A Covid-19 Patient with Complement-Mediated Coagulopathy and Severe Thrombosis.

We report a patient with severe Covid-19-associated coagulopathy and type 2 diabetes mellitus who tested positive for antiphospholipid antibodies (aPL). Analysis of skin specimens suggested direct SARS-CoV-2 viral-induced and complement-mediated vascular injury and thrombosis, consistent with prior reports. Serial aPL testing demonstrated high levels of anticardiolipin antibodies (aCL) that declined to insignificant levels over a period of 5 weeks. SARS-CoV-2 RNA was detected in nasopharyngeal swab specimens on serial assays performed over the same 5-week period, though it was not detected thereafter. We hypothesize that SARS-CoV-2 viral-induced aPL contributed to severe Covid-19-associated coagulopathy in this patient.

Case of adult-onset Kawasaki disease and multisystem inflammatory syndrome following SARS-CoV-2 vaccination.

Kawasaki disease (KD) and multisystem inflammatory syndrome (MIS) are rare conditions that occur predominately in children. Recent reports document KD and MIS in adult patients following infection with SARS-CoV-2. Rarely, MIS is observed following vaccination against SARS-CoV-2, mostly in patients with prior SARS-CoV-2 infection. We report a case of KD in a man after a second SARS-CoV-2 vaccine dose, in absence of concurrent or prior SARS-CoV-2 infection. This patient also met criteria for probable MIS associated with vaccination. He tested negative for SARS-CoV-2 RNA via reverse transcriptase PCR, negative for SARS-CoV-2 nucleocapsid antibodies and demonstrated high levels SARS-CoV-2 spike protein antibodies, commonly used to assess vaccine response. Symptom improvement followed treatment with intravenous immunoglobulin, including desquamation of the hands and feet. As widespread vaccination against SARS-CoV-2 continues, increased vigilance and prompt intervention is necessary to limit the effects of postvaccination inflammatory syndromes.

Tumor-associated macrophages in glioma: friend or foe?

Tumor-associated macrophages (TAMs) contribute substantially to the tumor mass of gliomas and have been shown to play a major role in the creation of a tumor microenvironment that promotes tumor progression. Shortcomings of attempts at antiglioma immunotherapy may result from a failure to adequately address these effects. Emerging evidence supports an independent categorization of glioma TAMs as alternatively activated M2-type macrophages, in contrast to classically activated proinflammatory M1-type macrophages. These M2-type macrophages exert glioma-supportive effects through reduced anti-tumor functions, increased expression of immunosuppressive mediators, and nonimmune tumor promotion through expression of trophic and invasion-facilitating substances. Much of our work has demonstrated these features of glioma TAMs, and together with the supporting literature will be reviewed here. Additionally, the dynamics of glioma cell-TAM interaction over the course of tumor development remain poorly understood; our efforts to elucidate glioma cell-TAM dynamics are summarized. Finally, the molecular pathways which underlie M2-type TAM polarization and gene expression similarly require further investigation, and may present the most potent targets for immunotherapeutic intervention. Highlighting recent evidence implicating the transcription factor STAT3 in immunosuppressive tumorigenic glioma TAMs, we advocate for gene array-based approaches to identify yet unappreciated expression regulators and effector molecules important to M2-type glioma TAMs polarization and function within the glioma tumor microenvironment.