Novel T Cell Subset, Nitric Oxide Effective Treatment Option, SoCal cases linked to New York: COVID-19 Updates

October 9, 2020 | MIT’s preprint reviewers debunk synthetic SARS-CoV-2 paper, genetic analysis of virus samples show most COVID-19 cases in Southern California early in the pandemic are linked to New York state via Europe, not directly from China, vaccines should not be affected by the dominant ‘G-strain’, severe cases of COVID-19 develop a novel T cell subset that can potentially kill B cells, and MS drug inhibits virus growth. Plus, NIH funds COVID-10 vaccine using bovine adenovirus.

Research Updates

Most COVID-19 cases in Southern California early in the pandemic are linked to New York state via Europe, not directly from China. These finding were based of a genetic analysis of the virus found in tissue samples from 192 patients diagnosed with the SARS-CoV-2 virus at Cedars-Sinai. The study, published in JAMA Network Open, found that about 15% of the samples taken between March 22 and April 15 were genetically similar to published profiles of SARS-CoV-2 viruses from Asia, while 82% shared close similarities with variants originating in Europe. DOI: 10.1001/jamanetworkopen.2020.24191

Vaccines under development for COVID-19 should not be affected by the dominant ‘G-strain’ that now accounts for about 85% of the published SARS-CoV-2 genomes. A new study from University of York looks at research by Australia’s Commonwealth Scientific and Industrial Research Organization (CSIRO) that tested blood samples from ferrets given a candidate vaccine against strains that either possessed or lacked this mutation, known as D614G. They found that despite this mutation to the spike protein, the vaccine candidate to still be effective. In addition, the G-strain is unlikely to require frequent ‘vaccine matching’ seasonally to combat the virus strains in circulation. This study is published in Vaccines. DOI: 10.1038/s41541-020-00246-8

A new international study led by scientists at La Jolla Institute for Immunology (LJI) and published in Cell, takes an in-depth look at how CD4+ T cells respond to the SARS-CoV-2 virus, and their work suggests that early in the illness, patients hospitalized with severe cases of COVID-19 develop a novel T cell subset that can potentially kill B cells and reduce antibody production. This may explain why the virus proves deadly for some and mild in others. The researchers used a cutting-edge technique called single-cell RNA-sequencing (RNA-seq) to analyze the types of CD4+ T cells that respond to SARS-CoV-2 in their 2 test groups – 22 hospitalized patients (nine treated in ICU) and 18 non-hospitalized patients with milder symptoms. The hospitalized patients were found have higher levels of “cytotoxic” TFH cells that were very similar to cells that have been seen killing B cells in previous studies. DOI: 10.1016/j.cell.2020.10.001

A new study grew Ebola virus in the presence of progressively increasing remdesivir concentrations to evaluate resistance of the antiviral drug. The resulting viruses were notably less susceptible to remdesivir than viruses unexposed to the drug. A single nucleotide substitution was identified that was common to all remdesivir-exposed cultures. Viruses containing this substitution had reduced susceptibility to this drug but not to other anti-Ebola drugs. The results suggest a common mechanism of action for remdesivir against Ebola virus and SARS-CoV-2. Substitutions identified in both viruses should be actively monitored for potential remdesivir resistance mutations. This study is published in PNAS. DOI: 10.1073/pnas.2012294117

Columbia Engineering researchers demonstrate that RNA terminated by Sofosbuvir is more resistant to the proofreader of SARS-CoV-2 than Remdesivir-terminated RNA. The results of the new study, published in Scientific Reports, support the use of FDA-approved hepatitis C drug EPCLUSA (sofosbuvir/velpatasvir) in combination with other drugs in COVID-19 clinical trials. Other investigators have demonstrated the ability for Sofosbuvir to inhibit SARS-CoV-2 replication in lung and brain cells. Currently, COVID-19 trials with a number of hepatitis C drugs, such as EPCLUSA, and the combination of Sofosbuvir and Daclatasvir are ongoing in several countries. The study notes that recent preprint from UC Berkeley indicates that a combination of Remdesivir and EPCLUSA increase Remdesivir’s efficacy 25-fold in inhibiting SARS-CoV-2, which offers a molecular basis supporting study of EPCLUSA in combination with Remdesivir for COVID-19 clinical trials. DOI: 10.1038/s41598-020-73641-9

SARS-CoV-2 can relieve pain, according to a new study by researchers at the University of Arizona Health Sciences. This finding may explain why nearly half of people who contract COVID-19 have few or no symptoms. The CDC released updated data estimating 50% of COVID-19 transmission occurs prior to the onset of symptoms and 40% of infections are asymptomatic. This research raised the possibility that pain may be reduced by the SARS-CoV-2 spike protein. Many biological pathways signal the body to feel pain, one is through the vascular endothelial growth factor-A (VEGF-A) protein which has been linked to COVID-19. With that knowledge, researchers performed a series of experiments in the lab and in rodent models to test their hypothesis that the SARS-CoV-2 spike protein acts on the VEGF-A/neuropilin pain pathway. What they found was that the spike protein completely reversed the VEGF-inducing pain signaling. These findings have massive implications on not only learning about viral spread but also looking at neuropilin as a new non-opiod method to fight the opioid epidemic, as published in the PAIN journal. DOI: 10.1097/j.pain.0000000000002097

