Immunogenicity and risk of disease flare after a three-dose regimen with SARS-CoV-2 vaccination in patients with systemic lupus erythematosus: results from the prospective cohort study COVAC-SLE.

OBJECTIVES: To investigate the humoral immune response and risk of disease flare in systemic lupus erythematosus (SLE) patients following three-doses of SARS-CoV-2 vaccines. METHODS: In adult patients with SLE, we measured SARS-CoV-2 spike IgG in blood samples drawn three weeks after the 1st dose (baseline), four and eight weeks after the 2nd dose and after the 3rd dose. A sufficient antibody response was ≥54BAU/mL. SLEDAI-2K, SLAQ and SDI were assessed at baseline and eight weeks after the 2nd dose along with adverse events. Demographic and treatment data were collected from hospital records. RESULTS: Of 123 patients, 115 (93.5%) received the BNT162b2 vaccine, the remaining received the 1st dose of ChAdOx-1 followed by a 2nd and 3rd dose of mRNA-1273. After the 2nd dose 102 (83%) patients had a sufficient antibody response (median 559.2, IQR 288.8-1180.5 BAU/mL), increasing to 115 (93.5%) (median 2416.9, IQR 1289-4603.8 BAU/mL) patients after the 3rd dose. Eight weeks after the 2nd dose patients treated with high dose prednisolone (p=0.034) and DMARDs (p<0.001) had significantly lower antibodies; however, this difference was not significant following the 3rd dose. Disease activity and damage were stable during the study period. Adverse events were more frequent in patients with a sufficient response. Breakthrough infections were reported in 39 (31.7%) patients; all with mild symptoms. CONCLUSIONS: A 3rd dose improved the humoral response to SARS-CoV-2 vaccines in patients with SLE to the level of healthy individuals. Vaccination did not affect SLE disease activity. Subsequent breakthrough infections were mild and did not require hospitalisation.

COVID-19. Scenarios of a superfluous crisis

PurposeThis study aims to highlight the critical role case fatality rates (CFR) have played in the emergence and the management of particularly the early phases of the current coronavirus crisis.Design/methodology/approachThe study presents a contrastive map of CFR for the coronavirus (SARS-CoV-2) and influenza (H1N1 and H2N2).FindingsThe mapped data shows that current CFR of SARS-CoV-2 are considerably lower than, or similar to those, of hospitalised patients in the UK, Spain, Germany or international samples. The authors therefore infer a possible risk that the virulence of the coronavirus is considerably overestimated because of sampling biases, and that increased testing might reduce the general CFR of SARS-CoV-2 to rates similar to, or lower than, of the common seasonal influenza.Originality/valueThis study concludes that governments, health corporations and health researchers must prepare for scenarios in which the affected populations cease to believe in the statistical foundations of the current coronavirus crisis and interventions.

Longitudinal changes in mental health following the COVID-19 lockdown: Results from the Survey of Health, Ageing, and Retirement in Europe.

BACKGROUND: To limit the spread of the coronavirus disease 2019 (COVID-19) pandemic, different restriction measures were implemented aiming to ensure social distancing and isolation. However, it is well known that such measures may lead to adverse effects on mental health. METHODS: Data from 36,478 adults aged 50+ from the Survey of Health, Ageing and Retirement in Europe was used to investigate the longitudinal changes in mental health from pre-COVID-19 to during the pandemic (summer 2020), considering national restriction levels across 26 European countries and Israel. Multilevel logistic regression models were used to assess changes in feeling 'sad or depressed', sleeping problems, and loneliness. RESULTS: Compared with the mental health status before the COVID-19 outbreak, participants had a lower risk of feeling "sad or depressed" (-14.4%) and having sleeping problems (-9.9%), while the risk of feeling lonely slightly increased (1.2%). However, for individuals in countries with high restriction levels, the risk of feeling "sad or depressed" was attenuated and the risk of loneliness was greater compared to countries with low restriction levels. CONCLUSION: Older people felt less depressed and had fewer sleeping problems during the pandemic as compared to before the pandemic, while the risk of loneliness increased slightly. Stricter policy measures attenuated the otherwise positive impact on mental health. Future studies are needed to investigate the long-term effects of COVID-19 on mental health.

