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IntroductionInfluenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression.MethodsWe conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission.ResultsPatients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71).DiscussionTherefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.

Background: Ischemic stroke is the most common and severe arterial thrombotic event in Antiphospholipid syndrome (APS). APS is an autoimmune disease characterized by the presence of thrombosis and antiphospholipid antibodies (aPL), which provide a pro-coagulant state. The aPL included in the classification criteria are lupus anticoagulant, anti-cardiolipin (aCL) and anti-β2-glycoprotein-I antibodies (aB2GPI) of IgG and IgM isotypes. Extra-criteria aPL, especially IgA aB2GPI and IgG/IgM anti-phosphatidylserine/prothrombin antibodies (aPS/PT), have been strongly associated with thrombosis. However, their role in the general population suffering from stroke is unknown. We aim (1) to evaluate the aPL prevalence in ischemic stroke patients, (2) to determine the role of aPL as a risk factor for stroke, and (3) to create an easy-to-use tool to stratify the risk of ischemic stroke occurrence considering the presence of aPL and other risk factors.Materials and Methods: A cohort of 245 consecutive ischemic stroke patients was evaluated in the first 24 h after the acute event for the presence of classic aPL, extra-criteria aPL (IgA aB2GPI, IgG, and IgM aPS/PT) and conventional cardiovascular risk factors. These patients were followed-up for 2-years. A group of 121 healthy volunteers of the same age range and representative of the general population was used as reference population. The study was approved by the Ethics Committee for Clinical Research (Reference numbers CEIC-14/354 and CEIC-18/182).Results: The overall aPL prevalence in stroke patients was 28% and IgA aB2GPI were the most prevalent (20%). In the multivariant analysis, the presence of IgA aB2GPI (OR 2.40, 95% CI: 1.03–5.53), dyslipidemia (OR 1.70, 95% CI: 1.01–2.84), arterial hypertension (OR 1.82, 95% CI: 1.03–3.22), atrial fibrillation (OR 4.31, 95% CI: 1.90–9.78), and active smoking (OR 3.47, 95% CI: 1.72–6.99) were identified as independent risk factors for ischemic stroke. A risk stratification tool for stroke was created based on these factors (AUC: 0.75).Conclusions: IgA aB2GPI are an important independent risk factor for ischemic stroke. Evaluation of aPL (including extra-criteria) in cardiovascular risk factor assessment for stroke can potentially increase the identification of patients at risk of thrombotic event, facilitating a decision on preventive treatments.

Objective To compare characteristics, pregnancies and treatments during pregnancies of seronegative and seropositive antiphospholipid syndrome (APS), to analyse factors associated with obstetrical outcome.Patients and methods Inclusion criteria were: (1) thrombotic and/or obstetrical APS (Sydney criteria); (2) absence of conventional antiphospholipid antibodies (APL); (3) at least one persistent non-conventional APL among IgA anticardiolipin antibodies, IgA anti-B2GPI, anti-vimentin G/M, anti-annexin V G/M, anti-phosphatidylethanolamine G/M and anti-phosphatidylserine/prothrombin G/M antibodies. The exclusion criteria were: (1) systemic lupus erythematosus ( SLE) or SLE-like disease; and (2) other connective tissue disease.Results A total of 187 women (mean 33±5 years) with seronegative APS were included from 14 centres in Austria, Spain, Italy, Slovenia and France and compared with 285 patients with seropositive APS. Seronegative APS has more obstetrical rather than thrombotic phenotypes, with only 6% of venous thrombosis in comparison to seropositive APS. Cumulative incidence of adverse obstetrical events was similar in seronegative and seropositive APS patients, although higher rates of intrauterine deaths (15% vs 5%; p=0.03), of preeclampsia (7% vs 16%, p=0.048) and lower live birth term (36±3 vs 38±3 weeks of gestation; p=0.04) were noted in seropositive APS. The cumulative incidence of adverse obstetrical events was significantly improved in treated versus untreated seronegative APS (log rank

The Th1/Th2 balance plays a crucial role in the progression of different pathologies and is a determining factor in the evolution of infectious diseases. This work has aimed to evaluate the early, or on diagnosis, T-cell compartment response, T-helper subsets and anti-SARS-CoV-2 antibody specificity in COVID-19 patients and to classify them according to evolution based on infection severity. A unicenter, randomized group of 146 COVID-19 patients was divided into four groups in accordance with the most critical events during the course of disease. The immunophenotype and T-helper subsets were analyzed by flow cytometry. Asymptomatic SARS-CoV-2 infected individuals showed a potent and robust Th1 immunity, with a lower Th17 and less activated T-cells at the time of sample acquisition compared not only with symptomatic patients, but also with healthy controls. Conversely, severe COVID-19 patients presented with Th17-skewed immunity, fewer Th1 responses and more activated T-cells. The multivariate analysis of the immunological and inflammatory parameters, together with the comorbidities, showed that the Th1 response was an independent protective factor for the prevention of hospitalization (OR 0.17, 95% CI 0.03–0.81), with an AUC of 0.844. Likewise, the Th1 response was found to be an independent protective factor for severe forms of the disease (OR 0.09, 95% CI: 0.01–0.63, p = 0.015, AUC: 0.873). In conclusion, a predominant Th1 immune response in the acute phase of the SARS-CoV-2 infection could be used as a tool to identify patients who might have a good disease evolution.

Background: COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL in COVID-19 patients is not sufficiently clear. Methods: A group of 360 COVID-19 patients were followed-up for 6 months. Classic aPL, anti-B2GPI IgA, anti-phosphatidylserine/prothrombin IgG/M and anti-SARS-CoV-2 antibodies were determined at acute phase and >12 weeks later. The reference group included 143 healthy volunteers of the same age-range distribution. Results: aPL prevalence was similar in COVID-19 patients and the reference population. aPL presence in both determinations was significantly associated with thrombosis (OR: 2.33 and 3.71), strong agreement being found for classic aPL and anti-B2GPI IgA (Weighted kappa: 0.85–0.91). Thrombosis-associated aPL occurred a median of 17 days after hospital admission (IQR: 6–28) vs. 4 days for the rest (IQR: 3–7). Although anti-SARS-CoV-2 antibodies levels increased during convalescence, aPL hardly changed. Conclusions: Most COVID-19 patients would carry these aPL before the infection. At least two mechanisms could be behind thrombosis, early immune-dysregulation-mediated thrombosis after infection and belated-aPL-mediated thrombosis, with SARS-CoV-2 behaving as a second hit.