Asymptomatic SARS-CoV-2 Infection and COVID-19 Mortality During an Outbreak Investigation in a Skilled Nursing Facility.

BACKGROUND: Outbreaks of coronavirus disease 2019 (COVID-19) have been reported in nursing homes and assisted living facilities; however, the extent of asymptomatic and presymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in this high-risk population remains unclear. METHODS: We conducted an investigation of the first known outbreak of SARS-CoV-2 at a skilled nursing facility (SNF) in Illinois on 15 March 2020 and followed residents for 30 days. We tested 126/127 residents for SARS-CoV-2 via reverse-transcription polymerase chain reaction and performed symptom assessments. We calculated the point prevalence of SARS-CoV-2 and assessed symptom onset over 30-day follow-up to determine: (1) the proportion of cases who were symptomatic, presymptomatic, and asymptomatic and (2) incidence of symptoms among those who tested negative. We used the Kaplan-Meier method to determine the 30-day probability of death for cases. RESULTS: Of 126 residents tested, 33 had confirmed SARS-CoV-2 on 15 March. Nineteen (58%) had symptoms at the time of testing, 1 (3%) developed symptoms over follow-up, and 13 (39%) remained asymptomatic. Thirty-five residents who tested negative on 15 March developed symptoms over follow-up; of these, 3 were re-tested and 2 were positive. The 30-day probability of death among cases was 29%. CONCLUSIONS: SNFs are particularly vulnerable to SARS-CoV-2, and residents are at risk of severe outcomes. Attention must be paid to preventing outbreaks in these and other congregate care settings. Widespread testing and infection control are key to help prevent COVID-19 morbidity and mortality in these high-risk populations.

Immunologic and Virologic Outcomes of Obese and Nonobese Incarcerated Adults on Antiretroviral Therapy for HIV Infection.

BACKGROUND: Obesity is common among patients with HIV. The objective of this study was to characterize response to antiretroviral therapy (ART) in a cohort of obese incarcerated adults compared to a nonobese cohort. METHODS: A retrospective matched cohort study was conducted in an HIV telemedicine clinic. Patients with body mass index (BMI) >30 kg/m2 who received the same ART with >95% adherence for at least 6 months were matched to nonobese patients by age, gender, ART, CD4 count, and viral load at baseline. RESULTS: Twenty pairs were included, with an average BMI of 24 kg/m2 in the nonobese cohort and 35 kg/m2 in the obese cohort. No difference was observed in the proportion of patients who achieved virologic suppression or the change in CD4 count from baseline to 6 to 12 months. CONCLUSION: This study revealed no differences in immunologic recovery or virologic suppression between obese and nonobese patients in an adult correctional population.

Staphylococcus aureus infection of the optic nerve.

A 71-year-old woman presented with painful vision loss in the right eye followed by ophthalmoplegia. Magnetic resonance imaging demonstrated optic nerve sheath enlargement and enhancement. Biopsy of the optic nerve sheath revealed purulent and necrotic material that was positive for methicillin-sensitive Staphylococcus aureus. The patient underwent enucleation of the right eye and was treated with systemic antibiotics with clinical stabilization. Imaging, pathological and treatment aspects of optic nerve sheath abscess are discussed.

Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults.

