Effectiveness of the BNT162b2 mRNA Covid-19 vaccine in Spanish healthcare workers

IntroductionFrontline health care workers (HCW) have higher risk than the general population to become infected by SARS.CoV.2, so they were a priority group for Covid-19 vaccine administration. We compared the incidence and prevalence of HCW infected pre-and post-vaccination with the BNT162b2 mRNA COVID-19 vaccine.Material and methodsProspective observational study carried out between 01/12/20 and 07/03/21 in La Paz University Hospital, Madrid (Spain). SARS.CoV.2 positive cases in HCW after vaccination were collected and compared to those hospitalized COVID-19 patients at the same hospital.ResultsTwo weeks after finishing the first round of vaccinations daily new cases of HCW infections (symptomatic and asymptomatic) decreased substantially and cumulative cases of infected HCW and hospitalized COVID-19 patients started to diverge. No new positive cases of HCW infection were registered seven days after the second dose of BNT162b2 mRNA COVID-19 vaccine.ConclusionsBNT162b2 mRNA COVID-19 vaccine is highly effective in Spanish HCW.     

Adverse reactions to BNT162b2 mRNA COVID-19 vaccine in medical staff with a history of allergy

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) vaccination is progressing globally. Several adverse reactions have been reported with vaccination against COVID-19. It is unknown whether adverse reactions to COVID-19 vaccination are severe in individuals with allergies.MethodsWe administered the COVID-19 vaccine to the medical staff at Yamagata University Hospital from March to August 2021. Subsequently, we conducted an online questionnaire-based survey to investigate the presence of allergy and adverse reactions after vaccination and examine the association between allergy and adverse reactions after immunization.ResultsResponses were collected from 1586 to 1306 participants after the first and second administration of the BNT162b2 mRNA COVID-19 vaccine, respectively. Adverse reactions included injection site pain, injection site swelling, fever, fatigue or malaise, headache, chills, nausea, muscle pain outside the injection site, and arthralgia. The frequency of some adverse reactions and their severity were higher, and the duration of symptoms was longer in participants with allergies than in those without allergies. Although several participants visited the emergency room for treatment after the first and second vaccinations, no participant was diagnosed with anaphylaxis.ConclusionsThis study suggests that the frequency and severity of adverse reactions after injection of BNT162b2 mRNA COVID-19 vaccine were higher in individuals with allergy; however, no severe adverse reactions such as anaphylaxis or death were observed. These results indicate that individuals with allergic histories may tolerate the BNT162b2 mRNA COVID-19 vaccine.     

Characterization of Serum and Mucosal SARS-CoV-2-Antibodies in HIV-1-Infected Subjects after BNT162b2 mRNA Vaccination or SARS-CoV-2 Infection

Only limited data are available regarding the immunogenicity of the BNT162b2 mRNA vaccine in HIV-1⁺ patients. Therefore, we investigated the humoral immune response after BNT162b2-mRNA vaccination or SARS-CoV-2 infection in HIV-1⁺ patients on antiretroviral therapy compared to HIV-1-uninfected subjects. Serum and saliva samples were analysed by SARS-CoV-2 spike-specific IgG and IgA ELISAs and a surrogate neutralization assay. While all subjects developed anti-spike IgG and IgA and neutralizing antibodies in serum after two doses of BNT162b2 mRNA vaccine, the HIV-1⁺ subjects displayed significantly lower neutralizing capacity and anti-spike IgA in serum compared to HIV-1-uninfected subjects. Serum levels of anti-spike IgG and neutralizing activity were significantly higher in vaccinees compared to SARS-CoV-2 convalescents irrespective of HIV-1 status. Among SARS-CoV-2 convalescents, there was no significant difference in spike-specific antibody response between HIV-1⁺ and uninfected subjects. In saliva, anti-spike IgG and IgA antibodies were detected both in vaccinees and convalescents, albeit at lower frequencies compared to the serum and only rarely with detectable neutralizing activity. In summary, our study demonstrates that the BNT162b2 mRNA vaccine induces SARS-CoV-2-specific antibodies in HIV-1-infected patients on antiretroviral therapy, however, lower vaccine induced neutralization activity indicates a lower functionality of the humoral vaccine response in HIV-1⁺ patients.     

