Parent-reported social-communication changes in children diagnosed with autism spectrum disorder during the COVID-19 pandemic in the UK.

Introduction: The coronavirus pandemic has swept across the United Kingdom (UK). Given the ever-evolving situation, little is known about the repercussions of coronavirus and the subsequent lockdowns for children diagnosed with Autism Spectrum Disorder (ASD). Therefore, this study explores the social-communicative impact of the first lockdown (March 2020 - July 2020) in the UK and the return to school period (September 2020 - October 2020), following prolonged disruption to routine, in children diagnosed with ASD. Methods : Parents of autistic children completed 2 separate online surveys following the first lockdown in the UK (n = 176) and also when children returned to school following the summer break (n = 54). Results : The results suggested that self-regulation skills (p < .05) and co-operation skills (p < .05) were most affected over the course of the lockdown. Children's physical activity levels were perceived to significantly increase during the return to school (p < .0001), which was associated with better social-communication outcomes (p < .05). Conclusion : Future work is needed to confirm and explore the findings. Such work could be implemented to protect and improve the social-communicative outcomes of autistic children.

Serological fingerprints link antiviral activity of therapeutic antibodies to affinity and concentration.

The effectiveness of therapeutic monoclonal antibodies (mAbs) against variants of the SARS-CoV-2 virus is highly variable. As target recognition of mAbs relies on tight binding affinity, we assessed the affinities of five therapeutic mAbs to the receptor binding domain (RBD) of wild type (A), Delta (B.1.617.2), and Omicron BA.1 SARS-CoV-2 (B.1.1.529.1) spike using microfluidic diffusional sizing (MDS). Four therapeutic mAbs showed strongly reduced affinity to Omicron BA.1 RBD, whereas one (sotrovimab) was less impacted. These affinity reductions correlate with reduced antiviral activities suggesting that affinity could serve as a rapid indicator for activity before time-consuming virus neutralization assays are performed. We also compared the same mAbs to serological fingerprints (affinity and concentration) obtained by MDS of antibodies in sera of 65 convalescent individuals. The affinities of the therapeutic mAbs to wild type and Delta RBD were similar to the serum antibody response, indicating high antiviral activities. For Omicron BA.1 RBD, only sotrovimab retained affinities within the range of the serum antibody response, in agreement with high antiviral activity. These results suggest that serological fingerprints provide a route to evaluating affinity and antiviral activity of mAb drugs and could guide the development of new therapeutics.

Complete Telehealth for Multidisciplinary Preoperative Workup Does Not Delay Time to Metabolic and Bariatric Surgery: a Pilot Study.

PURPOSE: The COVID-19 pandemic accelerated implementation of telehealth throughout the US healthcare system. At our institution, we converted a fully integrated multidisciplinary bariatric clinic from face-to-face visits to entirely telehealth video/telephone visits. We hypothesized telehealth would increase the number of provider/patient encounters and therefore delay time to surgery. METHODS: This is a retrospective review of consecutive patients who underwent total telehealth preoperative workup. Demographics, comorbidities, and surgical characteristics were compared to the same number of consecutive patients who underwent a face-to-face approach 12 months prior, using a Wilcoxon test for continuous variables and chi-square or Fisher's exact test for categorical variables. Differences between time and surgery were compared using inverse probability of treatment-weighted estimates and number of preoperative visits using Poisson regression with distance to hospital as a confounder. Noninferiority margin for time to surgery was set to 60 days, and the number of visits was set to 2 visits. RESULTS: Between March of 2020 and December of 2021, 36 patients had total telehealth workup, and were compared to 36 patients in the traditional group. Age, sex, body mass index, and comorbidities did not differ between groups. The average number of days to surgery was 121.1 days shorter in the telehealth group (90% bootstrap CI [- 160.4, - 81.8]). Estimated shift in the total number of visits was additional .76 visits in the traditional group (90% CI [.64, .91). CONCLUSIONS: The total telehealth approach to preoperative bariatric multidisciplinary workup did not delay surgery and decreased number of total outpatient visits and time to surgery.

Detection of neutralizing antibodies against multiple SARS-CoV-2 strains in dried blood spots using cell-free PCR.

An easily implementable serological assay to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies is urgently needed to better track herd immunity, vaccine efficacy and vaccination rates. Herein, we report the Split-Oligonucleotide Neighboring Inhibition Assay (SONIA) which uses real-time qPCR to measure the ability of neutralizing antibodies to block binding between DNA-barcoded viral spike protein subunit 1 and the human angiotensin-converting enzyme 2 receptor protein. The SONIA neutralizing antibody assay using finger-prick dried blood spots displays 91-97% sensitivity and 100% specificity in comparison to the live-virus neutralization assays using matched serum specimens for multiple SARS-CoV-2 variants-of-concern. The multiplex version of this neutralizing antibody assay, using easily collectable finger-prick dried blood spots, can be a valuable tool to help reveal the impact of age, pre-existing health conditions, waning immunity, different vaccination schemes and the emergence of new variants-of-concern.

