COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series.

OBJECTIVE: To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease. METHODS: We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed. RESULTS: Frequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2-53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection. CONCLUSION: In COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.

Symptomatology during previous SARS-CoV-2 infection and serostatus before vaccination influence the immunogenicity of BNT162b2 COVID-19 mRNA vaccine.

Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. This study presents detailed immunological evidence to clarify the requirements for one- or two-dose primary vaccination series for naturally primed individuals. The main objective was to evaluate the immune response to COVID-19 mRNA vaccination to establish the most appropriate vaccination regimen to induce robust immune responses in individuals with prior SARS-CoV-2 infection. The main outcome measure was a functional immunity score (zero to three) before and after vaccination, based on anti-RBD IgG levels, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools. One point was attributed for each of these three functional assays with response above the positivity threshold. The immunity score was compared based on subjects' symptoms at diagnosis and/or serostatus prior to vaccination. None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than individuals who were symptomatic during infection. These results indicate that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Altogether, these findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection.

The REinfection in COVID-19 Estimation of Risk (RECOVER) study: Reinfection and serology dynamics in a cohort of Canadian healthcare workers.

BACKGROUND: Understanding the immune response to natural infection by SARS-CoV-2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection. METHODS: We conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR-confirmed SARS-CoV-2 infection to (i) measure the average incidence rate of reinfection and (ii) describe the serological immune response to the primary infection. RESULTS: Our cohort comprised 569 HCWs; median duration of individual follow-up was 371 days. We detected six cases of reinfection in absence of vaccination between August 21, 2020, and March 1, 2022, for a reinfection incidence rate of 4.0 per 100 person-years. Median duration of seropositivity was 415 days in symptomatics at primary infection compared with 213 days in asymptomatics (p < 0.0001). Other characteristics associated with prolonged seropositivity for IgG against the spike protein included age over 55 years, obesity, and non-Caucasian ethnicity. CONCLUSIONS: Among unvaccinated healthcare workers, reinfection with SARS-CoV-2 following a primary infection remained rare.

Maxillofacial fractures in females: a 5-year retrospective review.

BACKGROUND: This retrospective study reviews the maxillofacial fractures (MF) over a 5-year period at the National Maxillofacial Unit, St James Hospital Dublin, with an emphasis on female patients. MATERIALS AND METHODS: The trauma database was analysed from January 2015 to December 2019. The following demographic details were recorded: patient age and gender, mechanism of injury, and facial fracture sites. This retrospective study did not require approval from the local IRB. RESULTS: A total of 4761 patients had facial fractures during the study: 1125 (24%) female, 3636, (76%) male. Females had 1190 facial fractures, with two fracture peaks: 20-39 years and 70-89 years. In males, the majority of fractures occurred between 20 and 39 peaking at 20-29 years and tailed off thereafter. In the females the most common fracture sites were zygomatic 402 (34%), nasal 311(26%), orbital (22%), and mandibular 141(12%). There were also smaller percentages of frontal (0.8%), maxillary (4%), and Le Fort fractures (1%). Two hundred and sixty-two (23%) females were managed surgically and 853 (77%) non-surgically. CONCLUSION: This study confirms maxillofacial fractures are less common in females. The female age distribution demonstrates two peaks, one in early adult and a second in old age. This may be explained by females living longer and independently and at risk for falls. The most commonly reported fracture aetiology in females was "falls." This raises concerns as to whether "falls" are used to explain an assault. There is an informal concern amongst maxillofacial surgeons that females presenting with facial trauma may be the victims of domestic violence, which may be denied by the victims.

Immunogenicity and safety of high-dose versus standard-dose inactivated influenza vaccine in rheumatoid arthritis patients: a randomised, double-blind, active-comparator trial.