Safety of the BNT162b2 mRNA COVID-19 vaccine in oncologic patients undergoing numerous cancer treatment options: A retrospective single-center study

The COVID-19 pandemic, caused by the SARS-CoV2 virus, has infected millions worldwide with cancer patients demonstrating a higher prevalence for severe disease and poorer outcomes. Recently, the BNT162b2 mRNA COVID-19 vaccine was released as the primary means to combat COVID-19. The currently reported incidence of local and systemic side effects was 27% in the general public. The safety of the BNT162b2 mRNA COVID-19 vaccine has not been studied in patients with an active cancer diagnosis who are either ongoing or plan to undergo oncologic therapy.This single center study reviewed the charts of 210 patients with active cancer diagnoses that received both doses of the BNT162b2 mRNA COVID-19 vaccine. The development of side effects from the vaccine, hospitalizations or exacerbations from various oncologic treatment were documented. Type of oncologic treatment (immunotherapy, chemotherapy, hormonal, biologic, radiation or mixed) was documented to identify if side effects were related to treatment type. The time at which the vaccine was administered in relation to treatment onset (on long term therapy, within 1 month of therapy or prior to therapy) was also documented to identify any relationships.Sixty five (31%) participants experienced side effects from the BNT162b2 mRNA COVID-19 vaccine, however most were mild to moderate. Treatment protocol was not linked to the development of vaccine related side effects (P = .202), nor was immunotherapy (P = .942). The timing of vaccine administered in relation to treatment onset was also not related to vaccine related side effects (P = .653). Six (2.9%) participants were hospitalized and 4 (2%) died.The incidence of side effects in cancer patients is similar to what has been reported for the general public (31% vs 27%). Therefore, we believe that the BNT162b2 mRNA COVID-19 vaccine is safe in oncologic patients undergoing numerous cancer treatments.     

Efficacy and safety results from a randomized double-blind study comparing proposed biosimilar ABP 798 with rituximab reference product in subjects with moderate-to-severe rheumatoid arthritis

Background/objectives

ABP 798 is a proposed biosimilar to the originator biologic rituximab, an anti-CD20 monoclonal antibody. This comparative clinical study evaluated the pharmacokinetics (PK), safety, and efficacy of ABP 798 versus rituximab reference product (RP) in patients with moderate-to-severe rheumatoid arthritis (RA).

Methods

Adults with moderate-to-severe RA with an inadequate response or intolerance to other disease-modifying anti-rheumatic drugs including 1 or more tumor necrosis factor inhibitor therapies (n = 311) received ABP 798, US-sourced rituximab RP (rituximab US), or EU-sourced rituximab RP (rituximab EU) (1000 mg, 2 weeks apart). At week 24, ABP 798- or rituximab EU-treated subjects received a second dose of the same treatment, while rituximab US-treated subjects transitioned to receive ABP 798. The key efficacy endpoint was DAS28-CRP change from baseline at week 24. Other efficacy endpoints included DAS28-CRP at other time points; ACR20, ACR50, and ACR70 criteria; and hybrid ACR. The rituximab RP groups were pooled for all efficacy endpoints since PK equivalence had been established between rituximab US and rituximab EU.

Results

Clinical equivalence between ABP 798 and rituximab RP was established as the 90% confidence interval for DAS28-CRP change from baseline at week 24 fell within the prespecified equivalence margin (− 0.6, 0.6). Safety and immunogenicity profiles of ABP 798 were comparable across treatment groups and not affected by single transition from RP to ABP 798.