Determinants of Antibody Response to a Third SARS-CoV-2 mRNA Vaccine Dose in Solid Organ Transplant Recipients: Results from the Prospective Cohort Study COVAC-Tx.

BACKGROUND: We studied factors related to humoral response in solid organ transplant (SOT) recipients following a three-dose regimen of an mRNA-based SARS-CoV-2 vaccine. METHOD: This was a prospective study of SOT recipients who received a third homologous dose of the BNT162b2 (Pfizer-BioNTech) vaccine. The anti-spike S1 IgG response was measured using the SARS-CoV-2 IgG II Quant assay (Abbott Laboratories) with a cut-off of 7.1 BAU/mL. Multiple logistic regression was used to determine the factors associated with humoral response. RESULTS: In total, 395 SOT recipients were included. Anti-spike IgG was detected in 195/395 (49.4%) patients after the second dose and 261/335 (77.9%) patients after the third dose. The overall mean increase in antibody concentration after the third dose was 831.0 BAU/mL (95% confidence interval (CI) 687.4-974.5) and 159 (47.5%) participants had at least a 10-fold increase in antibody concentration after the third dose. The increase in antibody concentration was significantly higher among patients with detectable antibodies after the second dose than those without. Cumulative time from transplantation and liver recipients was positively associated with an antibody response, whereas older age, administration of prednisolone, and proliferation inhibitors were associated with diminished antibody response. CONCLUSION: Although the third dose of the BNT162b2 vaccine improved humoral responses among SOT non-responders following the second dose, the overall response remained low, and 22.1% did not develop any response. Patients at risk of a diminished vaccine response require repeated booster doses and alternative treatment approaches.

SARS-CoV-2 seroprevalence among 7950 healthcare workers in the Region of Southern Denmark.

OBJECTIVE: Healthcare workers (HCWs) carry a pronounced risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of this study was to determine the seroprevalence and potential risk factors of SARS-CoV-2 infection among HCWs in the Region of Southern Denmark after the first pandemic wave in the spring of 2020. METHODS: This was an observational study conducted between May and June 2020. SARS-CoV-2 IgG and IgM antibodies were measured in plasma. Participants were asked to complete a questionnaire consisting of demographic information, risk factors, and COVID-19-related symptoms. RESULTS: A total of 7950 HCWs participated. The seroprevalence of SARS-CoV-2 antibodies was 2.1% (95% confidence interval (CI) 1.8-2.4%). Seropositive participants were significantly older (mean age 48.9 years vs 46.7 years in seronegative participants, P = 0.022) and a higher percentage had experienced at least one symptom of COVID-19 (P < 0.001). The seroprevalence was significantly higher among HCWs working on dedicated COVID-19 wards (3.5%; OR 2.02, 95% CI 1.44-2.84). Seroprevalence was significantly related to 11-50 close physical contacts per day outside work (OR 1.54, 95% CI 1.07-2.22). CONCLUSIONS: The prevalence of SARS-CoV-2 antibodies was low in HCWs. However, the occupational risk of contracting the infection was found to be higher for those working on dedicated COVID-19 wards. Further, the results imply that attention should be paid to occupational risk factors in planning pandemic preparedness.

Translational Potential of Metabolomics on Animal Models of Inflammatory Bowel Disease-A Systematic Critical Review.

