Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine.

Background: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Objectives: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination. Methods: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab. Results: After 2-vax, 8/33 (24.2%) patients in ocrelizumab group, 5/7 (71.4%) in fingolimod group, and 29/29 (100%) in HC group (P = 5.7 × 10-11) seroconverted. After 3-vax, 9/22 (40.9%) patients in ocrelizumab group, 19/21 (90.5%) in fingolimod group, and 7/7 (100%) in HC group seroconverted (P = 0.0003). The percentage of SARS-CoV-2 peptide reactive total CD4+ T cells increased in HC and ocrelizumab group but not in fingolimod group after 2-vax and 3-vax (P < 0.0001). The percentage of IFNγ and TNFα producing total CD4+ and CD8+ T cells increased in fingolimod group as compared to HC and ocrelizumab group after 2-vax and 3-vax (P < 0.0001). Conclusions: MS patients on ocrelizumab and fingolimod had attenuated humoral responses, but preserved cytokine producing T cell responses compared to HCs after SARS-CoV-2 mRNA vaccination. Clinical Trials Registration: NCT05060354.

Nasal administration of anti-CD3 mAb (Foralumab) downregulates NKG7 and increases TGFB1 and GIMAP7 expression in T cells in subjects with COVID-19.

T cells are present in early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and play a major role in disease outcome and long-lasting immunity. Nasal administration of a fully human anti-CD3 monoclonal antibody (Foralumab) reduced lung inflammation as well as serum IL-6 and C-reactive protein in moderate cases of COVID-19. Using serum proteomics and RNA-sequencing, we investigated the immune changes in patients treated with nasal Foralumab. In a randomized trial, mild to moderate COVID-19 outpatients received nasal Foralumab (100 µg/d) given for 10 consecutive days and were compared to patients that did not receive Foralumab. We found that naïve-like T cells were increased in Foralumab-treated subjects and NGK7+ effector T cells were reduced. CCL5, IL32, CST7, GZMH, GZMB, GZMA, PRF1, and CCL4 gene expression were downregulated in T cells and CASP1 was downregulated in T cells, monocytes, and B cells in subjects treated with Foralumab. In addition to the downregulation of effector features, an increase in TGFB1 gene expression in cell types with known effector function was observed in Foralumab-treated subjects. We also found increased expression of GTP-binding gene GIMAP7 in subjects treated with Foralumab. Rho/ROCK1, a downstream pathway of GTPases signaling was downregulated in Foralumab-treated individuals. TGFB1, GIMAP7, and NKG7 transcriptomic changes observed in Foralumab-treated COVID-19 subjects were also observed in healthy volunteers, MS subjects, and mice treated with nasal anti-CD3. Our findings demonstrate that nasal Foralumab modulates the inflammatory response in COVID-19 and provides a novel avenue to treat the disease.

Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma.

BACKGROUND: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings. METHODS: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events. RESULTS: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%). CONCLUSIONS: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).

Safety and Immunogenicity of SARS-CoV-2 Vaccination in Children with a History of MIS-C

Background. Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare sequela that typically develops 2-6 weeks after SARS-CoV-2 infection. According to CDC recommendations, children who recover from MIS-C should be vaccinated 90 days after diagnosis, but safety and immunogenicity data are lacking. Our aim was to evaluate the safety and immunogenicity of one dose of the BNT162b2 vaccine in children with a history of MIS-C. Methods. We conducted a longitudinal study of children with MIS-C admitted to Monroe Carell Jr. Children's Hospital at Vanderbilt from 7/11/2020 to 3/23/2022. Children were eligible if they met CDC's MIS-C criteria and had blood collected before and after SARS-CoV-2 vaccination. Clinical data were obtained from medical records and injection site and systemic reactions were recorded for a week following SARS-CoV-2 vaccination via memory aids. IgG against SARS-CoV-2 nucleocapsid (N), spike receptor-binding domain (RBD), and spike extracellular domain (ECD)was detected using an enzyme-linked immunosorbent assay. The first anti-RBD and anti-ECD levels prevaccination and post vaccination were compared using the paired-samples t-test. Results. Seven children were included, of whom five were male and five were non-Hispanic White. The first blood sample was collected 3-44 days following admission. The median age at admission was 15.8 years (IQR, 10.5-14.7 years), and the median time from admission to vaccination was 7 months (IQR, 6-8 months). Five children each had injection site or systemic reactions (Figure 1);the majority were mild or moderate and occurred within 2 days of vaccination. Children were followed for a median of 5.6 months (4.3-6.2 months) postvaccination;none developed MIS-C recurrence. Following vaccination, mean anti-RBD and anti-ECD levels increased by 2.0 (1.2-2.9;p < 0.001) and 1.9 (1.2-2.6;p < 0.001) absorbance units, respectively (Figure 2). A sensitivity analysis excluding children with antibody evidence of reinfection (increase in anti-N level >= 0.5) showed similar results. Conclusion. SARS-CoV-2 vaccination is safe and immunogenic in children with a history of MIS-C, with no documented recurrence of MIS-C-like illness. Further studies are needed to determine the optimal timing, safety, and immunogenicity of vaccination following MIS-C.