Limited Correlation between SARS-CoV-2 Serologic Assays for Identification of High-Titer COVID-19 Convalescent Plasma Using FDA Thresholds.

In August 2020, the Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for COVID-19 convalescent plasma (CCP) specified 12 authorized serologic assays and associated assay-specific cutoff values for the selection of high-titer CCP for use in hospitalized patients. The criteria used for establishing these cutoff values remains unclear. Here, we compare the overall agreement and concordance of five serologic assays included in the August 2020 FDA EUA at both the manufacturer-recommended qualitative cutoff thresholds and at the FDA-indicated thresholds for high-titer CCP, using serum samples collected as part of the CCP Expanded Access Program (EAP). The qualitative positive percent agreement (PPA) across assays ranged from 92.3% to 98.8%. However, the high-titer categorization across assays varied significantly, with the PPA ranging from 26.5% to 82.7%. The Roche anti-NC ECLIA provided the lowest agreement compared to all other assays. Efforts to optimize high-titer cutoffs could reduce, although not eliminate, the discordance across assays. The consequences of using nonstandardized assays are apparent in our study, and the high-titer cutoffs chosen for each assay are not directly comparable to each other. The generalized findings in our study will be relevant to any future use of convalescent plasma for either COVID-19 or future pandemics of newly emerged pathogens. IMPORTANCE COVID-19 convalescent plasma (CCP) was one of the first therapeutic options available for the treatment of SARS-CoV-2 infections and continues to be used selectively for immunosuppressed patients. Given the emergence of novel SARS-CoV-2 variants which are resistant to treatment with available monoclonal antibody (MAb) therapy, CCP remains an important therapeutic consideration. The FDA has released several emergency use authorizations (EUA) that have specified which serological assays can be used for qualification of CCP, as well as assay-specific cutoffs that must be used to identify high-titer CCP. In this study, a cohort of donor CCP was assessed across multiple serological assays which received FDA EUA for qualification of CCP. This study indicates a high degree of discordance across the assays used to qualify CCP for clinical use, which may have precluded the optimal use of CCP, including during clinical trials. This study highlights the need for assay standardization early in the development of serological assays for emerging pathogens.

Development of a rapid point-of-care test that measures neutralizing antibodies to SARS-CoV-2.

BACKGROUND: After receiving a COVID-19 vaccine, most recipients want to know if they are protected from infection and for how long. Since neutralizing antibodies are a correlate of protection, we developed a lateral flow assay (LFA) that measures levels of neutralizing antibodies from a drop of blood. The LFA is based on the principle that neutralizing antibodies block binding of the receptor-binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2). METHODS: The ability of the LFA was assessed to correctly measure neutralization of sera, plasma or whole blood from patients with COVID-19 using SARS-CoV-2 microneutralization assays. We also determined if the LFA distinguished patients with seasonal respiratory viruses from patients with COVID-19. To demonstrate the usefulness of the LFA, we tested previously infected and non-infected COVID-19 vaccine recipients at baseline and after first and second vaccine doses. RESULTS: The LFA compared favorably with SARS-CoV-2 microneutralization assays with an area under the ROC curve of 98%. Sera obtained from patients with seasonal coronaviruses did not show neutralizing activity in the LFA. After a single mRNA vaccine dose, 87% of previously infected individuals demonstrated high levels of neutralizing antibodies. However, if individuals were not previously infected, only 24% demonstrated high levels of neutralizing antibodies after one vaccine dose. A second dose boosted neutralizing antibody levels just 8% higher in previously infected individuals, but over 63% higher in non-infected individuals. CONCLUSIONS: A rapid, semi-quantitative, highly portable and inexpensive neutralizing antibody test might be useful for monitoring rise and fall in vaccine-induced neutralizing antibodies to COVID-19.

