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Abstract Introduction Post-COVID syndrome (PCS) is characterized by a polymorphism of symptoms with hypothetical pathophysiological mechanisms. Here, we aimed to analyze the profile of inflammatory cytokines in patients with PCS and to study the relationship between this profile, the clinical symptoms as well as the endothelial function in PCS. Methods Our analytical study involved all eligible patients (n = 66) with PCS included from April 2021 to December 2021. The serum concentration of cytokines IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-27, IP-10, MCP-1 and TNF-α was quantified by flow cytometry. Endothelial function was explored by assessing microvascular flow and reactivity using thermal probes. A comparative study was carried out according to the presence of each PCS symptom. Results The average age of our patients was 55.9 ± 16.2 years. The sex ratio was 0.69. Forty-one patients (62%) presented with a severe form of acute infection. The most frequently reported symptoms were dyspnea (67%), fatigue (50%), and memory problems (32%). Fifty-seven patients (86%) had endothelial dysfunction. The majority of patients had increased levels of IP-10 (100%), IL-8 (95%), IFN-γ (95%), MCP-1 (80%), and TNF-α (70%). The serum concentration of IL-10 was below the threshold of quantification in 89% of subjects. The severe form of acute infection was associated with elevated IL-10, MCP-1, and IL-27. Increased IL-6 and IL-27 levels were associated with fatigue while IL-8 concentrations were higher in patients who reported dyspnea. Elevation of IL-8 level was more common in patients with profound impairment of endothelial function. Conclusion Our results further support the presence of endothelial dysfunction in PCS and show an elevation of pro-inflammatory cytokines with a downmodulation of the IL-10- anti-inflammatory response. In addition, immuno-clinical phenotypes emerge, such as an inflammatory profile mediated by IL-6 and IL-27 in fatigue and IL-8 in dyspnea. The identification of immuno-clinical phenotypes would allow a better understanding of the pathophysiology of PCS symptoms.

Abstract Yellow urticaria is a variant of urticaria that is rarely reported in the literature. It usually occurs in the setting of a chronic liver disease and reflects the accumulation of bilirubin in the skin tissues. We report a case of yellow urticaria that occurred in a 33‐year‐old female patient suffering from systemic lupus erythematosus and overlap syndrome of autoimmune hepatitis and primary biliary cholangitis revealed by a migratory pruritic yellowish urticarial eruption on the trunk and limbs. Yellow urticaria may be an important clue to previously unknown liver or biliary disease as it generally occurs in the setting of hyperbilirubinemia.

ObjectiveNon-respiratory long-coronavirus disease 2019 (COVID-19) symptoms are mainly related to a long-lasting endothelial dysfunction and microcirculation impairment. We hypothesized that Sulodexide, a purified glycosaminoglycan mixture with a beneficial endothelial effect in arterial and venous peripheral diseases, may be effective in a subset of patients with long COVID-19.Approach and ResultsWe conducted a multicenter prospective quasi-experimental study. A total of 290 patients from the TUN-EndCOV study with long-COVID-19 symptoms and endothelial dysfunction were included. The endothelial function was clinically assessed using a post-occlusive reactive hyperemia protocol with finger thermal monitoring device. Endothelial quality index (EQI) was assessed at inclusion and at 21 days later. The study population was assigned to a sulodexide group (144 patients) or a no-medical treatment group (146 patients). Clinical characteristics were similar at inclusion in the two groups. Fatigue, shortness of breath, and chest pain were the most common symptoms, respectively, 54.5, 53.8, and 28.3%. At 21 days, the sulodexide group improved significantly better than the no-medical treatment group in chest pain (83.7 vs. 43.6%, p < 10−3), palpitations (85.2 vs. 52.9%, p = 0.009), and endothelial function [median delta-EQI 0.66 (0.6) vs. 0.18 (0.3); p < 10−3]. Endothelial function improvement was significantly correlated with chest pain and palpitations recovery (AUC, i.e., area under the curve = 0.66, CI [0.57– 0.75], p = 0.001 and AUC = 0.60, CI [0.51– 0.69], p = 0.03, respectively).ConclusionSulodexide significantly improves long-lasting post-COVID-19 endothelial dysfunction and alleviates chest pain and palpitations.