Conclusions

Clinical equivalence in terms of efficacy, safety, and immunogenicity was established between ABP 798 and rituximab RP in this comparative clinical trial in patients with moderate-to-severe RA.

Immunogenicity against the BNT162b2 mRNA COVID-19 Vaccine in Rheumatic Disease Patients Receiving Immunosuppressive Therapy

Objective To investigate the serum total antibody (immunoglobulin M and immunoglobulin G) titre against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain following BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination in Japanese rheumatic disease patients undergoing immunosuppressive therapy. Methods The serum antibody titre against SARS-CoV-2 spike protein was analysed in 123 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers who had received 2 doses of the BNT162b2 mRNA vaccine with at least 14 days elapsing since the second dose. Results The antibody titre in rheumatic disease patients was significantly lower than that in healthy subjects (p<0.0001). The antibody titres of the 41 patients who received biologics or Janus kinase inhibitors and the 47 patients who received conventional immunosuppressive agents were significantly lower than those of the 35 patients who did not receive immunosuppressive agents (p<0.0001 and p<0.0001, respectively). In addition, the mean antibody titre of the 43 patients on methotrexate was significantly lower than that of the 80 patients not on methotrexate (p=0.0017). Conclusion Immunogenicity to the BNT162b2 mRNA COVID-19 vaccine in rheumatic disease patients was found to be reduced under immunosuppressive treatment. In particular, methotrexate seems to be associated with a decreased antibody response.     

Antibody Responses to the BNT162b2 mRNA Vaccine in Healthcare Workers in a General Hospital in Japan: A Comparison of Two Assays for Anti-spike Protein Immunoglobulin G

Objective This study assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses to the BNT162b2 mRNA vaccine in Japanese healthcare workers. Methods In this prospective cohort study, participants received two doses of the BNT162b2 mRNA vaccine on days 0 and 21 and provided blood for anti-SARS-CoV-2 antibody testing before the first vaccine and on days 21 and 35 after vaccination. Anti-spike protein immunoglobulin G (S-IgG) was measured using Abbott and Fujirebio chemiluminescent immunoassays. Patients One hundred healthcare workers (median age: 39 years old, interquartile range: 30-48 years old), including 6 who had been previously infected with SARS-CoV-2 and 3 individuals taking immunosuppressive drugs, participated in the study. Results The S-IgG antibody titers (AU/mL) measured using both the Abbott and Fujirebio assays increased significantly (p＜0.001) over time, both with a prevalence of 100% at 35 days after the first vaccination. The multivariate log-normal linear regression analysis indicated the effect of immunosuppressant medication using both the Abbott (p=0.013) and Fujirebio (p=0.039) assays on S-IgG levels after complete vaccination. Pearson''s correlation coefficient between the Abbott and Fujirebio S-IgG results in all 300 samples collected before and after vaccination and 50 positive controls from patients with coronavirus disease 2019 were 0.963 [95% confidence interval (CI): 0.954-0.970, p＜0.001] and 0.909 (95% CI: 0.845-0.948, p＜0.001), respectively. Conclusion The BNT162b2 mRNA vaccine was effective at increasing S-IgG levels in Japanese immunocompetent healthcare workers. The Fujirebio S-IgG assay showed high diagnostic accuracy, using the Abbott S-IgG assay as the reference test.     

