Humoral response after mRNA COVID-19 primary vaccination and single booster dose in people living with HIV compared to controls: a French nationwide multicenter cohort study - ANRS0001s COV-POPART.

BACKGROUND: This study aimed to compare the humoral responses to mRNA COVID-19 vaccination in PWH and HIV-negative individuals. METHODS: We included PWH with an undetectable viral load under ART and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (< 200/mm3 and ≥ 200/mm3 CD4 cell counts) at 1, 6 and 12 months after primary vaccination. RESULTS: A total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm3) and 1092 controls. At 1 month, after adjustment on age, sex and BMI, PWH had lower seroneutralization titers than controls and PWH with < 200 CD4 cell/mm3 had lower anti- Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months post primary vaccination, we did not observe differences between PWH and controls at 12 months. CONCLUSION: PWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after six months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline.

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.

Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination.

OBJECTIVES: COVID-19 vaccine breakthrough infections were frequently reported during circulation of the Omicron variant. The ANRS|MIE CoviCompareP study investigated these infections in adults vaccinated and boosted with BNT162b2 [Pfizer-BioNTech] and with/without SARS-CoV-2 infection before vaccination. METHODS: In the first half of 2021, healthy adults (aged 18-45, 65-74 and 75 or older) received either one dose of BNT162b2 (n = 120) if they had a documented history of SARS-CoV-2 infection at least five months previously, or two doses (n = 147) if they had no history confirmed by negative serological tests. A first booster dose was administered at least 6 months after the primary vaccination, and a second booster dose, if any, was reported in the database. Neutralizing antibodies (NAbs) against the European (D614G) strain and the Omicron BA.1 variant were assessed up to 28 days after the first booster dose. A case-control analysis was performed for the 252 participants who were followed up in 2022, during the Omicron waves. RESULTS: From January to October 2022, 78/252 (31%) had a documented symptomatic breakthrough infection after full vaccination: 21/117 (18%) in those who had been infected before vaccination vs. 57/135 (42%) in those who had not. In a multivariate logistic regression model, factors associated with a lower risk of breakthrough infection were older age, a higher number of booster doses, and higher levels of Omicron BA.1 NAb titers in adults with infection before vaccination, but not in those without prior infection. CONCLUSION: Our results highlight the need to consider immune markers of protection in association with infection and vaccination history.

Xpert MTB/RIF Ultra Trace Results: Decision Support for the Treatment of Extrapulmonary Tuberculosis in Low TB Burden Countries.

OBJECTIVES: Extrapulmonary tuberculosis (EPTB) can be difficult to diagnose, especially in severe forms. The Xpert MTB/RIF Ultra test introduced an additional category called trace to reference very small amounts of Mycobacterium tuberculosis complex (MTBC) DNA. The objective of our multicenter study was to evaluate whether the trace result on an extrapulmonary (EP) sample is a sufficient argument to consider diagnosing tuberculosis and starting treatment, even in severe cases. METHODS: A retrospective, multicenter cohort study was conducted from 2018 to 2022. Patients strongly suspected of EPTB with a trace result on an EP specimen were included. Hospital records were reviewed for clinical, treatment, and paraclinical data. RESULTS: A total of 52 patients were included, with a severe form in 22/52 (42.3%) cases. Culture was positive for MTBC in 33/46 (71.7%) cases. Histological analysis showed granulomas in 36/45 (80.0%) cases. An Ultra trace result with a presumptive diagnosis of TB led to the decision to treat 41/52 (78.8%) patients. All patients were started on first-line anti-TB therapy (median duration of 6.1 months), with a favorable outcome in 31/35 (88.6%) patients. The presence of a small amount of MTBC genome in EPTB is a sufficient argument to treat patients across a large region of France.

Impact of vaccination on the presence and severity of symptoms in hospitalized patients with an infection of the Omicron variant (B.1.1.529) of the SARS-CoV-2 (subvariant BA.1).

