3 research outputs found

    FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation

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    SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood2. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD), leading to inflammatory death (pyroptosis) and release of potent inflammatory mediators3. Here we show that about 6% of blood monocytes in COVID-19 patients are infected with SARS-CoV-2. Monocyte infection depends on uptake of antibody-opsonized virus by Fcγ receptors. Vaccine recipient plasma does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in infected monocyte culture supernatants. Instead, infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from COVID-19 lung autopsies have activated inflammasomes. These findings taken together suggest that antibody-mediated SARS-CoV-2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis

    Diagnostic and therapeutic considerations in cases of civilian intravascular ballistic embolism: a review of case reports

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    Background Ballistic embolism (BE) is a rare complication of firearm injuries notoriously associated with a vexing clinical picture in the trauma bay. Unless considered early, the associated confusion can lead to needless delay in the management of the patient with a gunshot wound. Despite this known entity, there is a relative paucity of high-grade evidence regarding complications, management, and follow-up in these patients.Methods An electronic database literature search was conducted to identify cases of acute intravascular BE in pediatric and adult civilians occurring during index hospitalization, filtered to publications during the past 10 years. Exclusion criteria included non-vascular embolization, injuries occurring in the military setting, and delayed migration defined as occurring after discharge from the index hospitalization.Results A total of 136 cases were analyzed. Nearly all cases of BE occurred within 48 hours of presentation. Compared with venous emboli, arterial emboli were significantly more likely to be symptomatic (71% vs. 7%, p<0.001), and 43% of patients developed symptoms attributable to BE in the trauma bay. In addition, arterial emboli were significantly less likely to be managed non-invasively (19% vs. 49%, p<0.001). Open retrieval was significantly more likely to be successful compared with endovascular attempts (91% vs. 29%, p<0.001). Patients with arterial emboli were more likely to receive follow-up (52% vs. 39%) and any attempt at retrieval during the hospitalization was significantly associated with outpatient follow-up (p=0.034). All but one patient remained stable or had clinically improved symptoms after discharge.Conclusion Consideration for BE is reasonable in any patient with new or persistent unexplained signs or symptoms, especially during the first 48 hours after a penetrating firearm injury. Although venous BE can often be safely observed, arterial BE generally necessitates urgent retrieval. Patients who are managed non-invasively may benefit from follow-up in the first year after injury
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