Introduction of the BNT162b2 vaccine during a COVID-19 nursing home outbreak

BackgroundCoronavirus disease 2019 (COVID-19) outbreaks often occur in nursing homes and prompt frequent surveillance testing for SARS-CoV-2. A single dose of the BNT162b2 vaccine reduces viral load and transmission. In this study, we describe the real-world efficacy of BNT162b2 single-dose vaccination during a COVID-19 outbreak at a Veterans Affairs Community Living Center (CLC).MethodsFrom 12/2/20 to 5/14/21, twice weekly antigen testing was used to detect COVID-19 among 146 residents at the CLC. Residents without a prior history of COVID-19 who agreed to immunization were vaccinated with the BNT162b2 vaccine on 12/16/20 and 1/6/21. Single-dose vaccine efficacy was determined for days 1-21 and days 14-21 after the first vaccine dose.ResultsThe outbreak occurred from 12/2/20 to 1/7/21 with an attack rate of 30.8% (45/146); 46.7% (21/45) of the cases were due to asymptomatic COVID-19. One unit accounted for 77.8% (35/45) of the cases. In the vaccine analysis, 116 residents were a median age of 74.5 years and 93.1% (108/116) had ≥ 1 comorbid condition. Between the first and second dose, 15.5% (15/97) of vaccinated residents, and 21.2% (4/19) of unvaccinated residents developed COVID-19 (P = .81). One week after the second dose, no cases of COVID-19 occurred.ConclusionsAlbeit limited by the small numbers, a single dose of the BNT162b2 vaccine was not efficacious at preventing COVID-19 during this nursing home outbreak.     

Factors Associated with Change in SARS-CoV-2 Antibody Titers from Three to Six Months after the Administration of the BNT162b2 mRNA COVID-19 Vaccine among Healthcare Workers in Japan: A Prospective Study

Objective We evaluated the change in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers from three to six months after the administration of the BNT162b2 vaccine among healthcare workers. Methods A total of 337 healthcare workers who received 2 doses of the BNT162b2 vaccine were included in this study. Factors associated with SARS-CoV-2 antibody titers at three and six months and the change in SARS-CoV-2 antibody titers between three and six months after vaccine administration were analyzed using a logistic regression analysis. Results The SARS-CoV-2 antibody titer at 3 months was 4,812.1±3,762.9 AU/mL in all subjects and was lower in older workers than in younger ones. The SARS-CoV-2 antibody titer at 6 months was 1,368.9±1,412.3 AU/mL in all subjects. The SARS-CoV-2 antibody titers that were found to be high at three months were also high at six months. The change in SARS-CoV-2 antibody titers from 3 to 6 months was -68.9%±16.1%. The higher SARS-CoV-2 antibody titers at three months showed a more marked decrease from three to six months than lower titers. Conclusion This study demonstrates that SARS-CoV-2 antibody titers at three months decreased with age and were associated with the antibody titers at six months and the change in titer from three to six months. Older individuals in particular need to be aware of the declining SARS-CoV-2 antibody titers at six months after the BNT162b2 vaccine. The results of this study may provide insight into COVID-19 vaccine booster strategies.     

Behçet’s disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature

Objectives

The present work was conducted to estimate the prevalence of adult Behçet’s disease (BD) in adult Egyptian and to study the clinical pattern and influence of age at-onset and sex on disease phenotype. Also, we investigated the spectrum of presentation and frequencies along the north-to-south gradient of the country.

Patients and method

The population-based, multicenter, cross-sectional study included 1526 adult BD patients from 26 specialized Egyptian rheumatology centers. Demographic, clinical, and therapeutic data are assessed for all patients.

Results

The mean age of patients was 35.7 ± 9.84 years, disease duration 6.58 ± 5.25 years, and age at onset 29.37 ± 8.6 years; 91 were juvenile-onset (JoBD). There were 1102 males and 424 females (M:F 2.6:1). Regarding co-morbidities, 19.92% were diabetic, and 26.05% were hypertensive. The mean body mass index was 27.57 ± 5.24 (43.1% overweight; 25.9% obese). The mean BD current activity form was 4.48 ± 4.28. Regarding the medications use, systemic steroid and colchicine were the most common drugs used (947 (90.2%) and 611 (82.7%), respectively). The overall estimated prevalence of BD in Egypt was 3.6/100,000 population being highest in the two main cities: Alexandria (15.27) and Cairo (8.72). Pathergy test was positive in 43.4%. 90.2% were receiving systemic steroids and 8.3%, biologics. Disease characteristics were comparable between JoBD and adult-onset BD cases. Central nervous system (CNS), deep venous thrombosis (DVT), and gastrointestinal (GIT) involvement were significantly higher in males (p = 0.01, p = 0.001, and p = 0.001 respectively) while joint affection (p = 0.001) and disease activity (p = 0.011) were increased in females.