Environmental Contamination with SARS-CoV-2 in Nursing Homes

Background The COVID-19 pandemic has disproportionately affected nursing home (NH) patients, accounting for 5% of all cases and 32% of all COVID-19 deaths nationwide. Little is known about the frequency and persistence of SARS-CoV-2 environmental contamination in NHs. We characterize SARS-CoV-2 contamination in the rooms of COVID-19 patients and common areas in and around COVID-19 units. Methods A prospective cohort study was conducted at four NHs in Michigan between October 2020 and January 2021. Clinical research personnel obtained swab specimens from high-touch room surfaces of COVID-19 infected patients, up to three times per patient. Weekly swab specimens from six high-touch surfaces in common areas were also obtained. Demographic and clinical data were collected from patient clinical records. Our primary outcome of interest was the probability of SARS-CoV-2 detection from specific environmental surfaces in COVID-19 patient rooms. Results One hundred four patients with COVID-19 were enrolled and followed for 241 visits. Patient characteristics included: 61.5% over the age of 80;67.3% female;89.4% non-Hispanic white;50.1% short-stay. The study population had significant disabilities in activities of daily living (ADL;81.7% dependent in four or more ADLs) and comorbidities including dementia (55.8%), diabetes (40.4%) and heart failure (32.7) (Table 1). Over the 3-month study period, 2087 swab specimens were collected (1896 COVID-19 patient room surfaces, 191 common area swabs). Figure 1 shows contamination rates at sites proximate and distant to the patient bed. SARS-CoV-2 positivity was 28.4% (538/1896 swabs) on patient room surfaces and 3.7% (7/191 swabs) on common area surfaces. Over the course of follow-up, 89.4% (93/104) of patients had SARS-CoV-2 contamination in their room at least once (Figure 2). Environmental contamination detected on enrollment correlated with contamination of the same site during follow-up. Functional independence increased the odds of proximate contamination. Table 1. Clinical and Demographic Characteristics of the Study Population Including Short- and Long-stay Patients Figure 1. Contamination of Environmental Surfaces Relative to Distance from Patient Bed Figure 2. SARS-CoV-2 on Swab Specimens Collected – Patient-level, Visit-level, and Swab-level Conclusion We conclude that environmental contamination of surfaces in the rooms of COVID-19 patients is nearly universal and persistent. Patients with greater independence are more likely than fully dependent patients to contaminate their immediate environment. Disclosures All Authors: No reported disclosures

SARS-CoV-2 Serologic Assays Dependent on Dual-Antigen Binding Demonstrate Diverging Kinetics Relative to Other Antibody Detection Methods.

Longitudinal studies assessing durability of the anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) humoral immune response have generated conflicting results. This has been proposed to be due to differences in patient populations, the lack of standardized methodologies, and the use of assays that measure distinct aspects of the humoral response. SARS-CoV-2 antibodies were serially measured in sera from a cohort of 44 well-characterized convalescent plasma donors over 120 days post-COVID-19 symptom onset, utilizing eight assays, which varied according to antigen source, the detected antibody isotype, and the activity measured (i.e., binding, blocking, or neutralizing). While the majority of assays demonstrated a gradual decline in antibody titers over the course of 120 days, the two electrochemiluminescence immunoassay Roche assays (Roche Diagnostics Elecsys anti-SARS-CoV-2 [qualitative, nucleocapsid based] and Roche Diagnostics Elecsys anti-SARS-CoV-2 S [semiquantitative, spike based]), which utilize dual-antigen binding for antibody detection, demonstrated stable and/or increasing antibody titers over the study period. This study is among the first to assess longitudinal, rather than cross-sectional, SARS-CoV-2 antibody profiles among convalescent COVID-19 patients, primarily using commercially available serologic assays with Food and Drug Administration emergency use authorization. We show that SARS-CoV-2 antibody detection is dependent on the serologic method used, which has implications for future assay utilization and clinical value.

Environmental contamination with SARS-CoV-2 in nursing homes.

BACKGROUND: SARS-CoV-2 outbreaks in nursing homes (NHs) have been devastating and have led to the creation of coronavirus disease 2019 (COVID-19) units within NHs to care for affected patients. Frequency and persistence of SARS-CoV-2 environmental contamination in these units have not been studied. METHODS: A prospective cohort study was conducted between October 2020 and January 2021 in four Michigan NHs. Swabs from high-touch surfaces in COVID-19-infected patient rooms were obtained at enrollment and follow-up. Demographic and clinical data were collected from clinical records. Primary outcome of interest was the probability of SARS-CoV-2 RNA detection from specific environmental surfaces in COVID-19 patient rooms. We used multivariable logistic regression to assess patient risk factors for SARS-CoV-2 contamination. Pairwise Phi coefficients were calculated to measure correlation of site-specific environmental detection upon enrollment and during follow-up. RESULTS: One hundred and four patients with COVID-19 were enrolled (61.5% >80 years; 67.3% female; 89.4% non-Hispanic White; 51% short stay) and followed up for 241 visits. The study population had significant disabilities in activities of daily living (ADL; 81.7% dependent in four or more ADLs) and comorbidities, including dementia (55.8%), diabetes (40.4%), and heart failure (32.7%). Over the 3-month study period, 2087 swab specimens were collected (1896 COVID-19 patient rooms, 191 common areas). SARS-CoV-2 positivity was 28.4% (538/1896 swabs) on patient room surfaces and 3.7% (7/191 swabs) on common area surfaces. Nearly 90% (93/104) of patients had SARS-CoV-2 contamination in their room at least once. Environmental contamination upon enrollment correlated with contamination of the same site during follow-up. Functional independence increased the odds of proximate contamination. CONCLUSIONS: Environmental detection of viral RNA from surfaces in the rooms of COVID-19 patients is nearly universal and persistent; more investigation is needed to determine the implications of this for infectiousness. Patients with greater independence are more likely than fully dependent patients to contaminate their immediate environment.

