COVID-19 and antiphospholipid antibodies: A position statement and management guidance from AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION)

Lupus ◽  
2021 ◽  
pp. 096120332110625
Author(s):  
Xin Wang ◽  
Elena Gkrouzman ◽  
Danieli Castro Oliveira Andrade ◽  
Laura Andreoli ◽  
Medha Barbhaiya ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Neutrophil Extracellular Traps ◽  
Position Statement ◽  
Endothelial Damage ◽  
High Rate ◽  
Research Network ◽  
Extracellular Traps ◽  
Management Guidance

Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.

scholarly journals Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

2021 ◽  
Vol 12 ◽  
Author(s):  
Kathrin Becker ◽  
Georg Beythien ◽  
Nicole de Buhr ◽  
Stephanie Stanelle-Bertram ◽  
Berfin Tuku ◽  
...  
Keyword(s):  
Animal Models ◽  
Syrian Hamster ◽  
Neutrophil Extracellular Traps ◽  
Virus Antigen ◽  
Endothelial Damage ◽  
Vascular Lesions ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Pulmonary Lesions ◽  
Extracellular Traps

Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed. SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models. Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients. Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans. Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far. Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19. Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi. Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations. In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi. Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis.

scholarly journals SARS-CoV-2 mass vaccination: Urgent questions on vaccine safety that demand answers from international health agencies, regulatory authorities, governments and vaccine developers                  

2021 ◽  
Author(s):  
Roxana Bruno ◽  
Peter A Mccullough ◽  
Teresa Forcades I Vila ◽  
Alexandra Henrion-Caude ◽  
Teresa García-Gasca ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Risk Mitigation ◽  
Safety Data ◽  
Vaccine Safety ◽  
Endothelial Damage ◽  
Mass Vaccination ◽  
High Rate ◽  
Public Confidence ◽  
World Population

Since the start of the COVID-19 outbreak, the race for testing new platforms designed to confer immunity against SARS-CoV-2, has been rampant and unprecedented, leading to conditional emergency authorization of various vaccines. Despite progress on early multidrug therapy for COVID-19 patients, the current mandate is to immunize the world population as quickly as possible. The lack of thorough testing in animals prior to clinical trials, and authorization based on safety data generated during trials that lasted less than 3.5 months, raise questions regarding vaccine safety. The recently identified role of SARS-CoV-2 Spike glycoprotein for inducing endothelial damage characteristic of COVID-19, even in absence of infection, is extremely relevant given that most of the authorized vaccines induce endogenous production of Spike. Given the high rate of occurrence of adverse effects that have been reported to date, as well as the potential for vaccine-driven disease enhancement, Th2-immunopathology, autoimmunity, and immune evasion, there is a need for a better understanding of the benefits and risks of mass vaccination, particularly in groups excluded from clinical trials. Despite calls for caution, the risks of SARS-CoV-2 vaccination have been minimized or ignored by health organizations and government authorities. As for any investigational biomedical program, data safety monitoring boards (DSMB) and event adjudication committees (EAC), should be enacting risk mitigation. If DSMBs and EACs do not do so, we will call for a pause in mass vaccination. If DSMBs and EACs do not exist, then vaccination should be halted immediately, in particular for demographic groups at highest risk of vaccine-associated death or serious adverse effects, during such time as it takes to assemble these boards and commence critical and independent assessments. We urge for pluralistic dialogue in the context of health policies, emphasizing critical questions that require urgent answers, particularly if we wish to avoid a global erosion of public confidence in science and public health.

scholarly journals SARS-CoV-2 mass vaccination: Urgent questions on vaccine safety that demand answers from international health agencies, regulatory authorities, governments and vaccine developers

2021 ◽  
Author(s):  
Karina Acevedo-Whitehouse ◽  
Roxana Bruno ◽  
Peter A Mccullough ◽  
Teresa Forcades I Vila ◽  
Alexandra Henrion-Caude ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Risk Mitigation ◽  
Safety Data ◽  
Vaccine Safety ◽  
Endothelial Damage ◽  
Mass Vaccination ◽  
High Rate ◽  
Public Confidence ◽  
World Population

