COVID-19 Outcomes in Hospitalized Patients With Neurodegenerative Disease: A Retrospective Cohort Study.

Background and Objectives: COVID-19 outcomes in patients with neurodegenerative disorders (NDs) are not well understood, and we hypothesize that there may be increased morbidity and mortality in this group. Methods: This was a retrospective cohort study performed at 3 hospitals in the Chicagoland area. All patients hospitalized with COVID-19 infection with ND during a 3-month period (March 15, 2020-June 15, 2020) were included and compared with age-matched controls (CL) at 1:1 ratio. Primary outcomes were death, intensive care unit (ICU) admission, and invasive ventilation. Secondary outcomes included presenting COVID-19 symptoms, development of encephalopathy, supplementary oxygen use, discharge disposition, and risk factors for mortality. Results: The study included 132 patients with neurodegenerative disorders and 132 age-matched CL. Ninety-day mortality (ND 19.7% vs CL 23.5%, p = 0.45) and ICU admission (ND 31.5% vs CL 35.9%, p = 0.43) rates were not significantly different between the 2 groups. Patients with ND had a lower rate of invasive ventilation (ND 11.4% vs CL 23.2%, p = 0.0075) and supplementary oxygen use (ND 83.2% vs CL 95.1%, p = 0.0012). Patients with ND were also more likely to have altered mental status or confusion as their presenting COVID-19 symptom and less likely to present with respiratory symptoms. Patients with ND were discharged to nursing home or hospice at higher rates compared with CL. Discussion: We found that there was no difference in short-term mortality of patients with ND hospitalized for COVID-19 compared with CL, but they may have higher rates of neurologic complications and disability. Future studies should address long-term outcomes.

A pilot study of a 12-week community-based boxing program for Parkinson's disease.

INTRODUCTION: Community-based exercise programs for Parkinson's disease (PD) have gained popularity. Our understanding of such programs on non-motor features is limited. We characterized the effect of a 12-week community-based boxing exercise program on motor and non-motor symptoms in people with Parkinson's disease (PwPD). METHODS: In this prospective observational study, PwPD underwent a 12-week community-based boxing program (2 sessions per week, for a total of 24 sessions). The following assessments were performed by a movement disorders neurologist at baseline and after completion of the program: MDS-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) in a modified version since assessments were performed virtually due to COVID-19 pandemic, MDS Non-Motor Rating Scale (MDS-NMS), Hamilton Depression Rating Scale (HDRS), Lilli Apathy Rating Scale (LARS), Parkinson's Disease Questionaire-39 (PDQ-39), and Schwab and England Activities of Daily Living scale (SE-ADL). Pre- and post-assessments were compared using Wilcoxon signed rank test; only participants who completed the program and both assessments were analyzed. RESULTS: A total of 14 PwPD agreed to be a part of the study and completed assessments. All participants were ambulatory and functionally independent at baseline. Total non-motor feature severity (MDS-NMS, p = 0.0031), depression (HDRS, p = 0.015), and motor features (MDS-UPDRS PART 3 modified, p = 0.023) all improved significantly after the intervention. Scales on apathy (LARS, p = 0.29), Parkinson's disease-specific health related quality (PDQ-39, p = 0.093), and activities of daily living (SE-ADL, p = 0.32) did not demonstrate significant change. CONCLUSION: PwPD who participated in a community-based, pilot boxing program showed improvements in motor exam and non-motor symptoms.

HEALTHCARE WORKFORCE BURNOUT: INNOVATIVE SOLUTIONS PRE/DURING AND POST COVID-19 PANDEMIC

Burnout in healthcare is a common issue impacting individuals at all levels, especially frontline healthcare workers who face greater levels of stress in the workplace which impacts their emotional, physical, and mental health. Furthermore, the pandemic created a plethora of new stressors that continue to be prevalent among healthcare employees. As organizations seek to formulate the most effective burnout reduction strategies for their staff, it is imperative to pinpoint the stressors plaguing the workplace. Addressing burnout requires a longterm strategy to tackle the multitude of stressors in the work environment and achieve buy-in from staff and executive leadership.

The impact of COVID-19 on service delivery systems: evidence from a survey of United States refugee resettlement agencies.

BACKGROUND: Key to the US refugee resettlement effort is the role of non-governmental organizations (NGOs) who receive, place, and provide transitional programs and referrals to new and recently resettled refugees. Yet only one rapid assessment study thus far examined the impact of COVID-19 on service delivery systems of US refugee resettlement agencies. This exploratory study describes the capability and preparedness of US refugee resettlement agencies to provide services and care to clients during the COVID-19 pandemic. METHODS: Using both telephone interviews and an internet survey, we assessed the impact of COVID-19 on service delivery, agency capacity, and preparedness of 101 US refugee resettlement agencies. Descriptive statistics were used to describe the dataset, while chi-square (χ2) tests were used to examine relationships by resettlement agency size (number of employees in each agency). RESULTS: Despite a temporary pause on refugee admissions, restrictive stay-at-home orders, and refugee travel restrictions, the majority of responding US refugee resettlement agencies continued to provide specialized services and care to resettled refugees and other immigrants. Among the more important findings was that agencies that continued to provide refugee services and care onsite in their existing facilities or office rather than moving such services offsite differed by agency size [χ2 (9.494, n = 101), p < 0.05]. Almost all agencies (93.1%) strongly agreed or agreed that staff have timely access to COVID-19 information. Most of the refugee services were provided offsite (n = 72 agencies, some with multiple offices across the US). CONCLUSIONS: US refugee resettlement agencies continued to perform admirably despite a lack of funding. Future research is underway to obtain a more balanced understanding of the impact of COVID-19 on practice or operations.

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants.

Here we report on the antibody and memory B cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccine against SARS-CoV-21-4. Eight weeks after the second injection of vaccine, volunteers showed high levels of IgM and IgG anti-SARS-CoV-2 spike protein (S) and receptor-binding-domain (RBD) binding titre. Moreover, the plasma neutralizing activity and relative numbers of RBD-specific memory B cells of vaccinated volunteers were equivalent to those of individuals who had recovered from natural infection5,6. However, activity against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant S was reduced by a small-but significant-margin. The monoclonal antibodies elicited by the vaccines potently neutralize SARS-CoV-2, and target a number of different RBD epitopes in common with monoclonal antibodies isolated from infected donors5-8. However, neutralization by 14 of the 17 most-potent monoclonal antibodies that we tested was reduced or abolished by the K417N, E484K or N501Y mutation. Notably, these mutations were selected when we cultured recombinant vesicular stomatitis virus expressing SARS-CoV-2 S in the presence of the monoclonal antibodies elicited by the vaccines. Together, these results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid a potential loss of clinical efficacy.

Evolution of antibody immunity to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

Convergent antibody responses to SARS-CoV-2 in convalescent individuals.

During the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has led to the infection of millions of people and has claimed hundreds of thousands of lives. The entry of the virus into cells depends on the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2. Although there is currently no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19-convalescent individuals. Plasma samples collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres; titres were less than 50 in 33% of samples, below 1,000 in 79% of samples and only 1% of samples had titres above 5,000. Antibody sequencing revealed the expansion of clones of RBD-specific memory B cells that expressed closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on the RBD neutralized the virus with half-maximal inhibitory concentrations (IC50 values) as low as 2 ng ml-1. In conclusion, most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.