Serum and Salivary IgG and IgA Response After COVID-19 Messenger RNA Vaccination.

Importance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. Design, Setting, and Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023. Main Outcomes and Measures: An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times. Results: A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2-naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2-naive individuals. After vaccination, SARS-CoV-2-specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10-5 vs 37 × 10-5 at day 29; 107 × 10-5 vs 54 × 10-5 at day 57; and 104 × 10-5 vs 70 × 10-5 at day 180 [P < .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2-naive group increased only at day 57 (36 × 10-5 vs 49 × 10-5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2-naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P < .001). Conclusions and Relevance: The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.

Evaluating the Knowledge of and Behavior Toward COVID-19 and the Possibility of Isolating at a City Level: Survey Study.

BACKGROUND: Mass testing campaigns were proposed in France during the first wave of the COVID-19 pandemic to detect and isolate asymptomatic individuals infected by SARS-CoV-2. During mass testing in Saint-Étienne (February 2021), we performed a survey of the general population. OBJECTIVE: We evaluated, on the scale of a city's population, the literacy level about SARS-CoV-2 transmission, barrier gesture respect, and isolation acceptability or possibility in case of SARS-CoV-2 infection. METHODS: We used the validated CovQuest-CC questionnaire. Data were analyzed and correlated with volunteer characteristics and their SARS-CoV-2 screening results using multivariate analysis. RESULTS: In total, 4707 participants completed the CovQuest-CC questionnaire. Multivariate analysis revealed that female sex was a determinant of a higher score of knowledge about SARS-CoV-2 transmission (adjusted ß coefficient=0.14, 95% CI 0.04-0.23; corrected P=.02). Older ages of 50-59 years (adjusted ß coefficient=0.25, 95% CI 0.19-0.31; corrected P<.001) and ≥60 years (adjusted ß coefficient=0.25, 95% CI 0.15-0.34; corrected P<.001) were determinants of a higher score on barrier gesture respect compared to ages 20-49 years considered as reference. Female sex was also a determinant of a higher score on barrier gesture respect (adjusted ß coefficient=0.10, 95% CI 0.02-4.63; corrected P<.001). The knowledge score was correlated with the score on barrier gesture respect measures (adjusted ß coefficient=0.03, 95% CI 0.001-0.004; corrected P=.001). Older ages of 50-59 years (adjusted ß coefficient=0.21, 95% CI 0.13-0.29; corrected P<.001) and ≥60 years (adjusted ß coefficient=0.25, 95% CI 0.1-0.38; corrected P<.001) were determinants of a higher score on isolation acceptability or possibility compared to the age of 20-49 years considered as reference. Finally, the knowledge score regarding SARS-CoV-2 transmission was significantly associated with a lower risk of RT-PCR (reverse transcriptase-polymerase chain reaction) positivity (adjusted odds ratio 0.80, 95% CI 0.69-0.94; corrected P<.03), implying that a 1-point increase in the knowledge score lowers the risk of positivity by 20% on average. CONCLUSIONS: This study identified factors associated with health literacy regarding SARS-CoV-2 infection in asymptomatic individuals in a large French city's population. We can confirm that in the context of the COVID-19 pandemic, the determinants of better health literacy are not the same as those in other contexts. It seems critical to obtain a more detailed understanding of the determinants of individual citizens' behavior, as part of a strategy to combat the large-scale spread of the virus. The harsh experience of this pandemic should teach us how to nurture research to structure customized interventions to encourage the adoption of ad hoc behaviors to engage citizens in adapting behaviors more favorable to their health.

