Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine.

The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 µg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine how much of the 10 µg total dose to assign to this immunogen. We immunized mice with 0.3, 1.0, 3.0, or 10 µg of gD2 mRNA-LNP and measured serum IgG ELISA, neutralizing antibodies, and antibodies to six crucial gD2 epitopes involved in virus entry and spread. Antibodies to crucial gD2 epitopes peaked at 1 µg, while ELISA and neutralizing titers continued to increase at higher doses. The epitope results suggested no immunologic benefit above 1 µg of gD2 mRNA-LNP, while ELISA and neutralizing titers indicated higher doses may be useful. We challenged the gD2 mRNA-immunized mice intravaginally with HSV-2. The 1-µg dose provided total protection, confirming the epitope studies, and supported assigning less than one-third of the trivalent vaccine maximum dose of 10 µg to gD2 mRNA-LNP. Epitope mapping as performed in mice can also be accomplished in phase 1 human trials to help select the optimum dose of each immunogen in a multivalent vaccine.

Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models.

Nucleoside-modified mRNA vaccines have gained global attention because of COVID-19. We evaluated a similar vaccine approach for preventing a chronic, latent genital infection rather than an acute respiratory infection. We used animal models to compare an HSV-2 trivalent nucleoside-modified mRNA vaccine with the same antigens prepared as proteins, with an emphasis on antigen-specific memory B cell responses and immune correlates of protection. In guinea pigs, serum neutralizing-antibody titers were higher at 1 month and declined far less by 8 months in mRNA- compared with protein-immunized animals. Both vaccines protected against death and genital lesions when infected 1 month after immunization; however, protection was more durable in the mRNA group compared with the protein group when infected after 8 months, an interval representing greater than 15% of the animal's lifespan. Serum and vaginal neutralizing-antibody titers correlated with protection against infection, as measured by genital lesions and vaginal virus titers 2 days after infection. In mice, the mRNA vaccine generated more antigen-specific memory B cells than the protein vaccine at early times after immunization that persisted for up to 1 year. High neutralizing titers and robust B cell immune memory likely explain the more durable protection by the HSV-2 mRNA vaccine.

Sextus chest radiograph severity score correlates to clinical outcomes in patients with COVID-19: A cross-sectional study.

ABSTRACT: The value of chest radiography (CXR) in detection and as an outcome predictor in the management of patients with coronavirus disease-2019 (COVID-19) has not yet been fully understood.To validate a standardized CXR scoring system and assess its prognostic value in hospitalized patients found to have COVID-19 by imaging criteria and to compare it to computed tomography (CT).In this cross-sectional chart review study, patients aged 18-years or older who underwent chest CT at a single institution with an imaging-based diagnosis of COVID-19 between March 15, 2020 to April 15, 2020 were included. Each patient's CXR and coronal CT were analyzed for opacities in a 6-zonal assessment method and aggregated into a "Sextus score." Inter-reader variability and correlation between CXR and coronal CT images were investigated to validate this scoring system. Univariable and multiple logistic regression techniques were used to investigate relationships between CXR scores and clinical parameters in relation to patient outcomes.One hundred twenty-four patients (median [interquartile range] age 58.5 [47.5-69.0] years, 72 [58%] men, 58 [47%] Blacks, and 35 [28%] Hispanics) were included. The CXR Sextus score (range: 0-6) was reliable (inter-rater kappa = 0.76; 95% confidence interval [CI]: 0.69-0.83) and correlated strongly with the CT Sextus score (Spearman correlation coefficient = 0.75, P < .0001). Incremental increases of CXR Sextus scores of 2 points were found to be an independent predictor of intubation (adjusted odds ratio [95% CI]: 4.49 [1.98, 10.20], P = .0003) and prolonged hospitalization (≥10 days) (adjusted odds ratio [95% CI]: 4.06 [1.98, 8.32], P = .0001).The CXR Sextus score was found to be reproducible and CXR-CT severity scores were closely correlated. Increasing Sextus scores were associated with increased risks for intubation and prolonged hospitalization for patients with COVID-19 in a predominantly Black population. The CXR Sextus score may provide insight into identifying and monitoring high-risk patients with COVID-19.

The Radiology Resident Experience at a Large Tertiary Care Hospital During the COVID-19 Pandemic.

The COVID-19 pandemic has created unprecedented challenges in healthcare including pressure to provide efficient and timely patient care while maintaining a safe environment for physicians and staff. Radiology plays a vital role as part of a multidisciplinary team in the care of these patients. We address the experiences of our radiology residency at a large urban US academic institution with an underserved population in our fight against COVID-19. The unprecedented challenges faced during this pandemic has created monumental impacts on our training and allowed for development of skills and resources in order to better handle future situations.

Catheter-Directed Thrombolysis of Iliocaval Thrombosis in Patients With COVID-19 Infection.

We present the characteristics and outcomes of the first 2 cases of catheter-directed thrombolysis performed in patients presenting with coronavirus disease-2019 (COVID-19)-related iliocaval thrombosis. (Level of Difficulty: Beginner.).

Incidence of venous thromboembolism in coronavirus disease 2019: An experience from a single large academic center.

BACKGROUND: Infection with the novel severe acute respiratory syndrome coronavirus 2 has been associated with a hypercoagulable state. Emerging data from China and Europe have consistently shown an increased incidence of venous thromboembolism (VTE). We aimed to identify the VTE incidence and early predictors of VTE at our high-volume tertiary care center. METHODS: We performed a retrospective cohort study of 147 patients who had been admitted to Temple University Hospital with coronavirus disease 2019 (COVID-19) from April 1, 2020 to April 27, 2020. We first identified the VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]) incidence in our cohort. The VTE and no-VTE groups were compared by univariable analysis for demographics, comorbidities, laboratory data, and treatment outcomes. Subsequently, multivariable logistic regression analysis was performed to identify the early predictors of VTE. RESULTS: The 147 patients (20.9% of all admissions) admitted to a designated COVID-19 unit at Temple University Hospital with a high clinical suspicion of acute VTE had undergone testing for VTE using computed tomography pulmonary angiography and/or extremity venous duplex ultrasonography. The overall incidence of VTE was 17% (25 of 147). Of the 25 patients, 16 had had acute PE, 14 had had acute DVT, and 5 had had both PE and DVT. The need for invasive mechanical ventilation (adjusted odds ratio, 3.19; 95% confidence interval, 1.07-9.55) and the admission D-dimer level ≥1500 ng/mL (adjusted odds ratio, 3.55; 95% confidence interval, 1.29-9.78) were independent markers associated with VTE. The all-cause mortality in the VTE group was greater than that in the non-VTE group (48% vs 22%; P = .007). CONCLUSIONS: Our study represents one of the earliest reported from the United States on the incidence rate of VTE in patients with COVID-19. Patients with a high clinical suspicion and the identified risk factors (invasive mechanical ventilation, admission D-dimer level ≥1500 ng/mL) should be considered for early VTE testing. We did not screen all patients admitted for VTE; therefore, the true incidence of VTE could have been underestimated. Our findings require confirmation in future prospective studies.