A small but significant proportion of COVID‐19 patients develop life‐threatening cytokine storm. We have developed a new anti‐inflammatory drug, EXO‐CD24, a combination of an immune checkpoint (CD24) and a delivery platform (exosomes). CD24 inhibits the NF‐kB pathway and the production of cytokines/chemokines. EXO‐CD24 discriminates damage‐from pathogen‐associated molecular patterns (DAMPs and PAMPs) therefore does not interfere with viral clearance. EXO‐CD24 was produced and purified from CD24‐expressing 293‐TREx™ cells. Exosomes displaying murine CD24 (mCD24) were also created. EXO‐CD24/mCD24 were characterized and examined, for safety and efficacy, in vitro and in vivo . In a phase Ib/IIa study, 35 patients with moderate–high severity COVID‐19 were recruited and given escalating doses, 10 8 –10 10 , of EXO‐CD24 by inhalation, QD, for 5 days. No adverse events related to the drug were observed up to 443–575 days. EXO‐CD24 effectively reduced inflammatory markers and cytokine/chemokine, although randomized studies are required. EXO‐CD24 may be a treatment strategy to suppress the hyper‐inflammatory response in the lungs of COVID‐19 patients and further serve as a therapeutic platform for other pulmonary and systemic diseases characterized by cytokine storm.

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Bartonella species are fastidious, Gram-negative aerobic rods and a well-recognised pathogen responsible for culture-negative endocarditis. The histopathological appearance of glomerulonephritis (GN) caused by Bartonella endocarditis may include a pauci-immune GN similar to that usually seen in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Herein, we present an unusual case report of Bartonella endocarditis masquerading as ANCA-positive vasculitis, with crescentic GN. A 66-year-old woman, who had undergone aortic valve replacement 2 years prior to admission, presented with confusion and loss of vision in her right nasal field. Following an extensive diagnostic evaluation, the main findings were right central retinal artery occlusion, ground-glass appearance on chest CT and ANCA-positive, anti PR-3 negative, rapidly progressive GN. The patient was scheduled to start treatment with rituximab for presumed ANCA-positive GN, when a positive serological test for Bartonella henselae was received. In view of this result, a diagnosis of endocarditis was made, based on fulfilment of five Duke minor criteria, namely fever, predisposition, arterial emboli, immunological phenomena and serological evidence of active infection with an organism consistent with infective endocarditis. Immunosuppressive treatment was withheld and antibiotic treatment initiated. This case report emphasises the need for maintaining a high index of suspicion regarding the diagnosis of Bartonella infection, which might mimic ANCA-associated GN.

Severe COVID-19 infections present with cytokine storms, hypercoagulation, and acute respiratory distress syndrome, with extracellular vesicles (EVs) being involved in coagulation and inflammation. This study aimed to determine whether coagulation profiles and EVs reflect COVID-19 disease severity. Thirty-six patients with symptomatic COVID-19 infection with mild/moderate/severe disease (12 in each group) were analyzed. Sixteen healthy individuals served as controls. Coagulation profiles and EV characteristics were tested by nanoparticle tracking analysis (NTA), flow cytometry, and Western blot. While coagulation factors VII, V, VIII, and vWF were comparable, significant differences were found in patients’ D-Dimer/fibrinogen/free protein S levels compared to controls. Severe patients’ EVs displayed higher percentages of small EVs (<150 nm) with increased expression of exosome marker CD63. Severe patients’ EVs displayed high levels of platelet markers (CD41) and coagulation factors (tissue factor activity, endothelial protein C receptor). EVs of patients with moderate/severe disease expressed significantly higher levels of immune cell markers (CD4/CD8/CD14) and contained higher levels of IL-6. We demonstrated that EVs, but not the coagulation profile, may serve as biomarkers for COVID-19 severity. EVs demonstrated elevated levels of immune- and vascular-related markers in patients with moderate/severe disease, and may play a role in disease pathogenesis.