54 Busting some myths of online delivery of palliative care education

Background/IntroductionThere is an urgent need to continue palliative care professional development (CPD) for all those delivering health care, especially in view of health needs of the population currently affected by the Covid-19 pandemic. Face to face teaching, whilst preferable to date, has not been possible. The face to face interaction at the start of a Masters course in Palliative medicine was transitioned to virtual learning. We explored the impact of using technology on the learning experience of participants both in terms of comfort with the virtual environment and its impact on their learningMethodsProspective evaluation of a redesigned face to face teaching programme. Participants were asked if the virtual learning environment or technology had impacted on their learning using a 5 point scale for each of the sessions. A further delayed evaluation is underway, to explore the continued impact of the sessions.Results13 sessions forming a 3 day programme were evaluated. 252 responses were received (45% response rate) 223/252 responded that all was well, 18/252 mentioned some technical difficulties but with no negative impact on learning, 8 mentioned technical issues which did impact on learning, 2 mentioned being uncomfortable with the virtual learning environment with no impact on learning and 1 person described being uncomfortable with negative impact.Results to date of the delayed evaluation have been received from 16 participants (response rate of 32%).ConclusionsEnabling virtual CPD to continue to skill and enable the health care workforce to deliver palliative care to patients is paramount, especially while Covid-19 restrictions to face to face gatherings continue. With attention to teaching techniques (delivery style, focused content and use of interaction), neither the technology or a virtual learning environment, negatively impact learning for the majority of students. Further exploration of prospective data is underway.

Long-Term Persistence of Spike Antibody and Predictive Modeling of Antibody Dynamics Following Infection with SARS-CoV-2 (preprint)

Background: Antibodies to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been shown to neutralize the virus in-vitro and prevent disease in animal challenge models upon re-exposure. However, current understanding of SARS-CoV-2 humoral dynamics and longevity is conflicting.Methods: The Co-Stars study prospectively enrolled 3679 healthcare workers to comprehensively characterize the kinetics of SARS-CoV-2 spike (S), receptor-binding-domain (RBD) and nucleoprotein (N) antibodies in parallel. Participants screening seropositive had serial monthly serological testing for maximum 7 months with the Mesoscale Discovery Assay. Survival analysis determined the proportion of sero-reversion while two hierarchical Gamma models predicted the upper- and lower-bounds of long-term antibody trajectory.Results: A total of 1163 monthly samples were provided from 349 seropositive participants. At 200 days post-symptoms, 99% of participants had detectable S-antibodies compared to 75% with detectable N-antibodies. S-antibody was predicted to remain detectable in 95% of participants until 465 days [95%CI 370-575] using a ‘continuous-decay’ model and indefinitely using a ‘decay-to-plateau’ model to account for antibody secretion by long-lived plasma cells. S-antibody titers correlated strongly with surrogate neutralization in-vitro (R2=0.72). N-antibodies, however, decayed rapidly with a half-life of 60 days [95%CI 52-68].Conclusions: The Co-STAR's study data presented here provides evidence for long-term persistence of neutralizing S-antibodies. This has important implications for the duration of functional immunity following SARS-CoV-2 infection. In contrast, the rapid decay of N-antibodies must be considered in future seroprevalence studies and public health decision-making. This is the first study to establish a mathematical framework capable of predicting long-term humoral dynamics following SARS-CoV-2 infection.Trial Registration: NCT04380896.Funding Statement: GOSH charity, Wellcome Trust (201470/Z/16/Z and 220565/Z/20/Z). GOSH NIHR Funded Biomedical Research Centre.Declaration of Interests: The authors have declared that no competing interests exist.Ethics Approval Statement: This study was approved by the UK Health Research Authority (www.hra.nhs.uk). Written informed consent was obtained from all participants before recruitment to the study.

Misconceptions About COVID-19 Among Older Rohingya Adults (Forcefully Displaced Myanmar Nationals) in Bangladesh: Findings from a Cross-Sectional Study (preprint)

Background: Rohingya (Forcefully Displaced Myanmar Nationals or FDMNs) in Bangladesh are at increased risk of 2019 coronavirus disease (COVID-19), especially the older population. Given low health literacy among the FDMNs and the adverse situation of their residential camps, there are possibilities of misinformation related to COVID-19 among the older FDMNs who are at greater risk. Therefore, the present research aimed to assess the level of misconceptions and the factors associated with it among the older FDMNs in Bangladesh. Methods: This cross-sectional study was conducted among 416 FDMNs, aged 60 years and above, from a Rohingya camp situated in Cox’s Bazar, a South-Eastern district of Bangladesh. We collected information on 14 different locally relevant misconceptions related to the spread, prevention, and treatment of COVID-19, scored each misconception as one, and obtained a cumulative score of the 14-items, ranging from 0 to 14, with a higher score indicating a higher level of misconceptions. With backward selection based on the Akaike information criterion, a multiple linear regression model explored the factors associated with misconceptions. Findings: The participants had an average of five misconceptions. The most prevalent misconceptions were related to the prevention of COVID-19, i.e., everyone should wear personal protective equipment when outside (86.6%), and its prevention by nutritious food (62.5%) and drinking water (59.3%). Other notable misconceptions included the spread of COVID-19 through mosquito bites (42%) and its transmissions only to the non/less-religious person (31.5%). In regression analyses, memory or concentration problems, communication frequency with social networks, pre-existing conditions, and receiving information from health workers were significantly associated with higher COVID-19 misconceptions. These misconceptions were less likely among those overwhelmed by the pandemic, having COVID-19 diagnosed friends or family members, and receiving information from friends and family. Interpretation: Overall, we found that misconceptions were prevalent among the older FDMNs in Bangladesh. The associations have important implications for programs to prevent and manage COVID-19 in these settings. Health workers need to be adequately trained to provide clear communication and counter misconceptions. Funding: No funding was received for this study.Declaration of Interests: The authors have no conflict of interest to disclose.Ethics Approval Statement: The institutional review board of the Institute of Health Economics, University of Dhaka, Bangladesh, approved the study protocol. Informed written consent was sought from the participants (thumb impressions from those who could not read and write) before administering the survey. Participation was voluntary, and participants did not receive any compensation. Written approval was also sought from the Office of the Refugee Relief and Repatriation Commissioner (RRRC) prior to accessing the camps and conducting the survey.

