Update on and Future Directions for Use of Anti-SARS-CoV-2 Antibodies: National Institutes of Health Summit on Treatment and Prevention of COVID-19.

As the fourth wave of the SARS-CoV-2 pandemic encircles the globe, there remains an urgent challenge to identify safe and effective treatment and prevention strategies that can be implemented in a range of health care and clinical settings. Substantial advances have been made in the use of anti-SARS-CoV-2 antibodies to mitigate the morbidity and mortality associated with COVID-19. On 15 June 2021, the National Institutes of Health, in collaboration with the U.S. Food and Drug Administration, convened a virtual summit to summarize existing knowledge on anti-SARS-CoV-2 antibodies and to identify key unanswered scientific questions to further catalyze the clinical development and implementation of antibodies.

Human Immunodeficiency Virus/AIDS in the Era of Coronavirus Disease 2019: A Juxtaposition of 2 Pandemics.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted persons with human immunodeficiency virus (HIV), interfering with critical health services for HIV prevention, treatment, and care. While there are multiple profiles of persons living with HIV and the impact of COVID-19 may differ for each, the severity of COVID-19 in persons with HIV is related strongly to the presence of comorbidities that increase the risk of severe disease in COVID-19 patients in the absence of HIV. An effective response to the juxtaposition of the HIV and COVID-19 pandemics requires a novel coordinated and collaborative global effort of scientists, industry, and community partners to accelerate basic and clinical research, as well as implementation science to operationalize evidence-based interventions expeditiously in real-world settings. Accelerated development and clinical evaluation of prevention and treatment countermeasures are urgently needed to mitigate the juxtaposition of the HIV and COVID-19 pandemics.

Toward Understanding COVID-19 Recovery: National Institutes of Health Workshop on Postacute COVID-19.

Over the past year, the SARS-CoV-2 pandemic has swept the globe, resulting in an enormous worldwide burden of infection and mortality. However, the additional toll resulting from long-term consequences of the pandemic has yet to be tallied. Heterogeneous disease manifestations and syndromes are now recognized among some persons after their initial recovery from SARS-CoV-2 infection, representing in the broadest sense a failure to return to a baseline state of health after acute SARS-CoV-2 infection. On 3 to 4 December 2020, the National Institute of Allergy and Infectious Diseases, in collaboration with other Institutes and Centers of the National Institutes of Health, convened a virtual workshop to summarize existing knowledge on postacute COVID-19 and to identify key knowledge gaps regarding this condition.

Unraveling the Mysteries of Acute Flaccid Myelitis: Scientific Opportunities and Priorities for Future Research.

Since 2014, cases of acute flaccid myelitis (AFM) have been reported in the United States in increasing numbers biennially, occurring in the late summer and early fall. Although there is unlikely to be a single causative agent of this syndrome, non-polio enteroviruses, including enterovirus D-68 (EV-D68), have had epidemiological and laboratory associations with AFM. Much remains to be known about AFM and AFM-associated enteroviruses, including disease pathogenesis and the best strategies for development of therapeutics or preventive modalities including vaccines. To catalyze research that addresses these scientific and clinical gaps, the National Institute of Allergy and Infectious Diseases convened a workshop entitled "AFM Preparedness: Addressing EV-D68 and Other AFM-Associated Enteroviruses" on 19-20 February 2020.

The COVID-19 Serology Studies Workshop: Recommendations and Challenges.

The development, validation, and appropriate application of serological assays to detect antibodies to SARS-CoV-2 are essential to determining seroprevalence of this virus in the United States and globally and in guiding government leadership and the private sector on back-to-work policies. An interagency working group of the US Department of Health and Human Services convened a virtual workshop to identify knowledge gaps and key outstanding scientific issues and to develop strategies to fill them. Key outcomes of the workshop included recommendations for (1) advancing serology assays as a tool to better understand SARS-CoV-2 infection and (2) conducting crucial serology field studies to advance an understanding of immunity to SARS-CoV-2, leading to protection and duration of protection, including the correlation between serological test results and risk of reinfection.

