Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19.

BACKGROUND: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days. METHODS: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183. RESULTS: A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group. CONCLUSIONS: A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).

Association between humoral serological markers levels and risk of SARS-CoV-2 infection after the primary COVID-19 vaccine course among ANRS0001S COV-POPART cohort participants.

BACKGROUND: We assessed the prognostic value of serological humoral markers measured one month after the last dose of the primary COVID-19 vaccine course for predicting the risk of severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection over the following six months in specific populations. METHODS: ANRS0001SCOV-POPART is a French nationwide multicenter prospective observational cohort study assessing the immune response to Covid-19 vaccines routinely administered to 11 subgroups of patients with chronic disease and a control group. Participants from the ANRS0001S COV-POPART were included if they received at least two doses of Covid-19 vaccine for the primary vaccine course, had measurements of anti-Spike, anti-receptor binding domain (RBD) IgG-specific or neutralizing antibodies one month after the end of the primary vaccine course, without being infected by SARS-CoV-2 before the measurement. SARS-CoV-2 infections defined by a positive PCR/antigenic test or seroconversion to detectable anti nucleocapsid antibodies were evaluated until the first COVID-19 booster injection. Cox proportional hazards models taking into account interval-censored data were implemented to estimate the association between each antibody level and the risk of SARS-CoV-2 infection. Predictive performances were evaluated by the area under the receiving operating characteristic curve (AUROC). RESULTS: Two thousand five hundred seventy adults from a specific population and 1,123 from the control group were included. The cumulative probabilities of SARS-CoV-2 infections at five months after serological measurement were 6.0% 95% confidence interval: [5.0; 7.9] and 10.1% 95% confidence interval: [8.3; 11.9], respectively. Higher levels of anti-Spike IgG antibody were associated with a lower risk of SARS-CoV-2 infections in the control group, but not in the specific populations. Among the specific populations, AUROC were 74.5%, 74.9%, and 72.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. AUROC were superior in the specific populations, 82.0%, 81.2%, and 81.4% for anti-Spike IgG, anti-RBD IgG, and neutralizing antibodies, respectively. CONCLUSIONS: Vaccine-induced antibody response after the primary course of Covid-19 infection only moderately discriminated between participants developing a SARS-CoV-2 infection during the Omicron wave. TRIAL REGISTRATION: NCT04824651 (first posted: 2021-04-01).

T Cell Immunogenicity, Gene Expression Profile, and Safety of Four Heterologous Prime-Boost Combinations of HIV Vaccine Candidates in Healthy Volunteers: Results of the Randomized Multi-Arm Phase I/II ANRS VRI01 Trial.

Heterologous prime-boost strategies are of interest for HIV vaccine development. The order of prime-boost components could be important for the induction of T cell responses. In this phase I/II multi-arm trial, three vaccine candidates were used as prime or boost: modified vaccinia Ankara (MVA) HIV-B (coding for Gag, Pol, Nef); HIV LIPO-5 (five lipopeptides from Gag, Pol, Nef); DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, Env gp160 clade B). Healthy human volunteers (n = 92) were randomized to four groups: 1) MVA at weeks 0/8 + LIPO-5 at weeks 20/28 (M/L); 2) LIPO-5 at weeks 0/8 + MVA at weeks 20/28 (L/M); 3) DNA at weeks 0/4/12 + LIPO-5 at weeks 20/28 (G/L); 4) DNA at weeks 0/4/12 + MVA at weeks 20/28 (G/M). The frequency of IFN-γ-ELISPOT responders at week 30 was 33, 43, 0, and 74%, respectively. Only MVA-receiving groups were further analyzed (n = 62). Frequency of HIV-specific cytokine-positive (IFN-γ, IL-2, or TNF-α) CD4+ T cells increased significantly from week 0 to week 30 (median change of 0.06, 0.11, and 0.10% for M/L, L/M, and G/M, respectively), mainly after MVA vaccinations, and was sustained until week 52. HIV-specific CD8+ T cell responses increased significantly at week 30 in M/L and G/M (median change of 0.02 and 0.05%). Significant whole-blood gene expression changes were observed 2 wk after the first MVA injection, regardless of its use as prime or boost. An MVA gene signature was identified, including 86 genes mainly related to cell cycle pathways. Three prime-boost strategies led to CD4+ and CD8+ T cell responses and to a whole-blood gene expression signature primarily due to their MVA HIV-B component.

