SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy

Blood clots are a central feature of coronavirus disease-2019 (COVID-19) and can culminate in pulmonary embolism, stroke, and sudden death. However, it is not known how abnormal blood clots form in COVID-19 or why they occur even in asymptomatic and convalescent patients. Here we report that the Spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the blood coagulation factor fibrinogen and induces structurally abnormal blood clots with heightened proinflammatory activity. SARS-CoV-2 Spike virions enhanced fibrin-mediated microglia activation and induced fibrinogen-dependent lung pathology. COVID-19 patients had fibrin autoantibodies that persisted long after acute infection. Monoclonal antibody 5B8, targeting the cryptic inflammatory fibrin epitope, inhibited thromboinflammation. Our results reveal a procoagulant role for the SARS-CoV-2 Spike and propose fibrin-targeting interventions as a treatment for thromboinflammation in COVID-19. One-Sentence SummarySARS-CoV-2 spike induces structurally abnormal blood clots and thromboinflammation neutralized by a fibrin-targeting antibody.

Neurotoxicity Screening in a Multipotent Neural Stem Cell Line Established from the Mouse Brain

Neural stem cells (NSCs) have mainly been applied to neurodegeneration in some medically intractable neurologic diseases. In this study, we established a novel NSC line and investigated the cytotoxic responses of NSCs to exogenous neurotoxicants, glutamates and reactive oxygen species (ROS). A multipotent NSC line, B2A1 cells, was established from long-term primary cultures of oligodendrocyte-enriched cells from an adult BALB/c mouse brain. B2A1 cells could be differentiated into neuronal, astrocytic and oligodendroglial lineages. The cells also expressed genotypic mRNA messages for both neural progenitor cells and differentiated neuronoglial cells. B2A1 cells treated with hydrogen peroxide and L-buthionine-(S,R)-sulfoximine underwent 30-40% cell death, while B2A1 cells treated with glutamate and kainate showed 25-35% cell death. Cytopathologic changes consisting of swollen cell bodies, loss of cytoplasmic processes, and nuclear chromatin disintegration, developed after exposure to both ROS and excitotoxic chemicals. These results suggest that B2A1 cells may be useful in the study of NSC biology and may constitute an effective neurotoxicity screening system for ROS and excitotoxic chemicals.

Incidence of Esophagitis in Gastroesophageal Reflux Disease (GERD) / 대한소화기내시경학회지

The exact incidence of esophagitis in gastroesophageal reflux disease (GERD) remains poorly understood in Korea. To determine incidence of esophagitis in GERD, from August 1988 to July 1993, endoscopy, esophageal manometry with Bernstein test, and ambulatory 24 hour esophageal pH monitoring were carried out in a group of 349 patients with symptoms of heartburn or noncardiac chest pain. Based on these studies, 151(40%) patients had some degree of GERD and pstients were categorized as having: pathologic reflux, 98 patients; symptomatic reflux, 42 patients; and sensitive mucosal reflux, 11 patients. Among 151 patients with GERD, 27 patients(18%) had some degree of esophagitis. In conclusion, 40% of patients with symptoms suggestive of GERD have GERD. GERD is divided into subgroups; pathologic reflux, symptomatic reflux, and mucosal sensitive reflux. Less than 20% of GERD have esophagitis or esophageal mucosal injury and these low incidence of mucosal injury in Korean may be due to increased esophageal mucosal resistance.

A case of acute monocytic leukemia with multiple lymphadenopathy and multiple leukemic infiltration on the skin / 대한내과학회지

No abstract available.

Changes of segmental left ventricular wall motion after coronary artery bypass graft surgery ; two-dimensional echocardiographic study / 대한내과학회지

No abstract available.