Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases.

OBJECTIVE: To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response. METHODS: Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination. RESULTS: ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001). CONCLUSIONS: We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX. Trial registration number NCT04754698.

Influenza A/Singapore (H3N2) component vaccine in systemic lupus erythematosus: A distinct pattern of immunogenicity.

INTRODUCTION: Influenza A (H3N2) virus is the most important cause of seasonal influenza morbidity and mortality in the last 50 years, surpassing the impact of H1N1. Data assessing immunogenicity and safety of this virus component are lacking in systemic lupus erythematosus (SLE) and restricted to small reports with other H3N2 strains. OBJECTIVE: This study aims to evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in SLE. METHODS: 81 consecutive SLE patients and 81 age- and sex-matched healthy controls (HC) were vaccinated with the influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers(GMT), and factor increase in GMT(FI-GMT) and adverse events were assessed before and 4 weeks post-vaccination. Disease activity and therapies were also evaluated. RESULTS: Before immunization, SLE and HC groups had high SP rates (89% vs 77%, p = 0.061) and elevated GMT titer with higher levels in SLE (129.1(104.1-154.1) vs 54.8(45.0-64.6), p < 0.001). Frequency of two previous years' influenza vaccination was high and comparable in SLE and HC (89% vs 90%, p = 1.000). Four weeks post-vaccination, median GMT increased for both groups and remained higher in SLE compared to HC (239.9(189.5-290.4) vs 94.5(72.6-116.4), p < 0.0001) with a comparable FI-GMT (2.3(1.8-2.9) vs 1.9(1.5-2.3), p = 0.051). SC rates were low and comparable for both groups (16% vs 11%, respectively, p = 0.974). Disease activity scores remained stable throughout the study (p = 1.000) and severe adverse events were not identified. CONCLUSION: Influenza A/Singapore (H3N2) vaccine has an adequate safety profile. The distinct immunogenicity pattern from other influenza A components characterized by a remarkably high pre- and post-vaccination SP rate and high GMT levels may be associated with previous influenza A vaccination. (www.clinicaltrials.gov, NCT03540823).

Challenges of interpreting epidemiologic surveillance pertussis data with changing diagnostic and immunization practices: the case of the state of São Paulo, Brazil.

BACKGROUND: A significant increase in pertussis incidence occurred in Brazil, from 2011 to 2014, despite high coverage of childhood immunization with whole-cell-pertussis (wP) containing vaccines. This study presents pertussis surveillance data from São Paulo state and discusses the challenges to interpret them considering pertussis cyclic epidemic behavior, the introduction of new diagnostic techniques and new vaccination strategies, and enhanced disease awareness during epidemics. METHODS: Observational study including pertussis cases reported to the Surveillance System in São Paulo state, from January 2001 to December 2015. Pertussis cases data were retrieved from the National Notifiable Diseases Information System (SINAN) website and from São Paulo state Epidemiological Surveillance Center (CVE/SP) database. Vaccination coverage and homogeneity data were collected from the Unified Health System Department of Informatics (DATASUS). We presented cases distribution by year, age group and diagnostic criteria and calculated pertussis incidence rates. The proportions of cases among different age groups were compared using chi-square test for trend. RESULTS: Infants less than 1 year of age were the most affected during the whole period, but the proportions of cases in this age group had a significant decreasing trend, with significant increase in the proportions of cases reported among older age groups (1-4, 5-10 and ≥20 years). Cases among infants aged less than 6 months represented ≥90% of all cases in children less than 1 year of age in all but 2 years (2012 and 2015). A non-significant decrease in the proportion of cases among infants aged < 2 months was observed in parallel to a significant increase in the proportion of cases in infants aged 6-11 months. CONCLUSIONS: A pertussis outbreak has occurred in a state with universal use of wP vaccine. The disease cyclic behavior has probably had a major role in the increased incidence rates registered in São Paulo state, from 2011 to 2014, as well as in the decreased incidence in 2015. Maternal vaccination cannot explain the drop in the number of cases among all age groups, in 2015, as herd protection is not expected, but may have had an impact on the number of cases in infants aged < 2 months.

The decline of measles antibody titers in previously vaccinated adults: a cross-sectional analysis.