Numerous animals may be vulnerable to SARS-CoV-2. The study, published in Scientific Reports and led by researchers at University College London, shows evidence that 26 animals regularly in contact with people may be susceptible to infection. They found that most birds, fish, and reptiles do not appear to be at risk but the majority of the mammals they reviewed could potentially be infected. These findings may highlight the importance to employ hygiene measures when dealing with animals and for infected people to isolate from animals as well as other people. Large scale surveillance of animals, particularly pets and farms animals, may catch cases or clusters early on while they are still manageable. DOI: 10.1038/s41598-020-71936-5

There is considerable risk that humans transmit SARS-CoV-2 to wildlife, according to an article published in Mammal Review. Authors noted that if the virus were to infect and spread among wild animals, it could potentially cause disease in some populations, and in turn further endangering already threatening species. In addition, SARS-CoV-2 could be transmitted among some mammalian populations, thus creating new animal reservoirs that could repeatedly source new outbreaks in humans and other animals. The researchers urge people to take sanitary precautions when in direct or indirect contact with wild or feral mammal species to prevent human-to-wildlife COVID-19 transmission. DOI: 10.1111/mam.12225

A new study in the journal Nature Communications shows that a drug called dimethyl fumarate (DMF), which is approved for the treatment of multiple sclerosis patients, inhibits growth of a range of viruses in the body’s cells including SARS-CoV-2 – at least when tested in a test tube. Researchers at Aarhus University also found that the drug inhibited the immune reaction or inflammatory condition that constitutes a large portion of the actual threat for coronavirus patients. DMF, being an approved product, can be tested ‘here and now’ if clinicians and the company holding the patent are prepared to test it in human trials. DOI: 10.1038/s41467-020-18764-3

The MIT Press Journal Rapid Reviews: COVID-19 has published the first official scholarly peer reviews debunking pre-print research that claims to show unusual features of the SARS-CoV-2 genome suggest sophisticated lab modification rather than natural evolution. While this research has been widely debunked in popular media, scholarly peer review represents a different type of rebuke from the scientific community. These reviews are now openly published and collectively reviewers have debunked the authors’ claims that: (1) bat coronaviruses ZC45 or ZXC21 were used as a background strain to engineer SARS-CoV-2, (2) the presence of restriction sites flanking the RBD suggest prior screening for a virus targeting the human ACE2 receptor, and (3) the furin-like cleavage site is unnatural and provides evidence of engineering. Rapid Reviews: COVID-19.

Researchers at Uppsala University have found nitric oxide (NO) as an effective way of treating coronavirus. NO, a compound produced naturally in the body, acts like a hormone in controlling various organs and regulated tension in the blood vessels and blood flow between and within organs. One key reason for the successful results was that inflammation in the patients’ lungs decreased. This property of NO – the protection it affords against infections, by being both antibacterial and antiviral, is what now interests researchers. Until an effective vaccine is available, their hope is that inhalation of NO might be an effective form of treatment. The research group has plans to proceed with testing antiviral effects of NO emitted in gas form. This study is published in Redox Biology. DOI: 10.1016/j.redox.2020.10173

Drexel University researchers have developed a new technique to quickly identify and label mutated versions of COVID-19. Their analysis suggests that there are at least 8 to 14 different versions of the virus infecting people in the U.S. Using Informative Subtype Markers (ISM), they can spot patterns to categorize viruses with small genetic differences. The ISM tool is particularly useful because it does not require analysis of the full genetic sequence of the virus to identity its mutations. This ‘barcode’ can help scientists understand how the virus is changing and spreading and can reveal the portion of its genetic code that appears to remain resistant to mutations. This research is published in PLOS Computational Biology. DOI: 10.1371/journal.pcbi.1008269

The Blagosklonny Research Team reviews in Aging-US the reasons why COVID-19 vulnerability is an age-dependent syndrome, linking it to other age-related diseases. The authors contend that at its deepest level, aging is driven by inappropriately high cellular functioning. They go on to highlight that an anti-aging intervention, such as rapamycin (an anti-inflammatory agent), may slow aging and therefore potentially decrease COVID-19 vulnerability. Cytokine storm and hyper-inflammation is the main cause of the death in COVID-19 pneumonia and this agent may inhibit hyperfunctions, cellular senescence and decrease secretion of cytokines in those patients, according to this research. DOI: 10.18632/aging.103493

Industry Updates

NIH has awarded a nearly $3.9 million grant to a team of scientists working to develop a unique COVID-10 vaccine using bovine adenovirus. The team, led at Purdue University, explains that by using a delivery system based on an animal adenovirus means that the human population will have no preexisting immunity to the vector. This would improve its effectiveness and could make a significant contribution in flattening the pandemic’s trajectory particularly in managing the second wave. The researchers noted that because SARS-CoV-2 is a newly emerging virus for which humans have no previous immunity, any vaccine will have to be highly immunogenic to provide protection, especially in the eldering population. Press Release