ABSTRACT
Background. DNA vaccines are safe, tolerable, elicit humoral and cellular responses, allow for repeated dosing over time, are thermostable at room temperature, and are easy to manufacture. We present a compilation of Phase 1 and Phase 2 data of Inovio's US COVID-19 DNA Vaccine (INO-4800) targeting the full-length Spike antigen of SARS-CoV-2. A South Korean Phase 2 study is ongoing. Methods. Participants in the open-label Phase 1 trial received 0.5 mg, 1.0 mg or 2.0 mg intradermally (ID) followed by electroporation (EP) at Days 0 and 28. An optional booster dose was administered >6 months post-dose 2. The Phase 2 further compared the 1.0 mg and 2.0 mg doses against placebo in a total of 401 participants randomized at a 3:3:1:1 ratio. ClinicalTrials.gov identifiers: NCT04336410 and NCT04642638 Results. The majority of adverse events (AEs) related to INO-4800 across both trials were mild in severity and did not increase in frequency with age and subsequent doses. In Phase 1, 78% (14/18) and 84% (16/19) of subjects generated neutralizing antibody responses with geometric mean titers (GMTs) of 17.4 (95%CI 8.3, 36.5) and 62.3 (95% CI 36.4, 106.7) in the 1.0 and 2.0 groups, respectively (Figure 1). By week 8, 74% (14/19) and 100% (19/19) subjects generated T cell responses by Th1- associated IFNγ ELISPOT assay . Following a booster dose, neutralizing GMTs rose to 82.2 (95% CI 38.2, 176.9) and 124.7 (95% CI 62.8, 247.7) in the 1.0 mg and 2.0 mg groups, respectively, demonstrating the ability of INO-4800 to boost (Figure 2). In Phase 2, neutralizing antibody responses demonstrated GMTs of 93.6 (95%CI 77.3, 113.4) in the 1.0 mg dose group and 150.6 (95%CI 123.8, 183.1) in the 2.0 mg dose group (Figure 3). Conclusion. INO-4800 appears safe and tolerable as a primary series and as a booster with the induction of both humoral and cellular immune responses. In addition to eliciting neutralizing antibodies, INO-4800 also induced T cell immune responses as demonstrated by IFNγ ELISpot. Finally, as a homologous booster, INO-4800, when administered 6-10.5 months following the primary series, resulted in an increased immune response without increase in reactogenicity. The 2.0 mg dose was selected for Phase 3 evaluation.
ABSTRACT
Background : COVID-19 infection is characterized by immunothrombosis that likely reflects hypercoagulation, endothelial dysfunction, and increased formation of neutrophil extracellular traps. Aims : In this study, we investigated the utility of immunothrombosis biomarkers to distinguish between COVID-19 patients and non-COVID septic pneumonia patients. We also investigated the prognostic utility of the biomarkers in predicting ICU mortality in the two patients groups. Methods : The participants in this study were ICU COVID-19 patients ( n = 14), ICU non-COVID septic pneumonia patients ( n = 19), and age-and sex-matched healthy controls ( n = 14). Blood samples were collected on Days 4, 7, 10, and/or 14. We measured plasma levels of the following biomarkers: thrombin-antithrombin (TAT) complexes, protein C, antithrombin, soluble TM, soluble EPCR, fibrinogen, D-dimer, cell-free DNA (cfDNA), and citrullinated histones (H3-Cit). Data analysis was based on binomial logit models and receiver operating characteristic curve analyses. Results : We identified 8 biomarkers that distinguish COVID-19 patients from healthy individuals: cfDNA, D-dimer, sEPCR, PC, sTM, fibrinogen, H3-Cit, and TAT complexes. In comparison, 4 biomarkers distinguish COVID-19 from non-COVID septic pneumonia patients: fibrinogen, sEPCR, antithrombin, and cfDNA. With respect to prognosis, the main predictors of ICU mortality differ between the two patient groups. In COVID-19 patients, non-survivors have higher sTM and H3-Cit compared with survivors. In septic pneumonia patients, non-survivor patients have lower levels of protein C and higher cfDNA levels compared with survivors. In addition, the most recent values of the biomarkers have stronger prognostic value compared to their Day 1 values. Conclusions : Our results suggest that fibrinogen, sEPCR, antithrombin, and cfDNA have utility for distinguishing COVID-19 patients from non-COVID septic pneumonia patients. Our data also suggest that the predictors of ICU mortality differ between the two patient groups: sTM and H3-Cit for COVID-19 patients, and protein C and cfDNA for non-COVID septic pneumonia patients. These findings suggests that there are pathophysiological differences between the two patients groups.
ABSTRACT
In response to the coronavirus disease 2019 (COVID-19) pandemic, our NYU Langone Health Tisch/Kimmel/Orthopedic Hospital Consultation-Liaison (CL) Psychiatry service underwent a multifaceted transformation to become a primarily Virtual CL Psychiatry service. We aimed to provide the hospital system with comprehensive psychiatric consultation for all patients, regardless of isolation status, while preserving personal protective equipment and avoiding unnecessary exposure to COVID-19 for our team members. In this article, we discuss harnessing technology for video consultations and transforming the multiple facets of an academic CL Psychiatry Service to become a comprehensive, functioning virtual consultation team during the COVID-19 pandemic. We review the history, best practices, legal, and regulatory considerations of using telepsychiatry for psychiatric consultations, challenges to implementation across multiple clinical sites, and expansion of the liaison rote to include support of frontline colleagues. Finally, we provide the physician, trainee, and psychiatric nurse perspective as it relates to this transition.