BACKGROUND: Patients with rheumatoid arthritis have increased risk of seasonal influenza and influenza-related complications but have reduced vaccine immunogenicity. It is unknown whether patients with rheumatoid arthritis would benefit from more immunogenic vaccine formulations. This study investigated the immunogenicity and safety of a high-dose trivalent inactivated influenza vaccine (HD-TIV) in patients with rheumatoid arthritis compared to a standard-dose quadrivalent influenza vaccine (SD-QIV). METHODS: This study was a treatment-stratified, randomised, double-blind trial to compare the immunogenicity and safety of SD-QIV (15 µg of haemagglutinin [HA] per strain) versus HD-TIV (60 µg of HA per strain) in adults with rheumatoid arthritis who are positive for rheumatoid factor or anti-cyclic citrullinated peptide, or both, recruited during the 2016-17 and 2017-18 influenza seasons at three hospitals affiliated with McGill University (Montreal, QC, Canada). Participants had received treatment for rheumatoid arthritis with conventional or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) or biological DMARDs, or combinations of them, were still on treatment at the time of enrolment, and their treatment had not been modified during the 3 months before enrolment. They were stratified into one of three groups according to treatment. Patients who, at enrolment, were taking conventional or targeted synthetic DMARDs (methotrexate, hydroxychloroquine, and sulfasalazine) as monotherapy or in combination were stratified to group 1; those who were taking a biological DMARD (anti-tumour necrosis factor or anti-interleukin 6), with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 2; and those who were taking abatacept, tofacitinib, or rituximab, with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 3. Participants were randomly allocated (1:1) to receive the SD-QIV or HD-TIV vaccine. Randomisation was based on a computer-generated allocation sequence, and participants, investigators, and research nurses responsible for safety assessments were masked to vaccine assignment. The primary outcome was the seroconversion rate (as measured by haemagglutination-inhibition assay) per strain at day 28. Analysis was done in the modified intention-to-treat population, which included all randomly assigned participants for whom seroconversion status was available. Safety was assessed throughout the surveillance period (day 0-186). This trial is registered at ClinicalTrials.gov, number NCT02936180. FINDINGS: Between Oct 24, 2016, and Dec 6, 2017, 696 patients with rheumatoid arthritis were invited to participate in the study and 279 were randomly assigned and vaccinated (140 [50%] received SD-QIV and 139 [50%] HD-TIV). 136 patients who received SD-QIV and 138 who received HD-TIV were included in the modified intention-to-treat anaysis. Patients who received HD-TIV were more likely to seroconvert than those who received SD-QIV: the odds ratio was 2·99 (95% CI 1·46-6·11) for seroconversion to strain A/H3N2, 1·95 (1·19-3·22) for seroconversion to strain B/Bris, 3·21 (1·57-6·56) for seroconversion to strain A/H1N1 (in 2016-2017), and 2·44 (1·18-5·06) for seroconversion to strain A/H1N1 (in 2017-2018). Similar results were observed in patients from groups 1 and 2; the number of individuals in group 3 was insufficient to draw conclusions. Local and systemic adverse events were similar in both vaccine groups, no serious adverse events were reported between days 0 and 28 in any group, and neither vaccine increased rheumatoid arthritis disease activity. INTERPRETATION: Our data suggest that in patients with seropositive rheumatoid arthritis, HD-TIV is safe and more immunogenic than SD-QIV. These results are the first evidence to support the use of the HD-TIV in these patients. FUNDING: The Arthritis Society-Canada.

Case-control study of household contacts to examine immunological protection from Bordetella pertussis transmission - study protocol.

BACKGROUND: There is mounting evidence that the recent resurgence of pertussis in many countries is in part related to the acellular vaccine, which has been administered in Canada since 1997. This vaccine elicits a different cell-mediated immune response than the previously used whole-cell vaccine, and its effectiveness wanes over time. The aim of this study is to understand the immunological, demographic and clinical factors that mediate protection from pertussis on exposure. METHODS: This is a household case-control study protocol. Following notification of an index case in a household, a study team will conduct a home visit to collect data and biological specimens. The study team will return to the household 8 weeks from the onset of illness in the index case. The Th1, Th2 and Th17 responses, cytokine expression, IgG subclass, blood cell counts and presence of Bordetella pertussis will be determined. We will use laboratory and statistical analyses to determine immunological differences between contacts who are infected with B. pertussis and contacts who remain healthy, and to determine which clinical and demographic covariates are associated with a reduced risk of infection. INTERPRETATION: The results of this study will be essential for understanding the immune response required for protection from infection with B. pertussis and will contribute to our understanding of the shortcomings of the current vaccine.

