Umbilical Stem Cells Promising Treatment, Long Term Impacts on Brain, Smart Vaccine Patch Under Development: COVID-19 Updates

January 8, 2021 I Pfizer funds long-term safety study on their COVID-19 vaccine, Phase 3 clinical trial results show Moderna’s vaccine is both effective and safe, Radx-rad program supports innovative approaches to gaps in testing and surveillance, underreporting adjustments estimate over 14% of U.S. population infected by November last year, math model predicts best treatment strategies, and speed versus efficacy tradeoff of vaccine deployment. Plus: Protective immunity could last several months, asymptomatic cases account for over half of all transmission, and new survey estimates over 30% of U.S. population is vaccine hesitant.


Research News

Transmission of SARS-CoV-2 from asymptomatic individuals may account for more than half of all transmission, according to new research published in JAMA Network Open. Researchers used a decision analytical model of multiple scenarios of proportions of asymptomatic individuals with COVID-19 and infectious periods. Under a broad range of scenarios, the research team estimated that at least 50% of new infections originated from exposure to a SARS-CoV-2 positive individual without symptoms. The researchers suggest that reducing the risk of transmission though mask-wearing, hand-washing, and social distancing will be crucial in slowing the spread of the virus until vaccines are widely available. DOI:10.1001/jamanetworkopen.2020.35057

A new study published in the Journal of Clinical Endocrinology & Metabolism finds that Black and Hispanic people with COVID-19 and type 1 diabetes are more likely than White people to die or have serious complications. The researchers analyzed data from 180 patients with type 1 diabetes and COVID-19 from 52 clinical sites in the United States and determined that Black patients were four times more likely to be hospitalized for diabetic ketoacidosis than Caucasians. Black and Hispanic patients were less likely to use continuous glucose monitors (CGM) and insulin pumps and had worse glycemic control than White patients. The research team calls for urgent interventions for these minorities, such as diabetic awareness campaigns and increased CGM coverage for these patients. DOI:10.1210/clinem/dgaa920

Protective immunity against COVID-19 could last for at least eight months, new data published in Science suggests. The research team, led at La Jolla Institute for Immunology, analyzed blood samples from 188 COVID-19 patients to measure antibodies, memory B cells, helper T cells and killer T cells all at the same time. They found that all immune cell types were measurable for up to eight months after symptom onset. Importantly, they found that spike-specific memory B cells increased in the blood six months after infection. The researchers explain that this protective immunity varies dramatically from person to person, as they saw a 100-fold range in the magnitude of immune memory, and people with a weak immune memory could be vulnerable to reinfection. DOI:10.1126/science.abf4063

Smoking is associated with an increased risk of COVID-19 symptoms and hospital admission, finds a new study published in Thorax. King’s College London researchers analyzed data from the ZOE COVID Symptom Study App, which is the world’s largest ongoing study of COVID-19 with over 4 million contributors, and found that current smokers were 29% more likely to report more than five COVID-19 associated symptoms and 50% more likely to report more than ten symptoms from COVID-19 when compared to non-smokers. Current smokers who tested positive for SARS-CoV-2 were also more than twice as likely as non-smokers to be admitted to a hospital. The researchers recommend a smoking cessation strategy be included to address COVID-19. DOI:10.1136/thoraxjnl-2020-216422

According to a new study published in ESC Heart Failure, patients with acute heart failure could have nearly double the risk of death if they are positive for COVID-19. The study analyzed 283 patients with acute heart failure admitted to North Bristol NHS Trust and defined two groups as before-COVID and after-COVID. The 30-day mortality rate of patients with acute heart failure was determined to be 11% of patients in the before-COVID group and 21% in the after-COVID group. The researchers found that older age and admission during the pandemic were linked with death after adjusting for other factors, and there was no difference in mortality between the two groups when patients with a positive COVID-19 test were removed from the analysis. They note that their region had low rates of SARS-CoV-2 infection during the study and still found an apparent connection with higher mortality, which they believe warrants a larger analysis to confirm their findings. DOI:10.1002/ehf2.13158

Almost half of children under the age of five infected with COVID-19 are asymptomatic and half of those infected in that age group are infants, a new study published in Vaccine reports. A systematic review and meta-analysis of international COVID-19 literature, which included over 1,000 young children, found that 43% of cases were asymptomatic and 7% had severe disease that required intensive care unit admission. Among the 139 newborns from confirmed COVID-19-infected mothers, only five (3.6%) had laboratory-confirmed COVID-19 infection within several days of birth. Researchers highlight the need for further research on transmission from mothers to newborns. They also suggest the need for ongoing monitoring to better understand the epidemiology, clinical pattern and transmission of the virus in order to develop effective prevention strategies for young children, especially infants who comprised half of the confirmed cases. This study was led by the University of New South Wales. DOI:10.1016/j.vaccine.2020.11.078

