Prevalence of spondyloarthritis in inflammatory bowel disease according ASAS and ultrassonography and its correlation with plasma calprotectin.

BACKGROUND: Enteropathic spondyloarthritis is underdiagnosed and inflammatory biomarkers and ultrasonography (US) could be useful for screening inflammatory bowel disease (IBD) patients. The objective of this study was to evaluate the prevalence of spondyloarthritis (SpA) in IBD patients, according to the Assessment of SpondyloArthritis International Society (ASAS) criteria and the correlation of results of US of entheses and joints with plasma calprotectin levels. METHODS: This was an observational cross-sectional study. Patients from the IBD outpatient clinic of a reference center were evaluated according to ASAS criteria classification, results of US of entheses and joints, and inflammatory biomarker measurements (erythrocyte sedimentation rates, C-reactive protein levels, fecal and plasma calprotectin levels). A p value lower than 0.05 was considered significant. RESULTS: A total of 30.5% of the studied sample (n = 118) of patients with IBD presented at least one inflammatory musculoskeletal manifestation. The overall prevalence of enteropathic SpA was 13.55%, with 10.16% axial SpA and 4.23% peripheral SpA according to the ASAS criteria. A total of 42.1% of patients had an MASEI score greater than 18, 35.2% had synovitis, and 14.7% had tenosynovitis on US, increasing the frequency of diagnosis of enteropathic SpA to 22.8%. Plasma calprotectin levels were similar to those in healthy controls, and correlated only with the fecal calprotectin level (p 0.041). CONCLUSIONS: A total of 13.5% of patients met the criteria in accordance with the ASAS criteria for enteropathic SpA, which increased to 22.8% with the addition of US. The prevalence of enthesitis, synovitis and tenosynovitis by US of symptomatic joints and entheses were 42%, 35% and 14.7% respectively. Plasma calprotectin was correlated with fecal calprotectin but not with inflammatory biomarkers or US or ASAS criteria.

Plaque Reduction Neutralization Test (PRNT) Accuracy in Evaluating Humoral Immune Response to SARS-CoV-2.

Massive vaccination positively impacted the SARS-CoV-2 pandemic, being a strategy to increase the titers of neutralizing antibodies (NAbs) in the population. Assessing NAb levels and understanding the kinetics of NAb responses is critical for evaluating immune protection. In this study, we optimized and validated a PRNT50 assay to assess 50% virus neutralization and evaluated its accuracy to measure NAbs to the original strain or variant of SARS-CoV-2. The optimal settings were selected, such as the cell (2 × 105 cells/well) and CMC (1.5%) concentrations and the viral input (~60 PFU/well) for PRNT-SARS-CoV-2 with cut-off point = 1.64 log5 based on the ROC curve (AUC = 0.999). The validated PRNT-SARS-CoV-2 assay presented high accuracy with an intraassay precision of 100% for testing samples with different NAb levels (low, medium, and high titers). The method displays high selectivity without cross-reactivity with dengue (DENV), measles (MV), zika (ZIKV), and yellow fever (YFV) viruses. In addition, the standardized PRNT-SARS-CoV-2 assay presented robustness when submitted to controlled variations. The validated PRNT assay was employed to test over 1000 specimens from subjects with positive or negative diagnoses for SARS-CoV-2 infection. Patients with severe COVID-19 exhibited higher levels of NAbs than those presenting mild symptoms for both the Wuhan strain and Omicron. In conclusion, this study provides a detailed description of an optimized and validated PRNT50 assay to monitor immune protection and to subsidize surveillance policies applied to epidemiologic studies of COVID-19.

The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Half dose ChAdOx1 nCoV-19 vaccine was equivalent to full doses to reduce moderate and severe COVID-19 cases.

Objectives: Previously, we presented the effectiveness of ChAdOx1 nCoV-19 half-dose (HD) immunization for preventing new COVID-19 cases. Here, we evaluated the administration of an HD of ChAdOx1 nCoV-19 in the primary immunization protocol (up to two doses) in reducing moderate and severe cases, hospitalizations, and deaths when compared to the administration of full doses (FD) after a long-term follow-up. Methods: We evaluated data from 29,469 participants between January 2021 and November 2022 who received an HD or FD vaccine and crossed this information with their medical records to identify those who developed moderate or severe cases. All participants were classified into four groups according to their immunization status and followed 500 days after the last vaccine administration. Results: The propensity-score matching analysis indicates that the administration of the two HDs of ChAdOx1 nCoV-19 was equivalent to the use of two FDs to reduce moderate and severe COVID-19 cases. The relative risk of being infected and developing moderate or severe conditions after the administration of at least one HD or FD was similar 150 or 500 days after the administration of the immunizers. Conclusion: Administering two HDs can be used safely as a cost-effective alternative to the primary immunization protocol.

Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis.

OBJECTIVES: To analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). METHODS: For the present study, the following variables were selected for harmonization and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD. RESULTS: The results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. CONCLUSIONS: For the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.

Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome.

OBJECTIVES: To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. METHODS: For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. RESULTS: After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. CONCLUSIONS: Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.

Timeline kinetics of protective immunity to SARS-CoV-2 upon primary vaccination and humoral response to variants after booster dose.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4-6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

Serum soluble mediators as prognostic biomarkers for morbidity, disease outcome, and late-relapsing hepatitis in yellow fever patients.

This study described a soluble mediator storm in acute Yellow Fever/YF infection along the kinetics timeline towards convalescent disease. The analyses of the YF Viral RNAnemia, chemokines, cytokines, and growth factors were performed in YF patients at acute/(D1-15) and convalescent/(D16-315) phases. Patients with acute YF infection displayed a trimodal viremia profile spreading along D3, D6, and D8-14. A massive storm of mediators was observed in acute YF. Higher levels of mediators were observed in YF with higher morbidity scores, patients under intensive care, and those progressing to death than in YF patients who progress to late-relapsing hepatitis/L-Hep. A unimodal peak of biomarkers around D4-6 with a progressive decrease towards D181-315 was observed in non-L-Hep patients, while a bimodal pattern with a second peak around D61-90 was associated with L-Hep. This study provided a comprehensive landscape of evidence that distinct immune responses drive pathogenesis, disease progression, and L-Hep in YF patients.

Prevalence of Sjögren's syndrome according to 2016 ACR-EULAR classification criteria in patients with systemic lupus erythematosus.

BACKGROUND: Diagnosis of SS is a complex task, as no symptom or test is unique to this syndrome. The American-European Consensus Group (AECG 2002) and the American-European classification criteria of 2016 (ACR/EULAR 2016) emerged through a search for consensus. This study aims to assess the prevalence of Sjögren's Syndrome (SS) in patients with Systemic Lupus Erythematosus (SLE), according to AECG 2002 and ACR-EULAR 2016 classifications, as well as clinical and histopathological features in this overlap. To date, there is no study that has evaluated SS in SLE, using the two current criteria. METHODS: This cross-sectional study evaluated 237 SLE patients at the outpatient rheumatology clinic between 2016 and 2018. Patients were submitted to a dryness questionnaire, whole unstimulated salivary flow (WUSF), "Ocular Staining Score" (OSS), Schirmer's test I (ST-I), and labial salivary gland biopsy (LSGB). RESULTS: After verifying inclusion and exclusion criteria, a total of 117 patients were evaluated, with predominance of females (94%) and mixed ethnicity (49.6%). The prevalence of SS was 23% according to AECG 2002 and 35% to ACR-EULAR 2016. Kappa agreement between AECG 2002 and ACR-EULAR 2016 were 0.7 (p < 0.0001). After logistic regression, predictors for SS were: anti/Ro (OR = 17.86, p < 0.05), focal lymphocytic sialadenitis (OR = 3.69, p < 0.05), OSS ≥ 5 (OR = 7.50, p < 0.05), ST I positive (OR = 2.67, p < 0.05), and WUSF ≤ 0.1 mL/min (OR = 4.13, p < 0.05). CONCLUSION: The prevalence of SS in SLE was 23% (AECG 2002) and 35% (ACR-EULAR 2016). The presence of glandular dysfunction, focal lymphocytic sialadenitis, and anti/Ro were predictors of SS in SLE. The greatest advantage of the new ACR-EULAR 2016 criteria is to enable an early diagnosis and identify the overlapping of these two diseases. ACR-EULAR 2016 criteria is not yet validated for secondary SS and this study is a pioneer in investigating prevalence based on the new criteria.