Improving influenza vaccination in chronically ill children using a tertiary-care based vaccination clinic: Is there a role for the live-attenuated influenza vaccine (LAIV)?

BACKGROUND: Children with underlying medical conditions should receive influenza vaccine (IV) yearly; yet this remains sub-optimal. We aimed to describe our experience with a tertiary-care hospital-based influenza vaccination clinic for this at-risk population. METHODS: From October to December 2012, 2013, and 2014, we ran an influenza vaccination clinic at the Montreal Children's Hospital, where children with high-risk conditions come for their follow-up. Both injectable IV (IIV) and live-attenuated IV (LAIV) were offered free of charge to patients and their household contacts. Upon vaccination, parents were asked to fill a pre-piloted questionnaire. RESULTS: We vaccinated a total of 2640 high-risk children and 1912 household members during the three influenza vaccination seasons. In 2012 and 2013, 631 and 630 patients with chronic illnesses were vaccinated, compared to 1379 in 2014. Caregivers preferred LAIV primarily because no needle was involved (49.0%) and because it was perceived as less painful (46.9%). LAIV was administered to 69% (2012), 55% (2013) and 47% (2014) of high-risk children. The main reason for not receiving LAIV was because it was contra-indicated. A small fraction of children previously vaccinated with LAIV who did not present any contraindication to LAIV opted for IIV: 12/101 (11.8%) in 2013 and 16/272 (5.9%) in 2014. In 2014, this was mainly due to a previous negative experience with LAIV (11/16). CONCLUSION: Having an influenza vaccination clinic on site at a tertiary care hospital, where children come for their scheduled visits, facilitates yearly influenza vaccination in children with chronic illnesses. LAIV is preferred by caregivers and patients, when not contraindicated.

Safety and immunogenicity of two doses of quadrivalent meningococcal conjugate vaccine or one dose of meningococcal group C conjugate vaccine, both administered concomitantly with routine immunization to 12- to 18-month-old children.

OBJECTIVES: To describe the immunogenicity and safety of a two-dose series of a quadrivalent meningococcal (serogroups A, C, Y and W) polysaccharide diphtheria toxoid conjugate vaccine (MenACYW-D) administered to toddlers. METHODS: Children were randomly assigned (1:1) at study entry to receive MenACYW-D at 12 and 18 months of age (group 1; n=61) or meningococcal serogroup C conjugate vaccine (MCC) at 12 months of age (group 2; n=62). All received routine childhood immunizations. A, C, Y and W antibody titres were measured in group 1 before and one month after the 18-month MenACYW-D vaccination and were measured in group 2 at one and seven months post-MCC vaccination. Antibodies elicited by diphtheria and tetanus toxoids, and acellular pertussis vaccine adsorbed combined with inactivated poliomyelitis vaccine and Haemophilus influenzae b conjugate (DTaP-IPV-Hib) vaccine coadministered at the 18-month vaccination were measured one month later. Safety data were collected. RESULTS: At 19 months of age, ≥96% in group 1 achieved protective titres for the four meningococcal serogroups after dose 2; 67% in group 2 exhibited protective titres against serogroup C 28 days after MCC vaccination at 12 months of age, declining to 27% seven months later. DTaP-IPV-Hib elicited high antibody concentrations/titres in groups 1 and 2, consistent with historical values. The safety profiles after each dose generated no unexpected safety signals; no serious adverse events were related to vaccination. DISCUSSION: A two-dose series of MenACYW-D given concomitantly with a DTaP-IPV-Hib booster dose at 18 months of age demonstrated a good immunogenicity and safety profile. A two-dose series of MenACYW-D can be used as an alternative to one dose of MCC and provides protection against additional serogroups (NCT ID: NCT01359449).