Conclusions

This study provides current prevalence of BD in Egypt; 3.6/100,000 with no remarkable north-to-south gradient. The sex influences the disease phenotype with the CNS, DVT, and GIT involvement are higher in males, while the joint affection and disease activity were increased in females.

Key Points

• The prevalence and phenotype of Behçet’s disease across Egypt is presented in a multicenter nationwide study.

• The potential influence of the age at onset and sex on disease phenotype is highlightened.

• A review of the literature worldwide is presented allowing comparisons with studies from other nations.

     

Is Metrnl an Adipokine İnvolved in the Anti-inflammatory Response to Acute Exacerbations of COPD?

Purpose

Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by airflow limitation and systemic inflammation. Recently, there has been growing interest in adipose tissue-mediated inflammation in the pathogenesis of COPD. The aim of our study was to determine the relationships between a new adipocytokine, meteorin-like protein (Metrnl), and acute exacerbations of COPD, smoking, and comorbidities.

Materials and Methods

The study included 313 patients aged 40–65 years in four groups: Group 1: ex-smokers (≥ 20 pack-years) with COPD hospitalized for COPD exacerbation (n = 133), Group 2: current-smokers (≥ 20 pack-years) without COPD (n = 60), Group 3: ex-smokers (≥ 20 pack-years) without COPD (n = 60), and Group 4: never-smokers without COPD (n = 60). Peripheral venous blood samples (5 cc) were collected from all participants. Plasma Metrnl levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kit.

Results

Mean Metrnl levels were 28.45 ± 11.27 ng/ml in Group 1, 24.34 ± 4.38 ng/ml in Group 2, 18.84 ± 3.8 ng/ml in Group 3, and 19.44 ± 3.92 ng/ml in Group 4. Group 1 had significantly higher mean Metrnl level compared to the other groups (p = 0.006, p = 0.001, p = 0.001). Metrnl level was also significantly higher in Group 2 when compared with Groups 3 and 4 (p = 0.001, p = 0.005). Group 1 patients with diabetes mellitus and coronary artery disease showed significantly lower Metrnl levels compared to other patients in the group (p = 0.001, p = 0.001).

Conclusion

The high Metrnl level in COPD exacerbations and active smoking may be important in balancing the inflammatory response. However, plasma Metrnl levels were found to be lower in COPD patients with comorbidities.

     

Side effects and antibody titer transition of the BNT162b2 messenger ribonucleic acid coronavirus disease 2019 vaccine in Japan

BackgroundThe coronavirus disease (COVID-19) has afflicted large populations worldwide. Although vaccines aroused great expectations, their side effects on Japanese people and the antibody titer transition after vaccination are unclear.MethodsThe side effects of the BNT162b2 mRNA COVID-19 vaccine in participants who received vaccination at our center were investigated. Some participants were also surveyed for the antibody titer transition.ResultsIn this study, 983 and 798 Japanese participants responded to the first and second doses, respectively. Side effects occurred in 757 (77.0%) and 715 participants (90.0%) after the first and second doses, respectively. No Grade 4 side effects occurred. The second dose had significantly more side effects than the first dose (p < 0.001). Side effects occurred after the second dose in 571 female (92.1%) and 178 male participants (80.1%). Female participants had a higher incidence of side effects than the male participants (p < 0.001). A comparison among the age groups showed significant differences (p = 0.018), and the frequency of side effects decreased with age. Twenty-three individuals participated in the survey of antibody titer transition. After the second vaccine dose, the median antibody titers for IgG and IgM were 3.76 and 0.07 AU/mL, respectively. Both IgG and IgM titers showed a significant increase over the study period (p < 0.001).ConclusionsThe BNT162b2 mRNA COVID-19 vaccine might be safe for Japanese people, and the antibody titer increased with two doses of vaccination. Larger nationwide studies are warranted to verify these findings.     

