Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques

Coronavirus disease 2019 (COVID-19) is an acute and highly pathogenic infectious disease in humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six months after immunization with the SARS-CoV-2 vaccine, however, antibodies are almost depleted. Intradermal immunization could be a new way to solve the problem of nondurable antibody responses against SARS-CoV-2 or the poor immune protection against variant strains. We evaluated the preclinical safety of a SARS-CoV-2 vaccine for intradermal immunization in rhesus monkeys. The results showed that there were no obvious abnormalities in the general clinical condition, food intake, body weight or ophthalmologic examination except for a reaction at the local vaccination site. In the hematology examination, bone marrow imaging, serum biochemistry, and routine urine testing, the related indexes of each group fluctuated to different degrees after administration, but there was no dose-response or time-response correlation. The neutralization antibody and ELISpot results also showed that strong humoral and cellular immunity could be induced after vaccination, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The results of a repeated-administration toxicity test in rhesus monkeys intradermally inoculated with a SARS-CoV-2 inactivated vaccine showed good safety and immunogenicity.

Preclinical safety evaluation of intradermal SARS-CoV-2 inactivated vaccine (Vero cells) administration in macaques.

Coronavirus disease 2019 (COVID-19) is an acute and highly pathogenic infectious disease in humans caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six months after immunization with the SARS-CoV-2 vaccine, however, antibodies are almost depleted. Intradermal immunization could be a new way to solve the problem of nondurable antibody responses against SARS-CoV-2 or the poor immune protection against variant strains. We evaluated the preclinical safety of a SARS-CoV-2 vaccine for intradermal immunization in rhesus monkeys. The results showed that there were no obvious abnormalities in the general clinical condition, food intake, body weight or ophthalmologic examination except for a reaction at the local vaccination site. In the hematology examination, bone marrow imaging, serum biochemistry, and routine urine testing, the related indexes of each group fluctuated to different degrees after administration, but there was no dose-response or time-response correlation. The neutralization antibody and ELISpot results also showed that strong humoral and cellular immunity could be induced after vaccination, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The results of a repeated-administration toxicity test in rhesus monkeys intradermally inoculated with a SARS-CoV-2 inactivated vaccine showed good safety and immunogenicity.

Profile identification and characterization of risk perceptions and preventive behaviors during the COVID-19 pandemic: A latent profile analysis.

In a public health crisis, communication plays a vital role in making sure policies and recommendations from the government level get disseminated accurately to its people and is only considered as effective when the public accepts, supports, complies to, and engages in policies or behaves as per governments' recommendations. Adopting the multivariate audience segmentation strategy for health communication, this study uses a data-driven analytical method to (1) identify audience segments of public health crisis communication in Singapore based on knowledge, risk perception, emotional responses, and preventive behaviors; and (2) characterize each audience segment according to demographic factors, personality traits, information processing styles, and health information preferences. Results (N = 2033) from a web-based questionnaire executed in August 2021 have identified three audience segments: the less-concerned (n = 650), the risk-anxious (n = 142), and the risk-majority (n = 1,241). This study offers insights to how audiences of public health crisis communication perceive, process, and respond to information directed to them during the pandemic, thereby informing policy makers to tailor more targeted public health communication interventions in promoting positive attitude and behavior change.

Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION: This study demonstrates the benefit of early administration of the third dose among cancer patients.

Impact of Different Styles of Online Course Videos on Students' Attention During the COVID-19 Pandemic.

Background: The COVID-19 pandemic interfered with normal campus life, resulting in the need for the course to be conducted in an ideal online format. The purpose of this study is to analyze the impact of different styles of online political course videos on students' attention during the COVID-19 pandemic. Methods: Four college students participated in this small sample study. They were required to conduct two sessions of the experiment, in which they were required to watch three different styles of course videos in each session. While watching the videos, their EEG signals were acquired. For the acquired EEG signals, the sample entropy (SampEn) features were extracted. On the other hand, Mayer's theories of multimedia technology provide guidance for teachers' online courses to enhance students' attention levels. The results of EEG signals analysis and Mayer's theories of multimedia technology were combined to compare and analyze the effects of three styles of instructional videos. Results: Based on comparisons of the SampEn and Mayer's theories of multimedia technology analysis, the results suggest that online instruction in a style where the instructor and content appear on the screen at the same time and the instructor points out the location of the content as it is explained is more likely to elicit higher levels of students' attention. Conclusions: During the COVID-19 pandemic, online instructional methods have an impact on students' classroom attention. It is essential for teachers to design online instructional methods based on students' classroom attention levels and some multimedia instructional techniques to improve students' learning efficiency.

AggMapNet: enhanced and explainable low-sample omics deep learning with feature-aggregated multi-channel networks.

