Early expression of IL-10, IL-12, ARG1, and NOS2 genes in peripheral blood mononuclear cells synergistically correlate with patient outcome after burn injury.

BACKGROUND: No methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, noninvasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients. METHODS: This prospective observational study enrolled two patient cohorts within a single burn center into an institutionally approved institutional review board study. Blood draws were performed <48 hours after injury. Initial unbiased immune gene expression analysis compared 23 burn patients and 6 healthy controls using multiplex immune gene expression analysis of RNA from peripheral blood mononuclear cells. We then performed confirmatory outcomes analysis in 109 burn patients and 19 healthy controls using a targeted rapid quantitative polymerase chain reaction. Findings were validated and modeled associations with clinical outcomes using a regression model. RESULTS: A total of 149 genes with a significant difference in expression from burn patients compared with controls were identified. Pathway analysis identified pathways related to interleukin (IL)-10 and inducible nitric oxide synthase signaling to have significant z scores. quantitative polymerase chain reaction analysis of IL-10, IL-12, arginase 1 (ARG1), and inducible nitric oxide synthase demonstrated that burn injury was associated with increased expression of ARG1 and IL-10, and decreased expression of nitric oxide synthase 2 (NOS2) and IL-12. Burn severity, acute lung injury, development of infection, failure of skin autograft, and mortality significantly correlated with expression of one or more of these genes. Ratios of IL-10/IL-12, ARG1/NOS2, and (ARG1-IL-10)/(NOS2-IL-12) transcript levels further improved the correlation with outcomes. Using a multivariate regression model, adjusting for patient confounders demonstrated that (ARG1-IL-10)/(NOS2-IL-12) significantly correlated with burn severity and development of acute lung injury. CONCLUSION: We present a means to predict patient outcomes early after burn injury using peripheral blood, allowing early identification of underlying immune dysfunction. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level II.

Brain venography performance following the pause of Ad.26.COV2.S COVID-19 vaccine administration.

Cases of cerebral venous thrombosis (CVT) associated with vaccine induced thrombotic thrombocytopenia (VITT) were reported following administration of the adenoviral vector COVID-19 vaccines, resulting in a pause in Ad.26.COV2.S vaccine administration in the United States, beginning on April 14, 2021. We aimed to quantify and characterize an anticipated increase in brain venograms performed in response to this pause. Brain venogram cases were retrospectively identified during the three-week period following the vaccine pause and during the same calendar period in 2019. For venograms performed in 2021, we compared COVID vaccinated to unvaccinated patients. There was a 262% increase in venograms performed between 2019 (n = 26) and 2021 (n = 94), compared to only a 19% increase in all radiologic studies. Fifty-seven percent of patients in 2021 had a history of COVID-19 vaccination, with the majority being Ad.26.COV2.S. All patients diagnosed with CVT were unvaccinated. COVID vaccinated patients lacked platelet or D-dimer measurements consistent with VITT. Significantly more vaccinated versus unvaccinated patients had a headache (94% vs 70%, p = 0.0014), but otherwise lacked compelling CVT presentations, such as decreased/altered consciousness (7% vs 23%, p = 0.036), neurologic deficit (28% vs 48%, p = 0.049), and current/recent pregnancy (2% vs 28%, p = 0.0003). We found a dramatic increase in brain venograms performed following publicity of rare COVID-19 vaccine associated CVT cases, with no CVTs identified in vaccinated patients. Clinicians should carefully consider if brain venogram performance is indicated in COVID-19 vaccinated patients lacking thrombocytopenia and D-dimer elevation, especially without other compelling CVT risk factors or symptoms.