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Summary: Biomarkers for monitoring COVID-19 disease course are lacking. Study aim was to identify biomarkers associated with disease severity, survival, long-term outcome, and Long COVID. As excessive macrophages activation is a hallmark of COVID-19 and complement activation is key in this, we selected the following proteins involved in these processes: PTX3, C1q, C1-INH, C1s/C1-INH, and sMR. EDTA-plasma concentrations were measured in 215 patients and 47 controls using ELISA. PTX3, sMR, C1-INH, and C1s/C1-INH levels were associated with disease severity. PTX3 and sMR were also associated with survival and long-term immune recovery. Lastly, sMR levels associate with ICU admittance. sMR (AUC 0.85) and PTX3 (AUC 0.78) are good markers for disease severity, especially when used in combination (AUC 0.88). No association between biomarker levels and Long COVID was observed. sMR has not previously been associated with COVID-19 disease severity, ICU admittance or survival and may serve as marker for disease course.

Rationale & Objective: Pregnancy, delivery, and neonatal outcomes in women with complement-mediated thrombotic microangiopathy (cTMA) have not been well described. A better understanding of these outcomes is necessary to provide women with competent pregnancy counseling. Study Design: Cohort study. Setting and Participants: Women with a history of cTMA and pregnancies enrolled into the Vienna thrombotic microangiopathy cohort. Exposure: New onset or relapses of cTMA. Outcomes: Pregnancy, delivery, and neonatal outcomes of pregnancies in women (a) before cTMA manifestation, (b) complicated by pregnancy-associated cTMA (P-cTMA), and (c) after first manifestation of cTMA or P-cTMA. Analytical Approach: Mixed models were used to adjust the comparison of pregnancy, delivery, and neonatal outcomes between conditions (before, with, and after cTMA) for repeated pregnancies using the mother’s ID as random factor. In addition, the fixed factors, mother’s age and neonate’s sex, were used for adjustment. For (sex-adjusted and age-adjusted) centile outcomes, only the mother’s age was used. Adjusted odds ratios were derived from a generalized linear mixed model with live birth as the outcome. Least squares means and pairwise differences between them were derived from the linear mixed models for the remaining outcomes. Results: 28 women reported 74 pregnancies. Despite higher rates of fetal loss before the diagnosis of P-cTMA and preterm births with P-cTMA, most of the women were able to conceive successfully. Neonatal development in all 3 conditions of pregnancies was excellent. Pregnancy and neonatal outcomes were better in women with a pregnancy after the diagnosis of cTMA. Limitations: Although our data set comprises a considerable number of 74 pregnancies, the effective sample size is lower because only 28 mothers with multiple pregnancies were observed. The statistical power for detecting clinically relevant effects was probably low. A recall bias for miscarriages cannot be ruled out. Conclusions: Prepregnancy counseling of women with a history of cTMA can be supportive of their desire to become pregnant.

Abstract The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12‐15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020. Readers are also welcome to utilize capsules for teaching and ongoing education.

In patients with pregnancy-associated complement gene variant–mediated thrombotic microangiopathy (cTMA), terminal complement blockade is used for treatment of cTMA flares during pregnancy or following delivery. We report pregnancy and delivery outcomes of 2 genetically high-risk patients with cTMA, including 1 kidney transplant recipient, during ongoing eculizumab therapy. In both patients, the first manifestation of cTMA occurred independent from pregnancy. One patient has a history of 2 uneventful pregnancies with prophylactic plasma infusions, and the other has a history of early abortion during long-term eculizumab therapy following kidney transplantation. Overall, pregnancy and delivery outcomes under ongoing eculizumab therapy in our 2 patients with preserved kidney function were excellent as compared with other patients reported in the literature. Eculizumab plasma concentrations were maintained in the therapeutic range during pregnancy and were also detectable in cord blood. Results of cord blood analysis showed deficient complement activity, with low factor and regulator levels, most likely reflecting the age of the neonates and presence of eculizumab in cord blood. In conclusion, pregnancy during ongoing eculizumab treatment appeared to be safe in 2 women with a history of high-risk genetic cTMA and excellent kidney function, even following kidney transplantation. Index Words: Atypical hemolytic uremic syndrome (aHUS), complement-mediated thrombotic microangiopathy (cTMA), complement system, complement factor, complement blockade, eculizumab, pregnancy, gravidity, childbirth, gestation, kidney transplantation, chronic kidney disease, renal failure

Serological testing is a tool to predict protection against later infection. This potential heavily relies on antibody levels showing acceptable agreement with gold standard virus neutralization tests. The aim of our study was to investigate diagnostic value of the available serological tests in terms of predicting virus neutralizing activity of serum samples drawn 5–7 weeks after onset of symptoms from 101 donors with a history of COVID-19.Immune responses against Receptor Binding Domain (RBD), Spike1 and 2 proteins and Nucleocapsid antigens were measured by various ELISA tests. Neutralizing antibody activity in serum samples was assessed by a cell-based virus neutralization test.Spearman correlation coefficients between serological and neutralization results ranged from 0.41 to 0.91 indicating moderate to strong correlation between ELISA test results and virus neutralization. The sensitivity and specificity of ELISA tests in the prediction of neutralization were 35–100% and 35–90% respectively. No clear cut off levels can be established that would reliably indicate neutralization activity. For some tests, however, a value below which the sample is not expected to neutralize can be established. Our data suggests that several of the ELISA kits tested may be suitable for epidemiological surveys 1–2 months after the infection, estimating whether a person may have recently exposed to the virus. Sensitivities considerably superseding specificity at the cut-off values proposed by the manufacturers suggest greater potential in the identification of insufficient antibody responses than in confirming protection. Nevertheless, the former might be important in assessing response to vaccination and characterizing therapeutic plasma preparations.