Proton pump inhibitors and risk of severe COVID-19 in older people.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 is a viral respiratory infection that can cause systemic disorders and lead to death, particularly in older people. Proton pump inhibitors (PPIs) increase the risk of enteric and lung infections. Considering the broad use of PPIs in older people, the potential role of PPIs in COVID-19 could be of dramatic significance. The objective of our study was to evaluate the link between PPIs and severe COVID-19 in older people. METHOD: We performed a retrospective cohort study, including all patients aged ≥65, hospitalised for a diagnosis of COVID-19. Epidemiological, clinical and biological data were extracted and we performed an Inverse Probability of Treatment Weighing method based on a propensity score. RESULTS: From March 2020 to February 2021, a total of 834 patients were included, with a median age of 83 and 52.8% were male. A total of 410 patients had a PPIs prescription, 358 (87.3%) were long-term PPIs-users and 52 (12.7%) were recent PPIs-users. Among PPIs-users, 163 (39.8%) patients developed severe COVID-19 versus 113 (26.7%) in PPIs-non users (odds ratio (OR) = 1.59 [1.18-2.14]; P < 0.05). Moreover, the double dose PPI-users had a higher risk of developing severe COVID-19 (OR = 3.36 [1.17-9.66]; P < 0.05) than the full dose PPI-users (OR = 2.15 [1.22-3.76]; P < 0.05) and the half dose PPI-users (OR = 1.64 [1.13-2.37]; P < 0.05). CONCLUSION: Our study reports evidence that the use of PPIs was associated with an increased risk of severe COVID-19 in older people.

One Hundred Explicit Definitions of Potentially Inappropriate Prescriptions of Antibiotics in Hospitalized Older Patients: The Results of an Expert Consensus Study.

BACKGROUND: In geriatrics, explicit criteria for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. OBJECTIVE: To produce an expert consensus on explicit definitions of antibiotic-PIPs for hospitalized older patients. METHODS: We conducted a Delphi survey involving French experts on antibiotic stewardship in hospital settings. During the survey's rounds, the experts gave their opinion on each explicit definition, and could suggest new definitions. Definitions with a 1-to-9 Likert score of between 7 and 9 from at least 75% of the participants were adopted. The results were discussed during consensus meetings after each round. RESULTS: Of the 155 invited experts, 128 (82.6%) participated in the whole survey: 59 (46%) infectious diseases specialists, 45 (35%) geriatricians, and 24 (19%) other specialists. In Round 1, 65 explicit definitions were adopted and 21 new definitions were suggested. In Round 2, 35 other explicit definitions were adopted. The results were validated during consensus meetings (with 44 participants after Round 1, and 54 after Round 2). CONCLUSIONS: The present study is the first to have provided a list of explicit definitions of potentially inappropriate antibiotic prescriptions for hospitalized older patients. It might help to disseminate key messages to prescribers and reduce inappropriate prescriptions of antibiotics.

Compared Performance of the 2023 Duke-International Society for Cardiovascular Infectious Diseases, 2000 Modified Duke, and 2015 European Society of Cardiology Criteria for the Diagnosis of Infective Endocarditis in a French Multicenter Prospective Cohort.

BACKGROUND: The 2023 Duke-International Society for Cardiovascular Diseases (ISCVID) criteria for infective endocarditis (IE) were proposed as an updated diagnostic classification of IE. Using an open prospective multicenter cohort of patients treated for IE, we compared the performance of these new criteria to that of the 2000 Modified Duke and 2015 European Society of Cardiology (ESC) criteria. METHODS: Cases of patients treated for IE between January 2017 and October 2022 were adjudicated as certain IE or not. Each case was also categorized as either definite or possible/rejected within each classification. Sensitivity, specificity, and accuracy were estimated with 95% confidence intervals. RESULTS: Of the 1194 patients analyzed (mean age, 66.1 years; 71.2% males), 414 (34.7%) had a prosthetic valve and 284 (23.8%) had a cardiac implanted electronic device (CIED); 946 (79.2%) were adjudicated as certain IE; 978 (81.9%), 997 (83.5%), and 1057 (88.5%) were classified as definite IE in the 2000 modified Duke, 2015 ESC, and 2023 Duke-ISCVID criteria, respectively. The sensitivity of each set of criteria was 93.2% (95% confidence interval [CI], 91.6-94.8), 95.0% (95% CI, 93.7-96.4), and 97.6% (95% CI, 96.6-98.6), respectively (P < .001 for all 2-by-2 comparisons). Corresponding specificity rates were 61.3% (95% CI, 55.2-67.4), 60.5% (95% CI, 54.4-66.6), and 46.0% (95% CI, 39.8-52.2), respectively. In patients without CIED, sensitivity rates were 94.8% (95% CI, 93.2-96.4), 96.5% (95% CI, 95.1-97.8), and 97.7% (95% CI, 96.6-98.8); specificity rates were 59.0% (95% CI, 51.6-66.3), 56.6% (95% CI, 49.3-64.0), and 53.8% (95% CI, 46.3-61.2), respectively. CONCLUSIONS: Overall, the 2023 Duke-ISCVID criteria had a significantly higher sensitivity but a significantly lower specificity compared with older criteria. This decreased specificity was mainly attributable to patients with CIED.