Challenges in conducting efficacy trials for new COVID-19 vaccines in developed countries.

The protection from COVID-19 vaccination wanes a few months post-administration of the primary vaccination series or booster doses. New COVID-19 vaccine candidates aiming to help control COVID-19 should show long-term efficacy, allowing a possible annual administration. Until correlates of protection are strongly associated with long-term protection, it has been suggested that any new COVID-19 vaccine candidate must demonstrate at least 75% efficacy (although a 40%-60% efficacy would be sufficient) at 12 months in preventing illness in all age groups within a large randomized controlled efficacy trial. This article discusses four of the many scientific, ethical, and operational challenges that these trials will face in developed countries, focusing on a pivotal trial in adults. These challenges are (1) the comparator and trial population; (2) how to enroll sufficient numbers of adult participants of all age groups considering that countries will recommend COVID-19 booster doses to different populations; (3) whether having access to a comparator booster for the trial is actually feasible; and (4) the changing epidemiology of severe acute respiratory syndrome coronavirus 2 across countries involved in the trial. It is desirable that regulatory agencies publish guidance on the requirements that a trial like the one discussed should comply with to be acceptable from a regulatory standpoint. Ideally, this should happen even before there is a vaccine candidate that could fulfill the requirements mentioned above, as it would allow an open discussion among all stakeholders on its appropriateness and feasibility.

Striking differences in weight gain after cART initiation depending on early or advanced presentation: results from the ANRS CO4 FHDH cohort.

BACKGROUND: Many studies have reported weight gain in ART-naive people living with HIV (PWH) initiating an integrase strand-transfer inhibitor-based regimen. We studied the impact of early or advanced presentation and that of individual drugs in PWH initiating combined ART (cART) between 2012 and 2018. METHODS: From the French Hospital Database HIV cohort, we assessed factors associated with a weight gain  ≥10%, weight change after cART initiation or BMI increase  ≥5 kg/m2 up to 30 months. The analyses were conducted overall, and among PWH with early (primary infection or CD4 >350/mm3 and viral load  <100 000 copies/mL, without AIDS) and advanced presentation (AIDS or CD4 <200/mm3, not during primary infection). RESULTS: At 30 months, 34.5% (95% CI: 33.5-35.6) of the 12 773 PWH had a weight gain ≥10%, with 20.9% (95% CI: 19.6-22.2) among the 5794 with early presentation and 63.1% (95% CI: 60.9-65.3) among the 3106 with advanced presentation. Weight gain was 2.8 kg (95% CI: 2.0-3.7) for those with early presentation and 9.7 kg (95% CI: 8.4-11.1) for those with advanced presentation. Most weight gain occurred in the first 12 months. Underweight and obese PWH were at significantly higher risk of a BMI increase  ≥5 kg/m2 than normal-weight PWH. Results differed within classes and by outcome. Raltegravir and dolutegravir were consistently associated with greater weight gain than the other third agents. Tenofovir alafenamide was also associated with higher weight gain than tenofovir disoproxil or abacavir. CONCLUSIONS: After initiating cART, PWH with early presentation exhibited a small weight gain, whereas it was large among those with advanced presentation. The choice of ART should account for the risk of weight gain, especially for PWH who present with advanced disease and/or are obese.

Impact of corticosteroids use on midterm sequelae in survivors of COVID-19 admitted to hospital: A prospective cohort study.