A survey of over 5,000 Americans suggests that approximately 30% of the U.S. public does not plan to get a COVID-19 vaccine once it is available to them. The study, led by researchers at Texas A&M University, found that 71% of women surveyed were more likely to not pursue vaccination, followed by 41% of Black individuals. They also determined that for each one-point increase in conservatism, the odds of vaccine refusal increased by 18%. The top two reasons for COVID-19 vaccine hesitancy were concerns over its safety and effectiveness. The team now plans to explore which health interventions and promotion efforts are most effective in making the vaccine more appealing to these populations. These findings are published in Social Science and Medicine. DOI:10.1016/j.socscimed.2020.113638

Three new articles, published in Annals of Internal Medicine, discuss the most effective vaccination strategies for the greatest population protection against COVID-19. Collectively, researchers of these papers suggest that a single dose of a COVID-19 vaccine, even if it is less effective than two doses, could have a greater benefit for the entire population. For instance, researchers from Yale School of Public Health determined that a single-dose vaccine with 55% effectiveness may yield a greater population benefit than a 95% effective vaccine requiring two doses. In a separate paper, Stanford University researchers suggest that vaccinating more people as soon as possible, through use of a flexible approach, could increase benefits of vaccines while still allowing most to receive a second dose. DOI:10.7326/m20-7866

COVID-19 will likely have long-term effects on the brain and nervous system, based on a review of decades of scientific evidence published in Alzheimer’s & Dementia:The Journal of the Alzheimer’s Association. The lead author, from The University of Texas Health Science Center at San Antonio, cites past flu pandemics, H1N1, and SARS-CoV and their known association with brain disorders. The researchers explain that the coronavirus is known to enter cells via ACE2 receptors in the olfactory bulb, the brain structure involved in the sense of smell, and the olfactory bulb connects with the hippocampus, which is a brain structure responsible for short-term memory and believed to be one of the sources of cognitive impairment seen in COVID-19 patients. To further investigate these concerns, the Alzheimer’s Association is funding an international consortium to better understand these effects on the brain. The study will collect information from participants with confirmed COVID-19 cases over the next two to three years and will measure cognition, behavior, and brain volumes by magnetic resonance imaging (MRI) when possible. DOI:10.1002/alz.12255

Patient-reported loss of smell was prevalent in nearly 86% of mild COVID-19 cases in a new study published in the Journal of Internal Medicine. In the study of over 2,500 patients with varying degrees of severity of COVID-19 from 18 European hospitals, 85.9% of patients reported olfactory dysfunction with mild cases of infection. In moderate cases of COVID-19, 4.5% reported a reduced sense of smell and 6.9% in severe cases. The average duration of olfactory dysfunction reported by the patients was 21.6 days and nearly 25% of those affected patients reported that they did not recover their sense of smell at 60 days. They did find, however, that 95% of those patients recovered their sense of smell by six months after onset of the COVID-19 symptom. DOI:10.1111/joim.13209

A biology-based mathematical model, created by researchers at Massachusetts General Hospital with collaborators, predicts best treatment strategies for COVID-19 patients and indicates why outcomes vary widely. The model was originally developed for cancer research to analyze involvement of the renin angiotensin system in the development of fibrous tissues in tumors but was modified to better understand mechanisms specific to COVID-19. Through use of this model, the research team found that viral load increases during early lung infection and then takes a different course at Day 5, depending on the levels of T cells in the patient. This finding may explain why patients younger than 35 years old, with healthy immune systems and a sustained recruitment of T cells, have a lower risk of blood clot formation and faster recovery of oxygen levels in lung tissues. The model suggests various treatment approaches, depending on the patient, such as drugs specifically targeting cytokines in those with pre-existing conditions like obesity, diabetes, and high blood pressure. This work is published in PNAS. DOI:10.1073/pnas.2021642118

Umbilical cord derived mesenchymal stem cell (UC-MSC) infusions could safely reduce risk of death and shorten recovery time for patients with severe COVID-19, according to new research led by the University of Miami Miller School of Medicine. The double-blind study, published in STEM CELLS Translational Medicine, observed 24 patients hospitalized with COVID-19 and developed severe acute respiratory distress syndrome (ARDS). Each patient received two infusions given days apart of either UC-MSC infusion or placebo. Researchers found that the patient survival rate at one month was 91% in the stem cell treated group versus 42% in the control group. 100% of those treated under the age of 85 years old survived at one month. Recovery time was also faster in the stem cell treated group with more than 80% of the treatment group recovering by day 30, versus less than 37% in the control group. The team reports that the treatment was safe, with no infusion-related serious adverse events. DOI:10.1002/sctm.20-0472