Immune thrombocytopaenic purpura following the second dose of Pfizer COVID-19 vaccine

Immune thrombocytopaenic purpura (ITP) is often a diagnosis of exclusion with presentations ranging widely from asymptomatic patients to those with life-threatening bleeding. Secondary ITP following vaccination is relatively uncommon and underdiagnosed as majority of patients remain asymptomatic. Cases of severe thrombocytopaenia associated with SARS-CoV-2 messenger RNA (ribonucleic acid) vaccinations have been described previously, mostly as isolated occurrences, and typically occurring following the first dose. Here we present a case of severe ITP associated with the second dose of the Pfizer-BioNTech/BNT16B2b2 mRNA vaccine and provide a review of the current literature.

Humoral response to COVID-19 vaccination in MS patients on disease modifying therapy: Immune profiles and clinical outcomes.

BACKGROUND: Patients with multiple sclerosis (MS) on some disease modifying therapies (DMTs), particularly anti-CD20 and sphingosine-1-phosphate (S1P) modulators, are at increased risk of severe Coronavirus Disease 19 (COVID-19) and death. COVID-19 vaccinations are effective in preventing infection and severe disease, but humoral response to vaccination and outcomes of COVID-19 infection after vaccination in MS patients on DMTs remain less understood. METHODS: In this retrospective single-center study, patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital) study and biorepository who had been vaccinated against COVID-19 and had SARS-CoV-2 spike antibody (anti-SARS-CoV-2 S Roche-Elecsys) testing were identified and compared to healthy controls. Demographic data, serum immune profiles including lymphocyte count, B-cell count, and immunoglobulins, and clinical outcome of COVID-19 infection were collected. RESULTS: 254 patients (73.2% female, mean (SD) age 52.9 (11.2) years) were identified. When controlling for age, time since vaccination, and vaccine type, patients on fingolimod, ocrelizumab, rituximab, mycophenolate mofetil, natalizumab and teriflunomide had significantly lower levels of spike antibodies compared to healthy controls (n = 34). Longer duration of treatment was associated with lower spike antibody levels in patients on anti-CD20 therapy (p = 0.016) and S1P modulators (p = 0.016) compared to healthy controls. In patients on anti-CD20 therapy, higher spike antibody levels were associated with higher CD20 cell count (p<0.001), and longer time since last anti-CD20 therapy infusion (p<0.001). 92.8% (13/14) vaccine responders (spike antibody titer >100 ug/dL) on anti-CD20 therapy demonstrated B-cell reconstitution (mean CD20 3.6%). Only 1 out of 86 patients with CD20 of 0% had a measurable spike antibody response to vaccination. During follow-up (mean 270 days), five patients were diagnosed with COVID-19 after vaccination (incidence 1.9%), all of whom had spike antibody < 20 ug/dL. No patients required ICU care or died. CONCLUSIONS: Patients on some DMTs demonstrate reduced humoral immunity after Sars-CoV-2 vaccination. Longer duration of anti-CD20 therapy and reduced CD20 cell count is associated with blunted humoral response to vaccination. CD20 reconstitution >0.1% appears necessary, but not always sufficient, for humoral response to vaccination. Breakthrough COVID-19 infection in our cohort of MS patients on DMT was higher than in population studies. We propose that adjustment of B-cell therapy administration to allow for B-cell reconstitution prior to vaccination should be considered.