Comparing ethanol lock therapy versus vancomycin lock in a salvation strategy for totally implantable vascular access device infections due to coagulase-negative staphylococci (the ETHALOCK study): a prospective double-blind randomized clinical trial.

OBJECTIVES: Little is known about efficacy and safety of ethanol lock therapy (ELT) to treat totally implantable venous access device (TIVAD) infections. The objective of this trial was to evaluate the effectiveness and safety profile of a local treatment with ELT without removal for TIVAD infection due to coagulase-negative staphylococci. METHODS: We performed a prospective, multicenter, double-blind, randomized clinical trial comparing the efficacy of 40% ELT versus vancomycin lock therapy (VLT) in TIVAD infections due to coagulase-negative staphylococci, complicated or not by bloodstream infection. RESULTS: Thirty-one patients were assigned to the ELT group and 30 to the VLT arm. Concomitant bacteremia was present in 41 patients (67.2%). Treatment success was 58.1 % (18 of 31) for the ELT arm and 46.7% (14 of 30) for the VLT arm (p = 0.37). The overall treatment success was 52.5% (32). The risk of treatment failure due to uncontrolled infections, superinfections, and mechanical complications did not differ significantly between participants receiving ELT (13 out of 31 [42%]) and those receiving VLT (16 out of 30 [53%]) with a hazard ratio of 0.70 (p = 0.343; 95% CI [0.34-1.46], Cox model). Catheter malfunctions were significantly more frequent in the ELT arm (11 patients versus 2 in the VLT group, p = 0.01). CONCLUSIONS: We found an overall high rate of treatment failure that did not differ between the ELT arm and the VLT arm. TIVAD removal must be prioritized to prevent complications (uncontrolled infections, superinfections, and catheter malfunctions) except in exceptional situations.

Controlled human infection trials: Legitimacy and conditions of implementation in France.

This round table is the result of an observation. The observation being that controlled human infection clinical trials (also called "infectious challenge" trials or "Controlled Human Infection Models", "CHIM") recommended or even encouraged in the context of vaccine developments in particular, are not carried out in France. However, there are no formal prohibitions within regulations or ethical principles, which point to the prior assessment of risks and benefits for individuals and for society. The participants in this Round Table thus wished to examine, through the prism of their respective disciplines, the scientific and medical relevance of conducting such trials in France and, if possible, to imagine the conditions under which they would be carried out, thus resulting in recommendations on (1) the advisability of their conduct in France (2), the conditions under which they would be implemented in terms of logistics and regulations, and (3) their social acceptability. The recommendations on which the participants of the Round Table came to an agreement are presented as the analysis progresses.

[Vaccination against influenza, pneumococcus and herpes zoster in the elderly Survey of prescribing physicians: assessment of knowledge and identification of obstacles to the prescription of vaccination]. / Vaccination contre la grippe, le pneumocoque et le zona chez les sujets âgés Enquête menée autour des médecins prescripteurs : état des lieux des connaissances et identification des freins à la prescription de la vaccination.