More than 14% of the U.S. population were infected with SARS-CoV-2 by mid-November 2020 and cases were underreported, finds a new study published in JAMA Network Open. Researchers used data from 5 Centers for Disease Control and Prevention (CDC) seroprevalence surveys to estimate infection underreporting multipliers and symptomatic underreporting multipliers. They then looked at community serosurvey data from randomly selected participants of the general population to validate the underreporting multipliers. The researchers found the adjusted prevalence for COVID-19 infection to be an estimated 14.3% of the population in the United States by November 15, 2020. The team adds that although this number is higher due to underreporting, a substantial gap remains before herd immunity can be reached. DOI:10.1001/jamanetworkopen.2020.33706

Researchers have identified risk factors associated with mortality in nursing home residents with COVID-19 and have published their study in JAMA Internal Medicine. The study included over 5,000 nursing home residents with confirmed SARS-CoV-2 infection in approximately 350 nursing homes in the United States. They determined that increased age, male sex, and impaired cognitive and physical function were all independent risk factors for all-cause 30-day mortality. The research team hopes that understanding these risk factors can support development of clinical prediction models of mortality for nursing home residents. DOI:10.1001/jamainternmed.2020.7968

Psychological distress during the first month of the pandemic was equal to that experienced during the entire prior year, according to a new study published in Preventative Medicine. The longitudinal study used the RAND American Life Panel, a nationally representative internet panel, and participants were surveyed in February 2019 and again in May 2020. There were 2,555 respondents to the first wave of the survey and 1,870 respondents to the second wave, and researchers found that the past-month prevalence of serious psychological distress reported by participants of the second survey was as high as the past-year prevalence reported by individuals in the first survey (10.9% and 10.2%, respectively). The researchers also determined that those individuals with psychological distress prior to the pandemic, women, individuals under 60 years old, and Hispanic people were all more likely to report higher levels mental distress. DOI:10.1016/j.ypmed.2020.106362

A team of allergists led by Massachusetts General Hospital offers reassurance and guidance regarding potential allergic reactions to both the Pfizer-BioNTech and Moderna COVID-19 vaccines and have published these guidelines in the Journal of Allergy and Clinical Immunology: In Practice. The team proposes detailed advice for individuals with allergy histories on receiving their first COVID-19 vaccine, stressing that even those with food or medication allergies can safely be vaccinated against the virus. They explain that allergic reactions are rare and emphasize that vaccine clinics will be monitoring patients for 15 to 30 minutes after vaccination to manage any reactions. They also recommend that those with a history of anaphylaxis to vaccines containing polyethylene glycol or polysorbate consult with their allergists prior to receiving the vaccine, but those with severe allergies to food, oral drugs, latex, or venom can safely receive the COVID-19 vaccines. DOI:10.1016/j.jaip.2020.12.047

Results from the Phase 3 clinical trial evaluating Moderna’s COVID-19 vaccine show that the vaccine is both effective and safe. The vaccine, known as mRNA-1273, was 94.1% efficacious in preventing symptomatic COVID-19, including severe disease, and no safety concerns were identified. The randomized, placebo-controlled clinical trial enrolled over 30,000 adult volunteers with an average age of 51 years. Co-developed by Moderna and the National Institute of Allergy and Infectious Diseases (NIAID), the vaccine also showed no evidence of vaccine-associated enhanced respiratory disease (VAERD), which was a concern that arose from testing some SARS and MERS vaccine constructs using animal models. These results are reported in the New England Journal of Medicine. DOI:10.1056/NEJMoa2035389


Industry News

Swansea University researchers have received funding to develop the world’s first smart vaccine device that will both deliver the COVID-19 vaccine and monitor the body’s response. The team will use microneedles to create a ‘smart-patch’ that will measure a patient’s inflammatory response to the vaccination by monitoring biomarkers in the skin. The microneedles, which have tips that are measured in micrometers, are designed to break the skin barrier and deliver drugs in a minimally invasive fashion, comparable to a transdermal nicotine patch. The project’s primary goal is to create a prototype of smart vaccine delivery to change the way in which vaccine efficacy trials are performed from a statistical assessment to a scientific measurement of patient inflammatory response to the COVID-19 vaccine. This research will be funded by the Welsh Government. Press Release

Illumina and Helix will collaborate to track the emergence and prevalence of novel SARS-CoV-2 strains in the United States and expand the country’s surveillance infrastructure with support from the Centers for Disease Control and Prevention (CDC). Illumina’s sequencing technology combined with Helix’s national COVID-19 testing footprint has already identified more than 50 U.S. cases of B.1.1.7, which is the highly transmissible variant first found in the United Kingdom. Helix and Illumina plan to examine a higher volume of samples on an ongoing basis for both the presence of B.1.1.7 and new strains to allow public and private entities to quickly react to any changes in pathogenicity of the virus or effectiveness of diagnostics, therapeutics, and vaccines. Press Release