Barriers to access and utilisation of perinatal mental healthcare in the UK

Background Lack of access to mental health services during the perinatal period is a significant public health concern in the UK. Barriers to accessing services may occur at multiple points in the care pathway. However, no previous reviews have investigated multilevel system barriers or how they might interact to prevent women from accessing services. Aims and Objectives To explore: 1) the barriers affecting women's access to PMH care at different points in the care pathway, 2) how women's access to and experience of PMH care has been affected by the COVID-19 pandemic. Methods Findings from two studies will be presented: 1) A systematic review of women, their family members', and healthcare providers' perspectives of barriers to accessing PMH care in the UK;2) A qualitative study with women's (n = 18) experiences of accessing PMH services during the COVID-19 pandemic, in an ethnically diverse population in South East London. Results The systematic review identified several key barriers that affected help seeking and treatment during the perinatal period. Barriers were identified at four levels: Individual (e.g. stigma, poor awareness), organisational (e.g. resource inadequacies, service fragmentation), sociocultural (e.g. language, cultural barriers) and structural (e.g. unclear policy). Interviews with women highlighted that pandemic restrictions and social distancing created additional difficulties and disruptions to accessing PMH care, and increased feelings of anxiety and isolation. Women expressed mixed feelings about remote delivery of PMH. Interpretation/Discussion Complex interlinked barriers to accessing PMH care exist within the UK and services have been further disrupted by the COVID-19 pandemic. To improve access to mental healthcare for women during the perinatal period, multilevel strategies are recommended which address individual, organisational, sociocultural and structural-level barriers at different stages of the care pathway. Conclusions To address barriers and reduce inequity in access to care, multilevel national strategies combined with targeted approaches to identifying and responding to local population needs are required.

Corrigendum: Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study.

[This corrects the article DOI: 10.3389/fimmu.2021.709861.].

Persistence of Long COVID in SARS-CoV-2 Confirmed Cases One-Year Post Infection

Background. Regardless of severity of acute SARS-CoV-2 illness, adults infected with SARS-CoV-2 are at risk for post-acute sequelae of COVID-19. Long COVID is typically classified as symptoms lasting greater than four weeks post-infection. We aimed to evaluate the frequency of resolved and unresolved long COVID symptoms in adults residing in greater Nashville, TN. Methods. We conducted a longitudinal cohort study of SARS-CoV-2-positive and exposed individuals from March 20 to May 15, 2020. Participants for this analysis were included if: 1) ≥18 years;2) SARS-CoV-2 positive by molecular or antibody testing;and 3) completed a one-year visit. Demographic and illness information were collected at enrollment, and long COVID symptoms were systematically collected at the one-year survey. Long COVID symptoms are defined as an adult experiencing at least one of the following symptoms four weeks post-infection: fatigue, confusion, loss of smell or taste, shortness of breath, chest pain, cough, muscle aches, inability to exercise, or heart palpitations. Unresolved symptoms are defined as an individual with long COVID still experiencing symptoms at the one-year visit. Results. A total of 115 adults enrolled and completed the one-year survey, of which 63 (54.8%) were SARS-CoV-2-positive, with one asymptomatic individual. Of SARS-CoV-2-positive symptomatic adults, 32 (51%) were female, 5 (88%) were of Hispanic ethnicity, and 58 (92%) were white. At the one-year visit, 33 (52%) reported having long COVID, of which 17 (52%) reported having unresolved symptoms. Fatigue (89%), headache (89%), muscle aches (79%), and cough (77%) were the most common symptoms reported at illness onset (Figure 1). Among 33 adults with long COVID, fatigue (42%), loss of smell (39%), and loss of taste (33%) were most common (Figure 2A). In the 17 individuals with unresolved symptoms, loss of smell (29%) and loss of taste (24%) were commonly reported (Figure 2B). Figure 1. COVID-19 symptoms reported at enrollment (n=62) Figure 2. Long COVID (symptoms lasting ≥ 4 weeks) (n=33) (A) and unresolved long COVID symptoms one-year post-infection (n=17) (B) reported on the one-year survey Conclusion. Half of the adults in our cohort reported long COVID symptoms, with more than quarter of symptoms persisting one-year post-illness. Our findings support that prolonged symptoms up to year after SARS-CoV-2 exposure occur, and future studies should investigate the residual impacts of long COVID symptoms and conditions.