Vaccination coverage is insufficient for influenza, pneumococcus, and herpes zoster in people over the age of 65 in France, even though these are common infectious diseases. Using a computerised questionnaire, the aim of our study was to assess the knowledge of general practitioners, geriatricians, infectious diseases specialists and interns in the Loire region about the vaccination against these three diseases in elderly subjects, to identify the obstacles to vaccination, and to evaluate whether the provision of knowledge modifies the prescriptions and vaccination recommendations made to patients. Of the 125 responses from doctors and interns, 90.2 % are correct for influenza, 69.2 % for pneumococcus, and 32.8 % for herpes zoster, with no significant difference between specialities. By providing information, practitioners are more willing to vaccinate their patients against influenza (99 %), pneumococcus (93 %), and herpes zoster (39 %). The main obstacles to vaccination are the patient's refusal (85 %), the doctor's lack of knowledge and time (70 % and 41 % respectively), doubts about the vaccine's effectiveness (28 %), and fear of side effects (21 %).

Evaluation of intentions to get vaccinated against influenza, COVID 19, pertussis and to get a future vaccine against respiratory syncytial virus in pregnant women.

INTRODUCTION: Pregnant women (PW) are at increased risk of complications due to seasonal influenza and Covid-19. Immunization during pregnancy against pertussis and respiratory syncytial virus (RSV) protects newborns from severe diseases. Our aim was to assess intentions to get vaccinated against seasonal influenza, COVID-19, pertussis and RSV in PW and to identify factors associated with intentions. METHODS: Cross-sectional survey in PW followed at a University Hospital in France assessing their knowledge, and attitudes toward vaccination against influenza, Covid-19, and RSV during pregnancy. Primary outcome was intention to receive each vaccine or potential vaccine. Univariable and multivariable analysis were carried out to identify factors associated with intentions to get vaccinated for each vaccine. RESULTS: Among the 1199 PW followed during the study period, 310 completed the questionnaire. Intentions to get vaccinated were respectively 43.9 %, 36.8 %, 36.1 % and 39.4 % against influenza, Covid-19, pertussis and RSV. Overall confidence in vaccines using 5C-model, recommendation by a healthcare professional (HCP), good knowledge about diseases and vaccines and previous influenza vaccination were associated with flu vaccine acceptance with respective adjusted odds ratios and 95 % Confidence Intervals (aOR) 1.69 (1.09-2.61) by one-point increase in confidence score, 4.89 (2.24-10.7), 1.56 by one-point increase in knowledge score (1.26-1.93), 13.5 and (5.3-34.3). Confidence was also associated with Covid-19 and RSV vaccine acceptance with respective aOR and 95 % CI 2.63 (1.7-4.07) and 1.92 (1.3-2.84). For pertussis, previous flu vaccination or pertussis vaccination in the last 5 years were predictors of pertussis vaccine acceptance during the pregnancy with respective aOR and 95 % CI 1.97 (1.1-3.84) and 2.9 (1.6-5.18). CONCLUSION: Confidence is associated with seasonal influenza, COVID-19 and RSV vaccines acceptance in pregnant women. Receiving a recommendation from a HCP was strongly associated with acceptance of influenza vaccine. Recent vaccination against pertussis was not a barrier to pertussis vaccine acceptance during pregnancy.

Factors Contributing to Delayed Return to Work among French Healthcare Professionals Afflicted by COVID-19 at a Hospital in the Rhône-Alpes Region, 2021.

COVID-19 is an emerging disease whose impact on the return to work of hospital staff is not yet known. This study was aimed at evaluating the prevalence of delayed return to work associated with medical, personal, and professional factors in hospital staff who tested positive for COVID-19 during the second epidemic wave. A descriptive, analytical observational study was conducted. The source population consisted of all staff of a French University Hospital Center who had an RT-PCR test or an antigenic test positive for SARS-CoV-2 during the period from 6 September to 30 November 2020. A delayed return to work was defined as a return to work after a period of at least 8 days of eviction, whereas before the eviction period decided by the French government was 14 days. Data collection was carried out through an anonymous online self-questionnaire. The participation rate was 43% (216 participants out of 502 eligible subjects). Moreover, 40% of the staff had a delayed return to work, and 24% of them reported a delayed return to work due to persistent asthenia. Delayed return to work was significantly associated with age, fear of returning to work, and persistent asthenia, but the number of symptoms lasting more than 7 days was the only factor that remained significantly associated after multivariate analysis. From this study, it appears that interest in identifying the number of persistent symptoms as a possible indicator of delayed work emerges. Moreover, persistent asthenia should be given special attention by practitioners to detect a possible long COVID.

