The onset of de novo autoantibodies in healthcare workers after mRNA based anti-SARS-CoV-2 vaccines: a single centre prospective follow-up study

Nowadays, data concerning the risk of autoimmune disease after SARS-CoV-2 (COVID-19) vaccination is controversial. The aim of this single centre prospective follow-up study was to evaluate whether healthcare workers (HCWs) vaccinated with BNT162b2 mRNA and mRNA-1273 will show a development and/or a persistence of autoantibodies, focussing on the detection of antibodies against nuclear antigens (antinuclear antibodies, ANA). We enrolled 155 HCWs, however only 108 of them received the third dose and were considered for further analysis. Blood samples were collected before vaccine inoculation (T0), at 3 (T1) and 12 months (T2) after the first dose. All samples were analysed for the presence of a) ANA using indirect Immunofluorescence [IIF] (dilutions of 1:80, 1:160. 1:320 and 1:640), and anti-smooth muscle antibodies (ASMA); b) anti-myeloperoxidase (anti-MPO), anti-proteinase 3 (anti-PR3) and anti-citrullinated peptide antibodies (aCCP) [FEIA]; c) anti-phospholipid antibodies (anticardiolipin [aCL], anti-beta-2- glycoprotein I [anti-ß-2GPI] (Chemiluminescence). Line-blot technology was performed using the following kit: EUROLINE ANA profile 3 plus DFS70 (IgG). Our research suggests that mRNA based anti-SARSCoV-2 vaccines can induce the production of de novo ANA in 22/77(28,57%) of subjects and that the percentage of positivity seems to be directly correlated to the number of vaccine expositions: 6/77 (7,79%) after 2 doses; 16/77 (20,78%) after 3 doses. Since it is known that hyperstimulation of the immune system could lead to autoimmunity, these preliminary results seem to further sustain the idea that the hyperstimulation of the immune system might lead to an autoinflammatory mechanism and eventually to autoimmune disorders. However, the link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated

Alveolar haemorrhage in ANCA-associated vasculitis: Long-term outcome and mortality predictors

Introduction: Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). Objectives: The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. Materials and methods: A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. Results: One-hundred and six patients were included (median age at onset of 55 years [IQR 42\u201367]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13\u201377] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4\u20139.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51\u201313.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. Conclusions: Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial

High prevalence of fragility vertebral fractures in patients hospitalised in Internal Medicine Units. Results of the POINT (Prevalence of Osteoporosis in INTernal medicine) study

Background: Osteoporotic vertebral fractures (VFs) often go unrecognised in both healthy individuals and in pathological conditions. Few data exist on VFs in patients hospitalised in Internal Medicine Units (IMUs), who often suffer from multiple concomitant chronic disorders. Aim of the study: This multicentre cross-sectional study was aimed at assessing the prevalence of VFs in an unselected population of patients referring to IMUs. Correlations between VFs and the main coexisting diseases were also investigated. Methods: Information on demographic, clinical and laboratory findings, and on the presence of known risk factors for osteoporosis was recorded. The Genant's semi-quantitative method was used to evaluate, in a central reading centre, the presence and severity of VFs in the thoracic and lumbar spine. Results: A cohort of 995 patients was evaluated. At least one VF of any grade was found in 47.5% of patients, with similar prevalence between females (48.1%) and males (46.7%). Older age, chronic obstructive pulmonary disease, and previous diagnosis of osteoporosis showed a significant association with VFs in multivariable analysis. However, 79.7% of the VFs were observed in patients without previous diagnosis of osteoporosis. Moreover, a VF of grade 2 or greater was found in 20.8% of patients. Conclusions: Fragility VFs is a very frequent finding in patients hospitalised in IMUs. Consequently, more attention should be devoted in this clinical setting to this comorbidity, which is known to be an additional factor for mortality and, when localised in the thoracic part of the spine, may negatively influence a concomitant respiratory insufficiency

Simple parameters from complete blood count predict in-hospital mortality in covid-19

Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients (F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) (χ2 10.4; p < 0:001), neutrophil-to-lymphocyte (NL) ratio (χ2 7.6; p = 0:006), and platelet count (χ2 5.39; p = 0:02), along with age (χ2 87.6; p < 0:001) and gender (χ2 17.3; p < 0:001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4:68 was characterized by an odds ratio for in-hospital mortality ðORÞ = 3:40 (2.40-4.82), while the OR for a RDW > 13:7% was 4.09 (2.87-5.83); a platelet count > 166,000/μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment

Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)