OBJECTIVES: The emergence of SARS-CoV-2 variants raised questions about the extent to which vaccines designed in 2020 have remained effective. We aimed to assess whether vaccine status was associated with the severity of Omicron SARS-CoV-2 infection in hospitalized patients. METHODS: We conducted an international, multi-centric, retrospective study in 14 centres (Bulgaria, Croatia, France, and Turkey). We collected data on patients hospitalized for ≥24 hours between 1 December 2021 and 3 March 2022 with PCR-confirmed infection at a time of exclusive Omicron circulation and hospitalization related or not related to the infection. Patients who had received prophylaxis by monoclonal antibodies were excluded. Patients were considered fully vaccinated if they had received at least two injections of either mRNA and/or ChAdOx1-S or one injection of Ad26.CoV2-S vaccines. RESULTS: Among 1215 patients (median age, 73.0 years; interquartile range, 57.0-84.0; 51.3% men), 746 (61.4%) were fully vaccinated. In multivariate analysis, being vaccinated was associated with lower 28-day mortality (Odds Ratio [95% Confidence Interval] (OR [95CI]) = 0.50 [0.32-0.77]), intensive care unit admission (OR [95CI] = 0.40 [0.26-0.62]), and oxygen requirement (OR [95CI] = 0.34 [0.25-0.46]), independent of age and comorbidities. When co-analysing these patients with Omicron infection with 948 patients with Delta infection from a study we recently conducted, Omicron infection was associated with lower 28-day mortality (OR [95CI] = 0.53 [0.37-0.76]), intensive care unit admission (OR [95CI] = 0.19 [0.12-0.28]), and oxygen requirements (OR [95CI] = 0.50 [0.38-0.67]), independent of age, comorbidities, and vaccination status. DISCUSSION: Originally designed vaccines have remained effective on the severity of Omicron SARS-CoV-2 infection. Omicron is associated with a lower risk of severe forms, independent of vaccination and patient characteristics.

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.

Assessment of a fully automated RPR assay (Mediace RPR) for serological diagnosis and follow-up of syphilis: a retrospective study.

OBJECTIVES: This study assessed the Mediace RPR assay, an automated RPR (aRPR), for syphilis diagnosis and serological follow-up. METHODS: Serums from patients positively screened for syphilis between January 2017 and December 2019 were retrospectively selected. A focus was performed on patients with a serological follow-up after treatment and/or a reinfection. Serums were tested by both manual (mRPR) and aRPR tests. Categorical and Quantitative Agreements (CA and QA), and serological follow-up conclusions were analyzed. RESULTS: 236 serums from 85 patients (99% of male, 66% of HIV-infected) were included. The overall QA was 54.2%. CA was low (79.7%) especially for samples with low RPR titers. No prozone effect was observed. Serological follow-up after treatment led to similar conclusions, although aRPR titers often decreased faster. Over 26 episodes of reinfection, 4 (15.4%) were misdiagnosed with the aRPR. CONCLUSIONS: While the Mediace aRPR presents the advantages of an automated test, its poor sensitivity in low titers may limit its use.

Impact of vaccination on the symptoms of hospitalised patients with SARS-CoV-2 Delta variant (B.1.617.1) infection.

