A Retrospective Analysis of the Impact of the Covid-19 Infection on Neuro-Oncology Care and Patient Outcomes: A Two-Site Study

BACKGROUND: COVID-19 radically changed neuro-oncology care. In this retrospective study, we examine the impact of COVID-19 infection on neuro-oncological care and clinical outcomes in two geographically separate populations. METHOD(S): Descriptive statistics compared demographic and clinical history extracted from the medical records of COVID- 19 positive patients with primary brain tumors treated between 3/1/2020 and 3/31/2021. All subjects were unvaccinated given our cohort pre-dates the ubiquitous availability of vaccines. Patients were treated at Washington University (WashU) in St. Louis, MO and Duke University in Durham, NC. Each site's respective institutional review board approved the study, with a data transfer agreement in place. RESULT(S): We identified 62 total (WashU=13;Duke=49) subjects with positive COVID-19 infection. Patients were predominantly white (85.5%), male (56.5%), with KPS >=70 (82.3%) and never smoked (69.4%). WashU patients tended to be older with grade 4 tumors, but this was not significant. At the time of COVID infection 35.5% of patients were receiving cancer-directed therapy. Notably, 37.1% experienced delayed care due to a COVID-19 diagnosis, most often for scheduled systemic treatment or radiation treatment. A further 37.1% had an ER visit, hospitalization, or ICU stay attributed to COVID-19. Of the 17 patients who died during the study period, 4 deaths were attributed directly to COVID-19 and not to their underlying brain tumor or other cause. Finally, telehealth use differed between sites (84.6% at WashU vs 14.3% at Duke). However, this difference could not be attributed to patient age, performance status, or distance from treating institution. CONCLUSION(S): COVID-19 infection led to treatment delays and death for a subset, but not the majority of neuro-oncology patients. Telehealth use varied between sites and was not associated with commonly held assumptions about patient distance or performance status, suggesting evolving practice norms following telehealth's introduction. Study limitations include a small sample size.

Data analytics: Singapore's blood donation trends during the COVID-19 pandemic and following media appeals

Background: Globally, the COVID-19 pandemic has caused reduced donor attendance and disrupted blood collection activities. This has impacted the blood supply of many blood transfusion services (BTS). To secure the nation's blood supply, BTS resort to media appeal as an additional measure to call on potential and existing donors to come forward to donate when the blood supply is low. Singapore's Health Sciences Authority (HSA) partners with the Singapore Red Cross (SRC) to drive the awareness of blood donation and recruit donors. HSA and SRC had launched media appeals prior to the pandemic. During the pandemic, there were two media reports proactively run by the media reporters. Aims: This study aimed to gain insights into donor profiles, behaviours and blood donation trends before and during the COVID-19 pandemic, and during media appeals/media reports. This was to enable HSA and SRC to develop new measures and strategies to improve donor recruitment and retention. Methods: Blood donation records from 1st January 2018 to 31st December 2020 were extracted from HSA's blood bank computer system and de-identified. Data transformation was performed using Python (version 3.7.0). Only whole blood donors with successful donations were included in this analysis. Donors were classified according to donor type and donor behaviour. Geospatial analysis was conducted to identify geographical patterns of blood donation. Descriptive analyses were carried out using Tableau Desktop (version 2021.4.3) for data visualization. Results: A total of 72,536 and 74,683 donors donated in 2018 and 2019 respectively. This declined by 4.9% to 71,054 donors in 2020. Despite this, the number of whole blood donations increased from 116,789 in 2019 to 117,272 in 2020. Donation frequency increased from 1.56 in 2019 to 1.65 in 2020, with an 1.4% increase in new donors in 2020. The proportion of donors of Chinese ethnicity increased in 2020. Donors aged 16 to 19 years old drastically declined by 34% in 2020. There was a shift in donor behaviour with majority (78.3%) donating at blood banks as compared to the pre-pandemic period (64.4% in 2019). There were two media appeals (Sep 2018, Dec 2019) and two media reports (Feb 2020, Jun 2020). There was a spike in donors by 65.7% and 72.9% in 2018 and 2019, respectively after media appeals. There was a large spike in donors by 215% after the February 2020 media report and a 27.3% increase after the June 2020 media report. 49.7% and 39.7% of new donors who responded to media appeals returned to donate the following year. The data analytics insights and recommendations from this study were presented at the HSA-SRC Steering Committee and the Donor Recruitment & Retention Workgroup in March 2022. These included a recruitment and retention focus on youth donors, encouraging appointment bookings after donation, leveraging fixed sites and donor mobile app to retain donors etc. Summary/Conclusions: Data analytics is pivotal in helping HSA and SRC to better understand blood donation trends during the COVID- 19 pandemic and following media appeals/reports. New measures and strategies were developed to better engage donors so that they would return to donate and donate more regularly. Predictive analytics and data modelling could be explored as additional tools to secure the nation's blood supply. These will increase the resilience of the Singapore's National Blood Programme and ensure a sustainable blood supply to meet the increasing blood demand.

