"It was almost like it's set up for people to fail" A qualitative analysis of experiences and unmet supportive needs of people with Long COVID.

BACKGROUND: Almost twenty percent of adults with COVID-19 develop Long COVID, leading to prolonged symptoms and disability. Understanding the supportive needs of people with Long COVID is vital to enacting effective models of care and policies. DESIGN/METHODS: This qualitative sub-study explored the experiences of people with Long COVID and their unmet needs. Participants enrolled in a larger study to evaluate the post-acute cardiovascular impacts of COVID-19 were invited to participate in subsequent in-depth interviews. Participants were enrolled purposively until saturation at 24 participants. Data were analyzed using thematic content analysis. RESULTS: Participants focused on adaptations to life with Long COVID and their unmet needs in different life spheres. Three domains, 1) occupational and financial; 2) healthcare-related; and 3) social and emotional support, emerged as areas affecting quality of life. Although participants were motivated to return to work for financial and personal reasons, Long COVID symptoms often resulted in the inability to perform tasks required by their existing jobs, and unemployment. Those who maintained employment through employer accommodations still needed additional support. Participants encountered diagnostic challenges, challenges in accessing specialty appointments, insurance loopholes, high healthcare costs, and medical skepticism. Existing social networks provided support for completing daily tasks; however, those with Long COVID typically turned to others with similar lived experiences for emotional support. Participants found government support programs inadequate and difficult to access in all three domains. DISCUSSION: We propose a five-pronged policy approach to support persons with Long COVID. These overarching recommendations are (1) improve public awareness of Long COVID; (2) improve clinical care quality and access; (3) implement additional school and workplace accommodations; (4) strengthen socioeconomic benefits and social services; and (5) improve research on Long COVID.

Perplexing Initial Presentations of MOGAD in Two Children: Intracranial Hypertension and New-Onset Seizure.

We report two distinct challenging initial presentations of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Case 1 describes a 12-year-old boy who developed headaches refractory to pain medication followed by cranial neuropathies and intracranial hypertension, confirmed by lumbar puncture with an opening pressure >36 cm H2O. Case 2 describes a 3-year-old boy who developed new-onset seizures refractory to antiseizure medications, a presentation of FLAIR-hyperintense lesions in MOG-antibody associated encephalitis with seizures (FLAMES). On repeat magnetic resonance imaging, both patients were found to have cortical T2 hyperintensities, leptomeningeal contrast enhancement, and bilateral optic nerve enhancement. In the cerebrospinal fluid, both patients had CSF pleocytosis with neutrophilic predominance. The patients were treated with intravenous immunoglobulins, plasma exchange, and high-dose corticosteroids. The first patient achieved disease remission, whereas the second patient required the addition of rituximab for management of seizures. The two cases highlight the pleomorphic clinical phenotypes of MOGAD.

"Living like an empty gas tank with a leak": Mixed methods study on post-acute sequelae of COVID-19.

BACKGROUND: The burden and presentation of post-acute sequela of SARS-CoV-2 infection (PASC) are a developing major public health concern. OBJECTIVES: To characterize the burden of PASC in community-dwelling individuals and understand the experiences of people living with PASC. METHODS: This mixed-methods study of COVID-19 positive community-dwelling persons involved surveys and in-depth interviews. Main outcome was self-report of possible PASC symptoms 3 weeks or longer after positive COVID-19 test. In-depth interviews were guided by a semi-structured interview guide with open-ended questions and probes based on emerging literature on PASC and the impact of COVID-19. RESULTS: With a survey response rate of 70%, 442 participants were included in this analysis, mean (SD) age 45.4 (16.2) years, 71% female, 12% Black/African American. Compared to those with no PASC symptoms, persons who reported PASC symptoms were more likely to be older (mean age: 46.5 vs. 42; p = 0.013), female (74.3% vs. 61.2%; p = 0.010), to have pre-existing conditions (49.6% vs. 34%; p = 0.005), and to have been hospitalized for COVID-19 (14.2% vs. 2.9%; p = 0.002). About 30% of the participants experienced severe fatigue; the proportion of persons reporting severe fatigue was 7-fold greater in those with PASC symptoms (Adjusted Prevalence Ratio [aPR] 6.73, 95%CI: 2.80-16.18). Persons with PASC symptoms were more likely to report poor quality of life (16% vs. 5%, p<0.001) and worse mental health functioning (Mean difference: -1.87 95%CI: -2.38, -1.37, p<0.001). Themes from in-depth interviews revealed PASC was experienced as debilitating. CONCLUSIONS: In this study, the prevalence of PASC among community-dwelling adults was substantial. Participants reported considerable coping difficulties, restrictions in everyday activities, invisibility of symptoms and experiences, and impediments to getting and receiving PASC care.

Congenital lymphocytic choriomeningitis virus infection: spectrum of disease.