Omics-based biomedical learning frequently relies on data of high-dimensions (up to thousands) and low-sample sizes (dozens to hundreds), which challenges efficient deep learning (DL) algorithms, particularly for low-sample omics investigations. Here, an unsupervised novel feature aggregation tool AggMap was developed to Aggregate and Map omics features into multi-channel 2D spatial-correlated image-like feature maps (Fmaps) based on their intrinsic correlations. AggMap exhibits strong feature reconstruction capabilities on a randomized benchmark dataset, outperforming existing methods. With AggMap multi-channel Fmaps as inputs, newly-developed multi-channel DL AggMapNet models outperformed the state-of-the-art machine learning models on 18 low-sample omics benchmark tasks. AggMapNet exhibited better robustness in learning noisy data and disease classification. The AggMapNet explainable module Simply-explainer identified key metabolites and proteins for COVID-19 detections and severity predictions. The unsupervised AggMap algorithm of good feature restructuring abilities combined with supervised explainable AggMapNet architecture establish a pipeline for enhanced learning and interpretability of low-sample omics data.

Visual supports to enhance COVID-19 related healthcare encounters for children

BackgroundConsequent to the COVID-19 pandemic, healthcare visits have heightened infectious disease protocols and COVID-19 testing. These can result in additional stress and anxiety for children who have limited understanding of the rationale for these changes. Isolation protocols, unfamiliar appearance of healthcare workers with personal protective equipment and the discomfort of nasopharyngeal swabs are among the many new but potentially distressing experiences.A ‘Special Care Kit’1 was created to provide resources to support children (both neurotypical children and those with developmental needs), as well as their caregivers during their visit to healthcare facilities for COVID-19 related issues. The kit comprises a series of visual supports in the form of visual schedules, social stories, pictorial boards and animated videos with the aim of illustrating and explaining the different COVID-19 processes in a simple and clear manner. The kit was published online, and hard copies were distributed to general practitioner clinics managing COVID-19 suspects, ambulances and hospital emergency departments.ObjectivesThe objective of the study is to assess the effectiveness of the ‘Special Care Kit’ in improving the experience of children and caregivers during their COVID-19 related healthcare encounters in an emergency department setting.MethodsThe effectiveness of the visual supports was assessed through voluntary, anonymous surveys completed by parents or caregivers who had a COVID-19 related healthcare consult at a tertiary children’s emergency department. All children had been shown a relevant aspect of the special care kit prior to or during their medical encounter. Information collected included demographic data, developmental diagnosis, communication method of the children, as well as qualitative feedback. Descriptive statistics were used to analyse results.ResultsA total of 46 caregivers took part in the study. The mean age of patients was 5.14 years. Six (13%) patients were known to have developmental difficulties, with half of them being pre-verbal (using pictures or pointing and gestures to communicate).Almost all (98%, 45/46) caregivers felt that the visual supports helped their child have a better healthcare experience, with 39% (18/46) of them noting that their child was calmer and took the whole experience better than expected. 61% (28/46) of the caregivers felt that their child had a better understanding of what was going to happen during the encounter, and 28% (13/46) felt that the visual supports helped with the communication between the medical team and the family.The majority (91%, 42/46) would like to have access to other visual supports during their child’s future healthcare visits.ConclusionsThe use of visual supports in young children is potentially effective in improving their healthcare experience during the COVID-19 pandemic. The supports may allow for better understanding of the processes, reducing the anxiety of the encounter and may improve communication between the medical team and the family. In crisis or acute situations like a pandemic, efforts should be made to communicate in a developmentally appropriate manner to both neurotypical and non-neurotypical children to reduce the stress related to a new healthcare experience.ReferencesCOVID-19 Special Care Kit for Special Needs Individuals. (2020, June 1). Retrieved from https://www.nuh.com.sg/our-services/Specialties/Paediatrics/pages/covid-19-resources-for-parents-and-caregivers.aspx

Use of telemedicine in a developmental and behavioural paediatric service during the COVID-19 pandemic:initial experiences of caregivers & providers, singapore

BackgroundTelemedicine has been used increasingly as an alternative care model in the Coronavirus 2019 pandemic. The practice of Developmental and Behavioural Paediatrics (DBP) relies heavily on direct child observations and building trust and rapport with caregivers over time and telemedicine was not routinely used in the Singapore setting.ObjectivesWe aimed to describe the initial experiences of caregivers and providers with telemedicine in a DBP service in Singapore during this pandemic.MethodsThis cross-sectional survey included caregivers who accessed telemedicine (through telephone or video-based platforms) and healthcare providers at a tertiary DBP clinic between 8 April and 14 May 2020, coinciding with the Circuit Breaker (similar to a lockdown) period in Singapore. Participants completed a questionnaire on experiences, perceived benefits and limitations of teleconsultation. Descriptive statistics and tests of comparison were conducted.ResultsAround half of the patients (N = 216, 47.3%) who were offered a teleconsultation agreed to it, of which 105 caregivers (48.6%) participated. Caregivers had children with diagnosis including autism spectrum disorder (33.3%), language delay (28.6%), and attention deficit hyperactivity disorder (12.4%). Most caregivers felt that their concerns were adequately addressed (98.1%), with good technological connectivity (95.2%). Majority had no difficulty preparing for the teleconsultation (61.0%) and 44.8% reported ease of follow-up with plans after. Perceived benefits included safety (47.6%) and reduced need to take time off work (24.8%). Perceived benefits included safety (47.6%) and reduced time off work (24.8%). Caregivers who had video-based teleconsultation (compared to telephone-based) had more difficulties preparing for the teleconsultation (52.3% vs 27.4, p=0.03). These caregivers were also more likely to have difficulties with remembering and following up with plans discussed during the consultation, compared to those who had a telephone-based consultation (52.3% vs 25.0%, p value = 0.02).Twenty-five providers participated. Providers included paediatricians, allied health therapists e.g. psychologists, speech and occupational therapists and social workers. Fifty-two percent of providers were as satisfied with teleconsultation compared to in person consults. Only 28.0% of providers rated technology infrastructure to be good. Most providers (92.0%) felt safer with teleconsultation. The most common difficulty perceived by providers was incompleteness of consultation without assessing the child physically. The two main perceived benefits of teleconsultation by providers included feeling safer as they were able to minimize physical interaction with patients and being able to provide similarly good care with less inconvenience to patients.Overall 63.8% of caregivers and 56.0% of providers would continue teleconsultation services post-pandemic. Amongst providers, paediatricians were more likely to continue teleconsultation services after current restrictions were lifted, compared to non-physician providers (100% vs 38.9%, p=0.008).ConclusionsTelemedicine was generally well received by caregiver and physician providers. Teleconsultation in a DBP practice setting is a viable option in a pandemic situation and can be considered even beyond this pandemic for continued care.