COVID-19 Vaccine Perceptions in Adults from Greater Nashville Tennessee

Background. In December 2020, SARS-CoV-2 vaccines were made available to healthcare workers and soon thereafter offered to the general public according to age and risk of severe illness. Despite widespread access, vaccination rates vary by region, with Tennessee ranking lower than the national average. Therefore, we aimed to survey adults in greater Nashville, TN regarding SARS-CoV-2 vaccine perceptions. Methods. We conducted a cross-sectional study of an ongoing longitudinal cohort of individuals with confirmed and/or suspected SARS-CoV-2 infection and their household contacts with enrollment onset in March 2020. For this analysis, individuals were included if they were ≥ 18 years and available for a one-year follow-up visit. At the one-year visit individuals completed a survey about vaccine preferences, beliefs and risks. Demographic and social characteristics were collected at enrollment. Individuals were considered vaccinated if they had received at least one dose of a SARS-CoV-2 vaccine under FDA emergency use authorization. Vaccine perceptions were compared by SARS-CoV-2-infection and vaccination status using Pearson's chi-squared, alpha=5%. Results. Between April-May 2021, 115 individuals completed the one-year follow-up. Table 1 includes sociodemographic characteristics of adults, of which the majority were vaccinated and were unemployed or in non-essential occupations. Most individuals agreed the SARS-CoV-2 vaccine can prevent infection and hospitalization (Figure 1A & B). Unvaccinated participants more often agreed that those who contracted SARS-CoV-2 should not receive the vaccine (30%), whereas vaccinated persons less often agreed (11%, p< 0.001) (Figure 1A). Additionally, 44% of unvaccinated individuals were neutral or disagreed that benefits of SARS-CoV-2 vaccination outweighed the illness risk, compared to 10% in the vaccinated group, p=0.001 (Figure 1A). Minimal differences of vaccine perceptions were observed between SARS-CoV-2 positive and negative adults (Figure 1B). Conclusion. Although some unvaccinated individuals seemingly perceived the SARS-CoV-2 vaccine offered some protection, research should continue to evaluate the implications of vaccine hesitancy on the COVID-19 pandemic response as we prepare for the upcoming respiratory season.

Rising above the mask wars: using nonpharmaceutical interventions to lessen the burden of influenza.

The COVID-19 pandemic imparted important lessons, both through its direct impact on society and through the manner in which society's response influenced the trajectory of other diseases. The decrements in the rates of infection and morbidity from influenza during 2020 were significant, which is particularly important for pregnant women. Despite past attempts by public health authorities to encourage nonpharmaceutical interventions for the prevention of influenza, preventive efforts have focused largely on the use of vaccines. The COVID-19 experience has demonstrated that basic nonpharmaceutical interventions can potentially make a difference in lowering the rates of influenza during future outbreaks. In this article, we discuss the prepandemic role of nonpharmaceutical interventions in disease prevention, the outcomes that were seen in the flu season of 2020, and the role obstetricians should play in using nonpharmaceutical interventions in future influenza disease prevention efforts.

Exploratory study of acoustic neuromodulation improves pain, autonomic function, and symptoms of insomnia, stress, and anxiety in individuals with chronic pain

