Study Says Prior Infection Could Prevent Reinfection, Other COVID-19 News

July 10, 2020 | Animal models are showing how prior infection of the SARS-CoV-2 virus can provide protection against reinfection. Elsewhere, a coronavirus task force task force is examining genes associated with COVID-19 immune response by collecting samples from Japanese patients. This, plus more, are featured in this week’s COVID-19 news from the biotech and research industries.

Literature Updates

Using an animal model for COVID-19, scientists at the University of Wisconsin-Madison, the University of Tokyo and the Icahn School of Medicine at Mount Sinai show that prior infection with the SARS-CoV-2 virus provides protection against reinfection, and treatment with convalescent serum limits virus replication in their lungs. The study, published in the Proceedings of the National Academy of Sciences, point to the usefulness of Syrian hamsters in trying to understand SARS-CoV-2 and in evaluating vaccines, treatments and drugs against the disease it causes. Expanding on earlier work with the animals, researchers demonstrated that both low and high doses of the virus, from patient samples collected in the U.S. and Japan, replicate well in the airways of juvenile and adult hamsters and that the virus can infect both the upper and lower respiratory tracts. The research team also showed that SARS-CoV-2 causes severe disease in the lungs of infected animals, including lesions and the kind of "ground glass" appearance often found in lung scans in human patients. Scans additionally revealed a region of gas in the cavity surrounding the hamster's lungs, indicating severe lung damage. The most severe effects were observed within eight days after infection, and improvement by 10 days. DOI: 10.1073/pnas.2009799117

Researchers at the University of Toronto and National Jewish Health (Denver) have made a drug discovery that shows promise in fighting acute respiratory illnesses such as COVID-19. Called TAT CARMIL1, the "drug" is a combination of two naturally occurring peptides that together penetrate a cell's membrane to douse cytokine storms if deployed early enough. In its first ex vivo study, published in Cell Reports, the peptide duo reduced collagen degradation by up to 43%. It effectively blocks a family of cytokines, called interleukin1, from signaling and reproducing in vast quantities. It precisely targets two receptors, sticking to both the cell's surface and its cell substrate, where it adheres to other cells. Researchers believe the unusual nature of this pathway might restrict its side effects, making TAT CARMIL1 an unusually strong candidate as a potential drug. DOI: 10.1016/j.celrep.2020.107781

An international team of scientists has shown that the G614 variant of the SARS-CoV-2 virus came to dominate cases of COBID-19 around the world by mid-March. Its “spike” protein differs slightly from the D614 variant, helping the virus copy itself rather than making the virus more deadly (as was initially reported). The study, published in Cell, was led by scientists at Duke University, Los Alamos National Laboratory and La Jolla Institute (headquarters for the Coronavirus Immunotherapy Consortium). Based on experiments with samples from six San Diego residents, researchers showed that the human immune response could neutralize the new G virus as well or better than the original D virus—a finding in line with what doctors saw in COVID-19 patients. DOI: 10.1016/j.cell.2020.06.043

Scientists from the University of South Florida Health (USF Health) Morsani College of Medicine and the University of Arizona College of Pharmacy report in Cell Research that they’ve identified several existing compounds that block replication of the COVID-19 virus within human cells grown in the laboratory. The inhibitors all demonstrated potent chemical and structural interactions with the SARS-CoV-2 main protease that is critical to the virus's ability to proliferate and has already been validated as an antiviral drug target for genetically similar SARS and MERS. The most promising drug candidates include the FDA-approved hepatitis C medication boceprevir and an investigational veterinary antiviral drug known as GC-376. Calpain inhibitors II and XII, cysteine inhibitors investigated in the past for cancer, neurodegenerative diseases and other conditions, also showed strong antiviral activity. DOI: 10.1038/s41422-020-0356-z

Two recent papers (in Langmuir and ACS Nano) describe a “membrane on a chip” that allows continuous monitoring of how drugs and infectious agents interact with human cells. With funding from the U.S. Defense Research Projects Agency, the device will now be used to test potential drug candidates for COVID-19 using virus membranes identical to the SARS-CoV-2 membrane, but which don't contain the viral nucleic acid. The device was developed by researchers from the University of Cambridge, Cornell University and Stanford University and can mimic any cell type. Their research recently pivoted to how COVID-19 attacks human cell membranes and how it can be blocked. The device, which uses an electronic chip to measure any changes in an overlying membrane extracted from a cell, has been successfully used to monitor the activity of ion channels—the target of more than 60% of approved pharmaceuticals. It can be as small as the size of a human cell and easily fabricated in arrays. The method is compatible with high-throughput screening and would reduce the number of false positives making it through into the R&D pipeline. DOI: 10.1021/acs.langmuir.0c00804