Systemic lupus erythematosus myocarditis after COVID-19 vaccination

IntroductionCases of acute myocarditis have been after administration of the BNT162b2 and Ad26.COV2.S vaccine.ObjectiveDescribe another possible mechanism of myocarditis after COVID-19 vaccination.Case presentationWe describe the clinical case of a 72-year-old female with pleuritic chest pain one week after the third of the BNT162b2 mRNA vaccine. Serological tests for cardiotropic pathogens were negative, and autoimmunity screening was positive with anti-nuclear antibody (ANA) in 1:160 dilution, Anti-double-stranded DNA (anti-dsDNA), and anti-histone antibodies. ¹⁸F-fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) showed a focal myocardial and pericardial inflammatory process in the cardiac apex.Results and discussionSystemic lupus erythematosus (SLE) diagnosis was made with myocardial affection. As far as we know, this is the first report of a case of lupus myocarditis after the COVID-19 vaccine.ConclusionGiven the pathogenic rationales, the association between SLE and myocarditis should be considered.     

Clinical predictors of remission and low disease activity in Latin American early rheumatoid arthritis: data from the GLADAR cohort

Objectives

To identify baseline predictors of remission and low disease activity (LDA) in early rheumatoid arthritis (RA) from the GLADAR (Grupo Latino Americano De estudio de la Artritis Reumatoide) cohort.

Methods

Patients with 1- and 2-year follow-up visits were included. Remission and LDA were defined by DAS28-ESR (< 2.6 and ≤ 3.2, respectively). Baseline predictors examined were gender, ethnicity, age at diagnosis, socioeconomic status, symptoms’ duration, DMARDs, RF, thrombocytosis, anemia, morning stiffness, DAS28-ESR (and its components), HAQ-DI, DMARDs and corticosteroid use, and Sharp-VDH score. Multivariable binary logistic regression models (excluding DAS28-ESR components to avoid over adjustment) were derived using a backward selection method (α-level set at 0.05).

Results

Four hundred ninety-eight patients were included. Remission and LDA/remission were met by 19.3% and 32.5% at the 1-year visit, respectively. For the 280 patients followed for 2 years, these outcomes were met by 24.3% and 38.9%, respectively. Predictors of remission at 1 year were a lower DAS28-ESR (OR 1.17; CI 1.07–1.27; p = 0.001) and HAQ-DI (OR 1.48; CI 1.04–2.10; p = 0.028). At 2 years, only DAS28-ESR (OR 1.40; CI 1.17–1.6; p < 0.001) was a predictor. Predictors of LDA/remission at 1 year were DAS28-ESR (OR 1.42; CI 1.26–1.61; p < 0.001), non-use of corticosteroid (OR 1.74; CI 1.11–2.44; p = 0.008), and male gender (OR 1.77; CI 1.2–2.63; p = 0.036). A lower baseline DAS28-ESR (OR 1.45; CI 1.23–1.70; p < 0.001) was the only predictor of LDA/remission at 2 years.

Conclusions

A lower disease activity consistently predicted remission and LDA/remission at 1 and 2 years of follow-up in early RA patients from the GLADAR cohort.

Spike-specific humoral and cellular immune responses after COVID-19 mRNA vaccination in patients with cirrhosis: A prospective single center study