Protracted course of disseminated adenovirus disease with necrotizing granulomas in the liver.

A 52- year-old male with chronic lymphocytic leukemia was hospitalized with disseminated adenovirus disease. More than a month following recovery, hepatic necrotizing granulomas secondary to adenovirus were found. This case illustrates the protracted course that adenovirus disease may take and emphasizes an unusual presentation with hepatic necrotizing granulomas.

An Untethered Ankle Exoskeleton Improves Walking Economy in a Pilot Study of Individuals With Cerebral Palsy.

The high energy cost of walking in individuals with cerebral palsy (CP) contributes significantly to reduced mobility and quality of life. The purpose of this paper was to develop and clinically evaluate an untethered ankle exoskeleton with the ability to reduce the metabolic cost of walking in children and young adults with gait pathology from CP. We designed a battery-powered device consisting of an actuator-and-control module worn above the waist with a Bowden cable transmission used to provide torque to pulleys aligned with the ankle. Special consideration was made to minimize adding mass to the body, particularly distal portions of the lower-extremity. The exoskeleton provided plantar-flexor assistance during the mid-to-late stance phase, controlled using a real-time control algorithm and embedded sensors. We conducted a device feasibility and a pilot clinical evaluation study with five individuals with CP ages five through thirty years old. Participants completed an average of 130 min of exoskeleton-assisted walking practice. We observed a 19±5% improvement in the metabolic cost of transport (p = 0.011) during walking with untethered exoskeleton assistance compared to how participants walked normally. These preliminary findings support the future investigation of powered ankle assistance for improving mobility in this patient population.

Type I IFN signaling blockade by a PASylated antagonist during chronic SIV infection suppresses specific inflammatory pathways but does not alter T cell activation or virus replication.

Chronic activation of the immune system in HIV infection is one of the strongest predictors of morbidity and mortality. As such, approaches that reduce immune activation have received considerable interest. Previously, we demonstrated that administration of a type I interferon receptor antagonist (IFN-1ant) during acute SIV infection of rhesus macaques results in increased virus replication and accelerated disease progression. Here, we administered a long half-life PASylated IFN-1ant to ART-treated and ART-naïve macaques during chronic SIV infection and measured expression of interferon stimulated genes (ISG) by RNA sequencing, plasma viremia, plasma cytokines, T cell activation and exhaustion as well as cell-associated virus in CD4 T cell subsets sorted from peripheral blood and lymph nodes. Our study shows that IFN-1ant administration in both ART-suppressed and ART-untreated chronically SIV-infected animals successfully results in reduction of IFN-I-mediated inflammation as defined by reduced expression of ISGs but had no effect on plasma levels of IL-1ß, IL-1ra, IL-6 and IL-8. Unlike in acute SIV infection, we observed no significant increase in plasma viremia up to 25 weeks after IFN-1ant administration or up to 15 weeks after ART interruption. Likewise, cell-associated virus measured by SIV gag DNA copies was similar between IFN-1ant and placebo groups. In addition, evaluation of T cell activation and exhaustion by surface expression of CD38, HLA-DR, Ki67, LAG-3, PD-1 and TIGIT, as well as transcriptome analysis showed no effect of IFN-I blockade. Thus, our data show that blocking IFN-I signaling during chronic SIV infection suppresses IFN-I-related inflammatory pathways without increasing virus replication, and thus may constitute a safe therapeutic intervention in chronic HIV infection.

Forgiveness in health research and medical practice.

With the rising popularity of positive psychology, research on forgiveness has flourished. Forgiveness has been found to have application to the field of medicine. We review definitions and describe potential physical and mental benefits of forgiveness. We (1) address potential mechanisms by which forgiveness might affect physical health, (2) evaluate the research on forgiveness and mental health, (3) summarize research on interventions to promote forgiveness, (4) examine issues specifically related to medicine in which forgiveness might play an important role, and (5) discuss forgiveness of self and others and seeking forgiveness in light of those applications. We emphasize the importance of one's motive in forgiving, noting that altruistic motives hold greater benefits than do self-interested motives.