Long-Term Persistence of Spike Antibody and Predictive Modeling of Antibody Dynamics Following Infection with SARS-CoV-2 (preprint)

Background: Antibodies to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) have been shown to neutralize the virus in-vitro. Similarly, animal challenge models suggest that neutralizing antibodies isolated from SARS-CoV-2 infected individuals prevent against disease upon re-exposure to the virus. Understanding the nature and duration of the antibody response following SARS-CoV-2 infection is therefore critically important. Methods: Between April and October 2020 we undertook a prospective cohort study of 3555 healthcare workers in order to elucidate the duration and dynamics of antibody responses following infection with SARS-CoV-2. After a formal performance evaluation against 169 PCR confirmed cases and negative controls, the Meso-Scale Discovery assay was used to quantify in parallel, antibody titers to the SARS-CoV-2 nucleoprotein (N), spike (S) protein and the receptor-binding-domain (RBD) of the S-protein. All seropositive participants were followed up monthly for a maximum of 7 months; those participants that were symptomatic, with known dates of symptom-onset, seropositive by the MSD assay and who provided 2 or more monthly samples were included in the analysis. Survival analysis was used to determine the proportion of sero-reversion (switching from positive to negative) from the raw data. In order to predict long-term antibody dynamics, two hierarchical longitudinal Gamma models were implemented to provide predictions for the lower bound (continuous antibody decay to zero, 'Gamma-decay') and upper bound (decay-to-plateau due to long lived plasma cells, 'Gamma-plateau') long-term antibody titers. Results: A total of 1163 samples were provided from 349 of 3555 recruited participants who were symptomatic, seropositive by the MSD assay, and were followed up with 2 or more monthly samples. At 200 days post symptom onset, 99% of participants had detectable S-antibody whereas only 75% of participants had detectable N-antibody. Even under our most pessimistic assumption of persistent negative exponential decay, the S-antibody was predicted to remain detectable in 95% of participants until 465 days [95% CI 370-575] after symptom onset. Under the Gamma-plateau model, the entire posterior distribution of S-antibody titers at plateau remained above the threshold for detection indefinitely. Surrogate neutralization assays demonstrated a strong positive correlation between antibody titers to the S-protein and blocking of the ACE-2 receptor in-vitro [R2=0.72, p<0.001]. By contrast, the N-antibody waned rapidly with a half-life of 60 days [95% CI 52-68]. Discussion: This study has demonstrated persistence of the spike antibody in 99% of participants at 200 days following SARS-CoV-2 symptoms and rapid decay of the nucleoprotein antibody. Diagnostic tests or studies that rely on the N-antibody as a measure of seroprevalence must be interpreted with caution. Our lowest bound prediction for duration of the spike antibody was 465 days and our upper bound predicted spike antibody to remain indefinitely in line with the long-term seropositivity reported for SARS-CoV infection. The long-term persistence of the S-antibody, together with the strong positive correlation between the S-antibody and viral surrogate neutralization in-vitro, has important implications for the duration of functional immunity following SARS-CoV-2 infection.

Humoral Response Dynamics Following Infection with SARS-CoV-2 (preprint)

Introduction: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) specific antibodies have been shown to neutralize the virus in-vitro. Understanding antibody dynamics following SARS-CoV-2 infection is therefore crucial. Sensitive measurement of SARS-CoV-2 antibodies is also vital for large seroprevalence surveys which inform government policies and public health interventions. However, rapidly waning antibodies following SARS-CoV-2 infection could jeopardize the sensitivity of serological testing on which these surveys depend. Methods: This prospective cohort study of SARS-CoV-2 humoral dynamics in a central London hospital analyzed 137 serial samples collected from 67 participants seropositive to SARS-CoV-2 by the Meso-Scale Discovery assay. Antibody titers were quantified to the SARS-CoV-2 nucleoprotein (N), spike (S-)protein and the receptor-binding-domain (RBD) of the S-protein. Titers were log-transformed and a multivariate log-linear model with time-since-infection and clinical variables was fitted by Bayesian methods. Results: The mean estimated half-life of the N-antibody was 52 days (95% CI 42-65). The S- and RBD-antibody had significantly longer mean half-lives of 81 days (95% CI 61-111) and 83 days (95% CI 55-137) respectively. An ACE-2-receptor competition assay demonstrated significant correlation between the S and RBD-antibody titers and ACE2-receptor blocking in-vitro. The time-to-a-negative N-antibody test for 50% of the seropositive population was predicted to be 195 days (95% CI 163-236). Discussion: After SARS-CoV-2 infection, the predicted half-life of N-antibody was 52 days with 50% of seropositive participants becoming seronegative to this antibody at 195 days. Widely used serological tests that depend on the N-antibody will therefore significantly underestimate the prevalence of infection following the majority of infections.