OBJECTIVE: Lymphocytic choriomeningitis virus (LCMV) is a human pathogen and an emerging neuroteratogen. When the infection occurs during pregnancy, the virus can target and damage the fetal brain and retina. We examined the spectrum of clinical presentations, neuroimaging findings, and clinical outcomes of children with congenital LCMV infection. METHODS: Twenty children with serologically confirmed congenital LCMV infection were identified. The children underwent neuroimaging studies and were followed prospectively for up to 11 years. RESULTS: All children with congenital LCMV infection had chorioretinitis and structural brain anomalies. However, the presenting clinical signs, severity of vision disturbance, nature and location of neuropathology, and character and severity of brain dysfunction varied substantially among cases. Neuroimaging abnormalities included microencephaly, periventricular calcifications, ventriculomegaly, pachygyria, cerebellar hypoplasia, porencephalic cysts, periventricular cysts, and hydrocephalus. The combination of microencephaly and periventricular calcifications was the most common neuroimaging abnormality, and all children with this combination had profound mental retardation, epilepsy, and cerebral palsy. However, others had less severe neuroimaging abnormalities and better outcomes. Some children had isolated cerebellar hypoplasia, with jitteriness as their presenting sign and ataxia as their principal long-term neurological dysfunction. INTERPRETATION: Congenital LCMV infection can have diverse presenting signs, neuroimaging abnormalities, and clinical outcomes. In the companion article to this study, we utilize an animal model to show that the clinical and pathological diversity in congenital LCMV infection is likely due to differences in the gestational timing of infection.

Acute disseminated encephalomyelitis following pleural empyema owing to Boerhaave's syndrome.

Acute disseminated encephalomyelitis is reported in a 14-year-old male patient associated with a pleural empyema caused by an esophageal perforation. During the hospital course, the patient experienced an episode of cardiac arrest, raising the question of hypoxic-ischemic cerebral injury, but the magnetic resonance imaging (MRI) findings and clinical course were most consistent with acute disseminated encephalomyelitis. After a course of methylprednisolone, broad-spectrum antibiotics, and bilateral chest tube placement, the patient recovered with only mild residual deficits, along with resolution of his MRI findings.

Prevention of intestinal amebiasis by vaccination with the Entamoeba histolytica Gal/GalNac lectin.

Prevention of intestinal infection by Entamoeba histolytica would block both invasive disease and parasite transmission. The amebic Gal/GalNAc lectin mediates parasite adherence to the colonic surface and fecal anti-lectin IgA is associated with protection from intestinal reinfection in children. We tested if vaccination with the E. histolytica Gal/GalNAc lectin could prevent cecal infection in a C3H mouse model of amebic colitis. Two trials using native lectin purified from the parasite and two trials using a 64 kDa recombinant fragment ("LecA") were performed with a combined intranasal and intraperitoneal immunization regimen using cholera toxin and Freund's adjuvants, respectively. Two weeks after immunization mice were challenged intracecally with trophozoites, and 4-12 weeks after challenge mice were sacrificed for histopathologic evaluation of infection. Vaccination prevented intestinal infection with efficacies of 84 and 100% in the two native lectin trials and 91 and 34% in the two LecA trials. Mice with detectable pre-challenge fecal anti-lectin IgA responses were significantly more resistant to infection than mice without fecal anti-lectin IgA responses. These results show for the first time that immunization with the Gal/GalNAc lectin can prevent intestinal amebiasis in mice and suggest a protective role for fecal anti-lectin IgA in vivo.

A non-toxic lectin for antigen delivery of plant-based mucosal vaccines.

RicinB, the non-toxic galactose/N-acetylgalactosamine-binding subunit of ricin, was fused to a model antigen, green fluorescent protein (GFP), and expressed in tobacco plants and hairy root cultures to test for utility in mucosal vaccine delivery/adjuvancy. The fusion protein retained both GFP fluorescence and galactose/galactosamine-binding activity. Intranasal immunization of mice with galactosamine-affinity purified ricinB:GFP recovered from tobacco root cultures triggered significant increases in GFP-specific serum IgGs. This strong humoral response was comparable to that observed following GFP immunization with cholera toxin adjuvant. GFP at the same concentrations but without an adjuvant was non-immunogenic. Induction of higher levels of IgG(1) than IgG(2a) following ricinB:GFP immunization suggested the presence of a Th2 response. Serum and fecal anti-GFP IgA were also induced by immunization with ricinB:GFP. Our data suggest that ricinB can be used as an adjuvant and antigen carrier to the mucosa and is efficient in eliciting systemic and mucosal immune responses.

The mouse model of amebic colitis reveals mouse strain susceptibility to infection and exacerbation of disease by CD4+ T cells.

Amebic colitis is an important worldwide parasitic disease for which there is not a well-established animal model. In this work we show that intracecal inoculation of Entamoeba histolytica trophozoites led to established infection in 60% of C3H mice, while C57BL/6 or BALB/c mice were resistant, including mice genetically deficient for IL-12, IFN-gamma, or inducible NO synthase. Infection was a chronic and nonhealing cecitis that pathologically mirrored human disease. Characterization of the inflammation by gene chip analysis revealed abundant mast cell activity. Parasite-specific Ab and cellular proliferative responses were robust and marked by IL-4 and IL-13 production. Depletion of CD4(+) cells significantly diminished both parasite burden and inflammation and correlated with decreased IL-4 and IL-13 production and loss of mast cell infiltration. This model reveals important immune factors that influence susceptibility to infection and demonstrates for the first time the pathologic contribution of the host immune response in amebiasis.