Since the start of the COVID-19 outbreak, the race for testing new platforms designed to confer immunity against SARS-CoV-2, has been rampant and unprecedented, leading to conditional emergency authorization of various vaccines. Despite progress on early multidrug therapy for COVID-19 patients, the current mandate is to immunize the world population as quickly as possible. The lack of thorough testing in animals prior to clinical trials, and authorization based on safety data generated during trials that lasted less than 3.5 months, raise questions regarding vaccine safety. The recently identified role of SARS-CoV-2 Spike glycoprotein for inducing endothelial damage characteristic of COVID-19, even in absence of infection, is extremely relevant given that most of the authorized vaccines induce endogenous production of Spike. Given the high rate of occurrence of adverse effects that have been reported to date, as well as the potential for vaccine-driven disease enhancement, Th2-immunopathology, autoimmunity, and immune evasion, there is a need for a better understanding of the benefits and risks of mass vaccination, particularly in groups excluded from clinical trials. Despite calls for caution, the risks of SARS-CoV-2 vaccination have been minimized or ignored by health organizations and government authorities. As for any investigational biomedical program, data safety monitoring boards (DSMB) and event adjudication committees (EAC), should be enacting risk mitigation. If DSMBs and EACs do not do so, we will call for a pause in mass vaccination. If DSMBs and EACs do not exist, then vaccination should be halted immediately, in particular for demographic groups at highest risk of vaccine-associated death or serious adverse effects, during such time as it takes to assemble these boards and commence critical and independent assessments. We urge for pluralistic dialogue in the context of health policies, emphasizing critical questions that require urgent answers, particularly if we wish to avoid a global erosion of public confidence in science and public health.

European registry of babies born to mothers with antiphospholipid syndrome: a result update

Lupus ◽  
2009 ◽  
Vol 18 (10) ◽  
pp. 900-904 ◽  
Author(s):  
M-C Boffa ◽  
E Lachassinne ◽  
C Boinot ◽  
S De Carolis ◽  
P Rovere-Querini ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Antiphospholipid Syndrome ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Antiphospholipid Antibodies ◽  
Anticardiolipin Antibodies ◽  
High Rate ◽  
Neuropsychological Development ◽  
Premature Babies ◽  
European Registry

The registry is a prospective, European, multicentric, longitudinal study, which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). It was started in 2003. In this report, we update the results obtained from the study of 110 mothers and 112 children (two twin births). Eighty per cent of the mothers ( n = 86) had primary APS. Purely obstetrical, thrombotic and mixed (obstetrical and thrombotic) APS represent 65.5 %, 21.8 % and 12.7 % of the whole cohort respectively. Isolated antiphospholipid antibodies and isolated anticardiolipin antibodies positivity were present in 50 of 109 (46%) and in 34 of 109 (31%) of the pregnant women, respectively. In the babies, in spite of a high rate of prematurity (14.3%) with four (3.6%) of the premature babies born before 33 weeks of gestation and an increased number of newborns small for gestational age (17%), the large majority of the neonates were healthy. Thirty-one infants are now older than 24 months. Among them, three displayed behavioural abnormalities before 3 years of age. After completing data, there will be the possibility to evaluate the newborn status in relation to the mothers’ diseases, treatments and antibodies and to follow the neuropsychological development and immunological evolution of the babies during the next 5 years.

scholarly journals Comparative Analysis of Chromatin-Delivered Biomarkers in the Monitoring of Sepsis and Septic Shock: A Pilot Study

2021 ◽  
Vol 22 (18) ◽  
pp. 9935
Author(s):  
Jesús Beltrán-García ◽  
Juan J. Manclús ◽  
Eva M. García-López ◽  
Nieves Carbonell ◽  
José Ferreres ◽  
...  
Keyword(s):  
Septic Shock ◽  
Outcome Prediction ◽  
Fatal Outcome ◽  
Neutrophil Extracellular Traps ◽  
Endothelial Damage ◽  
Rapid Progression ◽  
Clinical Tool ◽  
Sepsis Management ◽  
Extracellular Traps ◽  
Sepsis And Septic Shock

Sepsis management remains one of the most important challenges in modern clinical practice. Rapid progression from sepsis to septic shock is practically unpredictable, hence the critical need for sepsis biomarkers that can help clinicians in the management of patients to reduce the probability of a fatal outcome. Circulating nucleoproteins released during the inflammatory response to infection, including neutrophil extracellular traps, nucleosomes, and histones, and nuclear proteins like HMGB1, have been proposed as markers of disease progression since they are related to inflammation, oxidative stress, endothelial damage, and impairment of the coagulation response, among other pathological features. The aim of this work was to evaluate the actual potential for decision making/outcome prediction of the most commonly proposed chromatin-related biomarkers (i.e., nucleosomes, citrullinated H3, and HMGB1). To do this, we compared different ELISA measuring methods for quantifying plasma nucleoproteins in a cohort of critically ill patients diagnosed with sepsis or septic shock compared to nonseptic patients admitted to the intensive care unit (ICU), as well as to healthy subjects. Our results show that all studied biomarkers can be used to monitor sepsis progression, although they vary in their effectiveness to separate sepsis and septic shock patients. Our data suggest that HMGB1/citrullinated H3 determination in plasma is potentially the most promising clinical tool for the monitoring and stratification of septic patients.

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