We present a retrospective study on the treatment outcomes of severely immunocompromised patients with persistent COVID-19. The study analyzed data from 14 patients who received a combination of ...tixegavimab/cilgavimab and antiviral medications. Response was evaluated based on symptom improvement, PCR cycle-threshold values, and C-reactive protein levels. Eleven patients achieved complete clinical and virological resolution, while three showed partial responses. The study suggests a potential association between non-response and tixegavimab/cilgavimab neutralization. The findings underscore the need for tailored treatment approaches and further research on optimal strategies for managing persistent COVID-19, as well as the development of antivirals and variant-specific monoclonal antibodies.
Brucellosis, a systemic infection, can affect various organs, including the genitourinary system, causing epididymo-orchitis in 2%–20 % of cases. This report details a 34-year-old Thai male migrant ...worker with febrile orchitis. Initial gentamicin treatment failed, but serological tests confirmed brucellosis, likely from raw dairy consumption. The patient was successfully treated with gentamicin, doxycycline, and rifampicin, resulting in complete symptom resolution. Brucella orchitis, though rare, should be considered in patients from endemic areas. Conservative treatment with combined antibiotics is typically effective.
Abstract
Background
HIV persists in a long-lived infected CD4 T cell reservoir, which harbors an integrated transcriptionally latent virus. We reported that cytotoxic CD8 T cells conjugate with, and ...kill, autologous HIV-infected CD4 T cells isolated from all stages of HIV infection including reservoir cells of patients under antiretroviral therapy (ART) (image 1). This killing is attenuated by HIV Nef protein. We also previously reported that FasL presented by the cytotoxic T cells interacts with Fas on the surface of the target cells, resulting in the apoptosis of the target cells. Wajant demonstrated that Fas/FasL interaction can result in the target cell activation through NFkB, whereas NFkB binding site is present in the Long Terminal Repeat of HIV. Therefore, we hypothesize that the interaction of FasL and autologous CD8 T cells with CD4 T cells can result in the reactivation of latent HIV.
Conjugation and apoptosis of CD4 T cells by autologous CD8 T cells procured from patients on ART and analyzed by ImageStream.
The CD4 T cells in apoptosis are positive for activated caspase 3 (yellow) and DNA fragmentation/ TUNEL assay (orange). CD4 T cells (green), CD8 T cells (red), DAPI (blue).
Methods
CD4 T cells and CD8 T cells were procured from the PBMC of 20 HIV-infected patients on ART with undetectable viral load and 10 healthy volunteers. The cells were isolated using magnetic beads. Resting memory CD4 T cells (CD25-, CD69- and HLA-DR-) were isolated using a two-step bead depletion purification procedure. These cells were then incubated with soluble FasL (sFasL) and autologous CD8 T cells, for 2 and 16 hours. P24 was looked for in the supernatant by ELISA, and the expression of viral proteins was looked for inside CD4 T cells using immunohistochemistry and confocal microscopy
Results
CD4 T cells and resting memory CD4 T cells, procured from PBMC of HIV-infected patients on ART, showed HIV reactivation after incubation with sFasL and autologous CD8 T cells. This reactivation was demonstrated by the appearance of P24 in the supernatant (figure 1). HIV proteins p24, gp120, and Nef appeared inside the CD4 T cells (Image 2). HIV reactivation was not demonstrated in the CD4 T cells procured from HIV-infected patients that were incubated without sFasL or autologous CD8 T cells for 18 hours (figure 1).
Immunohistochemistry and confocal microscopy of CD4 T cells incubated with sFasL for 18 hours.
The cells were then incubated with a primary fluorescent antibody against HIV proteins (P24, Nef, GP120) and a secondary antibody ALEXA594 (red). The cells were also marked with DAPI (blue). We can see the expression of HIV proteins inside the CD4 T cells (red arrows).
ELISA for the expression of P24 in the supernatant of CD4 T cells procured from HIV-infected patients, following different manipulations
On the left, we note positive ELISA for P24 in the supernatant of the CD4 T cells of patients 11 to 16 (pg/ml). On the right, we note positive ELISA for P24 in the supernatant of the latent CD4 T cells of patients 17-20 (pg/ml).
Conclusion
HIV manipulates the cellular immune system in two ways; First, HIV attenuates CD8 T cells killing of HIV-infected CD4 T cells by the HIV-Nef protein. Second, reactivation of latent HIV by CD8 T cells and sFasL, that results in further infection of additional CD4 T cells.
Disclosures
All Authors: No reported disclosures
Background: Respiratory syncytial virus (RSV) is a significant cause of illness in adults, especially older adults and those with underlying conditions. This study aimed to assess the incidence of ...RSV hospitalizations in adults and identify risk factors for hospitalization and poor outcomes. Methods: A retrospective cohort study was conducted using data from two hospitals in southern Israel from 2016–2022. We calculated incidence rates of RSV and influenza hospitalizations. Risk factors for hospitalization were analyzed using Poisson regression. We evaluated poor outcomes (death, ICU admission, or mechanical ventilation) among RSV-hospitalized patients. Results: The median annual incidence of RSV hospitalization was 28.2/100,000 population, increasing with age to 199/100,000 in those ≥75 years. Significant risk factors for RSV hospitalization included pulmonary diseases (RR 4.2, 95% CI 3.4–5.2), cardiovascular diseases (RR 3.3, 95% CI 2.6–4.2), and chronic renal failure (RR 2.9, 95% CI 2.3–3.7). Among hospitalized RSV patients, 13.9% had poor outcomes. Renal failure (RR 1.81, 95% CI 1.23–2.66), neutropenia (RR 2.53, 95% CI 1.19–5.35), neutrophilia (RR 1.66, 95% CI 1.81–2.34), and lymphopenia (RR 2.03, 95% CI 1.37–3.0) were associated with poor outcomes. Conclusions: RSV causes a substantial burden of hospitalizations in adults, particularly among older adults and those with comorbidities. Identifying high-risk groups can help target prevention and treatment strategies, including vaccination.