Cellid and the International Vaccine Institute (IVI) have exchanged a collaborative research agreement to analyze the immunogenicity of the COVID-19 vaccine developed by Cellid, “AdCLD-CoV-19”. IVI will analyze samples from Phase 1/2a clinical trials of the vaccine to determine whether it induced the right immune responses. Cellid is developing the COVID-19 vaccine based on an adenovirus vector, and the company received approval for a Phase 1/2a clinical trial plan from the Korean Ministry of Food and Drug Safety in December 2020. Following this approval, Cellid signed a contract with Korea University Guro Hospital and is currently conducting clinical trials with them. Cellid and IVI aim to expedite the clinical trials through their collaboration and hope to commercialize the COVID-19 vaccine as early as summer of this year. Press Release

A Phase 2/3 trial will test a combination monoclonal antibody therapy for the treatment of mild-to-moderate COVID-19. The two experimental antibodies, BRII-196 and BRII-198, are synthetic versions of antibodies naturally produced by humans and are manufactured by Brii BioSciences. The trial, known as ACTIV-2, will determine the safety and efficacy of the two synthetic antibodies through a placebo-controlled study on 220 enrolled participants with mild to moderate COVID-19 who are at risk for disease progression. The trial, which is funded by NIAID, will transition to Phase 3 if no serious safety concerns are identified and the results seem promising. Press Release

RedHill Biopharma has announced preliminary data from the Phase 2 COVID-19 study of opaganib that shows the drug was safe and demonstrated a consistent trend of greater improvement in reducing oxygen requirement. The randomized, double-blind, placebo-controlled study enrolled 40 patients requiring oxygen support, and the opaganib-treated arm demonstrated a greater improvement in reaching room air within 14 days, greater improvement in reduction to 50% supplemental oxygen by Day 14, a higher proportion of patients discharged by Day 14, and a greater reduction in the median total oxygen requirement over 14 days. Opaganib acts as both an anti-inflammatory and antiviral and targets a human cell component involved in viral replication, not the virus itself, which has the potential to minimize the likelihood for resistance due to SARS-CoV-2 mutations. Press Release

The Duke Clinical Research Institute (DCRI) and Verily are launching a long-term safety study of the Pfizer-BioNTech COVID-19 vaccine. The study, named HERO-TOGETHER, will enroll nearly 20,000 healthcare workers after receiving the vaccine and follow them for two years. Participants will be current or new members of the HERO Registry, a nationwide community of healthcare workers established to better understand their needs and experiences during the pandemic. This safety study is funded by Pfizer. Press Release

Royal Phillips and BioIntelliSense announced that they have been selected to receive nearly $2.8 million from the U.S. Department of Defense (DoD) through a Medical Technology Enterprise Consortium (MTEC) award to validate BioIntelliSense’s FDA-cleared BioSticker device for early detection of COVID-19 symptoms. The award aims to accelerate the use of wearable diagnostics for the military and public health through early detection and containment of pre-symptomatic cases of COVID-19. In collaboration with the University of Colorado, the clinical study will consist of 2,500 participants with a recent, known exposure to the virus or experiencing early symptoms, and the research will focus on validation of the BioSticker technology to accurately detect early COVID-19 symptoms. Press Release

A team of eleven experts from eight labs across three continents have come together to form the Global T cell Expert Consortium (GTEC) to maximum the use and direction of T cell research in the fight against COVID-19. The group believes that long-term control of the pandemic will require a combination of antibody and T cell assessment, standardization in research, and increased data pools. The immediate goals of the consortium include driving further research into the role of T cell measurement for SARS-CoV-2, increasing education on the role of T cell immunity, and stimulating creation of innovative research studies by facilitating enhanced networking among T cell researchers. Press Release

The National Institutes of Health (NIH) has awarded over $107 million to support non-traditional and repurposed technologies for COVID-19 testing and surveillance. These funds, under the Rapid Acceleration of Diagnostics-Radical program (RADx-rad), will support 49 research projects and grant supplements at 43 institutions across the United States that focus on new viral screening approaches, such as biological or physiological markers and home-based testing. The RADx-rad program aims to support efforts in addressing gaps in testing and surveillance to fight the ongoing pandemic and address future COVID-19 outbreaks or other infectious diseases by using innovative approaches and reimagined uses of existing tools. Press Release

The NIH will fund pediatric COVID-19 studies to develop approaches for identifying children at a high risk for Multisystem Inflammatory Syndrome in Children (MIS-C). The awards, part of the RADx-rad program, will fund studies enrolling children with diverse geographic, racial and ethnic backgrounds across the United States, Canada, United Kingdom, and South America. These studies will explore how several factors influence the severity of COVID-19 in children and their risk of progression to MIS-C. Artificial intelligence and machine learning will be utilized to interpret the acquired data. Press Release

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