OBJECTIVES: The diffusion of the SARS-CoV-2 Delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status. METHODS: We performed a retrospective observational study on patients hospitalised in 10 centres with a SARS-CoV-2 infection (Delta variant) from July to November 2021 by including all patients who had completed their primary vaccination at least 14 days before hospital admission and the same number of completely unvaccinated patients. We assessed the impact of vaccination and other risk factors through logistic regression. RESULTS: We included 955 patients (474 vaccinated and 481 unvaccinated). Vaccinated patients were significantly older (75.0 [63.25-84.0] vs. 55.0 [38.0-73.0]; p < 0.001), more frequently males (55.1% (261/474) vs. 46.4% (223/481); p = 0.009), and had more comorbidities (2.0 [1.0-3.0] vs. 1.0 [0.0-2.0]; p < 0.001). Vaccinated patients were less often admitted for Covid-19 (59.3% (281/474) vs. 75.1% (361/481); p < 0.001), had less extended lung lesions (≤25%: 64.3% (117/182) vs. 38.4% (88/229); p < 0.001), required oxygen less frequently (57.5% (229/398) vs. 73.0% (270/370); p < 0.001), at a lower flow (3.0 [0.0-8.7] vs. 6.0 [2.0-50.0] L/min, p < 0.001), and for a shorter duration (3 [0.0-8.0] vs. 6 [2.0-12.0] days, p < 0.001)., and required less frequently intensive care unit admission (16.2% (60/370) vs. 36.0% (133/369); p < 0.001) but had comparable mortality in bivariate analysis (16.7% (74/443) vs. 12.2% (53/433); p = 0.075). Multivariate logistic regression showed that vaccination significantly decreased the risk of death (0.38 [0.20-0.70](p = 0.002), ICU admission (0.31 [0.21-0.47](p < 0.001) and oxygen requirement (0.16 [0.10-0.26](p < 0.001), even among older patients or with comorbidities. CONCLUSIONS: Among patients hospitalised with a delta variant SARS-CoV-2 infection, vaccination was associated with less severe forms, even in the presence of comorbidities.

Measles seroprevalence in human immunodeficiency virus-infected adults born in the era of measles vaccination.

OBJECTIVE: Widespread use of the measles vaccine should lead to the elimination of this disease. Here, we study the seroprevalence of measles in a cohort of adults living with HIV born after the introduction of measles vaccine in France and attempt to identify risk factors for the absence of serum measles antibody. DESIGN: In this multi-centre cross-sectional study, adult outpatients born after 1980 were screened for the presence of measles IgG antibody. Demographic and clinical data were obtained from the standardized electronic medical record system. Univariate and multivariate logistic regressions were performed to identify factors associated with the absence of measles antibodies. RESULTS: Between April 2019 and April 2020, 648 participants were enrolled. The median age was 33 years, 53.6% were born outside of France, and 74% were considered as socially deprived. Plasma HIV RNA was undetectable in 86% of patients. Among 603 evaluable patients, measles serology was positive in 87.2%. Only 81.8% of the patients with documented vaccination tested positive for measles IgG. Younger age was significantly associated with the absence of measles serum antibodies ( P  = 0.004 for each 10-year lower), as was birth in France ( P  < 0.001) and absence of social vulnerability ( P  = 0.04). CONCLUSION: The current study revealed a low seroprevalence of measles compared with that previously reported in France 6 years earlier and to the expected rate to achieve herd immunity. Checking vaccination record should be systematically carried out in patients living with HIV to fill the immunity gaps.

Microelimination or Not? The Changing Epidemiology of Human Immunodeficiency Virus-Hepatitis C Virus Coinfection in France 2012-2018.

BACKGROUND: The arrival of highly effective, well-tolerated, direct-acting antiviral agents (DAA) led to a dramatic decrease in hepatitis C virus (HCV) prevalence. Human immunodeficiency virus (HIV)-HCV-coinfected patients are deemed a priority population for HCV elimination, while a rise in recently acquired HCV infections in men who have sex with men (MSM) has been described. We describe the variations in HIV-HCV epidemiology in the French Dat'AIDS cohort. METHODS: This was a retrospective analysis of a prospective cohort of persons living with HIV (PLWH) from 2012 to 2018. We determined HCV prevalence, HCV incidence, proportion of viremic patients, treatment uptake, and mortality rate in the full cohort and by HIV risk factors. RESULTS: From 2012 to 2018, 50 861 PLWH with a known HCV status were followed up. During the period, HCV prevalence decreased from 15.4% to 13.5%. HCV prevalence among new HIV cases increased from 1.9% to 3.5% in MSM but remained stable in other groups. Recently acquired HCV incidence increased from 0.36/100 person-years to 1.25/100 person-years in MSM. The proportion of viremic patients decreased from 67.0% to 8.9%. MSM became the first group of viremic patients in 2018 (37.9%). Recently acquired hepatitis represented 59.2% of viremic MSM in 2018. DAA treatment uptake increased from 11.4% to 61.5%. More treatments were initiated in MSM in 2018 (41.2%) than in intravenous drug users (35.6%). In MSM, treatment at the acute phase represented 30.0% of treatments in 2018. CONCLUSIONS: A major shift in HCV epidemiology was observed in PLWH in France from 2012 to 2018, leading to a unique situation in which the major group of HCV transmission in 2018 was MSM. Clinical Trials Registration. NCT02898987.