OBJECTIFS: Décrire l'immunogénicité et l'innocuité d'une série de deux doses du vaccin polysaccharadique conjugué quadrivalent contre le méningocoque (des sérogroupes A, C, Y et W) et l'anatoxine diphtérique (Men-ACYW-D) administrée aux tout-petits. MÉTHODOLOGIE: En début d'étude, les enfants ont été répartis au hasard (1:1) entre l'administration du vaccin Men-ACYW-D à 12 et 18 mois (groupe 1; n=61) ou du vaccin conjugué contre le méningocoque de sérogroupe C (Men-C-C) à 12 mois (groupe 2; n=62). Tous ont reçu les vaccins systématiques pour les enfants. Les chercheurs ont mesuré les titres d'anticorps A, C, Y et W dans le groupe 1 avant et un mois après l'administration du vaccin Men-ACYW-D à 18 mois et dans le groupe 2 un et sept mois après l'administration du vaccin Men-C-C. Un mois plus tard, ils ont mesuré les anticorps induits par les anatoxines diphtérique et tétanique et par le vaccin adsorbé contre la coqueluche acellulaire combiné au vaccin inactivé contre la poliomyélite et au vaccin conjugué contre l'Haemophilus influenzae de type b (DCaT-VPI- Hib) coadministrés lors du vaccin de 18 mois. Ils ont colligé des données d'innocuité. RÉSULTATS: À 19 mois, au moins 96 % des enfants du groupe 1 avaient des titres protecteurs contre les quatre sérogroupes du méningocoque après la dose 2, tandis que 67 % de ceux du groupe 2 présentaient des titres protecteurs contre le sérogroupe C 28 jours après le vaccin Men-C-C à 12 mois, reculant à 27 % sept mois plus tard. Le vaccin DCaT-VPI-Hib conférait de fortes concentrations et titres d'anticorps dans les groupes 1 et 2, conformément aux valeurs antérieures. Les profils d'innocuité après chaque dose ne s'associaient à aucun signe d'innocuité inattendu, et aucun événement indésirable grave n'était lié à la vaccination. EXPOSÉ: Une série de deux doses du vaccin Men-ACYW-D administrée en même temps que la dose de rappel du DCaT-VPI-Hib à 18 mois présente un bon profil d'immunogénicité et d'innocuité. Elle peut remplacer une dose du vaccin Men-C-C et conférer une protection contre des sérogroupes supplémentaires (ID NCT : NCT01359449).

Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: results of a double-blinded randomized controlled trial.

BACKGROUND: Esophagectomy represents an exemplar of controlled major trauma, with marked metabolic, immunologic, and physiologic changes as well as an associated high incidence of complications. Eicosapentaenoic acid (EPA) enriched enteral nutrition (EN) modulates immune function and limits catabolism in patients with advanced cancer, but its impact in the peri-operative period is unclear. OBJECTIVES: To examine the effects of perioperative EPA enriched EN on the metabolic, nutritional, and immuno-inflammatory response to esophagectomy, and on postoperative complications. METHODS: In a double-blind design, patients were randomized to a standard EN formula or a formula enriched with 2.2 g EPA/d for 5 days preoperatively (orally) and 21 days postoperatively (jejunostomy). Segmental bioelectrical impedance analysis was performed preoperatively and on POD 21. Postoperative complications were monitored, as well as the acute phase response, coagulation markers, and serum cytokines. RESULTS: Fifty-three patients (28 EPA, 25 standard) completed the study, and both groups were well matched. Serum and peripheral blood mononuclear cell (PBMC) membrane EPA levels were significantly increased in the EPA group. There was no difference in the incidence of major complications. The EPA group maintained all aspects of body composition postoperatively, whereas patients in the standard EN group lost significant amounts of fat-free mass (1.9 kg, P = 0.030) compared with the EPA group [leg (0.3 kg, P = 0.05), arm (0.17 kg, P = 0.01), and trunk (1.44 kg, P = 0.03)]. The EPA group had a significantly (P < 0.05) attenuated stress response for TNFalpha, IL-10, and IL-8 compared with the standard group. CONCLUSIONS: EPA supplemented early EN is associated with preservation of lean body mass post esophagectomy compared with a standard EN. These properties may merit longer-term study to address its impact on recovery of function and quality of life in models of complex surgery or multimodal cancer treatment regimens.