co-circulation of several lineages at the time of sampling. All SARS-CoV-2 genomes detected were nested within the 20A clade (Nextclade), together with SARS-CoV-2 genomes from humans sampled at the same period. The percentage of SARS-CoV-2 seropositivity by ELISA varied between 0.5 and 1.2% in the three other farms. Interestingly, among these three farms, 11 pharyngo-tracheal swabs and 3 fecal pools from two farms were positive by end-point RT-PCR for an Alphacoronavirus highly similar to a mink coronavirus sequence observed in Danish farms in 2015. In addition, a mink Caliciviridae was identified in one of the two positive farms for Alphacoronavirus . The clinical impact of these unapparent viral infections is not known. The co-infection of SARS-CoV-2 with other viruses in mink farms could contribute to explain the diversity of clinical symptoms noted in different infected farms in Europe. In addition, the co-circulation of an Alphacoronavirus and SARS-CoV-2 within a mink farm would increase potentially the risk of viral recombination between alpha and betacoronaviruses already suggested in wild and domestic animals, as well as in humans. Author summary: France is not a country of major mink fur production. Following the SARS-CoV-2 contamination of mink farms in Denmark and the Netherlands, the question arose for the four French farms.The investigation conducted at the same time in the four farms revealed the contamination of one of them by a variant different from the one circulating at the same time in Denmark and the Netherlands mink farms. Investigation of three other farms free of SARS-CoV-2 contamination revealed the circulation of other viruses including a mink Alphacoronavirus and Caliciviridae , which could modify the symptomatology of SARS-CoV-2 infection in minks.

Capturing SARS-CoV-2 from patient samples with low viral abundance: a comparative analysis.

Since the beginning of the SARS-CoV-2 coronavirus pandemic, genome sequencing is essential to monitor viral mutations over time and by territory. This need for complete genetic information is further reinforced by the rapid spread of variants of concern. In this paper, we assess the ability of the hybridization technique, Capture-Seq, to detect the SARS-CoV-2 genome, either partially or in its integrity on patients samples. We studied 20 patient nasal swab samples broken down into five series of four samples of equivalent viral load from CT25 to CT36+ . For this, we tested 3 multi-virus panel as well as 2 SARS-CoV-2 only panels. The panels were chosen based on their specificity, global or specific, as well as their technological difference in the composition of the probes: ssRNA, ssDNA and dsDNA. The multi-virus panels are able to capture high-abundance targets but fail to capture the lowest-abundance targets, with a high percentage of off-target reads corresponding to the abundance of the host sequences. Both SARS-CoV-2-only panels were very effective, with high percentage of reads corresponding to the target. Overall, capture followed by sequencing is very effective for the study of SARS-CoV-2 in low-abundance patient samples and is suitable for samples with CT values up to 35.

Rapid investigation of BA.4/BA.5 cases in France.

Aim: We aimed to describe the characteristics of individuals infected by BA.4 or BA.5 in France in comparison to BA.1, and analyze the factors associated with hospitalization among BA.4 and BA.5 cases. Methods: A standardized questionnaire was used to collect information on confirmed and probable Omicron cases. Hospitalization risk factors among BA.4/BA.5 cases were analyzed using Poisson regression. Variables with a p-value below 0.2 in the univariate analysis and a priori confounders were included in the multivariable regression model. Results: The median age of the 301 cases investigated was 47 years and 97% of cases were symptomatic. The most common clinical signs were asthenia/fatigue (75.7%), cough (58.3%), fever (58.3%), headache (52.1%) and rhinorrhea (50.7%). Twelve cases were hospitalized, and 27.1% reported risk factors. No admissions to intensive care and no deaths were reported. Vaccination status was available for 292 cases, 20.9% were unvaccinated, 1.4% had received one dose, 38.3% two doses and 39.4% three doses. Cases presenting at least one risk factor were almost seventeen times more likely to be hospitalized than those with no risk factors (aRR = 16.72 [95% CI2.59-326.86]). Conclusion: Despite the longer duration of and the differences in symptoms and their possible immune escape, BA.4/BA.5 Omicron sub-lineages globally showed no severe clinical presentation. The presence of at least one risk factor for severe disease significantly increased the risk of hospitalization for those infected with BA.4 or BA.5.

Dynamics of SARS-CoV-2 lineages in French Guiana in 2020-2021: 4 epidemic waves with cross-influences from Europe and South America.

Since the first cases of SARS-CoV-2 infection in Wuhan in December 2019, this RNA virus gave rise to different viral lineages with different virological, epidemiological and immunological properties. Here we describe the dynamics of circulation of SARS-CoV-2 lineages in an Amazonian South American French overseas territory, French Guiana (FG). The data analyzed are based on the general epidemic course, and genomic surveillance data come from whole genome sequencing (WGS) as well as typing PCRs. From March 2020 to October 2021, four COVID-19 epidemic waves were observed in FG with an evolution of viral lineages influenced by virus introductions from continental France and above all by land-based introductions from neighbouring countries. The third epidemic wave from March to June 2021 was driven by a predominant Gamma introduced from Brazil and a less frequent Alpha introduced from France. This coexistence was completely substituted by Delta that initiated the fourth epidemic wave.

