COVID-19 mRNA Based Vaccine Immune-Response Assessment in Nursing Home Residents for Public Health Decision.

Nursing home residents (NHR) have been targeted as a vaccination priority due to their higher risk of worse outcome after COVID-19 infection. The mRNA-based vaccine BTN2b2 was first approved in Europe for NHRs. The assessment of the specific vaccine immune response (both humoral and cellular) at long term in NHRs has not been addressed yet. A representative sample of 624 NHR subjects in Northern region of Spain was studied to assess immune response against full vaccination with BTN2b2. The anti-S1 antibody levels and specific T cells were measured at two and six months after vaccination. 24.4% of NHR had a previous infection prior to vaccination. The remaining NHR were included in the full vaccination assessment group (FVA). After two months, a 94.9% of the FVA presented anti-S1 antibodies, whereas those seronegative without specific cellular response were 2.54%. At long-term, the frequency of NHR within the FVA group with anti-S1 antibodies at six months were 88.12% and the seronegative subjects without specific cellular response was 8.07%. The cellular immune assays complement the humoral test in the immune vaccine response assessment. Therefore, the cellular immune assessment in NHRs allows for the fine tuning of those seronegative subjects with potential competent immune responses against the vaccine.

Vaccinate fast but leave no one behind: a call to action for COVID-19 vaccination in Spain.

During the first five months of 2021, Spain's COVID-19 vaccination campaign progressed slowly and failed to reach marginalised populations. Here, we discuss how, despite recent improvements, it remains important to further engage key stakeholders to ensure nobody is left behind.

Current laboratory and clinical practices in reporting and interpreting anti-nuclear antibody indirect immunofluorescence (ANA IIF) patterns: results of an international survey.

BACKGROUND: The International Consensus on Antinuclear Antibody (ANA) Patterns (ICAP) has recently proposed nomenclature in order to harmonize ANA indirect immunofluorescence (IIF) pattern reporting. ICAP distinguishes competent-level from expert-level patterns. A survey was organized to evaluate reporting, familiarity, and considered clinical value of ANA IIF patterns. METHODS: Two surveys were distributed by European Autoimmunity Standardization Initiative (EASI) working groups, the International Consensus on ANA Patterns (ICAP) and UK NEQAS to laboratory professionals and clinicians. RESULTS: 438 laboratory professionals and 248 clinicians from 67 countries responded. Except for dense fine speckled (DFS), the nuclear competent patterns were reported by > 85% of the laboratories. Except for rods and rings, the cytoplasmic competent patterns were reported by > 72% of laboratories. Cytoplasmic IIF staining was considered ANA positive by 55% of clinicians and 62% of laboratory professionals, with geographical and expertise-related differences. Quantification of fluorescence intensity was considered clinically relevant for nuclear patterns, but less so for cytoplasmic and mitotic patterns. Combining IIF with specific extractable nuclear antigens (ENA)/dsDNA antibody testing was considered most informative. Of the nuclear competent patterns, the centromere and homogeneous pattern obtained the highest scores for clinical relevance and the DFS pattern the lowest. Of the cytoplasmic patterns, the reticular/mitochondria-like pattern obtained the highest scores for clinical relevance and the polar/Golgi-like and rods and rings patterns the lowest. CONCLUSION: This survey confirms that the major nuclear and cytoplasmic ANA IIF patterns are considered clinically important. There is no unanimity on classifying DFS, rods and rings and polar/Golgi-like as a competent pattern and on reporting cytoplasmic patterns as ANA IIF positive.

Non-Criteria Antiphospholipid Antibodies: Risk Factors for Endothelial Dysfunction in Women with Pre-Eclampsia.