The global reemergence of measles in 2018-2019 reinforces the relevance of high-coverage immunization to maintain the disease elimination. During an outbreak in the Sao Paulo State in 2019, several measles cases were reported in individuals who were adequately vaccinated according to the current immunization schedule recommends. This study aimed to assess measles IgG antibody seropositivity and titers in previously vaccinated adults. A cross-sectional study was conducted at CRIE-HC-FMUSP (Sao Paulo, Brazil) in 2019. It included healthy adults who had received two or more Measles-Mumps-Rubella vaccines (MMR) and excluded individuals with immunocompromising conditions. Measles IgG antibodies were measured and compared by ELISA (Euroimmun®) and chemiluminescence (LIASON®). The association of seropositivity and titers with variables of interest (age, sex, profession, previous measles, number of measles-containing vaccine doses, interval between MMR doses, and time elapsed since the last MMR dose) was analyzed. A total of 162 participants were evaluated, predominantly young (median age 30 years), women (69.8%) and healthcare professionals (61.7%). The median interval between MMR doses was 13.2 years, and the median time since the last dose was 10.4 years. The seropositivity rate was 32.7% by ELISA and 75.3% by CLIA, and a strong positive correlation was found between the tests. Multivariate analyses revealed that age and time since the last dose were independently associated with positivity. Despite being a single-center evaluation, our results suggest that measles seropositivity may be lower than expected in adequately immunized adults. Seropositivity was higher among older individuals and those with a shorter time since the last MMR vaccine dose.

Clinical and epidemiological features of mpox in a Brazilian reference center for HIV and sexually transmitted infections: A cross-sectional study.

Background: The 2022 mpox outbreak has affected disproportionately people living with HIV (PLWH) and pre-exposure prophylaxis (PrEP) users. Methods: We conducted a cross-sectional study to evaluate factors associated with laboratory diagnosis of mpox among suspected cases, and access differences between PrEP users and PLWH with confirmed diagnostic. Results: 394 mpox suspected cases were analyzed, 309 (78.4%) confirmed. Most patients with mpox were PLWH (54.4%) and 99 (32%) PrEP users. Mpox cases were likely to be between 25 and 39 years old (aOR=2.8; p=0.042), men who have sex with men/bisexual or transgender women (aOR=17.2; p< 0.001) and to have fever (aOR=4.7; p< 0.001), adenomegaly (aOR=7.2; p< 0.001) and multiple vesicular lesions (aOR=4.2; p< 0.001). Comparing PrEP users to PLWH with confirmed mpox, PrEP users had lesions predominantly with exclusive genital involvement (p=0.016); while PLWH had higher extragenital involvement (p=0.018). Conclusions: PrEP users and PLWHA were the main epidemiological groups in our cohort. Recognizing the differences between vulnerable populations can contribute to the development public policies to control mpox in settings with reduced access to vaccines.

Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons.

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

Quantitative PCR as a marker for preemptive therapy and its role in therapeutic control in Trypanosoma cruzi/HIV coinfection.

BACKGROUND: Trypanosoma cruzi and HIV coinfection can evolve with depression of cellular immunity and increased parasitemia. We applied quantitative PCR (qPCR) as a marker for preemptive antiparasitic treatment to avoid fatal Chagas disease reactivation and analyzed the outcome of treated cases. METHODOLOGY: This mixed cross-sectional and longitudinal study included 171 Chagas disease patients, 60 coinfected with HIV. Of these 60 patients, ten showed Chagas disease reactivation, confirmed by parasites identified in the blood, cerebrospinal fluid, or tissues, 12 exhibited high parasitemia without reactivation, and 38 had low parasitemia and no reactivation. RESULTS: We showed, for the first time, the success of the timely introduction of benznidazole in the non-reactivated group with high levels of parasitemia detected by qPCR and the absence of parasites in reactivated cases with at least 58 days of benznidazole. All HIV+ patients with or without reactivation had a 4.0-5.1 higher chance of having parasitemia than HIV seronegative cases. A positive correlation was found between parasites and viral loads. Remarkably, treated T. cruzi/HIV-coinfected patients had 77.3% conversion from positive to negative parasitemia compared to 19.1% of untreated patients. Additionally, untreated patients showed ~13.6 times higher Odds Ratio of having positive parasitemia in the follow-up period compared with treated patients. Treated and untreated patients showed no differences regarding the evolution of Chagas disease. The main factors associated with all-cause mortality were higher parasitemia, lower CD4 counts/µL, higher viral load, and absence of antiretroviral therapy. CONCLUSION: We recommend qPCR prospective monitoring of T. cruzi parasitemia in HIV+ coinfected patients and point out the value of pre-emptive therapy for those with high parasitemia. In parallel, early antiretroviral therapy introduction is advisable, aiming at viral load control, immune response restoration, and increasing survival. We also suggest an early antiparasitic treatment for all coinfected patients, followed by effectiveness analysis alongside antiretroviral therapy.