Bronchiolitis epidemics in France during the SARS-CoV-2 pandemic: The 2020-2021 and 2021-2022 seasons.

OBJECTIVES: We described bronchiolitis epidemics during the 2020-2021 and 2021-2022 seasons in France and their interaction with the COVID outbreak. PATIENTS AND METHODS: Data on family physician (FP) visits, emergency department (ED) visits, hospitalizations for bronchiolitis for children˂2 years, and hospital virological data were analyzed and compared with previous seasons (2015-2020). RESULTS: The 2020-2021 epidemic arrived very late, and its impact was lower than in previous seasons (2015-2020) (FP visits: -23%, ED visits: -38%, and hospitalizations: -30%). The 2021-2022 epidemic started early (week 40) and lasted for a relatively long time (13 weeks). The impact was higher than in 2015-2020 (FP visits: +13%, ED visits: +34%, hospitalizations: +28%). CONCLUSION: Findings from the 2020-2021 epidemic may be linked to the implementation of non-pharmaceutical COVID-19 prevention measures. For 2021-2022, findings may be linked to an "immunity debt" resulting from the lower impact of the previous season.

Antibody escape and global spread of SARS-CoV-2 lineage A.27.

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.

A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study.

OBJECTIVES: In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant. METHODS: Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown. RESULTS: From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006). CONCLUSION: We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.

Prospective evaluation of ID NOW COVID-19 assay used as point-of-care test in an emergency department.

BACKGROUND: Rapid testing for COVID-19 has been clearly identified as an essential component of the strategy to control the SARS-CoV-2 epidemic, worldwide. The ID NOW COVID-19 assay is a simple, user-friendly, rapid molecular biology test based on nicking and extension amplification reaction (NEAR). OBJECTIVES: The aim of this study was to evaluate the ID NOW COVID-19 assay when used as a point-of-care test (POCT) in our Emergency Department (ED). TYPE OF STUDY: This prospective study enrolled 395 consecutive patients; paired nasopharyngeal swabs were collected from each study participant. The first swab was tested with the ID NOW COVID-19 assay at the point-of-care by ED nurses. The second swab was diluted in viral transport medium (VTM) and sent to the clinical microbiology department for analysis by both the RT-PCR Simplexa test COVID-19 Direct assay as the study reference method, and the ID NOW COVID-19 assay performed in the laboratory. RESULTS: Nasopharyngeal swabs directly tested with the ID NOW COVID-19 assay yielded a sensitivity, specificity, PPV and NPV of 98.0%, 97.5%, 96.2% and 98.7%, respectively, in comparison with the RT-PCR study reference assay. When the ID NOW COVID-19 assay was performed in the laboratory using the VTM samples, the sensitivity decreased to 62.5% and the NPV to 79.7%. Three false negative test results were reported with the ID NOW COVID-19 assay when performed using undiluted swabs directly in the ED; these results were obtained from patients with elevated CT values (> 30). CONCLUSION: We demonstrated that the ID NOW COVID-19 assay, performed as a point of care test in the ED using dry swabs, provides a rapid and reliable alternative to laboratory-based RT-PCR methods.

A Comprehensive Evaluation of GeneLEAD VIII DNA Platform Combined to Deeplex Myc-TB® Assay to Detect in 8 Days Drug Resistance to 13 Antituberculous Drugs and Transmission of Mycobacterium tuberculosis Complex Directly From Clinical Samples.

The GeneLEAD VIII (Diagenode, Belgium) is a new, fully automated, sample-to-result precision instrument for the extraction of DNA and PCR detection of Mycobacterium tuberculosis complex (MTBC) directly from clinical samples. The Deeplex Myc-TB® assay (Genoscreen, France) is a diagnostic kit based on the deep sequencing of a 24-plexed amplicon mix allowing simultaneously the detection of resistance to 13 antituberculous (antiTB) drugs and the determination of spoligotype. We evaluated the performance of a strategy combining the both mentioned tools to detect directly from clinical samples, in 8 days, MTBC and its resistance to 13 antiTB drugs, and identify potential transmission of strains from patient-to-patient. Using this approach, we screened 112 clinical samples (65 smear-negative) and 94 MTBC cultured strains. The sensitivity and the specificity of the GeneLEAD/Deeplex Myc-TB approach for MTBC detection were 79.3% and 100%, respectively. One hundred forty successful Deeplex Myc-TB results were obtained for 46 clinical samples and 94 strains, a total of 85.4% of which had a Deeplex Myc-TB susceptibility and resistance prediction consistent with phenotypic drug susceptibility testing (DST). Importantly, the Deeplex Myc-TB assay was able to detect 100% of the multidrug-resistant (MDR) MTBC tested. The lowest concordance rates were for pyrazinamide, ethambutol, streptomycin, and ethionamide (84.5%, 81.5%, 73%, and 55%, respectively) for which the determination of susceptibility or resistance is generally difficult with current tools. One of the main difficulties of Deeplex Myc-TB is to interpret the non-synonymous uncharacterized variants that can represent up to 30% of the detected single nucleotide variants. We observed a good level of concordance between Deeplex Myc-TB-spoligotyping and MIRU-VNTR despite a lower discriminatory power for spoligotyping. The median time to obtain complete results from clinical samples was 8 days (IQR 7-13) provided a high-throughput NGS sequencing platform was available. Our results highlight that the GeneLEAD/Deeplex Myc-TB approach could be a breakthrough in rapid diagnosis of MDR TB in routine practice.