Background and AimsCOVID-19 mRNA vaccines were approved to prevent severe forms of the disease, but their immunogenicity and safety in cirrhosis is poorly known.MethodIn this prospective single-center study enrolling patients with cirrhosis undergoing COVID-19 vaccination (BNT162b2 and mRNA-1273), we assessed humoral and cellular responses vs healthy controls, the incidence of breakthrough infections and adverse events (AEs). Antibodies against spike- and nucleocapsid-protein (anti-S and anti-N) and Spike-specific T-cells responses were quantified at baseline, 21 days after the first and second doses and during follow-up.Results182 cirrhotics (85% SARS-CoV-2-naïve) and 38 controls were enrolled. After 2 doses of vaccine, anti-S titres were significantly lower in cirrhotics vs controls [1,751 (0.4–25,000) U/mL vs 4,523 (259–25,000) U/mL, p=0.012] and in SARS-CoV-2-naïve vs previously infected cirrhotics [999 (0.4–17,329) U/mL vs 7,500 (12.5–25,000) U/mL, (p<0.001)]. T-cell responses in cirrhotics were similar to controls, although with different kinetics. In SARS-CoV-2-naïve cirrhotics, HCC, Child-Pugh B/C and BNT162b2 were independent predictors of low response. Neither unexpected nor severe AEs emerged. During follow-up, 2% turned SARS-CoV-2 positive, all asymptomatic.ConclusionHumoral response to COVID-19 vaccines appeared suboptimal in patients with cirrhosis, particularly in SARS-CoV-2-naïve decompensated cirrhotics, although cellular response appeared preserved, and low breakthrough infections rate was registered.     

Exercise Self-Efficacy and patient global assessment were associated with 6-min walk test distance in persons with rheumatoid arthritis

Introduction

Low functional capacity is related to future loss of daily function and cardiovascular events. The present study explored the associations of patient-reported outcome measures (PROMs) and disease-specific measures with functional capacity as measured by the 6-min walk test (6MWT) in persons with rheumatoid arthritis (RA).

Methods

Seventy-nine participants from rheumatology outpatient clinics were included. The distance walked during the 6MWT (6MWD) was the dependent variable in multivariable regression analyses. Model 1 included the independent variables sex, age (in tertiles to improve model fit), and body mass index (BMI). Building on Model 1, Model 2 added smoking, patient global assessment (PGA), Exercise Self-Efficacy, Hospital Anxiety and Depression Scale’s Depression score, and Cohen’s Perceived Stress Scale score, whereas Model 3 added smoking, disease duration, present use of glucocorticosteroids, seropositivity, Disease Activity Score 28—C-Reactive Protein (DAS28-CRP), and a comorbidity variable.

Results

Median age was 65 years, 76% were female, and median 6MWD was 493 m. In Model 1, BMI and age were significantly associated with the 6MWD (R² = 0.42). In Model 2, PGA and Exercise Self-Efficacy were also significantly associated with the 6MWD, with standardized regression coefficients of − 0.21 (p = 0.03) and 0.26 (p = 0.004) respectively (R² = 0.54). The RA-specific variables in Model 3 were not significantly associated with the 6MWD (R² = 0.49).

Conclusion

The PROMs PGA and Exercise Self-Efficacy were significantly associated with functional capacity as measured by the 6MWT in persons with RA, whereas disease-specific measures such as DAS28-CRP and disease duration were not.

Antibody Response Induced by BNT162b2 and mRNA-1273 Vaccines against the SARS-CoV-2 in a Cohort of Healthcare Workers

The aim of this study was to characterize the antibody response induced by SARS-CoV-2 mRNA vaccines in a cohort of healthcare workers. A total of 2247 serum samples were analyzed using the Elecsys^® Anti-SARS-CoV-2 S-test (Roche Diagnostics International Ltd., Rotkreuz, Switzerland). Sex, age, body mass index (BMI), arterial hypertension, smoking and time between infection and/or vaccination and serology were considered the confounding factors. Regarding the medians, subjects previously infected with SARS-CoV-2 who preserved their response to the nucleocapsid (N) protein showed higher humoral immunogenicity (BNT162b2: 6456.0 U/mL median; mRNA-1273: 2505.0 U/mL) compared with non-infected (BNT162b2: 867.0 U/mL; mRNA-1273: 2300.5 U/mL) and infected subjects with a lost response to N protein (BNT162b2: 2992.0 U/mL). After controlling for the confounders, a higher response was still observed for mRNA-1273 compared with BNT162b2 in uninfected individuals (FC = 2.35, p < 0.0001) but not in previously infected subjects (1.11 FC, p = 0.1862). The lowest levels of antibodies were detected in previously infected non-vaccinated individuals (39.4 U/mL). Clinical variables previously linked to poor prognoses regarding SARS-CoV-2 infection, such as age, BMI and arterial hypertension, were positively associated with increasing levels of anti-S protein antibody exclusively in infected subjects. The mRNA-1273 vaccine generated a higher antibody response to the S protein than BNT162b2 in non-infected subjects only.     