Evaluation of the acceptability in France of the vaccine against papillomavirus (HPV) among middle and high school students and their parents.

BACKGROUND: The pathogenic and oncogenic roles of papillomavirus (HPV) infections have been documented and shown to occur in women as well as in men. While other countries have already extended their vaccination guidelines to include boys, in 2019 the French National Authority for Health validated implementation of HPV vaccination in the 2020 vaccination schedule. There is, however, a climate of distrust in regard to vaccination in France, and there have been few studies to date regarding the acceptability of HPV vaccination in boys in France. The aim of this study was, therefore, to evaluate the acceptability of extending the recommendations for HPV vaccination in men, among middle and high school students and their parents. METHODS: Our study (HPVac) was a prospective, multicenter, departmental, and descriptive survey applied to a sample of male middle and high school students attending schools in the Loire-Atlantique department and their parents. It took place from January 2017 to January 2018. RESULTS: We analyzed the information obtained from 127 parent questionnaires and 145 children questionnaires. In terms of acceptability, 36.6% (n = 53) of the children and 37.8% (n = 48) of the parents were in favour of being vaccinated or of having their children vaccinated against HPV (51.7% (n = 75) and 50.4% (n = 64), respectively, were undecided). The perception of a risk stemming from HPV infection was positively associated with acceptability of the HPV vaccine. Being against vaccines in general, being discouraged by their parents, parents thinking that their child is not at risk, and the belief that the vaccine is not mandatory were arguments cited and significantly associated with a willingness to be vaccinated. CONCLUSION: This study revealed a lack of information among boys and their parents about HPV and its vaccination. It also clearly showed that taking time to discuss the consequences of an infection and the merits of being vaccinated can help parents overcome their reluctance. The children then generally go along with their parent's choice.

Switch from parenteral to oral antibiotics for brain abscesses: a retrospective cohort study of 109 patients.

OBJECTIVES: Brain abscess is one of the most serious diseases of the CNS and is associated with high morbidity and mortality. With regard to the lack of data supporting an optimal therapeutic strategy, this study aimed to explore the prognostic factors of brain abscess, putting emphasis on the impact of therapeutic decisions. METHODS: We retrospectively included patients hospitalized for brain abscess during a period of 13 years. Comorbidities (Charlson scale), clinical presentation, microbiology culture, radiological features and therapeutic management were collected. Glasgow Outcome Scale (GOS) at 3 months and length of hospital stay were, respectively, the main and the secondary outcomes. Logistic regression was used to determine factors associated with outcome independently. RESULTS: Initial Glasgow Coma Scale (GCS) ≤14 and comorbidities (Charlson scale ≥2) were associated with poor neurological outcome while oral antibiotic switch was associated with better neurological outcome. Oral switch did not appear to be associated with an unfavourable evolution in the subset of patients without initial neurological severity (GCS >14) on admission. Duration of IV regimen and time to oral switch were associated with the length of inpatient stay. CONCLUSIONS: This study confirms the role of GCS and comorbidities as prognostic factors and presents reassuring data regarding the safety of oral switch for the antibiotic treatment of brain abscesses. Oral switch could prevent catheter-induced iatrogenic complications and allow a higher quality of life for patients.

Chronic meningococcemia: a report of 26 cases and literature review.