Secreted Extracellular Cyclophilin A Is a Novel Mediator of Ventilator-induced Lung Injury.

Rationale: Mechanical ventilation is a mainstay of intensive care but contributes to the mortality of patients through ventilator-induced lung injury. eCypA (extracellular CypA [cyclophilin A]) is an emerging inflammatory mediator and metalloproteinase inducer, and the gene responsible for its expression has recently been linked to coronavirus disease (COVID-19). Objectives: To explore the involvement of eCypA in the pathophysiology of ventilator-induced lung injury. Methods: Mice were ventilated with a low or high Vt for up to 3 hours, with or without blockade of eCypA signaling, and lung injury and inflammation were evaluated. Human primary alveolar epithelial cells were exposed to in vitro stretching to explore the cellular source of eCypA, and CypA concentrations were measured in BAL fluid from patients with acute respiratory distress syndrome to evaluate the clinical relevance. Measurements and Main Results: High-Vt ventilation in mice provoked a rapid increase in soluble CypA concentration in the alveolar space but not in plasma. In vivo ventilation and in vitro stretching experiments indicated the alveolar epithelium as the likely major source. In vivo blockade of eCypA signaling substantially attenuated physiological dysfunction, macrophage activation, and MMPs (matrix metalloproteinases). Finally, we found that patients with acute respiratory distress syndrome showed markedly elevated concentrations of eCypA within BAL fluid. Conclusions: CypA is upregulated within the lungs of injuriously ventilated mice (and critically ill patients), where it plays a significant role in lung injury. eCypA represents an exciting novel target for pharmacological intervention.

Cerebral Venous Thrombosis in Patients with COVID-19 Infection: a Case Series and Systematic Review.

BACKGROUND: There has been increasing reports associating the coronavirus disease 2019 (COVID-19) with thromboembolic phenomenon including ischemic strokes and venous thromboembolism. Cerebral venous thrombosis (CVT) is a rare neurovascular emergency that has been observed in some COVID-19 patients, yet much remains to be learnt of its underlying pathophysiology. OBJECTIVE: We present a case series of local patients with concomitant COVID-19 infection and CVT; and aim to perform a systematic review of known cases in the current literature. METHODS: We describe two patients with concomitant COVID-19 infection and CVT from a nationwide registry in Singapore. We then conducted a literature search in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 11th June 2020. All studies reporting CVT in COVID-19 patients were included. RESULTS: Nine studies and 14 COVID-19 patients with CVT were studied. The median age was 43 years (IQR=36-58) and majority had no significant past medical conditions (60.0%). The time taken from onset of COVID-19 symptoms to CVT diagnosis was a median of 7 days (IQR=6-14). CVT was commonly seen in the transverse (75.0%) and sigmoid sinus (50.0%); 33.3% had involvement of the deep venous sinus system. A significant proportion of patients had raised D-dimer (75.0%) and CRP levels (50.0%). Two patients reported presence of antiphospholipid antibodies. Most patients received anticoagulation (91.7%) while overall mortality rate was 45.5%. CONCLUSIONS: The high mortality rate of CVT in COVID-19 infection warrants a high index of suspicion from physicians, and early treatment with anticoagulation should be initiated.

COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature.

Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean D-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated D-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.

The role of palliative medicine in ICU bed allocation in COVID-19: a joint position statement of the Singapore Hospice Council and the Chapter of Palliative Medicine Physicians.

Facing the possibility of a surge of COVID-19-infected patients requiring ventilatory support in Intensive Care Units (ICU), the Singapore Hospice Council and the Chapter of Palliative Medicine Physicians forward its position on the guiding principles that ought to drive the allocation of ICU beds and its role in care of these patients and their families.