The methodological quality of economic evaluations of measles outbreaks: A systematic review of cost-of-illness studies.

OBJECTIVES: To identify the main cost components included in the economic evaluations of measles outbreaks, their items and cost drivers, and evaluate the quality of costing methodology, analyzing the key features that may affect the validity of these studies in countries with different income levels. METHODS: We systematically searched multiple databases EMBASE, MEDLINE (via PubMed), Biblioteca Virtual em Saúde do Ministério da Saúde (BVS MS), NHS Economic Evaluation Database (NHS EED) and NHS Health Technology Assessment (NHS HTA) (via The Centre for Reviews and Dissemination Library - CRD), and EconLit, SCOPUS, and Web of Science, selecting cost analysis and cost of illness studies (COI) of measles outbreaks. Two independent reviewers screened articles for relevance and extracted the data. The quality of costing methods was assessed using a guide to critical evaluation of COI studies. We performed a qualitative narrative synthesis. RESULTS: Twenty-two studies were reviewed. Most studies evaluated outbreaks that occurred from 2011 to 2013 and 2017 to 2019. Total costs varied from $40,147 to $39.3 million. Per case cost varied from $168 to $49,439. The main drivers of measles outbreak costs were outbreak response, personnel, and productivity losses. Most studies (20/22) did not report the costing methodology adopted, the degree of disaggregation used in the identification and measurement of resource and costs components and the method for the valuation of resource and cost components. CONCLUSIONS: The quality of the costing methodology, its transparency and accuracy are essential to the validity of these studies results and their potential use to allocate public health resources in the most efficient manner and to inform measles outbreak control strategies, with rapid and effective response.

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation.

The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

Risk factors for reduction in adherence to protective measures following coronavirus disease 2019 (COVID-19) vaccination and vaccine perceptions among healthcare workers, in São Paulo, Brazil.

A survey evaluated 2,300 healthcare workers following the first dose of a coronavirus disease 2019 (COVID-19) vaccine in a tertiary-quaternary hospital in São Paulo, Brazil. Adherence to protective measures following vaccination was compared to previous non-work-related behaviors. Younger age, previous COVID-19, and burnout symptoms were associated with reduced adherence to mitigation measures.

Correction: Clinical profile and mortality in patients with T. cruzi/HIV co-infection from the multicenter data base of the "Network for healthcare and study of Trypanosoma cruzi/HIV co-infection and other immunosuppression conditions".

[This corrects the article DOI: 10.1371/journal.pntd.0009809.].

TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients.

OBJECTIVE: To evaluate the immunogenicity of the anti-influenza A H1N1/2009 vaccine in RA and spondyloarthritis (SpA) patients receiving distinct classes of anti-TNF agents compared with patients receiving DMARDs and healthy controls. METHODS: One hundred and twenty patients (RA, n = 41; AS, n = 57; PsA, n = 22) on anti-TNF agents (monoclonal, n = 94; soluble receptor, n = 26) were compared with 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection, seroconversion (SC), geometric mean titre, factor increase in geometric mean titre and adverse events were evaluated 21 days after vaccination. RESULTS: After immunization, SC rates (58.2% vs 74.3%, P = 0.017) were significantly lower in SpA patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared with healthy controls (P = 0.067). SpA patients receiving mAbs (infliximab/adalimumab) had a significantly lower SC rate compared with healthy controls (51.6% vs 74.3%, P = 0.002) or those on DMARDs (51.6% vs 74.7%, P = 0.005), whereas no difference was observed for patients on etanercept (86.7% vs 74.3%, P = 0.091). Further analysis of non-seroconverting and seroconverting SpA patients revealed that the former group had a higher mean age (P = 0.003), a higher frequency of anti-TNF (P = 0.031) and mAbs (P = 0.001) and a lower frequency of MTX (P = 0.028). In multivariate logistic regression, only older age (P = 0.015) and mAb treatment (P = 0.023) remained significant factors for non-SC in SpA patients. CONCLUSION: This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in SpA patients using mAbs. TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01151644.

