Nanosponges Soak Up Virus, AI Tracks Mutations: The Week’s COVID-19 Updates
June 19, 2020 | Questions are being raised about interferon’s role in treating SARS-CoV-2 infection, and the likelihood that it could inhibit lung tissue healing. And a new AI tool could track changes in the genetic structure of the SARS-CoV-2 virus. Plus more from this week’s COVID-19 news and research in the clinical research industry.
Research Updates
Different groups are raising red flags about using type III interferons (IFN- λ) to treat SARS-CoV-2 infection in the lungs. In three different studies published this week in Science, separate teams presented research that calls for rethinking the pathophysiological role of IFN-λ and its possible use in the clinical practice against endemic viruses. The team from Boston Children's Hospital and the University of Milan reports that IFN-λ is present in the lower, but not upper, airways of COVID-19 patients. In mice, we demonstrate IFN-λ produced by lung dendritic cells in response to a synthetic viral RNA induces barrier damage, causing susceptibility to lethal bacterial superinfections. DOI: 10.1126/science.abc3545. Researchers from the Francis Crick Institute found that interferon signaling interferes with lung repair during influenza recovery, with IFN-λ driving these effects most potently. Excessive or prolonged IFN-production aggravates viral infection by impairing lung epithelial regeneration, they say. The team advises that the timing and duration of any interferon therapeutic strategies be carefully considered. DOI: 10.1126/science.abc2061
Researchers have shown that nanoparticles cloaked in human lung cell membranes and human immune cell membranes can attract and neutralize the SARS-CoV-2 virus in cell culture, causing the virus to lose its ability to hijack host cells and reproduce. They published their findings in ACS Nano Letters. The "nanosponges" were developed by engineers at the University of California San Diego and tested by researchers at Boston University. In the next few months, the UC San Diego researchers and collaborators will evaluate the nanosponges' efficacy in animal models. The UC San Diego team has already shown short-term safety in the respiratory tracts and lungs of mice. If and when these COVID-19 nanosponges will be tested in humans depends on a variety of factors, but the researchers are moving as fast as possible. DOI: 10.1021/acs.nanolett.0c02278.
Italian researchers surveyed 204 patients with COVID-19 and found that taste reduction was present in 55.4% of patients, and smell reduction was present in 41.7% of patients. They recommend that COVID-19 should be suspected when severe reduction of taste and smell are present in the absence of nasal obstruction. Their results are published in JAMA Otolaryngology. DOI: 10.1001/jamaoto.2020.1155
Massachusetts General Hospital reported on the prevalence of SARS-CoV-2 infections in women admitted to such maternity units in four affiliated Boston hospitals. The findings are published in Infection Control & Hospital Epidemiology. Universal testing in the labor and delivery units began more than 30 days after physical distancing orders were placed in Massachusetts. Over 18 days of universal testing, 757 women were tested. Eleven women tested positive who reported some symptoms of COVID-19; nine women who reported no symptoms tested positive. None of the positive asymptomatic women developed COVID-19 symptoms during their hospitalization. DOI: 10.1017/ice.2020.255
University Health Network (Toronto) researchers have designed an AI tool to track changes in the genetic structure of the SARS-CoV-2 virus. The COVID-19 Genotyping Tool (CGT) offers an online, user-friendly platform where researchers can compare the genome sequence of the SARS-CoV-2 virus in their hospital against the global picture. By following these changes, researchers can learn more about how the virus is moving and evolving, which has direct implications for vaccine design, drug development, and our collective effort to combat COVID-19. The work was published in Lancet Digital Health. DOI: 10.1016/S2589-7500(20)30140-0
Researchers at the University of Iowa Carver College of Medicine and Medical University, Guangzhou, in China, have created a gene therapy approach that can convert any lab mouse into one that can be infected with SARS-CoV-2 and develops COVID-like lung disease. The international team has published their work in Cell and made their gene therapy vector freely available to any researchers who want to use it. The "trick" is the use of an adenovirus gene therapy vector that is inhaled by the mice to deliver the human ACE2 protein into mouse airway cells. This is the protein that SARS-CoV-2 uses to infect cells. Once the mouse airway cells express the hACE2 protein, the mice become susceptible to infection with SARS-CoV-2 and they develop COVID-19-like lung symptoms. DOI: 10.1016/j.cell.2020.06.010
Researchers at Regeneron investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared following in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization. The research was published in Science. DOI: 10.1126/science.abd0831
Also in Science, researchers from the Netherlands and the US isolated monoclonal antibodies from three convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3 and VH1-24 gene usage. A subset of the antibodies were able to potently inhibit authentic SARS-CoV-2 infection. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention. DOI: 10.1126/science.abc5902
Finally, a team led by Scripps Research studied a cohort of recovered SARS-CoV-2 patients and isolated potent neutralizing antibodies to two epitopes on the receptor binding domain and to distinct non-RBD epitopes on the spike protein. The researchers developed neutralization assays to interrogate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen over 1800 antibodies, and established an animal model to test protection. The work is published in Science. DOI: 10.1126/science.abc7520
Researchers from Norway and Estonia explored how existing treatment options could work for COVID-19. They looked at convalescent sera and broad-spectrum antivirals and published their findings in Viruses. The findings were mixed. The team identified six existing safe-in-humans broad-spectrum antivirals that worked against the disease in laboratory tests. Two of the six, when combined, showed an even stronger effect in infected cell cultures. However, they found the use of antibody-laden plasma from recovered patients to treat the severely ill may only work if the donor has recently recovered from COVID-19. DOI: 10.3390/v12060642
Company Updates
The All of Us Research Program is seeking new insights into COVID-19--through antibody testing, a survey on the pandemic's impacts, and collection of electronic health record information. All of Us will test blood samples from 10,000 or more participants who joined the program most recently, starting with samples from March 2020 and working backward until positive tests are no longer found. The tests will show the prevalence of novel coronavirus exposure among All of Us participants, and help researchers assess varying rates across regions and communities. All of Us has also deployed a new online survey to better understand the effects of the COVID-19 pandemic on participants' physical and mental health. This 20- to 30-minute survey is designed both for participants who have been ill with COVID-19 and those who have not, and includes questions on COVID-19 symptoms, stress, social distancing and economic impacts. Finally, All of Us is rapidly collecting relevant information from participants' electronic health records. More than 200,000 participants have shared their electronic health records with the program so far, offering a rich dataset for analysis. A number of participants have either been diagnosed with COVID-19 or sought health care for related symptoms. The program is working to standardize EHR information to help researchers look for patterns and learn more about COVID-19 symptoms and associated health problems, as well as the effects of different medicines and treatments. Press release.
