Prior COVID-19 Immunization Does Not Cause IgA- or IgG-Dependent Enhancement of SARS-CoV-2 Infection.

Antibody-dependent enhancement (ADE) can increase the rates and severity of infection with various viruses, including coronaviruses, such as MERS. Some in vitro studies on COVID-19 have suggested that prior immunization enhances SARS-CoV-2 infection, but preclinical and clinical studies have demonstrated the contrary. We studied a cohort of COVID-19 patients and a cohort of vaccinated individuals with a heterologous (Moderna/Pfizer) or homologous (Pfizer/Pfizer) vaccination scheme. The dependence on IgG or IgA of ADE of infection was evaluated on the serum samples from these subjects (twenty-six vaccinated individuals and twenty-one PCR-positive SARS-CoV-2-infected patients) using an in vitro model with CD16- or CD89-expressing cells and the Delta (B.1.617.2 lineage) and Omicron (B.1.1.529 lineage) variants of SARS-CoV-2. Sera from COVID-19 patients did not show ADE of infection with any of the tested viral variants. Some serum samples from vaccinated individuals displayed a mild IgA-ADE effect with Omicron after the second dose of the vaccine, but this effect was abolished after the completion of the full vaccination scheme. In this study, FcγRIIIa- and FcαRI-dependent ADE of SARS-CoV-2 infection after prior immunization, which might increase the risk of severe disease in a second natural infection, was not observed.

Monitoring of Both Humoral and Cellular Immunities Could Early Predict COVID-19 Vaccine Efficacy Against the Different SARS-CoV2 Variants.

Reliable immunoassays are essential to early predict and monitor vaccine efficacy against SARS-CoV-2. The performance of an Interferon Gamma Release Assay (IGRA, QuantiFERON® SARS-CoV-2), and a current anti-spike serological test, compared to a plaque reduction neutralization test (PRNT) taken as gold standard were compared. Eighty vaccinated individuals, whose 16% had a previous history of COVID-19, were included in a longitudinal prospective study and sampled before and two to four weeks after each dose of vaccine. In non-infected patients, 2 doses were required for obtaining both positive IGRA and PRNT assays, while serology was positive after one dose. Each dose of vaccine significantly increased the humoral and cellular response. By contrast, convalescent subjects needed a single dose of vaccine to be positive on all 3 tests. Both IGRA and current serology assay were found predictive of a positive titer of neutralizing antibodies that is correlated with vaccine protection. Patients over 65 or 80 years old had a significantly reduced response. The response tended to be better with the heterologous scheme (vs. homologous) and with the mRNA-1273 vaccine (vs. BNT162b2) in the homologous group, in patients under 55 and under 65 years old, respectively. Finally, decrease intensity or absence of IGRA response and to a less extent of anti-spike serology were also correlated to reinfection which has occurred during the follow up. In conclusion, both IGRA and current anti-spike serology assays could be used at defined thresholds to monitor the vaccine response against SARS-CoV-2 and to simply identify non-responding individuals after a complete vaccination scheme. Two available specific tests (IGRA and anti-spike antibodies) could early assess the vaccine-induced immunity against SARS-CoV-2 at the individual scale, to potentially adapt the vaccination scheme in non-responder patients.

Neutralizing antibodies against SARS-CoV-2 variants following mRNA booster vaccination in adults older than 65 years.

Immune response induced by COVID-19 vaccine booster against delta and omicron variants was assessed in 65 adults (65-84 years old) early aftesr a first booster dose. An increase in SARS-CoV-2 neutralizing antibodies was shown in individuals not previously infected without evidence of an age-related effect, with lower increase in those infected before a single dose of primary vaccination. Of note, humoral response was observed only starting from the 5th day after the boost.

Social conformism and confidence in systems as additional psychological antecedents of vaccination: a survey to explain intention for COVID-19 vaccination among healthcare and welfare sector workers, France, December 2020 to February 2021.

BackgroundThe start of the COVID-19 vaccination campaign among French healthcare and welfare sector workers in January 2021 offered an opportunity to study psychological antecedents of vaccination in this group.AimWe explored whether knowledge and attitude items related to social conformism and confidence in systems contributed to explaining intention for COVID-19 vaccination.MethodsWe developed a knowledge and attitude questionnaire with 30 items related to five established and two hypothetical psychological antecedents of vaccination (KA-7C). The online questionnaire was distributed from 18 December 2020 to 1 February 2021 through chain-referral via professional networks, yielding a convenience sample. We used multivariable logistic regression to explore the associations of individual and grouped KA-7C items with COVID-19 vaccine intention.ResultsAmong 5,234 participants, the vaccine intention model fit (pseudo R-squared values) increased slightly but significantly from 0.62 to 0.65 when adding social conformism and confidence in systems items. Intention to vaccinate was associated with the majority opinion among family and friends (OR: 11.57; 95% confidence interval (CI): 4.51-29.67) and a positive perception of employer's encouragement to get vaccinated (vs negative; OR: 6.41; 95% CI: 3.36-12.22). The strongest association of a knowledge item was identifying the statement 'Some stages of vaccine development (testing) have been skipped because of the epidemic emergency.' as false (OR: 2.36; 95% CI: 1.73-3.22).ConclusionThe results suggest that social conformism and confidence in systems are distinct antecedents of vaccination among healthcare and welfare workers, which should be taken into account in vaccine promotion.