Chronic meningococcemia is defined by blood culture(s) positive for Neisseria meningitidis, symptoms duration > 7 days, and neither meningitis nor shock on admission. This series of 26 consecutive cases illustrates that this is a rare disease (< 5% of meningococcemia, < 0.05 cases per 100,000 inhabitants per year), mostly affecting young adults, males, with no predisposing condition. Major symptoms include fever, rash, and arthralgia. Median time between symptoms onset, and diagnosis is 28 days. Most patients fully recover with a 1-week course of parenteral betalactams.

Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses.

Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. However, some rare severe clinical cases have been reported without investigation of host immune responses or viral virulence. In the present study, we investigate for the first time phenotypic and functional features, together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty primary HCMV-infected patients (PHIP) were enrolled, as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls. PHIP had extensive lymphocytosis marked by massive expansion of natural killer (NK) and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C+ NK cells, CD16+ Vδ2(-) γδ T cells, and conventional HCMV-specific CD8+ T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV infection in immunocompetent individuals.IMPORTANCE HCMV-specific immune responses have been extensively documented in immunocompromised patients and during in utero acquisition. While it usually goes unnoticed, some rare severe clinical cases of primary HCMV infection have been reported in immunocompetent patients. However, host immune responses or HCMV virulence in these patients has not so far been investigated. In the present study, we show massive expansion of NK and T cell compartments during the symptomatic stage of acute HCMV infection. The patients mounted efficient innate and adaptive immune responses with a deep HCMV imprint. The massive lymphocytosis could be the result of nonadapted or uncontrolled immune responses limiting the effectiveness of the specific responses mounted. Both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage. Furthermore, we cannot exclude a delayed immune response caused by immune escape established by HCMV strains.

First isolation of Tropheryma whipplei from bronchoalveolar fluid and clinical implications.

A patient presented diffuse pulmonary parenchymal micronodules. Tropheryma whipplei was detected in the saliva, a bronchial biopsy and bronchoalveolar fluid. PAS staining, immunohistochemistry and PCR for T. whipplei were negative in the duodenal biopsies. T. whipplei was isolated from the bronchoalveolar fluid, reinforcing its role as a respiratory pathogen.

Vertebral osteomyelitis: an unusual presentation of Bartonella henselae infection.

OBJECTIVES: To report cases of cat scratch disease with vertebral osteomyelitis. METHODS: We describe clinical features, diagnostic, treatment, and outcome of 2 patients with vertebral osteomyelitis due to Bartonella henselae and provide a review of the relevant literature. RESULTS: A 47-year-old man was investigated for fever, splenomegaly, and cervical adenopathy. A lymphoma was suspected on the clinical picture, the laboratory tests, and the computed tomographic scan. [(18)F]-fluoro-2-deoxy-d-glucose-positron emission tomography detected splenic nodules and a hypermetabolic focus of C7 vertebral body compatible with a vertebral osteomyelitis on magnetic resonance imaging. B henselae infection was confirmed by polymerase chain reaction performed on lymph node biopsy. A 34-year-old woman was investigated for fever and right upper quadrant abdominal pain. She had consulted 2 weeks before for a unique lesion of right index and an axillar adenopathy that have improved spontaneously. A technetium bone scan performed 1 week later because of a thoracic backache demonstrated an increased uptake of the T6 vertebra. Vertebral magnetic resonance imaging was compatible with a T6 osteomyelitis. B henselae infection was confirmed by serology (seroconversion). Both patients were treated with rifampin and doxycycline and recovered within 3 months. CONCLUSIONS: B henselae vertebral osteomyelitis can involve immunocompetent adults. In the case of vertebral osteomyelitis with negative blood cultures, recent history of local lymphadenopathy and cat exposure must be investigated and B henselae serology must be performed. Nevertheless, even if serology is positive, vertebral biopsy is required to rule out other pathogens or malignancy. B henselae infection can be confirmed by polymerase chain reaction performed on vertebral or lymph node biopsy.