BERG will use the Summit supercomputer at the Department of Energy's Oak Ridge National Laboratory for rapid drug discovery research in the fight against COVID-19. Summit is already used to conduct computational simulations to analyze drug compounds that could prevent host cell infection. The partnership will extend this effort by combining BERG's human derived disease model for rapid identification of targets with ORNL's drug development research to identify the best-ranked treatment candidates. Press release.
Researchers from Scripps Research Institute, Johns Hopkins University, and University of California, Los Angeles are developing better statistical models and visualization software to look at how SARS-CoV-2 is moving around the world and what factors may be driving its spread and evolution. The project has won a $1.3 million grant from the National Institutes of Health, with operations based out of the Scripps Research-led Center for Viral Systems Biology. The funding supplements an initial $15 million NIH grant that enabled Andersen to launch the center in 2018, with the goal of helping eradicate infectious diseases such as Ebola and Lassa. Press release.
Data scientists at Columbia University Mailman School of Public Health have compiled a state-level COVID-19 dashboard that sorts data by age, race/ethnicity, and sex. The Demographics by State COVID-19 Reporting (DSCovR) Dashboard allows policymakers, scientists, and the lay public to visualize and compare COVID-19 trends and demographic information among cases, hospitalizations, and deaths across states. Dashboard.
Researchers at the University of South Florida are using wearable wrist and chest sensor technology from Shimmer Research to look at the human body’s physiological response to COVID-19. The researchers hope to monitor the physiological conditions of more than 100 study participants that have tested positive for COVID-19. Shimmer’s wearable device will track a variety of markers, including skin temperature, thoracic bioimpedance, oxygen saturation (SpO2) and more. Once the data is collected, scientists will use machine learning and artificial intelligence to synthesize the information and find patterns within the physiological fluctuations. These patterns will then be used to develop various profiles for potential patient outcomes and predict patients who may be at risk for severe infection. Press release.
Ethos Laboratories has entered a strategic partnership with Genscript to offer the first quantitative surrogate Viral Neutralization Test (sVNT) to evaluate COVID-19 protective immunity in the United States. This test, marketed as Tru-Immune, will measure and quantify the neutralizing capacity of antibodies against the SARS-CoV-2 virus. The Tru-Immune lab test will identify patients with the most effective antibody response capable of inhibiting virus replication. The commercialization of the new serological test, marketed by Ethos Labs in the U.S., will assist government officials and medical authorities to determine population health immunity levels for re-entry into the workforce. Press release.
The University of Rochester has made its self-screening chatbot tool available free as open source software. University of Rochester Medical Center (URMC) employees have been using the tool since April 9, to self-check for COVID-19 symptoms before they report to work. The University's chatbot technology also is the foundation of a "ROC COVID" community screening tool recently launched in thirteen counties in the Finger Lakes, N.Y. region to track potential new outbreaks of COVID-19 cases. University of Rochester's open source code includes a simple user interface accessible from an employee's smartphone, tablet, PC or other device, seven avatars representing a range of friendly onscreen health professionals who conduct the daily symptom checks on a rotating basis, a survey with questions determined by individual employers, and daily email or text messages to remind employees to complete the brief survey questions. Press release.
Cobra Biologics has signed a supply agreement with AstraZeneca UK to provide GMP manufacture of the adenovirus vector-based COVID-19 vaccine candidate AZD1222, previously known as ChAdOx1 n-CoV-19. The production agreement is part of AstraZeneca’s recently announced in-licensed program with the University of Oxford to ensure broad and equitable supply of the vaccine throughout the world, at no profit during the COVID-19 pandemic. Cobra, AstraZeneca, and other manufacturing organizations are working to provide large scale manufacturing capacity of AZD1222 vaccine. Cobra, along with other consortium members, will be manufacturing the vaccine with first deliveries to begin in the UK in September 2020. Press release.
GreenLight Biosciences, Boston, has closed two recent funding rounds: a $17 million special purpose funding round in May and a $102 million round in June. Both rounds come from new and existing investors. The May $17 million round was directed toward building out its scalable mRNA production capability targeting the production of billions of doses of COVID-19 vaccine. In addition to expanding its manufacturing capacity, GreenLight is developing several differentiated mRNA vaccine candidates against SARS-CoV-2, the virus responsible for COVID-19. mRNA-based vaccines offer the potential to address pandemics because of shorter pre-clinical development times compared to traditional vaccines. The June $102 million round is broader, meant to rapidly expand production of its RNA products for agricultural and life sciences applications. Press release.