Coadministration of seasonal influenza and COVID-19 vaccines: A systematic review of clinical studies.

The lifting of non-pharmaceutical measures preventing transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources and fears of an increased number of cases of influenza and COVID-19. For the 2021-2022 influenza season, the WHO and >20 European countries promoted coadministration of influenza and COVID-19 vaccines. Recently, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022-2023 influenza vaccination campaign for healthcare professionals and people at risk of severe COVID-19. The present systematic review examines published data on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. The results should reassure vaccinees and vaccinators in case of coadministration and increase vaccine coverage. Healthcare systems promoting coupled campaigns must provide the necessary means for successful coadministration.

The lifting of non-pharmaceutical measures recommended to prevent transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources, already under pressure. It also raises fears of an increase in the number of cases of influenza or COVID-19 infection during the winter season. For the 2021­2022 influenza season, the World Health Organization and several European countries promoted concomitant administration in distinct anatomic sites (i.e., coadministration) of influenza and COVID-19 vaccines to avoid additional stress on healthcare systems. In May 2022, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022­2023 influenza vaccination campaign (i.e., starting COVID-19 vaccination at the date of influenza vaccination) for healthcare professionals and people at risk of severe COVID-19, in case of epidemic wave. Coadministration of influenza and COVID-19 vaccines is one of the factors of success for a coupled campaign. The present systematic review examines all published data (articles or reports, clinical trials, or surveys) on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. The PRISMA method was used to collect information. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. Acceptability and acceptance were good but could be improved. By reassuring vaccinees and vaccinators, these results are expected to favor coadministration and ultimately increase vaccine coverage, thus offering better protection. Healthcare systems promoting coupled campaigns with coadministration must provide the necessary means for their successful implementation.

Midwives' attitudes toward participation of pregnant individuals in a preventive vaccine hypothetical clinical trial.

INTRODUCTION: Pregnant individuals are frequently excluded from clinical trials. Yet, inclusion of Pregnant individuals is of interest in vaccinology including during health crisis. Promotion of clinical trials by midwives may facilitate the decision making of Pregnant individuals. Attitudes of midwives about pregnant individuals participation in a vaccine clinical trial have been little explored. METHODS: We conducted an anonymous survey from the 11th of September to the 11th of November 2020. Primary endpoint was the willingness to encourage Pregnant individuals to participate in a hypothetical respiratory syncytial virus (RSV) vaccine clinical trial. RESULTS: Among 398 midwives who answered the questionnaire, 113 (28.3 %) were likely to encourage Pregnant individuals to participate in the vaccine clinical trial, this proportion ranged from 25 % in senior midwives to 34.5 % among the students. After adjustment on age, parenthood, previous personal attitudes of vaccine hesitancy, and psychological antecedents of vaccinations (5C-model), the only predictor of the promotion of the clinical trial was the experience of vaccine education (evaluated by a 20-point score) with an adjusted odds ratio of 1.09 (1.01-1.18, p = 0.027) for a one-point increase. Vaccine hesitancy and psychological antecedents of vaccinations were not associated with a lower promotion of pregnant individuals trial participation by midwives. CONCLUSION: Few respondents were likely to encourage Pregnant individuals to participate in a vaccine clinical trial. Midwives who considered themselves to have a good training about vaccines were more prone to encourage Pregnant individuals to participate in a RSV vaccine clinical trial.

Factors associated with COVID-19 vaccine uptake among French population aged 65 years and older: results from a national online survey.