Clinical risk factors for predicting anti-Sars-Cov-2 antibody immunoreactivity duration after mild COVID-19 infection / Fatores de risco clínicos para predizer a duração da imunoresatividade do anticorpo anti-Sars-Cov-2 após infecção leve por COVID-19

Introduction: coronavirus disease 2019 (COVID-19) is a complex multisystem disorder. It is not yet well known whether symptoms in the acute phase correlate with the duration of the immune response and the persistence of chronic symptoms.Objective: this study aimed to assess and monitor the clinical symptoms of COVID-19 and correlate them with the production of neutralizing antibodies.Methods: a cohort of 69 health workers at the University Hospital of the Federal University of Espírito Santo (HUCAM-UFES/EBSERH) diagnosed with SARS-CoV-2 infection confirmed via RT-PCR (Real-Time Reverse Transcription­Polymerase Chain Reaction) were evaluated from the onset of symptoms up to six months. SARS-CoV-2 IgG and IgM assays were used to detect the presence of IgG and IgM against the nucleocapsid protein of SARS-CoV-2 in serum samples. IgG and IgM antibody serology, pulmonary function via spirometry, and the clinical evolution of patients were performed at 15, 30, 45, 60, 90, and 180 days after the onset of COVID-19 symptoms.Results: sixty-nine health workers (age, 40 ± 10 years; 74% women) were evaluated for six months. All subjects showed mild to moderate COVID-19. The mean number of symptoms was 5.1 (± 2.3). The most common initial symptoms were muscle pain (77%), headache (75%), anosmia (70%), ageusia (64%), runny nose (59%), fever (52%), and coughing (52%). After 30 days, the patients had anosmia (18%), asthenia (18%), adynamia (14%), muscle pain (7%), and ageusia (7%). Regarding lung function, 9.25% presented with an obstructive pattern, and all recovered after six months. Of all analyzed participants, 18/69 (26%) did not have any reactive IgG or IgM values in any of the assessments. The IgG serology curve showed a peak, whereas IgM had the highest mean value on the 15th day. There was a progressive decrease and levels similar to those at baseline after 90 days, and 15/53 (28%) remained with reactive IgG after six months. Sore throat and shortness of breath were found to be independent risk factors, and patients with these symptoms were 5.9 times more likely to have reactive IgG on the 180th day. Patients with diarrhea were four times more likely to have reactive IgM.Conclusion: our findings showed that 26% of patients did not produce a humoral response post-mild COVID-19. Their antibody titers dropped significantly after 90 days, and only 28% maintained reactive IgG antibodies after six months. Sore throat and shortness of breath are predictors of a longer duration of the humoral immune response.

Introdução: a doença causada pelo coronavírus (COVID-19) é complexa e multissistêmica. Ainda não se sabe se os sintomas da fase aguda estão correlacionados com a duração da resposta imune e com a persistência dos sintomas crônicos.Objetivo: o presente estudo visa acessar e monitorar os sintomas clínicos do COVID-19, correlacionando-os com a produção de anticorpos neutralizantes.Método: uma coorte de 69 profissionais da saúde da Universidade Federal do Espírito Santo (HUCAM-UFES/EBSERH) diagnosticados com infecção por SARS-CoV-2 confirmada via RT-PCR (Real-Time Reverse Transcription-Polymerase Chain Reaction) foram avaliados do início dos sintomas até seis meses depois. Exames laboratoriais de IgG e IgM foram utilizados para detectar a presença de IgG e IgM contra a proteína do nucleocapsídeo do vírus SARS-CoV-2 nas amostras de plasma sanguíneo. Sorologia de anticorpos IgG e IgM, função pulmonar via espirometria e avaliação clínica dos pacientes foram realizadas nos dias 15, 30, 45, 60, 90 e 180 após o início dos sintomas da doença.Resultados: sessenta e nove profissionais da saúde (idade, 40 ± 10 anos; 74% mulheres) foram avaliados por seis meses. Todos apresentaram a forma leve a moderada do COVID-19. O número médio de sintomas foi 5.1 (± 2.3). O sintoma inicial mais comum foi dor muscular (77%), cefaleia (75%), anosmia (70%), ageusia (64%), coriza (59%), febre (52%), e tosse (52%). Após 30 dias, os pacientes mantiveram anosmia (18%), astenia (18%), adinamia (14%), dor muscular (7%), e ageusia (7%). Em relação à função pulmonar, 9.25% apresentaram padrão obstrutivo e todos recuperaram ao final dos seis meses. Dentre todos os participantes analisados, 18/69 (26%) não obtiveram nenhum valor de IgG e IgM considerados reagentes nos exames realizados. A curva sorológica de IgG mostrou um pico enquanto a de IgM apresentou seu maior valor médio no 15º dia. Houve um declínio progressivo e níveis similares aos basais aos 90. 15/53 (28%) permaneceram com IgG reagente após seis meses. Dor de garganta e dispneia foram considerados fatores de risco independentes, e os pacientes com esses sintomas tiveram 5,9 vezes mais chances de apresentar IgG reativa no 180º dia. Pacientes com diarreia tiveram quatro vezes mais chances de apresentar IgM reagente.Conclusão: nossos achados mostraram que 26% dos pacientes não produziram uma resposta humoral pós-COVID-19 leve. Seus títulos de anticorpos caíram significativamente após 90 dias e apenas 28% mantiveram anticorpos IgG reativos após seis meses. Dor de garganta e dispneia foram preditores de maior duração da resposta imune humoral