Engaging blood donors through social media

Social media is an integrated communication platform in modern societies. To secure the blood supply, most blood transfusion services (BTS) have effectively leveraged social media as a tool to engage both the public and blood donors. It is used to promote the awareness of blood donation and to improve donor recruitment and retention. BTS can utilize social media to better understand the social psychology and donation intention among its donors. Through social media, blood donors and blood mobile organizers are empowered via cocreation and content sharing. Social media has also proven to be essential in overcoming blood shortages during the COVID-19 pandemic by providing a platform for BTS, blood donors and blood mobile organizers to rally the community to give the gift of life. Because the global social media penetration and the number of social media users are projected to increase in the coming years, social media will continue to be an invaluable tool for BTS. BTS will need to develop a social media strategy to unlock its full potential and to tap into the vast social network. There is not a one-size-fits-all approach. BTS need to understand the local social media landscape, from the appropriate types of social media and content, to the donor population and stakeholders. It should be managed by a dedicated social media marketing team with the knowledge and creativity to keep the messages relevant and engaging. There should also be engagement metrics for monitoring and benchmarking purposes using the right social media analytics to gain insights to improve donor engagement. In doing so, BTS will be able to catch the donors' attention and continue to keep them engaged. While social media presents appealing opportunities to BTS, it also presents challenges including cybersecurity risks, data security and reputational liability. Used appropriately, social media can be an effective tool for social marketing to bring about positive change in social behaviour towards voluntary non-remunerated blood donation and to ensure the sustainability of the blood supply. Social media is pervasive and becoming increasingly integrated throughout all communications and marketing channels. It is dynamic and goes beyond the 'likes', 'clicks' and 'shares'. It has and will continue to transform the donor engagement landscape, especially among the social media-savvy users and the youths. BTS will need to be agile and strategic to catch the opportunities of the new waves of technology, such as the metaverse, to take donor engagement into the future.

DAMPs/PAMPs induce monocytic TLR activation and tolerance in COVID-19 patients; nucleic acid binding scavengers can counteract such TLR agonists.

Millions of COVID-19 patients have succumbed to respiratory and systemic inflammation. Hyperstimulation of toll-like receptor (TLR) signaling is a key driver of immunopathology following infection by viruses. We found that severely ill COVID-19 patients in the Intensive Care Unit (ICU) display hallmarks of such hyper-stimulation with abundant agonists of nucleic acid-sensing TLRs present in their blood and lungs. These nucleic acid-containing Damage and Pathogen Associated Molecular Patterns (DAMPs/PAMPs) can be depleted using nucleic acid-binding microfibers to limit the patient samples' ability to hyperactivate such innate immune receptors. Single-cell RNA-sequencing revealed that CD16+ monocytes from deceased but not recovered ICU patients exhibit a TLR-tolerant phenotype and a deficient anti-viral response after ex vivo TLR stimulation. Plasma proteomics confirmed such myeloid hyperactivation and revealed DAMP/PAMP carrier consumption in deceased patients. Treatment of these COVID-19 patient samples with MnO nanoparticles effectively neutralizes TLR activation by the abundant nucleic acid-containing DAMPs/PAMPs present in their lungs and blood. Finally, MnO nanoscavenger treatment limits the ability of DAMPs/PAMPs to induce TLR tolerance in monocytes. Thus, treatment with microfiber- or nanoparticle-based DAMP/PAMP scavengers may prove useful for limiting SARS-CoV-2 induced hyperinflammation, preventing monocytic TLR tolerance, and improving outcomes in severely ill COVID-19 patients.

