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The wide spectrum of symptoms observed in coronavirus disease 2019 appears to defy explanation. Apart from geographic limitation to people with prior exposure to other coronaviruses and air pollutants, inflammatory comorbidities and older ages are also among the main factors of susceptibility to severe illness. The unusual epidemiological data pointed out in children and African territories have revealed new insights in host‐pathogen interplay with more focus on epigenetic regulation of cognitive compartments belonging to innate immunity. Should trained immunity be proven to be involved in timely immune responsiveness against severe acute respiratory syndrome coronavirus 2 and that adaptive memory could be detrimental, both treatment regimens and vaccine design will tremendously change accordingly with more focus on upper respiratory tissue innate immunity to subdue this threat underway.

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Treatment of atypical hemolytic uremic syndrome (aHUS) by the complement C5 inhibitor eculizumab (Soliris®) is highly effective but unfortunately, associated with an economic pressure on the health care systems even in high incomes countries. Despite spacing infusions having been proposed as the unique solution to minimize this economic impact, no reliable laboratory assays are available to tailor such therapy optimization. We aimed to propose and evaluate a complement composite marker for eculizumab efficacy monitoring in aHUS. We have retrospectively analyzed complement profiles data of eight aHUS patients under eculizumab from the International Registry of HUS/Thrombotic Thrombocytopenia Purpura, and calculated a novel marker "C3:CH ratio" by dividing C3 value by CH one for each sample during induction and maintenance periods. The results significance was compared to the currently used biomarkers for eculizumab tailoring. In contrast to the current biomarkers used for eculizumab efficacy monitoring like CH and soluble or deposit membrane attack complexes, "C3:CH ratio" seems to be the most interesting one since its value at pre-eculizumab dosage equaled 0.92 ± 0.2 while the post-eculizumab one increased significantly to reach 24.54 ± 10.7; P < 0.001. Furthermore, this ratio correlated negatively with platelets count (r = -0.722, P = 0.018) while no correlation was found within the thrombotic microangiopathy (TMA) biomarkers and complement blockade for the other parameters that change in pre and post-eculizumab therapy. As far as we know, this is the first study that suggests a post-eculizumab parameter correlating simultaneously with drug's activity (complement inhibition) and disease activity (platelets counts). Nonetheless, the limited number of patients enrolled in this study should be considered in larger studies to guide eculizumab optimization by indicating the time when subsequent withdrawal or infusion spacing is allowed or recommended.

Problem: Progress in understanding the underlying mechanism responsible for the syndrome pre-eclampsia should reconfigure antenatal clinical care and minimize human and financial costs, yet at present there is no accurate theory that permits development of reliable predictive tests and prophylactic intervention to mitigate disease. To contribute to this ongoing effort, we aimed to assess various circulating markers pertaining to different theories. Method of study:Serum samples from thirty-four women with established early onset preeclampsia (ePE) were assessed in terms of oxidative stress (malondialdehyde-MDA), angiogenic status (PlGF & sFLT-1), complement system (The alternative pathway-AP 50 and complement factor H-CFH) and circulating inflammatory markers (Interleukin 6-IL-6 & Procalcitonin-PCT). Control groups of gestational age matched patients included 20 gestational hypertensive (GH) and six normotensive pregnant women (NPW).Results: Our work shows that PlGF is the only serum marker who does exhibit a continued decrease from NPW to GH to ePE (r pearson = -.428, p = .002). The ePE group had a profound impairment in circulating PlGF (66.93 ± 20.62 pg/ml) compared to GH (142.67 ± 39.79 pg/ml; p = .069) and NPW (636.83 ± 392.66 pg/ml; p = .002). Then, PlGF >71.29 pg/ml pg/ml is the cut-off that has the highest negative predictive value enabling exclusion of ePE (Sp 78%, Se 70%, p = .000). No such interesting results could be obtained with the other markers. Conclusion:Our data confirm that the angiogenic factor PlGF may be highly relevant in biological mechanisms underlying the development of ePE.