Objective: Evaluate the impact of Cereset Research™ (CR), on pain, autonomic function, insomnia, stress, and anxiety for those with chronic pain. Background: Chronic pain is a worldwide crisis causing negative health outcomes, and risk for psychological disorders. Effective non-drug, noninvasive, cost-effective, durable modalities are lacking. CR is a noninvasive, closed-loop, acoustic neuromodulation technology, echoing brainwaves in real time as auditory tones. Design/Methods: 19 adults (10 females, median age 48) with chronic pain (median 5 years), and insomnia (ISI, of ≥8 points for ≥1 month), stress (PSS of ≥14), or anxiety (GAD-7 of ≥5), enrolled in this exploratory trial. Subjects received 6-12, sixty-minute sessions of tones linked to brainwaves plus continued current care. Data was collected at baseline (V1), 0-21 days (V2) after intervention, 4-7 weeks after V2 (V3), and 4-7 weeks after V3 (V4). HRV (SDNN and rMSSD) was obtained as primary outcome based on 10-minute BP and HR recordings using a continuous non-invasive blood pressure system, with change in ISI, PSS, GAD-7, CES-D, PCL-C, and MPQ as secondary outcomes. We report interim results for symptom and HRV outcomes across visits. Results: 19 subjects completed V1-V2 measures. Due to COVID-19, V1-V4=10. Median change V1 to V4 ISI:-6.5 (p=0.001);PSS score:-5.5 (p<0.01);GAD-7:-6 (p<0.01), CES-D:-7 (p<0.01);and PCL-C:-8 (p<0.01);MPQ:-8.5 (p=0.52). Mean (median) SDNN and rMSSD significantly increased by 45.7 % (30.9%) and 89.1% (47.1%) respectively from V1 to V2. SDNN improved from V1 to V4 36.6% (39.0%), p=0.02. Conclusions: Interim results suggest significant, durable reductions in self-reported scores for insomnia, anxiety, depression, post-traumatic stress, and pain in those with chronic pain. In this small cohort, many reductions were clinically meaningful and there were also trends for improved HRV. Further evaluation is needed for this scalable, non-drug intervention.

Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study.

BACKGROUND: Immune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease. METHODS: Thirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication. RESULTS: We observed reduction of serum IL-6 and C-reactive protein in Foralumab alone vs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjects vs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events. CONCLUSIONS: This pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.

Should i bronch or should i go: The need for bronchoscopy in an immunosuppressed child with COVID-19

Introduction: Flexible bronchoscopy with bronchoalveolar lavage (FB+BAL) is routinely used for diagnostic evaluation in immunocompromised patients with pulmonary infiltrates. However, during the current COVID-19 pandemic, this procedure has usually been deferred in those with suspected or known diagnosis of COVID-19, given the risk of aerosolization and subsequent transmission of SARS-CoV-2 to healthcare personnel. We report the case of an immunosuppressed teenager with persistent fever and progressive respiratory symptoms after an initial diagnosis of COVID-19 in whom the need of FB+BAL represented a clinical dilemma. Description: A 14-year-old female on treatment for relapsed acute lymphoblastic leukemia was diagnosed with SARS-CoV-2 infection by polymerase chain reaction (PCR) in a nasal sample after having a positive household contact. Her symptoms were initially mild until she developed fever, cough, and dyspnea ∼2 weeks after diagnosis. Her laboratory evaluation was notable for lymphopenia and her chest CT revealed extensive lower lobe consolidations with scattered ground-glass opacities (Figure A), prompting hospitalization. Despite broad-spectrum antibiotics, her respiratory status worsened and she eventually required high-flow nasal cannula support. Pediatric pulmonology was consulted for consideration of FB+BAL to rule out opportunistic infections. Her repeat SARSCoV-2 PCR nasal test at that time, done ∼3 weeks after her initial diagnosis, was inconclusive. Because of this, as well as her tenuous respiratory status, it was decided not to proceed with FB+BAL. She then received steroids, remdesivir, and immunoglobulin, with gradual resolution of her hypoxemia. She was subsequently discharged home. Unfortunately, her fever and dyspnea returned ∼1 week after, prompting re-admission. Her repeat SARS-CoV-2 PCR nasal test was positive and her chest CT demonstrated shifting consolidative and ground-glass opacities, now more predominant in the upper and mid-lung fields (Figure B). We then proceeded with FB+BAL, which was unremarkable. Evaluations for a broad range of viral, bacterial, and fungal pathogens were negative, except for positive SARS-CoV-2 by PCR from BAL fluid. Her symptoms slowly improved with supportive treatment, so she was again discharged home. Her SARS-CoV-2 PCR nasal testing ∼2 months after initial diagnosis continued to be positive. Discussion: There is limited evidence regarding the safety and utility of FB+BAL in those with suspected or diagnosed COVID-19, particularly in the pediatric population. This case highlights an immunosuppressed child with prolonged viral shedding and emphasizes that in certain clinical situations FB+BAL may be required for further microbiologic data, especially when illness is protracted, the differential diagnosis is broad, and imaging findings are non-specific for COVID-19.