BACKGROUND: The current goal of human immunodeficiency virus type 1 (HIV-1) therapy is to maximally suppress viral replication. Securing this goal requires new drugs and treatment classes. The chemokine receptor CCR5 provides an entry portal for HIV-1, and PRO 140 is a humanized monoclonal antibody that binds to CCR5 and potently inhibits CCR5-tropic (R5) HIV-1 in vitro. METHODS: A randomized, double-blind, placebo-controlled, dose-escalating study was conducted in 39 individuals with HIV-1 RNA levels or =5000 copies/mL, CD4(+) cell counts > or =250 cells/microL, no antiretroviral therapy for 3 months, and only R5 HIV-1 detectable. Cohorts were randomized 3:10 to receive placebo or doses of PRO 140 of 0.5, 2, or 5 mg/kg. Subjects were monitored for 58 days for safety, antiviral effects, and serum concentrations of PRO 140. RESULTS: PRO 140 was generally well tolerated and demonstrated potent, rapid, prolonged, and dose-dependent antiviral activity. Mean reductions in HIV-1 RNA level of 0.58 log(10), 1.20 log(10) (P= .0002) and 1.83 log(10) (P= .0001) were observed for the 0.5-, 2-, and 5-mg/kg dose groups, respectively. Reductions in mean viral load of > or =10-fold were observed within 4 days and persisted for 2-3 weeks after treatment. CONCLUSIONS: This trial established clear proof of concept for PRO 140 as a potent antiretroviral agent with extended activity after a single dose. TRIAL REGISTRATION: ISRCTN Register: ISRCTN45537485 .

Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins.

BACKGROUND: The HIV epidemic is a major threat to health in the developing and western worlds. A modality that targets and kills HIV-1-infected cells could have a major impact on the treatment of acute exposure and the elimination of persistent reservoirs of infected cells. The aim of this proof-of-principle study was to demonstrate the efficacy of a therapeutic strategy of targeting and eliminating HIV-1-infected cells with radiolabeled antibodies specific to viral proteins in vitro and in vivo. METHODS AND FINDINGS: Antibodies to HIV-1 envelope glycoproteins gp120 and gp41 labeled with radioisotopes bismuth 213 ((213)Bi) and rhenium 188 ((188)Re) selectively killed chronically HIV-1-infected human T cells and acutely HIV-1-infected human peripheral blood mononuclear cells (hPBMCs) in vitro. Treatment of severe combined immunodeficiency (SCID) mice harboring HIV-1-infected hPBMCs in their spleens with a (213)Bi- or (188)Re-labeled monoclonal antibody (mAb) to gp41 resulted in a 57% injected dose per gram uptake of radiolabeled mAb in the infected spleens and in a greater than 99% elimination of HIV-1-infected cells in a dose-dependent manner. The number of HIV-1-infected thymocytes decreased 2.5-fold in the human thymic implant grafts of SCID mice treated with the (188)Re-labeled antibody to gp41 compared with those treated with the (188)Re-control mAb. The treatment did not cause acute hematologic toxicity in the treated mice. CONCLUSIONS: The current study demonstrates the effectiveness of HIV-targeted radioimmunotherapy and may provide a novel treatment option in combination with highly active antiretroviral therapy for the eradication of HIV.

L. micdadei PVE successfully treated with levofloxacin/valve replacement: case report and review of the literature.

Prosthetic valve endocarditis (PVE) due to Legionella micdadei was diagnosed in a man a year after valve replacement with a bovine xenograft. He did not have pneumonia. The microbiologic diagnosis was established after valvectomy, which was necessitated by failure of empiric antibiotics to eradicate the infection. The fastidious organism grew only on buffered charcoal yeast extract agar and was confirmed as L. micdadei by gene sequence analysis. We believe this to be the first culture-proven case of L. micdadei PVE reported in the literature.

Vaccines for the prevention of diseases caused by potential bioweapons.

The development of vaccines and implementation of vaccination programs are among the most important medical contributions to humanity. To date, vaccination has reduced morbidity and mortality from infectious diseases more than any other specific medical intervention. The intentional use of bioweapons against civilians (bioterrorism), recently highlighted by events around the world, has fueled interest in the development of vaccines for potential microbial agents of bioterror. This review discusses the microbial agents that are considered to pose the greatest risk to the public, the diseases associated with them, and the vaccines that are available for their prevention. The paucity of such vaccines and uncertainty regarding mechanisms of vaccine efficacy and the microbial antigens that elicit protection underscore the need for continued study of host-microbe interaction and the immune response to potential agents of bioterror for the development of new vaccines and immune-based therapies to combat their potential to harm the public.