Impact of influenza, herpes zoster, and pneumococcal vaccinations on the incidence of cardiovascular events in subjects aged over 65 years: a systematic review.

This systematic review aims to summarize the impact of vaccination against influenza, shingles, and pneumococcus on the incidence on the risk of cardiovascular events in the elderly. This protocol was developed in accordance with PRISMA guidelines. We conducted a literature search and identified all relevant articles published regarding the matter up to September 2022. We retrieved 38 studies (influenza vaccine = 33, pneumococcal vaccine = 5, and zoster vaccine = 2). A total of 28 and 2 studies have shown that influenza and pneumococcal vaccines significantly lower the risk of cardiovascular disease in the elderly. Also, repeated influenza vaccination shows a consistent and dose-dependent protective effect against acute coronary syndromes and stroke. Moreover, dual influenza and pneumococcal vaccination was associated with lower risks of some cardiovascular events (stroke, congestive heart failure, ischemic heart disease, and myocardial infarction). However, the impact of PCV13 on cardiovascular events has not been studied, nor has the currently recommended vaccination schedule (PCV13 + PPV23). As for herpes zoster vaccination, only the protective effect against stroke has been studied with the live attenuated herpes zoster vaccine, but no studies have been conducted with the recombinant subunit herpes zoster vaccine. This review outlines the benefits of the vaccines mentioned above beyond their preventive action on infectious diseases. It is intended for health professionals who wish to inform and advise their elderly patients.

Anti-staphylococcus aureus adaptive immunity is impaired in end-stage renal disease patients on hemodialysis: one-year longitudinal study.

Introduction: Patients with end-stage renal disease (ESRD) display defects in adaptive and innate immunity, increasing susceptibility to infection. Staphylococcus aureus (S. aureus) is a major cause of bacteraemia in this population and is associated with increased mortality. More information on the immune response to S. aureus in these patients is needed to inform effective vaccine development. Methods: A longitudinal prospective study was carried out at two medical centers and included 48 ESRD patients who started chronic hemodialysis (HD) treatment ≤3 months before inclusion. Control samples were taken from 62 consenting healthy blood donors. Blood samples were obtained from ESRD patients at each visit, on month (M) 0 (beginning of HD), M6 and M12. Around 50 immunological markers of adaptive and innate immunity were assessed to compare immune responses to S. aureus in ESRD patients versus controls to document the changes on their immune profile during HD. Results: S. aureus survival in whole blood was significantly higher in ESRD patients than in controls at M0 (P=0.049), while impaired oxidative burst activity was observed in ESRD patients at all timepoints (P<0.001). S. aureus-specific immunoglobulin G (IgG) responses to iron surface determinant B (IsdB) and S. aureus α hemolysin (Hla) antigens were lower in ESRD patients than in healthy donors at M0 (P=0.003 and P=0.007, respectively) and M6 (P=0.05 and P=0.03, respectively), but were restored to control levels at M12. Moreover, S. aureus-specific T-helper cell responses were comparable to controls for IsdB but were impaired for Hla antigen at all timepoints: 10% of ESRD patients responded to Hla at M0, increasing to 30% at M12, compared with 45% of healthy donors. B-cell and T-cell concentrations in blood were significantly reduced (by 60% and 40%, respectively) compared with healthy controls. Finally, upregulation of Human Leucocyte Antigen-DR (HLA-DR) and C-C chemokine Receptor type 2 (CCR2) was impaired at M0 but was restored during the first year of HD. Conclusion: All together, these results show that adaptive immunity was largely impaired in ESRD patients, whereas innate immunity was less impacted and tended to be restored by HD.