A researcher at St. Petersburg State University (Russia) has advanced a hypothesis that the severe course of COVID-19 may be associated with von Willebrand factor (VWF), one of the main components of the blood coagulation system. As she explains it, replication of the virus stimulates the development of microdamage on vessel walls that prompts the body to release VWF into the blood to “patch” possible holes. This increases the risk of thromboses, which has been associated with a significant number of deaths from COVID-19. Different levels of VWF in the blood of patients may explain why infection can happen in completely different ways person to person. VWF levels also differ markedly among healthy people—e.g., higher among African Americans than Europeans, in men than in women, in adults than in children, and in the elderly than in middle-aged people—and also appear to be higher among those in blood group A and lower among those in blood group O. The article published in Ecological Genetics. DOI: 10.17816/ecogen33973

Researchers from the University of Houston and Medistar Corporation report in Materials Today Physics that they have designed a "catch and kill" nickel foam air filter that can trap the virus responsible for COVID-19, killing it instantly. In testing at the Galveston National Laboratory, run by the University of Texas Medical Branch, they found 99.8% of SARS-CoV-2 was killed in a single pass through the filter when heated to 392 degrees Fahrenheit. It is reportedly compatible with conventional heating, ventilation and air conditioning systems. High-priority venues—including hospitals and healthcare facilities—would be in the initial roll-out of the device. DOI: 10.1016/j.mtphys.2020.100249

Scientists from Germany and Israel have isolated potent SARS-CoV-2 neutralizing antibodies which are currently being further characterized and developed together with Boehringer Ingelheim. They’re expected to enter clinical development later this year. Results, published in Cell, were based on an investigation of the SARS-CoV-2 antibody response in 12 individuals recovered from COVID-19. Of the 255 antibodies reconstructed in the laboratory, 28 neutralizing antibodies were found. SARS-CoV-2-specific B cells carry similar antibody characteristics to those of SARS-CoV-2 neutralizing antibodies, they say, suggesting they can be readily formed and that an active vaccine may provide rapid protection. The antibodies have been developed for protecting against and treating COVID-19 and could also be used for post-exposure prophylaxis. DOI: 10.1016/j.cell.2020.06.044

A researcher at Virginia Tech and two colleagues at the National Institutes of Health have found that Bacille Calmette-Guérin (BCG)—a tuberculosis vaccine routinely given to children in countries with high rates of TB infection—might play a significant role in mitigating mortality rates from COVID-19. Countries with higher rates of BCG vaccinations also had lower peak mortality rates from COVID-19, and the correlation held even after adjusting for variables such as income, access to education and health services, population size and densities, and age distribution. One sample that stood out was Germany, which had different vaccine plans prior to the country's unification in 1990 that has left older Germans (the population most at risk from COVID-19) in the country's eastern states better protected from the current pandemic than their peers in western German states where mortality rates are 2.9 times higher. The BCG vaccines have already been shown to provide broad cross-protections for several viral respiratory illnesses in addition to TB. Researchers stress that the findings are preliminary. The World Health Organization doesn’t currently recommend BCG vaccinations for the prevention of COVID-19, but clinical trials are underway to establish whether it confers protection. Their work has published in the Proceedings of the National Academy of Sciences. Article

Using data covering a longer period than previously reported, researchers report in The Journals of Gerontology that ApoE e4e4 genotype is associated with COVID-19 test positivity at genome-wide significance in the UK Biobank. Similarly, the e4e4 genotype was associated with a four-fold increase in mortality after testing positive for COVID-19. The findings demonstrate that risks for COVID-19 mortality are not simply related to advanced chronological age or the comorbidities commonly seen in aging. DOI: 10.1093/gerona/glaa169

Updates from Industry

A joint research Coronavirus Task Force has been established by researchers from eight leading universities and medical institutions in Japan. The task force will examine genes associated with COVID-19 immune response by collecting samples from Japanese patients and apply the findings to development of a mucosal vaccine and predictive modeling for COVID-19 treatment. Its focus is on the fact that the number of COVID-19 deaths per capita among Japanese people is far fewer than those in Western countries. By comparing severe and mild/asymptomatic cases among Japanese people, the group will search for genetic susceptibilities unique to Japanese people associated with exacerbation of COVID-19. As of June 15, collection of patient samples had already begun at 30 facilities, with 60 more awaiting approval from a research ethics committee to start their own large-scale sample collection. The research team plans to collect 600 blood samples from its joint research institutes and use them to conduct comprehensive analyses. After identifying the genes involved in disease exacerbation in Japanese patients, they will try to identify candidate antigens for SARS-CoV-2 using supercomputer simulations. Vaccine efforts will use proprietary molecular needle technology. The goal is to analyze the human genes of samples collected in July and compile results by September. Press release.

The Innovation Center of NanoMedicine (iCONM) has initiated a collaborative study with the Tokyo Metropolitan Institute of Medical Science (TMIMS), aiming to rapidly develop an mRNA vaccine in preparation for the re-pandemic of COVID-19 and attacks by other new coronaviruses. The study will adapt iCONM's basic technology—an mRNA-loaded smart nanomachines—to the TMIMS's expertise in recombinant vaccine discovery. Press release.

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