BACKGROUND: In France, the increase in COVID-19 vaccine uptake among older adults slowed down between May and June 2021. Using the data from a national survey, we aimed to assess COVID-19 vaccine uptake among French residents aged 65 years and older, particularly at risk of severe form of the infection, and identify factors associated with non-vaccination. METHODS: A cross-sectional online survey collected the immunization status/intention to get the COVID-19 vaccine, reasons for vaccination/non-vaccination and factors potentially associated with vaccine uptake between May 10 and 23, 2021 among a large sample of French residents. Characteristics of participants were compared according to immunization status. Factors potentially associated with non-vaccination were computed into a multivariate logistic regression. RESULTS: Among the 1941 survey participants, 1612 (83%) reported having received at least one dose of COVID-19 vaccine. Among the 329 unvaccinated, 197 (60%) declared having the intention to get vaccinated. Younger age (adjusted odds ratio (aOR) = 1.50; 95% confidence interval (CI), 1.05-2.14), thinking previously having COVID-19 (aOR = 4.01; 95% CI, 2.17-7.40), having suffered economic impact due to the pandemic (aOR = 2.63; 95% CI, 1.71-4.04), reporting an "unsafe" opinion about COVID-19 vaccine safety (aOR = 6.79; 95% CI, 4.50-10.26), reporting an "unsupportive" opinion about vaccination in general (aOR = 4.24; 95% CI, 2.77-6.49) were independent risk factors for non-vaccination. On the other hand, trust in COVID-19 vaccine information delivered by the doctor (aOR = 0.28; 95% CI, 0.16-0.48) and trust in the government's actions (aOR = 0.50; 95% CI, 0.34-0.74) were independent protective factors for non-vaccination. Political affiliation also remained significantly associated with vaccine uptake. CONCLUSIONS: Despite high overall COVID-19 vaccine uptake among the study participants, differences in vaccine uptake according to the level of concerns regarding COVID-19 vaccine safety, socioeconomic profile and trust in the government were observed. Our results reinforce the importance of "reaching out" vaccination strategy that specifically targets the most vulnerable fringe of older adult population.

Management of Long COVID-The CoviMouv' Pilot Study: Importance of Adapted Physical Activity for Prolonged Symptoms Following SARS-CoV2 Infection.

Context: After a COVID-19 infection, some patients have persistent symptoms, the most common is fatigue. To prevent it from becoming chronic (post-COVID-19 syndrome), early management before 3 months could be useful. Exercise and education are recommended. Objective: To assess fatigue in patients with prolonged symptoms after COVID-19 infection and who received a mixed program of remote adapted physical activity and therapeutic education. The secondary objective was to evaluate the efficacy and safety of this training method thanks to aerobic and anaerobic parameters. Methods: "CoviMouv': From Coaching in Visual to Mouv in real" is a nonrandomized controlled pilot study. Patients in telerehabilitation followed 12 remote exercise sessions and 3 therapeutic education workshops. Patients on traditional rehabilitation followed their program with a community-based physiotherapist. Results: Fatigue was reduced after the one-month intervention in both groups (p = 0.010). The majority of aerobic parameters were significantly improved, e.g., maximal oxygen uptake (p = 0.005), walking distance (p = 0.019) or hyperventilation values (p = 0.035). The anaerobic parameter was not improved (p = 0.400). No adverse event was declared. Discussion: Telerehabilitation is a good alternative when a face-to-face program is not possible. This care at an early stage of the disease could help prevent the chronicity of post-COVID-19 symptoms and the installation of vicious circles of physical deconditioning. A larger study would be necessary.

Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial.

Background: Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination. Methods: We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467. Findings: Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 (p < 0·0001). Interpretation: The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic. Funding: French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna.

Que reste-t-il du BCG 100 après ? BCG : 100 years later

Résumé Le BCG a fêté ses 100 ans en juillet 2021, en pleine pandémie de COVID-19, alors qu'une baisse des prises en charge de cas de tuberculose avait lieu suite à la diminution des activités de dépistage à travers le monde. Si le développement vaccinal permet d'envisager un vaccin plus efficace et mieux toléré que le BCG, on peut retenir que celui-ci réduit, lorsqu'il est administré dans l'enfance, le risque de tuberculose maladie mais aussi de mortalité toute cause, notamment dans les pays à faibles revenus. Son impact chez l'adulte reste moins évident. Cependant, l'effet protecteur observé vis-à-vis d'autres pathogènes (pressenti par Calmette lui-même) a conduit à évaluer l'efficacité de la revaccination par le BCG à l’âge adulte.

Que reste-t-il du BCG 100 après ?