The association between unconventional antiphospholipid antibodies and pre-eclampsia in patients without thrombotic manifestations and its relationship with endothelial dysfunction after delivery has been studied poorly. We included 157 pregnant women, 122 of them having developed pre-eclampsia (56 non-severe and 66 severe). The determination of classical and unconventional, as well as pulse wave velocity and ankle-brachial index were performed at three months after delivery. The prevalence of unconventional antiphospholipid antibodies was 22.9% and 54.9% in patients included in control and pre-eclampsia groups, respectively (p = 0.001). The most frequent antiphospholipid antibody was IgM anti-phosphatidylserine/prothrombin in both cohorts. The presence of IgM anti-phosphatidylserine/prothrombin showed an association with the development of pre-eclampsia (OR = 5.4; CI 95% (2.0-14.9), p = 0.001) with an AUC of 0.744 (p < 0.001). Likewise, IgM anti-phosphatidylserine/prothrombin exhibited a positive linear correlation with pulse wave velocity values (rho = 0.830; p < 0.001) and an association with the presence of pulse wave velocity altered values (OR = 1.33; CI95% (1.10-1.59), p = 0.002). With regard to ankle braquial index values, the presence of IgM anti-phosphatidylserine/prothrombin displayed a weak negative correlation (rho = -0.466; p < 0.001) and an association with altered ankle braquial index values (OR = 1.08; CI 95% (1.04-1.13), p < 0.001). In patients who developed preeclampsia, the presence of IgM anti-phosphatidylserine/prothrombin could be associated with endothelial dysfunction, causing alteration of cardiovascular parameters.

Portal Thrombosis in Cirrhosis: Role of Thrombophilic Disorders.

In patients with liver cirrhosis the contribution of inherited and acquired prothrombotic disorders in the development of non-malignant portal vein thrombosis (PVT) is inconclusive. The purpose of this retrospective study was to examine the prevalence of thrombophilia in this setting at our center from January 2012 to November 2019. Tests included gene mutational analysis for Factor V Leiden, prothrombin G20210A, JAK2 (V617F), Calreticulin (CARL), in addition to activated protein C resistance, antithrombin III, protein C and S levels, and antiphospholipid antibodies. We included 77 patients, six of whom (7.8%) had a thrombophilic disorder: antiphospholipid syndrome in four patients, prothrombin gene mutation in one and factor V Leiden mutation in one. This latter patient had also been diagnosed with polycythemia vera years before PVT development. Complete thrombosis of the main portal vein and re-thrombosis after stopping anticoagulation were more frequent in patients with thrombophilia, but the rates of recanalization under anticoagulant therapy were similar among groups. No other difference was accounted between groups. The low prevalence of acquired and inherited thrombophilia found in patients with cirrhosis and PVT support testing for these disorders on an individual basis and avoiding universal screening to reduce costs and unwarranted testing.

A novel automated indirect immunofluorescence autoantibody evaluation.

Autoantibodies (AAb), especially antinuclear (ANAs) and anticytoplasmatic antibodies (ACyA), are essential diagnosing markers for several autoimmune diseases. The current gold standard method for ANA detection is manual indirect immunofluorescence (IIF) on human epithelial-2 (HEp-2) cells. However, this technique is cost and time consuming, and characterized by considerable intra- and interlaboratory variability. Thus, an automated IIF-HEp-2 reader has been developed recently. In the current study, we compared the performance of the automated AAb IIF-HEp-2 interpretation to conventional detection methods. Autoantibody detection by IIF on HEp-2 cells was performed in a total of 260 sera of patients, including 34 with systemic lupus erythematosus, 111 with dermatomyositis or polymyositis, 74 with systemic sclerosis, 41 with rare AAb patterns, and 137 healthy individuals. Visual interpretation and routine immunoassays were compared with a novel automated IIF-HEp-2 system using Aklides pattern recognition algorithms. Positive AAbs were detected in 95-100% of rheumatic patients by automated interpretation, in 74-100% with manual reading, and in 64-100% by immunodot assay. Receiver operating characteristic curve analysis of fluorescent intensity revealed a high sensitivity and specificity for automated reading of AAb with an agreement ranging from 90% to 95% between manual and automated interpretation (kappa 0.554-0.69) for systemic sclerosis and myositis, respectively. This study demonstrates a good correlation between manual and automated interpretation of AAb including ANA and ACyA in patients with autoimmune diseases. Full automation of HEp-2 cell assay reading may minimize errors in ANA pattern interpretation and thus help in the standardization of ANA assessment.