An understanding of the midterm sequelae in COVID-19 and their association with corticosteroids use are needed. Between March and July 2020, we evaluated 1227 survivors of COVID-19, 3 months posthospitalization, of whom 213 had received corticosteroids within 7 days of admission. Main outcome was any midterm sequelae (oxygen therapy, shortness of breath, one major clinical sign, two minor clinical signs or three minor symptoms). Association between corticosteroids use and midterm sequelae was assessed using inverse propensity-score weighting models. Our sample included 753 (61%) male patients, and 512 (42%) were older than 65 years. We found a higher rate of sequelae among users than nonusers of corticosteroids (42% vs. 35%, odds ratio [OR] 1.40 [1.16-1.69]). Midterm sequelae were more frequent in users of low-dose corticosteroids than nonusers (64% vs. 51%, OR 1.60 [1.10-2.32]), whereas no association between higher doses (≥20 mg/day equivalent of dexamethasone) and sequelae was evidenced (OR 0.95 [0.56-1.61]). Higher risk of sequelae with corticosteroids use was observed among subjects with propensity score below the 90th percentile. Our study suggest that corticosteroids use during hospitalization for COVID-19 is associated with higher risk of midterm sequelae.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021.

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022.

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

In-hospital and midterm post-discharge complications of adults hospitalised with respiratory syncytial virus infection in France, 2017-2019: an observational study.

OBJECTIVES: The purpose of this study was to describe the clinical characteristics and in-hospital and post-discharge outcomes of respiratory syncytial virus (RSV) infection among adults hospitalised with influenza-like illness (ILI) and compared against patients admitted for influenza. METHODS: Adults hospitalised with ILI were prospectively included from five French university hospitals over two consecutive winter seasons (2017/2018 and 2018/2019). RSV and influenza virus were detected by multiplex reverse transcription PCR on nasopharyngeal swabs. RSV-positive patients were compared to RSV-negative and influenza-positive hospitalised patients. Poisson regression models were used to estimate the adjusted prevalence ratio (aPR) associated with in-hospital and post-discharge outcomes between RSV and influenza infections. The in-hospital outcome was a composite of the occurrence of at least one complication, length of stay ≥7 days, intensive care unit admission, use of mechanical ventilation and in-hospital death. Post-discharge outcome included 30- and 90-day all-cause mortality and 90-day readmission rates. RESULTS: Overall, 1428 hospitalised adults with ILI were included. RSV was detected in 8% (114 of 1428) and influenza virus in 31% (437 of 1428). Patients hospitalised with RSV were older than those with influenza (mean age 73.0 versus 68.8 years, p=0.015) with a higher frequency of chronic respiratory or cardiac disease (52% versus 39%, p=0.012, and 52% versus 41%, p=0.039, respectively) and longer hospitalisation duration (median stay 8 versus 6 days, p<0.001). Anti-influenza therapies were less prescribed among RSV patients than influenza patients (20% versus 66%, p<0.001). In-hospital composite outcome was poorer in RSV patients (aPR 1.5, 95% CI 1.1-2.1) than in those hospitalised with influenza. No difference was observed for the post-discharge composite outcome (aPR 1.1, 95% CI 0.8-1.6). CONCLUSION: RSV infection results in serious respiratory illness, with worse in-hospital outcomes than influenza and with similar midterm post-discharge outcomes.

Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens for T cell responses requires three DNA injections. Results of the randomized multicentre EV03/ANRS VAC20 Phase I/II Trial.

DNA vectors have been widely used as a priming of poxvirus vaccine in prime/boost regimens. Whether the number of DNA impacts qualitatively or quantitatively the immune response is not fully explored. With the aim to reinforce T-cell responses by optimizing the prime-boost regimen, the multicentric EV03/ANRS VAC20 phase I/II trial, randomized 147 HIV-negative volunteers to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n = 74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n = 73) groups. T-cell responses (IFN-γ ELISPOT) to at least one peptide pool were higher in the 3xDNA than the 2xDNA groups (91% and 80% of vaccinees) (P = 0.049). In the 3xDNA arm, 26 (37%) recipients developed a broader T-cell response (Env plus at least to one of the Gag, Pol, Nef pools) than in the 2xDNA (15; 22%) arms (primary endpoint; P = 0.047) with a higher magnitude against Env (at week 26) (P<0.001). In both groups, vaccine regimens induced HIV-specific polyfunctional CD4 and CD8 T cells and the production of Th1, Th2 and Th17/IL-21 cytokines. Antibody responses were also elicited in up to 81% of vaccines. A higher percentage of IgG responders was noted in the 2xDNA arm compared to the 3xDNA arm, while the 3xDNA group tended to elicit a higher magnitude of IgG3 response against specific Env antigens. We show here that the modulation of the prime strategy, without modifying the route or the dose of administration, or the combination of vectors, may influence the quality of the responses.