Measuring adherence to antiretroviral treatment: the role of pharmacy records of drug withdrawals.

This study aimed to evaluate adherence to antiretroviral treatment (ART) among HIV + adults, assess its association with HIV viral load (VL) and identify factors associated to adherence. A survey involving a random sample of adults followed at a HIV/AIDS reference center in São Paulo city, Brazil, from 2007 to 2009 was done. A questionnaire was applied and data were retrieved from the pharmacy and medical records. The study involved 292 subjects: 70.2% men; median age: 43 years; median duration of ART: 8 years. 89.3% self-reported taken all prescribed pills in the last 3 days but only 39.3% picked up ≥95% of the prescribed ART from the pharmacy in the last 12 months. At the multivariate analysis having symptoms prior to ART, taking fewer ART pills, and not missing medical appointments were independently associated to higher adherence. Adherence was strongly associated with undetectable HIV VL. Rates of undetectable HIV VL did not differ from 80 to ≥95% of adherence.

Facilitating access to pneumococcal vaccine for people living with HIV: an experience report.

OBJECTIVE: The article describes a strategy to facilitate access to pneumococcal conjugate vaccine 13 (PCV-13) for people living with HIV/AIDS (PLHIV) during the COVID-19 pandemic. METHOD: report on the experience regarding the organization of a care service for PLHIV in the city of São Paulo to facilitate access to PCV-13 in the framework of the 2020 influenza vaccination campaign during the COVID-19 pandemic. RESULTS: through the integration between a PLHIV care service and an Immunization Center (CRIE in Portuguese), it was possible to offer PCV-13 to PLHIV at the point of care, reducing physical barriers to access to immunization. Thus, of the 1,906 PLHIV who passed through the service during the period March 23-July 31, 2020, 84.4% (1,609) received the influenza vaccine, PCV-13 or both. Of the 1609 vaccinated, 50.6% (814) were eligible and received PCV-13. CONCLUSION: offering the vaccine at the point of care and orienting PLHIV on the importance of vaccination as a disease prevention strategy, identifying those eligible to receive it, was an important action carried out by the institution together with the nursing team, as a strategy to facilitate access to vaccination.

Impact of polio vaccines (oral polio vaccine - OPV or inactivated polio vaccine - IPV) on rotavirus vaccine-associated intussusception.

Although safe, rotavirus vaccines have been associated with increased intussusception risk. In Brazil, after the oral human rotavirus vaccine (OHRV) introduction in the childhood immunization, in 2006, increased intussusception risk was identified after the second OHRV dose, whereas in other countries, higher risk was associated to the first vaccine dose. It was hypothesized that the concomitant use of oral poliovirus vaccine (OPV) in Brazil might explain this difference. In 2012, the inactivated polio vaccine (IPV) was adopted in the first two doses of Brazilian childhood immunization schedule, creating an opportunity to study the subject. Our objective was analyzing the impact of polio vaccines on rotavirus-associated intussusception. We used surveillance data on intussusception in infants living in São Paulo State. Two periods were considered: an OPV-period (March 2006 to June 2012) and an IPV-period (October 2012 to December 2017). The period from June to September 2012 were considered as transition. Self-controlled case series analysis with event-dependent exposure was performed, considering two risk periods (7 and 21 days post-vaccination). We identified 325 intussusception cases in infants reported to the surveillance systems during the study period. The statistical analysis included 221 cases that occurred within 60 days after vaccination. Overall, a higher intussusception risk was observed in the first week after vaccination for both the first (Relative Incidence [RI] = 4.3, 95%CI 2.8-6.5, p < .001) and second vaccine doses (RI = 4.2, 95%CI 2.7-6.4; p < .001). There were no statistically significant differences in intussusception risk according to the rotavirus vaccine dose and the polio vaccine (OPV or IPV) administered concomitantly.