Impact of original, B.1.1.7, and B.1.351/P.1 SARS-CoV-2 lineages on vaccine effectiveness of two doses of COVID-19 mRNA vaccines: Results from a nationwide case-control study in France.

BACKGROUND: We aimed to assess the effectiveness of two doses of mRNA COVID-19 vaccines against COVID-19 with the original virus and other lineages circulating in France. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults with onset of symptoms between 14 February and 3 May 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire on recent activity-related exposures and vaccination history. Information about the infecting virus was based on a screening RT-PCR for either B.1.1.7 or B.1.351/P.1 variants. FINDINGS: Included in our analysis were 7 288 adults infected with the original SARS-CoV-2 virus, 31 313 with the B.1.1.7 lineage, 2 550 with B.1.351/P1 lineages, and 3 644 controls. In multivariable analysis, the vaccine effectiveness (95% confidence interval) seven days after the second dose of mRNA vaccine was estimated at 88% (81-92), 86% (81-90) and 77% (63-86) against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Recent (2 to 6 months) history of virologically confirmed SARS-CoV-2 infection was found to be 83% (76-88), 88% (85-91) and 83% (71-90) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively; and more distant (> 6 months) infections were 76% (54-87), 84% (75-90), and 74% (41-89) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. INTERPRETATION: In real-life settings, two doses of mRNA vaccines proved to be effective against COVID-19 with the original virus, B.1.1.7 lineage and B.1.351/P.1 lineages. FUNDING: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance "Tous unis contre le virus").

Lessons learned from the investigation of a COVID-19 cluster in Creil, France: effectiveness of targeting symptomatic cases and conducting contact tracing around them.

BACKGROUND: This study presents the methods and results of the investigation into a SARS-CoV-2 outbreak in a professional community. Due to the limited testing capacity available in France at the time, we elaborated a testing strategy according to pre-test probability. METHODS: The investigation design combined active case finding and contact tracing around each confirmed case with testing of at-risk contact persons who had any evocative symptoms (n = 88). One month later, we performed serology testing to test and screen symptomatic and asymptomatic cases again (n = 79). RESULTS: Twenty-four patients were confirmed (14 with RT-PCR and 10 with serology). The attack rate was 29% (24/83). Median age was 40 (24 to 59), and the sex ratio was 15/12. Only three cases were asymptomatic (= no symptoms at all, 13%, 95% CI, 3-32). Nineteen symptomatic cases (79%, 95% CI, 63-95) presented a respiratory infection, two of which were severe. All the RT-PCR confirmed cases acquired protective antibodies. Median incubation was 4 days (from 1 to 13 days), and the median serial interval was 3 days (0 to 15). We identified pre-symptomatic transmission in 40% of this cluster, but no transmission from asymptomatic to symptomatic cases. CONCLUSION: We report the effective use of targeted testing according to pre-test probability, specifically prioritizing symptomatic COVID-19 diagnosis and contact tracing. The asymptomatic rate raises questions about the real role of asymptomatic infected people in transmission. Conversely, pre-symptomatic contamination occurred frequently in this cluster, highlighting the need to identify, test, and quarantine asymptomatic at-risk contact persons (= contact tracing). The local lockdown imposed helped reduce transmission during the investigation period.

Prior infection by seasonal coronaviruses, as assessed by serology, does not prevent SARS-CoV-2 infection and disease in children, France, April to June 2020.

BackgroundChildren have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections.AimWe tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection.MethodsWe set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36). SARS-CoV-2 antibodies directed against the nucleoprotein (N) and S1 and S2 domains of the spike (S) proteins were monitored by an in-house luciferase immunoprecipitation system assay. We randomly selected 69 SARS-CoV-2-seropositive patients (including 15 with MIS) and 115 matched SARS-CoV-2-seronegative patients (controls (CTL)). We measured antibodies against SARS-CoV-2 and HCoV as evidence for prior corresponding infections and assessed if SARS-CoV-2 prevalence of infection and levels of antibody responses were shaped by prior seasonal coronavirus infections.ResultsPrevalence of HCoV infections were similar in HOS, MIS and CTL groups. Antibody levels against HCoV were not significantly different in the three groups and were not related to the level of SARS-CoV-2 antibodies in the HOS and MIS groups. SARS-CoV-2 antibody profiles were different between HOS and MIS children.ConclusionPrior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.

Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.