Outcome of Hospitalized Parkinson's Disease Patients with and without COVID-19.

Background: The Parkinson's disease (PD) patient population, with an already reduced life expectancy, is rendered particularly vulnerable by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Objectives: We determined the risk factors that increase the risk of death in patients with Parkinson's disease who are infected by SARS-CoV-2. Methods: Patients with a diagnosis of PD admitted to Montefiore Hospital (Bronx, New York) and tested for SARS-CoV-2 were identified. Retrospective review of electronic medical records confirmed the diagnosis; patients were classified by severity of PD. PD severity, demographic, socioeconomic factors, and co-morbidities were correlated with mortality rates in patients with SARS-CoV-2. Results: We identified 162 patients meeting criteria; chart review confirmed a diagnosis of PD in 70 patients. Of the 70 patients, 53 were positive for SARS-CoV-2 and 17 were negative. PD patients with SARS-CoV-2 infection had a higher mortality rate (35.8%) compared to PD patients without the infection (5.9%, P = 0.028). PD patients older than 70 years of age, those with advanced Parkinson's disease, those with reductions in their medications, and non-Hispanics (largely comprised of Black/African- Americans) had a statistically significant higher mortality rate, if infected. Conclusions: PD did not increase mortality rates from SARS-CoV-2 infection when age was controlled. However, certain unalterable factors (advanced disease and age greater than 70 years) and alterable ones (reductions in PD medications) placed PD patients at increased risk for mortality. Also several socioeconomic factors contributed to mortality, for example, non-Hispanic patients with SARS-CoV-2 infection fared worse, likely driven by poorer outcomes in the Black/African-American cohort.

Outbreak of COVID-19 among school auction attendees: Was it a “silent auction” or “silent transmission”?

Background: One day after the pandemic was announced, Tennessee declared a state of emergency on March 12, 2020 with implementation of a stay-at-home order on March 23, 2020. Data regarding the routes and patterns of community transmission of SARS-CoV-2 are limited. We initiated an investigation after clusters of confirmed COVID-19 cases attended a large social gathering. Methods: We were notified of clinical providers who attended a “Silent School Auction” on March 7, 2020, of which several confirmed-cases were identified as targeted participants. To derive a standardized REDCap web-survey, we conducted a hypothesis-generating interview with three confirmed attendees to collect event details. Once finalized, enrollment included collecting sociodemographic, epidemiologic, and clinical data. Attendees were classified as: 1) confirmed if they had a positive SARS-CoV-2 test;2) suspected if they developed symptoms 21-days before or after the auction;and 3) asymptomatic if no symptoms were noted. Results: From March 20-June 16, 100/166 (60%) of attendees were enrolled, with a median age of 41 years, 54% female, and 99% white. Of those, 34 and 32 were confirmed- and suspect-cases, respectively. Table 1 compares sociodemographic behaviors of all attendees, with the majority of confirmed-cases eating late in the evening. From March 6 to March 8, 58 participants reported attending other social events, of which three (i.e., church service, women's retreat, and a birthday party) were common among 43 attendees and five individuals reported onset of mild respiratory symptoms prior to the event (Figure 1). Confirmed-cases were more likely to report having shortness of breath, chest tightness, loss of taste, loss of smell, and fever compared to suspect-cases (Figure 2) and no one required hospitalization. Dining tables from the school auction depicted a clustering of cases occurring at each table, with some individuals visiting more than one table during the event (Figure 3). Conclusion: We identified several COVID-19 cases from a single event that occurred prior to social mitigation strategies. Our investigation highlights the importance of staying home when sick and the significance of social distancing to halt transmission of COVID-19. (Table Presented).