Résumé Le BCG a fêté ses 100 ans en juillet 2021, en pleine pandémie de COVID-19, alors qu'une baisse des prises en charge de cas de tuberculose avait lieu suite à la diminution des activités de dépistage à travers le monde. Si le développement vaccinal permet d'envisager un vaccin plus efficace et mieux toléré que le BCG, on peut retenir que celui-ci réduit, lorsqu'il est administré dans l'enfance, le risque de tuberculose maladie mais aussi de mortalité toute cause, notamment dans les pays à faibles revenus. Son impact chez l'adulte reste moins évident. Cependant, l'effet protecteur observé vis-à-vis d'autres pathogènes (pressenti par Calmette lui-même) a conduit à évaluer l'efficacité de la revaccination par le BCG à l’âge adulte. BCG celebrated its 100th birthday in July 2021 in the midst of the COVID-19 pandemic, while a decrease in tuberculosis case management was observed as a direct result of a decrease in screening activities throughout the world. If the vaccine development makes it possible to envisage a more effective and better tolerated vaccine than BCG, we can remember that BCG reduces, in childhood, the risk of tuberculosis disease but also of all-cause mortality, particularly in low-income countries. Its impact in adults remains less clear. However, its ability to protect against other pathogens (anticipated by Calmette himself) has led to an evaluation of the efficacy of revaccination with BCG in adulthood.

Reprint of: Development of vaccines and vaccinal strategies against COVID-19: the information contributing to shared decision-making

The public has many questions about COVID-19 vaccines. The informing of general practitioners and other vaccinators provides healthcare users with clear and reliable information conducive to shared decision-making. While they constitute a bulwark against widespread vaccine hesitancy, informative supports can be tainted by doubt if they are not backed up by solid arguments convincingly addressing the manifold questions and concerns of healthcare users.

Development and Validation of the COVID-19 Knowledges and Behavior Questionnaire in a French Population (CoVQuest-CC).

BACKGROUND: The SARS-CoV-2 pandemic has led most countries to take restrictive measures affecting social activities and individual freedoms to limit viral transmission. It was shown that practical, motivational and social barriers impact on adherence to the isolation and social distancing measures advocated by the health authorities. The purpose of this study was to develop and validate a COVID-19 Knowledges and Behavior Questionnaire adapted to a teenager and adult French population. METHODS: CoVQuest-CC was developed by a multidisciplinary team made of infectious diseases physicians, medical virologist, specialists of infectious control, experts of the questionnaires methodology, experts in public health and prevention, and statisticians. CoVQuest-CC was responded to by a big cohort from the general population during their participation in a massive SARS-CoV-2 screening campaign in 2021 in Saint-Etienne, France. RESULTS: The confirmatory factorial analysis yielded good results (CFI = 0.94, TLI = 0.94, RMSEA = 0.04), and confirmed the five-dimensional structure of the questionnaire. Each dimension had a satisfying internal consistency, with Cronbach alphas of 0.83, 0.71, 0.65, 0.72 and 0.83 for transmission knowledge, barrier gesture respect, tests acceptability, home isolation possibility and test practicability, respectively. CONCLUSIONS: According to our knowledge, CoVQuest-CC is the first validated, consistent and reliable self-administrated French-specific questionnaire investigating the general population's knowledge and attitudes towards COVID-19. It shows acceptable psychometric properties and can be use by Public Health teams or caregivers for public health and research purposes. TRIAL REGISTRATION: The study protocol was approved by the IRB ILE-DE-FRANCE 1 (No. IRB: I ORG0009918). All participants were given written and verbal information about the study and gave informed consent to participate. CLINICALTRIALS: gov identifier (NCT number): NCT04859023.

Prospective evaluation of the point-of-care use of a rapid antigenic SARS-CoV-2 immunochromatographic test in a paediatric emergency department.

OBJECTIVES: This study aimed to evaluate the immunochromatographic coronavirus disease 2019 (COVID-19) speed antigen test (BioSpeedia, France) as an antigen point-of-care test (AgPOCT) to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at the paediatric emergency department of the University Hospital of Saint-Etienne in France. METHODS: Between 15 January and 28 May, 2021, children presenting with respiratory symptoms compatible with COVID-19 infection (symptomatic group) or those requiring hospitalization for any reason (asymptomatic group) were included prospectively and received a nasopharyngeal aspiration to carry out both AgPOCT and quantitative reverse transcription (RT) PCR (RT-qPCR) tests, with the latter being used as the reference standard, for the diagnosis of SARS-CoV-2 infection. RESULTS: Among the 1009 enrolled children, we obtained a result from both techniques for 990: 33 (3.3%) tested positive with AgPOCT and 46 (4.6%) with RT-qPCR. The overall sensitivity and specificity of the AgPOCT were 69.6% (95% confidence interval (CI), 54.3-82.3) and 99.9% (95% CI, 99.4-100), respectively, compared with the RT-qPCR. Sensitivity increased to 82.9% (95% CI, 66.4-93.4) in symptomatic children. The mean cycle threshold value was significantly lower in positive samples for AgPOCT than in negative samples in the overall population and in both the symptomatic and asymptomatic groups. DISCUSSION: The use of the COVID-19 speed antigen test at the bedside in the emergency department has satisfactory performance for diagnosing SARS-CoV-2 infection in symptomatic children.