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

Preliminary accuracy of COVID-19 odor detection by canines and HS-SPME-GC-MS using exhaled breath samples.

The novel coronavirus SARS-CoV-2, since its initial outbreak in Wuhan, China has led to a worldwide pandemic and has shut down nations. As with any outbreak, there is a general strategy of detection, containment, treatment and/or cure. The authors would argue that rapid and efficient detection is critical and required to successful management of a disease. The current study explores and successfully demonstrates the use of canines to detect COVID-19 disease in exhaled breath. The intended use was to detect the odor of COVID-19 on contaminated surfaces inferring recent deposition of infectious material from a COVID-19 positive individual. Using masks obtained from hospitalized patients that tested positive for COVID-19 disease, four canines were trained and evaluated for their ability to detect the disease. All four canines obtained an accuracy >90% and positive predictive values ranging from ~73 to 93% after just one month of training.

When planning meets reality: COVID-19 interpandemic survey of Michigan Nursing Homes.

BACKGROUND: Nursing home (NH) populations have borne the brunt of morbidity and mortality of COVID-19. We surveyed Michigan NHs to evaluate preparedness, staffing, testing, and adaptations to these challenges. METHODS: Interpandemic survey responses were collected May 1-12, 2020. We used Pearson's Chi-squared test, Fisher's exact test, and logistic regression to evaluate relationships. RESULTS: Of 452 Michigan NHs contacted via e-mail, 145 (32.1%) opened the survey and of these, 143 (98.6%) responded. Sixty-eight percent of respondents indicated their response plan addressed most issues. NHs reported receiving rapidly changing guidance from many sources. Two-thirds reported shortages of personal protective equipment and other supplies. Half (50%) lacked sufficient testing resources with only 36% able to test residents and staff with suspected COVID-19. A majority (55%) experienced staffing shortages. Sixty-three percent experienced resignations, with front-line clinical staff more likely to resign, particularly in facilities caring for COVID-19 patients (P < .001). Facilities adapted quickly, creating COVID-19 units (78%) to care for patients on site. To reduce isolation, NHs facilitated communication via phone calls (98%), videoconferencing (96%), and window visits (81%). A majority continued to provide requisite therapies (90%). CONCLUSIONS: NHs experienced shortages of resources, testing supplies, and staffing challenges. COVID-19 in the facility was a key predictor of staff resignations. Facilities relied on rapidly changing, often conflicting advice from multiple sources, suggesting high-yield areas of improvement.

Partnering with Local Hospitals and Public Health to Manage COVID-19 Outbreaks in Nursing Homes.

BACKGROUND/OBJECTIVES: Almost half of deaths related to COVID-19 in the United States are linked to nursing homes (NHs). We describe among short-term and long-term residents at three NHs in Michigan the outbreak identification process, universal testing, point prevalence of COVID-19, and subsequent containment efforts, outcomes, and challenges. DESIGN: Outbreak investigation. SETTING: Three NHs in southeast Michigan. PARTICIPANTS: All residents (N = 215) at three NHs (total beds = 356) affiliated with a large academic healthcare system. METHODS: Upon detection of confirmed cases within the facility, each NH in collaboration and consultation with local hospital, public health officials, and parent corporation implemented immediate facility-wide testing and the following intervention measures: cohorting of COVID-19 positive residents; communication regarding testing and results with residents, healthcare professionals, and families; personal protective equipment reeducation and use throughout facilities; and dedicated staffing for infected patients cohorted in a dedicated COVID-19 wing. We collected patient data regarding demographics, symptoms, comorbidities, hospitalization, and 14-day outcomes. RESULTS: A total of 29 cases of COVID-19 were identified at three participating NHs. Nineteen cases of COVID-19 were identified through symptom-triggered testing from March 23 to April 23, 2020; 10 (4.7%) additional cases were identified through universal testing of 215 residents conducted from April 7 to 15, 2020. The hospitalization rate was 37.9%. The case fatality rate was 20.7% (6/29); these patients had multiple comorbidities. No residents who tested positive through the point-prevalence survey required hospitalization, and five were discharged home within 14 days. CONCLUSION: Proactive and coordinated steps between NH medical directors and administrators, referral hospitals including their laboratories, and local public health officials are necessary to rapidly respond to an outbreak and limit the transmission of COVID-19. This coordinated public health approach may save lives, minimize the burden to the healthcare system, and reduce healthcare costs.

Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).