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.

Staphylococcus aureus nasal colonization level and intracellular reservoir: a prospective cohort study.

Staphylococcus aureus is a major pathogen in humans. The nasal vestibule is considered as the main reservoir of S. aureus. However, even though the nasal cavity may also be colonized by S. aureus, the relationships between the two sites are still unclear. We conducted a prospective study in humans to assess the S. aureus colonization profiles in the vestibule and nasal cavity, and to investigate the presence of intracellular S. aureus in the two sites. Patients undergoing ear, nose, and throat surgery were swabbed during endoscopy to determine S. aureus nasal load, genotype, and presence of intracellular S. aureus. Among per-operative samples from 90 patients, the prevalence of S. aureus carriage was 32.2% and 33.3% in the vestibule and the nasal cavity, respectively. The mean S. aureus load was 4.10 and 4.25 log10 CFU/swab for the nasal vestibule and nasal cavity, respectively (P > 0.05). Genotyping of S. aureus revealed that all nasal strains isolated from a given individual belong to the same clonal complex and spa-type. An intracellular carriage was observed in 5.6% of the patients, all of whom exhibited a S. aureus vestibule load higher than 3 log10 CFU/swab. An intracellular niche was observed in the vestibule as well as in the nasal cavity. In conclusion, the nasal cavity was also found to be a major site of S. aureus carriage in humans and should draw attention when studying host-pathogen interactions related to the risk of infection associated with colonization.

Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial.

BACKGROUND: In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women. METHODS: In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively. RESULTS: RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 µg RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9-10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth. CONCLUSIONS: RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns. CLINICAL TRIALS REGISTRATION: NCT04126213.

WHAT IS THE CONTEXT?: Infants, especially those less than 6 months of age, are at increased risk of lung infection caused by respiratory syncytial virus (RSV). However, this risk could be reduced with maternal vaccination against RSV during pregnancy. A previous clinical trial found that a vaccine candidate (named RSVPreF3) was well tolerated when given to non-pregnant women. WHAT IS NEW?: In pregnant women, RSVPreF3 was also well tolerated. Occurrence of unsolicited adverse events was similar between vaccine and placebo recipients. None of the serious adverse events or events of interest for pregnant women or newborns were considered related to the study intervention. One month after vaccination, mothers who received RSVPreF3 had 11­15 times higher levels of antibodies against RSV than before vaccination. These antibody levels remained similar until 43 days after delivery. In the infants born to mothers vaccinated during pregnancy with RSVPreF3, antibody levels were highest at birth, when levels were higher than in their mothers, and declined through day 181 postbirth. WHAT IS THE IMPACT?: RSVPreF3 had an acceptable safety risk profile in pregnant women and their babies. This vaccine induced potent immune responses against RSV, with maternal antibodies transferred to infants of the vaccinated mothers.

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.

Bacteremia and adrenal gland abscess due to Nocardia cyriacigeorgica: a case report and review.

BACKGROUND: Nocardia cyriacigeorgica is one of the most common Nocardia species found in human infections, recently reclassified. Even though Nocardia may affect all organs by hematogenous dissemination, bacteremia are uncommon. Among all possible dissemination sites, the involvement of the adrenal glands is particularly rare. CASE PRESENTATION: We report here a rare case of Nocardia disseminated infection with notably bacteremia and adrenal gland abscess, in a 77-years-old immunocompetent man. Adrenal gland abscess diagnosis was made by imaging (computerized tomography, magnetic resonance and positron emission tomography scan). A complete regression of all lesions including the left adrenal gland was obtained after 6 months of antibiotics. A review of literature was also performed. CONCLUSION: Nocardia bacteremia is a rare event but blood cultures may help to improve detection of Nocardia spp. in a non-invasive way. Adrenal abscess due to Nocardia spp. is very rare with only fourteen cases reported in the literature, but it is a true cause of adrenal masses. Our report suggests that clinician should be aware of this rare location and prioritize a non-invasive diagnosis strategy.

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.