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.

Replacing vaccine paper package inserts: a multi-country questionnaire study on the acceptability of an electronic replacement in different target groups.

BACKGROUND: In the European Union it is mandatory to include paper package leaflets (PPL) with all medicines, including vaccines, to inform the recipient. However, it is difficult to meet the necessity for localized PPLs in each of the 24 official European languages. Replacing PPLs with electronic versions offers many advantages including redistribution across nations, reduced storage space, accessibility by the visually impaired, easily updated information or the addition of video content. We wanted to assess the attitudes of patients (vaccine recipients or their parents) to the potential of replacing PPL with electronic versions. METHODS: We surveyed vaccinees or their parents in four European countries-Belgium, Italy, Bulgaria and France-for their actual use of vaccine PPLs and their opinions about switching to an electronic package leaflet. Our survey was conducted online because of the COVID-19 pandemic and resulted in 2518 responses to a questionnaire targeted at three specific groups with particular information needs: parents of young children, pregnant women and the elderly (≥ 60 years). RESULTS: Our main findings are that currently vaccine PPLs are rarely used and frequently unavailable for the vaccinee. Across the four countries surveyed 55-82% of vaccinees would accept an electronic version, as did 64% when there was an option to request a printout of the leaflet. CONCLUSIONS: We found that switching to electronic versions of vaccine PPLs is an acceptable alternative for the public, potentially increasing the quality and amount of information reaching vaccinees while eliminating some barriers to redistribution of vaccines between countries.

Attitudes about COVID-19 Lockdown among General Population, France, March 2020.

Because the effectiveness of a coronavirus disease lockdown in curbing coronavirus disease spread depends on public support, acquiring real-time information about the way populations reacted to the lockdown is crucial. In France, such public support remained fragile among low-income persons, probably because the lockdown exacerbated preexisting social inequalities and conflicts.

Multiple sclerosis: Is there a risk of worsening after yellow fever vaccination?

BACKGROUND: Yellow fever vaccine (YFV) is not advised for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses. OBJECTIVE: To assess the risk of relapsing-remitting multiple sclerosis (RR-MS) worsening after YFV. METHODS: Non-interventional observational retrospective, exposed/non-exposed cohort study nested in the French national cohort including MS. RESULTS: 128 RR-MS were included. The 1-year annualized relapse rate (ARR) following YFV did not differ between exposed: 0.219 (0.420) and non-exposed subjects: 0.208 (0.521) (p = 0.92). Time to first relapse was not different between groups (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI) = 0.53-3.30, p = 0.54). CONCLUSION: These results suggest that YFV does not worsen the course of RR-MS.

Effect of Internet use for searching information on vaccination on the uptake of human papillomavirus vaccine in France: A path-analysis approach.