Systemic antiviral immunization by virus-mimicking nanoparticles-decorated erythrocytes.

New vaccine technologies are urgently needed to produce safe and effective vaccines in a more timely manner to prevent future infectious disease pandemics. Here, we describe erythrocyte-mediated systemic antiviral immunization, a versatile vaccination strategy that boosts antiviral immune responses by using erythrocytes decorated with virus-mimetic nanoparticles carrying a viral antigen and a Toll-like receptor (TLR) agonist. As a proof of concept, polydopamine nanoparticles were synthesized via a simple in situ polymerization in which the nanoparticles were conjugated with the SARS-CoV-2 spike protein S1 subunit and the TLR7/8 agonist R848. The resulting SARS-CoV-2 virus-mimetic nanoparticles were attached to erythrocytes via catechol groups on the nanoparticle. Erythrocytes naturally home to the spleen and interact with the immune system. Injection of the nanoparticle-decorated erythrocytes into mice resulted in greater maturation and activation of antigen-presenting cells, humoral and cellular immune responses in the spleen, production of S1-specific immunoglobulin G (IgG) antibodies, and systemic antiviral T cell responses than a control group treated with the nanoparticles alone, with no significant negative side effects. These results show that erythrocyte-mediated systemic antiviral immunization using viral antigen- and TLR agonist-presenting polydopamine nanoparticles-a generalizable method applicable to many viral infections-is effective new approach to developing vaccines against severe infectious diseases.

Modeling SARS-CoV-2 infection in individuals with opioid use disorder with brain organoids.

The COVID-19 pandemic has aggravated a preexisting epidemic: the opioid crisis. Much literature has shown that the circumstances imposed by COVID-19, such as social distancing regulations, medical and financial instability, and increased mental health issues, have been detrimental to those with opioid use disorder (OUD). In addition, unexpected neurological sequelae in COVID-19 patients suggest that COVID-19 compromises neuroimmunity, induces hypoxia, and causes respiratory depression, provoking similar effects as those caused by opioid exposure. Combined conditions of COVID-19 and OUD could lead to exacerbated complications. With limited human in vivo options to study these complications, we suggest that iPSC-derived brain organoid models may serve as a useful platform to investigate the physiological connection between COVID-19 and OUD. This mini-review highlights the advances of brain organoids in other neuropsychiatric and infectious diseases and suggests their potential utility for investigating OUD and COVID-19, respectively.

A materials-science perspective on tackling COVID-19.

The ongoing SARS-CoV-2 pandemic highlights the importance of materials science in providing tools and technologies for antiviral research and treatment development. In this Review, we discuss previous efforts in materials science in developing imaging systems and microfluidic devices for the in-depth and real-time investigation of viral structures and transmission, as well as material platforms for the detection of viruses and the delivery of antiviral drugs and vaccines. We highlight the contribution of materials science to the manufacturing of personal protective equipment and to the design of simple, accurate and low-cost virus-detection devices. We then investigate future possibilities of materials science in antiviral research and treatment development, examining the role of materials in antiviral-drug design, including the importance of synthetic material platforms for organoids and organs-on-a-chip, in drug delivery and vaccination, and for the production of medical equipment. Materials-science-based technologies not only contribute to the ongoing SARS-CoV-2 research efforts but can also provide platforms and tools for the understanding, protection, detection and treatment of future viral diseases.