Human Papillomavirus (HPV) seroprevalence, cervical HPV prevalence, genotype distribution and cytological lesions in solid organ transplant recipients and immunocompetent women in Sao Paulo, Brazil.

INTRODUCTION: Solid organ transplant (SOT) recipients are at increased risk of Human Papillomavirus (HPV) persistent infection and disease. This study aimed to evaluate HPV seroprevalence, cervical HPV prevalence, genotype distribution, and frequency of HPV-related cervical lesions in SOT recipients in comparison to immunocompetent women. METHODS: Cross-sectional study including SOT and immunocompetent women aged 18 to 45 years who denied previous HPV-related lesions. Cervical samples were screened for HPV-DNA by a polymerase chain reaction (PCR)-based DNA microarray system (PapilloCheck®) and squamous intraepithelial lesions (SIL) by liquid-based cytology. A multiplexed pseudovirion-based serology assay (PsV-Luminex) was used to measure HPV serum antibodies. RESULTS: 125 SOT and 132 immunocompetent women were enrolled. Cervical samples were collected from 113 SOT and 127 immunocompetent women who had initiated sexual activity. HPV-DNA prevalence was higher in SOT than in immunocompetent women (29.6% vs. 20.2%, p = 0.112), but this difference was not statistically significant. High-risk (HR)-HPV was significantly more frequent in SOT than in immunocompetent women (19.4% vs. 7.9%, p = 0.014). Simultaneous infection with ≥2 HR-HPV types was found in 3.1% of SOT and 0.9% of immunocompetent women. HPV seropositivity for at least one HPV type was high in both groups: 63.8% of 105 SOT and 69.7% of 119 immunocompetent women (p = 0.524). Low-grade (LSIL) and high-grade SIL (HSIL) were significantly more frequent in SOT (9.7% and 5.3%, respectively) than in immunocompetent women (1.6% and 0.8%, respectively) (p = 0.001). CONCLUSIONS: These results may reflect the increased risk of HPV persistent infection and disease progression in SOT women due to chronic immunosuppression.

Adverse events following immunization of elderly with COVID-19 inactivated virus vaccine (CoronaVac) in Southeastern Brazil: an active surveillance study.

Healthcare workers, the elderly and other vulnerable populations were the first to receive COVID-19 vaccines in public health programs. There were few vaccine safety data available on the elderly. This observational study aimed to evaluate the inactivated vaccine (CoronaVac) safety in the elderly, at the beginning of the vaccination program, in Sao Paulo city, Brazil. The elderly people that received CoronaVac at the Reference Center for Special Immunobiologicals (CRIE) or at home, administered by the Interdisciplinary Home Care Team (NADI) of the Hospital das Clinicas were invited to participate in this phase 4 observational study. The vaccination schedule included two CoronaVac doses 28 days apart. The information on solicited and unsolicited adverse events following immunization were collected by phone calls on days 4 and 8 after each vaccine dose. We enrolled 158 adults aged 65 to 101 years (mean of 84.1 years); 63.9% were females and 95.6% had chronic conditions, 21.5% had moderate or severe impairment in daily living activities; 34.2% were pre-frail and 19.6% were frail. We were able to contact 95.6% and 91.6% of the vaccinated people, after the first and second doses, respectively; 31.8% and 23.4% of the contacted participants reported some adverse events (AE) following the first and second doses, respectively. Pain at the injection site, fatigue, myalgia and headaches were the most frequent solicited AE. Most AE were mild to moderate. There were eight severe adverse events, but none of them were considered related to the vaccine. The CoronaVac was safe and well tolerated by these adults of advanced age with frailty and comorbidities.

An Open-label Randomized Controlled Parallel-group Pilot Study Comparing the Immunogenicity of a Standard-, Double-, and Booster-dose Regimens of the 2014 Seasonal Trivalent Inactivated Influenza Vaccine in Kidney Transplant Recipients.