Participating as a research team during the COVID-19 pandemic benefits mental health of undergraduate medical students in Brazil.

During the COVID-19 pandemic, undergraduate medical students (UMS) exposed to isolation, social distancing and complete or partial face-to-face educational activities interruption may present increased stress, depression and anxiety. This study was undertaken to evaluate if, during isolation, UMS involved in online group activities as investigators of a research project (volunteer group) would present better mental health than their colleagues, not involved in that research (control group). A Web-based survey, via the Google Forms platform, including details on demographic data, life habits, previous health conditions, worries with the COVID-19 pandemic, sleep pattern modifications and depression, anxiety and mental stress, using the DASS-21 (Depression, Anxiety and Stress Scale) was implemented from 20 July to 31 August 2020. Statistical analysis was performed using the SPSS version 20.0. A p-value <0.05 was significant. A total of 684 UMS were included, 228 as a volunteer group and 456 as a control group. Mean age was 23.15 (3.16) years. The groups were paired for age, gender, ethnicity, life habits and previous health conditions. Older age, male gender, participation in the research project, unchanged sleep pattern during the pandemic, lack of fear from getting the COVID-19 and lack of previous health conditions were associated with lower DASS21 scores (better mental health). Participating as investigators of a research project foreseeing frequent interaction with patients, colleagues and professors (other investigators) lead to better mental health during the COVID-19 quarantine in Brazil.

Prevalence of Sjögren's syndrome according to 2016 ACR-EULAR classification criteria in patients with systemic lupus erythematosus

Abstract Background Diagnosis of SS is a complex task, as no symptom or test is unique to this syndrome. The American-European Consensus Group (AECG 2002) and the American-European classification criteria of 2016 (ACR/EULAR 2016) emerged through a search for consensus. This study aims to assess the prevalence of Sjögren's Syndrome (SS) in patients with Systemic Lupus Erythematosus (SLE), according to AECG 2002 and ACR-EULAR 2016 classifications, as well as clinical and histopathological features in this overlap. To date, there is no study that has evaluated SS in SLE, using the two current criteria. Methods This cross-sectional study evaluated 237 SLE patients at the outpatient rheumatology clinic between 2016 and 2018. Patients were submitted to a dryness questionnaire, whole unstimulated salivary flow (WUSF), "Ocular Staining Score" (OSS), Schirmer's test I (ST-I), and labial salivary gland biopsy (LSGB). Results After verifying inclusion and exclusion criteria, a total of 117 patients were evaluated, with predominance of females (94%) and mixed ethnicity (49.6%). The prevalence of SS was 23% according to AECG 2002 and 35% to ACR- EULAR 2016. Kappa agreement between AECG 2002 and ACR-EULAR 2016 were 0.7 (p < 0.0001). After logistic regression, predictors for SS were: anti/Ro (OR = 17.86, p < 0.05), focal lymphocytic sialadenitis (OR = 3.69, p < 0.05), OSS ≥ 5 (OR = 7.50, p < 0.05), ST I positive (OR = 2.67, p < 0.05), and WUSF ≤ 0.1 mL/min (OR = 4.13, p < 0.05). Conclusion The prevalence of SS in SLE was 23% (AECG 2002) and 35% (ACR-EULAR 2016). The presence of glandular dysfunction, focal lymphocytic sialadenitis, and anti/Ro were predictors of SS in SLE. The greatest advantage of the new ACR-EULAR 2016 criteria is to enable an early diagnosis and identify the overlapping of these two diseases. ACR- EULAR 2016 criteria is not yet validated for secondary SS and this study is a pioneer in investigating prevalence based on the new criteria.

Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients.

The present study applied distinct models of descriptive analysis to explore the integrative networks and the kinetic timeline of serum soluble mediators to select a set of systemic biomarkers applicable for the clinical management of COVID-19 patients. For this purpose, a total of 246 participants (82 COVID-19 and 164 healthy controls - HC) were enrolled in a prospective observational study. Serum soluble mediators were quantified by high-throughput microbeads array on hospital admission (D0) and at consecutive timepoints (D1-6 and D7-20). The results reinforce that the COVID-19 group exhibited a massive storm of serum soluble mediators. While increased levels of CCL3 and G-CSF were associated with the favorable prognosis of non-mechanical ventilation (nMV) or discharge, high levels of CXCL10 and IL-6 were observed in patients progressing to mechanical ventilation (MV) or death. At the time of admission, COVID-19 patients presented a complex and robust serum soluble mediator network, with a higher number of strong correlations involving IFN-γ, IL-1Ra and IL-9 observed in patients progressing to MV or death. Multivariate regression analysis demonstrates the ability of serum soluble mediators to cluster COVID-19 from HC. Ascendant fold change signatures and the kinetic timeline analysis further confirmed that the pairs "CCL3 and G-CSF" and "CXCL10 and IL-6" were associated with favorable or poor prognosis, respectively. A selected set of systemic mediators (IL-6, IFN-γ, IL-1Ra, IL-13, PDGF and IL-7) were identified as putative laboratory markers, applicable as complementary records for the clinical management of patients with severe COVID-19.

Safety and efficacy of SARS-CoV-2 vaccination in 1237 patients with primary Sjögren syndrome.

OBJECTIVES: To investigate the safety and efficacy of SARS-Cov-2 vaccination in patients with primary Sjögren syndrome (pSS) due to scarcity of data in this population. METHODS: By the first week of May 2021, all Big Data SS Consortium centres patients who had received at least one dose of any SARS-CoV-2 vaccine were included in the study. The in-charge physician asked patients about local and systemic reactogenicity to collect SARS-CoV-2 vaccination data. RESULTS: The vaccination data of 1237 patients were received. A total of 835 patients (67%) reported any adverse events (AEs), including local (53%) and systemic (50%) AEs. Subjective symptoms (63%) were the most common local AEs, followed by objective signs at the injection site (16%), and general symptoms were the most commonly reported systemic AEs (46%), followed by musculoskeletal (25%), gastrointestinal (9%), cardiopulmonary (3%), and neurological (2%). In addition, 141 (11%) patients reported a significant worsening/exacerbation of their pre-vaccination sicca symptoms and fifteen (1.2%) patients reported active involvement in the glandular (n=7), articular (n=7), cutaneous (n=6), pulmonary (n=2), and peripheral nervous system (n=1) domains due to post-vaccination SS flares. In terms of vaccination efficacy, breakthrough SARS-CoV-2 infection was confirmed after vaccination in three (0.24 %) patients, and positive anti-SARS-Cov-2 antibodies were detected in approximately 95% of vaccinated SS patients, according to data available. CONCLUSIONS: Our data suggest that patients with pSS develop adequate humoral response and no severe AEs after SARS-CoV-2 vaccination and therefore raise no concerns about the vaccine's efficacy or safety profile in this population.

Pesquisas em vacinas contra a Covid-19 de interesse para o sistema público de saúde: uma experiência de integração de instituições de ensino e pesquisa com o Sistema Único de Saúde do Brasil