In the development of inflammatory bowel disease (IBD), the gut microbiota has been established as a key factor. Recently, metabolomics has become important for understanding the functional relevance of gut microbial changes in disease. Animal models for IBD enable the study of factors involved in disease development. However, results from animal studies may not represent the human situation. The aim of this study was to investigate whether results from metabolomics studies on animal models for IBD were similar to those from studies on IBD patients. Medline and Embase were searched for relevant studies up to May 2017. The Covidence systematic review software was used for study screening, and quality assessment was conducted for all included studies. Data showed a convergence of ~17% for metabolites differentiated between IBD and controls in human and animal studies with amino acids being the most differentiated metabolite subclass. The acute dextran sodium sulfate model appeared as a good model for analysis of systemic metabolites in IBD, but analytical platform, age, and biological sample type did not show clear correlations with any significant metabolites. In conclusion, this systematic review highlights the variation in metabolomics results, and emphasizes the importance of expanding the applied detection methods to ensure greater coverage and convergence between the various different patient phenotypes and animal models of inflammatory bowel disease.

Quality of Life in Danish Patients with Multiple Myeloma during the COVID-19 Pandemic

In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce the viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the related immunodeficiency. We investigated how Danish patients with MM reported their quality of life (QoL) pre-COVID and during COVID, in an ongoing longitudinal QoL survey. The responses given during the first and second wave of the COVID-19 pandemic were pooled, analyzed and compared to the same period the year before. We hypothesized that locking down the society would have caused deteriorated QoL and that patients living alone and those under the age of 65 would be particularly affected by the situation. Surprisingly, our study showed the opposite. Statistically significant and clinically relevant differences were primarily found during the first lock down and represented reduced fatigue, improved role functioning, decreased insomnia and improved physical health summaries in patients below 65 years of age. These results indicate that Danish patients with MM might have felt protected and safe by COVID restrictions. Otherwise, the questionaries used in QoL-MM survey may not have been able to capture the impact of the COVID-19 pandemic. Importantly, this indicates that QoL survey data obtained in clinical studies, in countries with highly developed health-care systems using standard questionnaires during the pandemic, allow room for interpretation without being adjusted for the impacts of the pandemic.

Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial.

OBJECTIVES: Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA). METHODS: In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26. RESULTS: Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)). CONCLUSIONS: In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA. TRIAL REGISTRATION NUMBER: NCT03058900.

Burden and prevalence of risk factors for severe COVID-19 in the ageing European population - a SHARE-based analysis.

Aim: International health authorities suggest that individuals aged 65 years and above and people with underlying comorbidities such as hypertension, chronic lung disease, cardiovascular disease, cancer, diabetes, and obesity are at increased risk of severe Coronavirus Disease 2019 (COVID-19); however, the prevalence of risk factors is unknown in many countries. Therefore, we aimed to describe the distribution of these risk factors across Europe. Subject and methods: Prevalence of risk factors for severe COVID-19 was identified based on interviews from 73,274 Europeans aged 50+ participating in the Survey of Health, Ageing and Retirement in Europe (SHARE) in 2017. Burden of disease was estimated using population data from Eurostat. Results: A total of 75.3% of the study population (corresponding to approx. 60 million European men and 71 million women) had at least one risk factor for severe COVID-19, 45.9% (approx. 36 million men and 43 million women) had at least two factors, and 21.2% (approx. 17 million men and 20 million women) had at least three risk factors. The prevalence of underlying medical conditions ranged from 4.5% for cancer to 41.4% for hypertension, and the region-specific prevalence of having at least three risk factors ranged from 18.9% in Northern Europe to 24.6% in Eastern Europe. Conclusions: Information about the prevalence of risk factors might help authorities to identify the most vulnerable subpopulations with multiple risk factors of severe COVID-19 and thus to decide appropriate strategies to mitigate the pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01537-7.

Variability Matters.

Much of science, including public health research, focuses on means (averages). The purpose of the present paper is to reinforce the idea that variability matters just as well. At the hand of four examples, we highlight four classes of situations where the conclusion drawn on the basis of the mean alone is qualitatively altered when variability is also considered. We suggest that some of the more serendipitous results have their origin in variability.