BACKGROUND: Immunogenicity of influenza vaccine in transplant recipients is suboptimal and alternative vaccination regimens are necessary. METHODS: We compared the immunogenicity of a standard-dose trivalent inactivated influenza vaccination (SDTIIV), double-dose trivalent inactivated influenza vaccination (DDTIIV), and booster-dose trivalent inactivated influenza vaccination (BDTIIV) of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients. We randomized 176 participants to SDTIIV (59), DDTIIV (59), and BDTIIV regimens (58). Antibody titers were determined by hemagglutination inhibition at enrollment and 21 d postvaccination. Seroprotection rates (SPRs), seroconversion rates (SCRs), and geometric mean ratios (GMRs) were analyzed separately for participants with low (<1:40) and high (≥1:40) prevaccination antibody titers. RESULTS: Vaccination was confirmed for 172 participants. Immunogenicity analysis was done for 149 participants who provided postvaccination blood samples. In the subgroup with high prevaccination antibody titers, all vaccination regimens induced SPR > 70% to all antigens, but SCR and GMR were below the recommendations. In the subgroup with low prevaccination antibody titers, DDTIIV and BDTIIV regimens induced adequate SCR > 40% and GMR > 2.5 for all antigens, whereas SDTIIV achieved the same outcomes only for influenza B. SPRs were >70% only after DDTIIV (A/H1N1-77.8%) and BDTIIV (A/H3N2-77.8%). BDTIIV regimen independently increased seroprotection to A/H1N1 (PR = 2.58; P = 0.021) and A/H3N2 (PR = 2.21; P = 0.004), whereas DDTIIV independently increased seroprotection to A/H1N1 (PR = 2.59; P = 0.021). CONCLUSIONS: Our results suggest that DDTIIV and BDTIIV regimens are more immunogenic than SDTIIV, indicating the need for head-to-head multicenter clinical trials to further evaluate their efficacy.

Immunogenicity and safety of two doses of the CoronaVac SARS-CoV-2 vaccine in SARS-CoV-2 seropositive and seronegative patients with autoimmune rheumatic diseases in Brazil: a subgroup analysis of a phase 4 prospective study.

BACKGROUND: We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. METHODS: CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo) in São Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 µg in 0·5 mL of ß-propiolactone inactivated SARS-CoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15·0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of ≥30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARS-CoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. FINDINGS: Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38-56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52·3 [95% CI 42·9-63·9] at day 0 vs 128·9 [105·6-157·4] at day 28; seropositive controls 53·3 [45·4-62·5] at day 0 vs 202·0 [174·8-233·4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39-83] at day 0 vs 82% [54-96] at day 28; seropositive controls 58% [41-79] at day 0 vs 92% [79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137·1 [116·2-161·9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188·6 [167·4-212·6] and neutralising antibody activity was 92% [75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2·3 (95% CI 2·2-2·3) at day 0, 5·7 (5·1-6·4) at day 28, and 29·6 (26·4-33·3) at day 69, and in seronegative controls were 2·3 (2·1-2·5) at day 0, 10·6 (8·7-13·1) at day 28, and 71·7 (63·5-81·0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. INTERPRETATION: By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3-Bolsa de Valores do Brasil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Cost-effectiveness analysis of a universal infant immunization program with meningococcal C conjugate vaccine in Brazil.

OBJECTIVE: To analyze the cost-effectiveness of a meningococcal C vaccination program in Brazil. METHODS: A hypothetical cohort of 3,194,038 children born in Brazil in 2006 was followed for 10 years. A decision tree model was developed using the TreeAge Pro 2007 software program to compare universal infant vaccination with the current program. Epidemiological and cost estimates were based on data retrieved from National Health Information Systems and the literature. The analysis was conducted from the public health care system and societal perspectives. Costs are expressed in 2006 Brazilian reals (R$). RESULTS: At 94% coverage, the program would avoid 1,218 cases, 210 deaths, and 14,473 life-years lost, a reduction of, respectively, 45%, 44%, and 44%, for the 10-year period. Vaccination costs of R$320.9 million would not be offset by R$4 to R$7.9 million decreases in disease treatment costs. A national vaccination program would cost R$21,620 per life-year saved from the perspective of the health-care system and R$21,896 per life-year saved from society's perspective. Results were most sensitive to case fatality rate, disease incidence, and vaccine cost. CONCLUSIONS: A universal childhood vaccination program against meningococcal C proved to be a cost-effective strategy, supporting the recent decision of the Brazilian government. These results could contribute to defining the most favorable price of the vaccine and to monitoring its impact on the population.