Internet is a popular source of information regarding vaccination. This study aimed to determine whether there is a negative association between Internet use among French vaccine-hesitant mothers and HPV vaccine uptake by their daughters, and to gain insight into the pathways that would link Internet use to the lack of HPV vaccine uptake. We conducted a pooled cross-sectional analysis across the 2015, 2016, 2017 and 2018 Vaccinoscopie® Survey. Multivariate logistic regression and path models were used in the analysis. The study sample included a total of 2038 respondent mothers. Of those, 89 (4.4%) declared having never been in the situation of searching for information regarding a vaccination they had hesitated about, leaving 1949 mothers for the present analysis. Approximately 24% (466/1949) of the mothers declared using the Internet as a source of vaccine information. In multivariate logistic regression adjusted for physician recommendation of HPV vaccination, attitudes towards vaccines in general, perception of HPV vaccine usefulness, maternal level of education, region of residence, and the survey year, the use of Internet by the mothers was significantly associated with a lower HPV vaccination among their daughters (adjusted odds ratio (aOR), 0.66; 95% confidence interval (CI), 0.47-0.91). Path analysis further confirmed the negative effect of Internet use (ß = -0.10, standard error (SE) = 0.02, P < 0.0001), highlighting how the Internet plays a detrimental role in HPV vaccine uptake through a lower perceived level of HPV vaccine usefulness, a lower perceived level of information on childhood vaccination, and unfavorable attitudes towards vaccination in general.

Non-influenza respiratory viruses in adult patients admitted with influenza-like illness: a 3-year prospective multicenter study.

PURPOSE: To describe the burden, and characteristics, of influenza-like illness (ILI) associated with non-influenza respiratory viruses (NIRV). METHODS: We performed a prospective, multicenter, observational study of adults admitted with ILI during three influenza seasons (2012-2015). Patients were screened for picornavirus, respiratory syncytial virus (RSV), coronavirus, human metapneumovirus, adenovirus, bocavirus, parainfluenza virus, and influenza, by PCR on nasopharyngeal samples. We excluded patients coinfected with NIRV and influenza. RESULTS: Among 1421 patients enrolled, influenza virus was detected in 535 (38%), and NIRV in 215 (15%), mostly picornavirus (n = 61), RSV (n = 53), coronavirus 229E (n = 48), and human metapneumovirus (n = 40). In-hospital mortality was 5% (NIRV), 4% (influenza), and 5% (no respiratory virus). As compared to influenza, NIRV were associated with age (median, 73 years vs. 68, P = 0.026), chronic respiratory diseases (53% vs. 45%, P = 0.034), cancer (14% vs. 9%, P = 0.029), and immunosuppressive drugs (21% vs. 14%, P = 0.028), and inversely associated with diabetes (18% vs. 25%, P = 0.038). On multivariable analysis, only chronic respiratory diseases (OR 1.5 [1.1-2.0], P = 0.008), and diabetes (OR 0.5 [0.4-0.8], P = 0.01) were associated with NIRV detection. CONCLUSIONS: NIRV are common in adults admitted with ILI during influenza seasons. Outcomes are similar in patients with NIRV, influenza, or no respiratory virus.

The French general population's attitudes toward lockdown against COVID-19: a fragile consensus.

BACKGROUND: In March 2020, as the coronavirus disease 2019 (COVID- 19) pandemic was spreading across the globe, many countries have implemented unprecedented lockdown measures. But how populations did react to these measures? We examined the case of France. Our aims were threefold: assessing some aspects of their impact on French's daily living conditions; investigating their attitudes toward the lockdown; investigating the factors associated with these attitudes. METHODS: A cross-sectional online survey was carried out 10 days after the nationwide lockdown (from March 27th to March 29th 2020), among a representative sample of the mainland French population aged 18 and over. A quota sampling method was applied to achieve a sample of 1012 respondents. We used a cluster analysis to obtain contrasted attitudinal profiles, and logistic regressions to investigated which factors were associated to these profiles. RESULTS: After 10 days of lockdown, there were already significant consequences regarding respondents' living conditions and mental health. Most respondents supported the current lockdown. However, it appeared as a stopgap measure due to a lack of alternatives, and a large majority acknowledged its heavy drawbacks. We found three contrasted attitudinal profiles: full support (38%), strong but critical support (31%), limited support (31%). Regarding respondents' SES, low-income and low-education respondents were more likely to display critical or limited support to the lockdown, as well as those who reported deteriorated living conditions or psychological distress. CONCLUSIONS: In France, the large public support to the lockdown was fragile. First, it was a critical consensus anchored in current controversies and recent social struggles. Second, it was weaker among people with a lows SES, especially since the lockdown have exacerbated preexisting social inequalities.