Low estimated glomerular filtration rate is an independent risk factor for higher hydroxychloroquine concentration

Background

The aim of this study was to analyze the relationship of the estimated glomerular filtration rate (eGFR) to hydroxychloroquine (HCQ) blood concentrations in systemic lupus erythematosus (SLE) patients.

Method

Patients with SLE who had been taking HCQ for more than 12 months were recruited. All subjects gave written informed consent. Various clinical characteristics and laboratory values were examined. The blood concentration of HCQ was measured by high-performance liquid chromatography, and the relationship of eGFR to HCQ blood concentration was mainly investigated.

Result

In total, 115 patients with SLE receiving long-term HCQ therapy were included in the study. The median concentration of HCQ was 1096 ng/ml (range 116–8240 ng/ml). The eGFR was strongly associated with blood concentration of HCQ (P = 0.011, P < 0.05), when adjusted for age, sex, body mass index (BMI), weight-adjusted dose, prednisone use and immunosuppressive drug use. No statistically significant association were found between age, duration, BMI, weight-adjusted HCQ dose, corticosteroid use, immunosuppressant use and blood concentrations of HCQ.

Conclusion

We provided novel evidence that impaired renal function influenced the blood concentration of HCQ. Patients with low eGFR need to adjust the HCQ dosage according to the monitoring results of HCQ blood concentrations.

Lung Transplant Recipients Immunogenicity after Heterologous ChAdOx1 nCoV-19—BNT162b2 mRNA Vaccination

(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0–491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0–159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2.     

Immunogenicity Following Administration of BNT162b2 and Ad26.COV2.S COVID-19 Vaccines in the Pregnant Population during the Third Trimester

Globally, COVID-19 vaccines are currently being used to prevent transmission and to reduce morbidity and death associated with SARS-CoV-2 infection. Current research reveals that vaccines such as BNT162b2 and Ad26.COV2.S are highly immunogenic and have high short-term effectiveness for most of the known viral variants. Clinical trials showed satisfying results in the general population, but the reluctance in testing and vaccinating pregnant women left this category with little evidence regarding the safety, efficacy, and immunogenicity following COVID-19 vaccination. With the worldwide incidence of COVID-19 remaining high and the possibility of new transmissible SARS-CoV-2 mutations, data on vaccination effectiveness and antibody dynamics in pregnant patients are critical for determining the need for special care or further booster doses. An observational study was developed to evaluate pregnant women receiving the complete COVID-19 vaccination scheme using the BNT162b2 and Ad26.COV2.S, and determine pregnancy-related outcomes in the mothers and their newborns, as well as determining adverse events after vaccination and immunogenicity of vaccines during four months. There were no abnormal findings in pregnancy and newborn characteristics comparing vaccinated versus unvaccinated pregnant women. COVID-19 seropositive pregnant women had significantly higher spike antibody titers than seronegative patients with similar characteristics, although they were more likely to develop fever and lymphadenopathy following vaccination. The same group of pregnant women showed no statistically significant differences in antibody titers during a 4-month period when compared with case-matched non-pregnant women. The BNT162b2 and Ad26.COV2.S vaccines are safe to administer during the third trimester of pregnancy, while their safety, efficacy, and immunogenicity remain similar to those of the general population.