Este é um relato da experiência de parcerias entre instituições públicas para o desenvolvimento de pesquisas de vacinas contra a COVID-19 implementadas no âmbito do Sistema Único de Saúde (SUS), no Estado do Espírito Santo, com ênfase nas vacinas de produção nacional, pela Fiocruz e Butantan. A decisão política e estratégica dos gestores do SUS de investir em pesquisa e inovação, aplicados nos projetos de pesquisa descritos nesse relato, está alinhada com os aspectos políticos centrais do Complexo Econômico Industrial da Saúde (CEIS) que considera: 1) a inovação como um processo de transformação política, econômica e social; 2) a articulação entre lógica econômica e social; 3) assimetrias e sustentabilidade do SUS; 4) visão sistêmica e 5) papel do estado. O artigo faz uma revisão dos conceitos do CEIS, da formação dos Programas de Parcerias para o Desenvolvimento Produtivo (PDPs) na última década, e da importância dessas políticas na incorporação de tecnologias para produção nacional de vacinas, e financiamento de pesquisas de interesse do SUS para as estratégias de vacinação do Brasil. O artigo descreve as parcerias, as formas de financiamento e a integração ensino-pesquisa-serviço no âmbito do SUS para viabilizar 4 estudos e 2 colaborações em estudos nacionais, desenvolvidos pelo Hospital Universitário Cassiano Antônio Moraes da Universitário do Espírito Santo, da rede de Empresa Brasileira de Serviços Hospitalares (HUCAM-UFES/EBSERH), por meio do Instituto Capixaba de Ensino, Pesquisa e Inovação (ICEPI), uma instituição de Ciência e Tecnologia (IC&T) do governo do Estado do Espírito Santo.

Anti-SARS-CoV-2 antibody immunoreactivity profiles during COVID-19 recurrence.

BACKGROUND: This study aimed to evaluate IgG and IgM levels in COVID-19 recurrence. METHODS: The serum antibody levels and clinical data from 73 healthcare workers with SARS-CoV-2 divided into seroconverted (n=51) and non-seroconverted (n=22) groups were assessed. The presence of specific anti-nucleocapsid (anti-N) IgM and IgG for SARS-CoV-2 was evaluated. IgG antibodies to the SARS-CoV-2 spike receptor-binding domain were used to confirm non-seroconversion in all negative anti-N. RESULTS: Four recurrent cases displayed mild symptoms and were non-seroconverted until the recurrence of symptoms. CONCLUSIONS: Undetectable anti-nucleocapsid IgM and IgG levels may be correlated with symptomatic COVID-19 recurrence.

Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sjögren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian society of rheumatology (hepatic, gastrointestinal and pancreatic).

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.

Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project.

Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.

VI Brazilian consensus guidelines for detection of anti-cell autoantibodies on HEp-2 cells.

BACKGROUND: The VI Brazilian Consensus on Autoantibodies against HEp-2 cells for determination of autoantibodies against cellular constituents on HEp-2 cells was held on September, 2019, in Fortaleza (CE, Brazil). The guidelines in this edition were formulated by the group of Brazilian experts discussing the classification of complex patterns, the classification of the nuclear discrete dots (few and multiple), the identification of the discrete fine speckled pattern (AC-4a) and improvements on the ANA report. MAINBODY: Sixteen Brazilian researchers and experts from universities and clinical laboratories representing the various geographical regions of Brazil participated in the meeting. Four main topics were discussed: (1) How to classify patterns with fluorescence in more than one cell compartment considering three relevant categoris: composite patterns, mixed patterns and multiple patterns; (2) The splitting of the discrete nuclear dots pattern into the multiple discrete nuclear dots (AC-6) and few discrete nuclear dots (AC-7) patterns, respectively; (3) Inclusion of a novel nuclear pattern characterized by discrete fine speckled pattern highly associated with antibodies to SS-A/Ro60, classified as AC-4a. In addition, adjustments on the Brazilian Consensus nomenclature were implemented aiming to harmonize the designation of some patterns with the International Consensus on ANA Patterns (ICAP). Furthermore, the designations of the PCNA-like pattern (AC-13), CENP-F-like pattern (AC-14) and Topo I-like pattern (AC-29) were adjusted in accordance to ICAP. Finally, there was a recommendation for adjustment in the test report in order to address the status of nuclear envelope staining. For all topics, the aim was to establish specific guidelines for laboratories and clinicians. All recommendations were based on consensus among participants. All recommendations from the V Consensus were maintained and there was relevant progress in the BCA/HEp-2 guidelines and further harmonization with ICAP. CONCLUSION: The VI BCA/HEp-2 edition was successful in establishing important recommendations regarding the classification of complex patterns, in supporting the identification of a novel pattern within the AC-4 group and in the harmonization process with the ICAP terminology.