Immunogenicity and Safety of 3 Formulations of a Respiratory Syncytial Virus Candidate Vaccine in Nonpregnant Women: A Phase 2, Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of respiratory tract illness and hospitalization in neonates and infants. RSV vaccination during pregnancy may protect offspring in their first months of life. METHODS: This randomized, observer-blind, multicenter, phase 2 study evaluated the immunogenicity and safety of an RSV candidate vaccine in healthy nonpregnant women aged 18-45 years. Four hundred participants were randomized (1:1:1:1) to receive a single intramuscular dose of vaccine containing 30 µg, 60 µg, or 120 µg of RSV fusion protein engineered to preferentially maintain a prefusion conformation (RSV-PreF vaccine) or placebo. RESULTS: Thirty days postvaccination, RSV-A neutralizing antibody geometric mean titers (GMTs) increased 3.75-, 4.42- and 4.36-fold; RSV-B neutralizing antibody GMTs 2.36-, 2.54- and 2.76-fold; and palivizumab competing antibody (PCA) concentrations 11.69-, 14.38- and 14.24-fold compared with baseline levels in the 30 µg, 60 µg, and 120 µg RSV-PreF groups, respectively. Antibody titers and PCA concentrations at day 30 were significantly higher with the 120 µg compared to the 30 µg RSV-PreF vaccine. All RSV-PreF vaccine formulations and the placebo had similar reactogenicity profiles. No serious adverse events were considered to be related to the RSV-PreF vaccine. CONCLUSIONS: The 3 formulations of the investigational RSV-PreF vaccine were well-tolerated and induced RSV-A and RSV-B neutralizing antibodies and PCAs in healthy, nonpregnant women. CLINICAL TRIALS REGISTRATION: NCT02956837.

Influenza epidemiology and influenza vaccine effectiveness during the 2015-2016 season: results from the Global Influenza Hospital Surveillance Network.

BACKGROUND: The Global Influenza Hospital Surveillance Network is an international platform whose primary objective is to study severe cases of influenza requiring hospitalization. METHODS: During the 2015-2016 influenza season, 11 sites in the Global Influenza Hospital Surveillance Network in nine countries (Russian Federation, Czech Republic, Turkey, France, China, Spain, Mexico, India, and Brazil) participated in a prospective, active-surveillance, hospital-based epidemiological study. Influenza infection was confirmed by reverse transcription-polymerase chain reaction. Influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza was estimated using a test-negative approach. RESULTS: 9882 patients with laboratory results were included of which 2415 (24.4%) were positive for influenza, including 1415 (14.3%) for A(H1N1)pdm09, 235 (2.4%) for A(H3N2), 180 (1.8%) for A not subtyped, 45 (0.5%) for B/Yamagata-lineage, 532 (5.4%) for B/Victoria-lineage, and 33 (0.3%) for B not subtyped. Of included admissions, 39% were < 5 years of age and 67% had no underlying conditions. The odds of being admitted with influenza were higher among pregnant than non-pregnant women (odds ratio, 2.82 [95% confidence interval (CI), 1.90 to 4.19]). Adjusted IVE against influenza-related hospitalization was 16.3% (95% CI, 0.4 to 29.7). Among patients targeted for influenza vaccination, adjusted IVE against hospital admission with influenza was 16.2% (95% CI, - 3.6 to 32.2) overall, 23.0% (95% CI, - 3.3 to 42.6) against A(H1N1)pdm09, and - 25.6% (95% CI, - 86.3 to 15.4) against B/Victoria lineage. CONCLUSIONS: The 2015-2016 influenza season was dominated by A(H1N1)pdm09 and B/Victoria-lineage. Hospitalization with influenza often occurred in healthy and young individuals, and pregnant women were at increased risk of influenza-related hospitalization. Influenza vaccines provided low to moderate protection against hospitalization with influenza and no protection against the predominant circulating B lineage, highlighting the need for more effective and broader influenza vaccines.