FOXP3 Protein Inhibited, Blocking Factor D Protein May Prevent Inflammatory Response, App Crowdsources Drug Candidates: COVID-19 Updates

October 16, 2020 I Cloud-based tool, IDseq, allows tracking of emerging pathogens, scientist who discovered SARS captures detailed look of immune system response to COVID-19, SARS-CoV-2 may become endemic, ORF3B identified as viral factor that impairs immune response, age is an independent factor to virus susceptibility, group of 80 researchers warns against herd immunity approach, high dose favipiravir had significant effect on preventing and treating virus in hamster model, REGN-COV2 antibody ‘cocktail’ offers protection in pre-clinical trial on macaques. Plus: SARS-CoV antibodies effectively neutralize SARS-CoV-2 infection in cultured cells, international open access database aims to reduce duplication of ongoing COVID-19 research and more.

Research News

SARS-CoV-2 may become endemic according to a new article published in Science. The authors identify factors contributing to this prediction, including recurrence of reinfection, availability and efficacy of a vaccine, as well as seasonal differences in transmissibility. The paper references current modeling of post-pandemic scenarios that indicate a duration of immunity may occur that is similar to other endemic betacoronaviruses (around 40 weeks), and we would experience yearly outbreaks. Another scenario may be prolonged immunity to SARS-CoV-2 and elimination of the virus, followed by a resurgence after a few years. DOI: 10.1126/science.abe5960

In an open letter referred to as the John Snow Memorandum, published in The Lancet, a group of 80 international researchers warn against the herd immunity approach to COVID-19 management. The authors present their collective scientific consensus on our understanding of COVID-19 and best practices to be put in place to protect societal and economic health. They go on to explain that uncontrolled transmission in younger populations poses significant risks to the entire population, with evidence of this from many countries showing that it is not feasible to restrict uncontrolled outbreaks to certain sections of society. They also warn that the herd immunity approach risks impacting the workforce as a whole and overwhelming healthcare systems. DOI: 10.1016/S0140-6736(20)32153-X

A new cloud-based tool, called IDseq, allows rapid detection, identification, and tracking of emerging pathogens such as SARS-CoV-2. IDseq can identify pathogens before there is an available complete genome sequence, which makes it useful for current infectious diseases and emerging ones. Scientists in Cambodia used this new technology to confirm and sequence the whole genome of the country’s first case of COVID-19, confirming that it can in fact detect the presence of an emerging pathogen prior to the existence of a full reference genome. This study is published in GigaScience. DOI: 10.1093/gigascience/giaagiaa111

A team of scientists led by one of the first doctors to diagnose SARS has captured a detailed look at the immune system’s response to COVID-19. The study, published in Frontiers in Immunology, provides insight into the immune cells of 23 COVID-19 patients over three different stages of infection. By studying the immune system fingerprints of the infected patients, the research team revealed the expansion and contraction of all seven chains in the immune repertoire. They specifically discovered that early in the infection T cell discovery is significantly depleted, and these T cells recovered as patients improved, suggesting this may be an important marker in predicting disease progression. Their findings also suggest that for B-cells, those that proliferate might point to antibodies that can themselves serve as potential treatments for those who are already infected, but not recovering. DOI: 10.3389/fimmu.2020.582010

University of Arizona Health Sciences researchers have found that antibodies provide immunity for several months after COVID-19 infection. The team studied the production of antibodies from nearly 6,000 infected people and saw antibodies still being produced five to seven months after SARS-CoV-2 infection. The key to this finding was looking for the creation of long-lived plasma cells, noting that previous studies have focused on only short-lived plasma cells, which provide high-quality and long-lasting immunity. These findings are published in the journal Immunity. DOI: 10.1016/j.immuni.2020.10.004

A collaborative study, published in Cell Systems, has identified 219 molecules and genes that impact COVID-19 severity. Researchers analyzed 102 blood samples from SARs-CoV-2 positive patients and 26 samples from patients with acute respiratory distress syndrome (ARDS) that were negative for COVID-19 as their control group. The team used mass spectrometry, RNA sequencing, machine learning, and then also explored a database of more than 17,000 different proteins, metabolites, lipids, and RNA transcripts associated with clinical outcomes. Pinpointing several specific molecules, they uncovered the strong interplay between hypercoagulation, leading to thrombotic events, and inflammatory response in severe COVID-19 cases. DOI: 10.1016/j.cels.2020.10.003

New research provides insight into COVID-19 immune response, specifically as the degree of severity and age of the patient increases, through a serology study published in Clinical and Translational Immunology. Serum samples were collected from 32 hospitalized COVID-19 patients and from 17 asymptomatic individuals who had antibodies for SARS-CoV-2, and researchers found that the level of antibodies correlated with severity of the viral infection. The patients requiring long-term ICU care had antibody levels that increased as their length of stay in the ICU increased. In addition, those patients requiring hospitalization in general had higher antibody levels compared to those who had exposure or with mild infection not requiring hospitalization. The study also noted that through serological testing, they discovered that many elderly patients (80 years and older) produced just as strong of an antibody response as the 40-year-olds in the study. DOI: 10.1002/cti2.1189

A research team at The Institute of Medical Science, The University of Tokyo has identified a viral factor that impairs immune responses in patients with SARS-CoV-2. One distinguishing feature of COVID-19, when compared to SARS, is the poor induction of a type I interferon (IFN) response by SARS-CoV-2, and these impaired IFN responses are linked to the severity of the virus. The study, published in Cell Reports, discovered that ORF3b, a gene encoded by SARS-CoV-2, is a strong IFN antagonist. The researchers also compared the sequences of SARS-CoV-2 encoding genes to those of SARS-CoV and found that the gene length of SARS-CoV-2 ORF3b is notably shorter than that of SARS-CoV ORF3b. They hypothesize the difference in length of the ORF3b gene in SARS-CoV-2 and SARS-CoV may change their anti-IFN activity and explain the difference in symptoms of the two viral infections. DOI: 10.1016/j.celrep.2020.108185

A team of scientists have modeled data from Japan, Spain, and Italy to show that age is an independent factor related to COVID-19 susceptibility. They did find, however, that the occurrence of symptomatic COVID-19, severe cases and mortality from the virus is likely age dependent. Although age distribution of mortality was similar between the three countries, the model indicated the age should not influence susceptibility but only negatively influence severity and mortality to explain this. The results from this mathematical model are published in Scientific Reports. DOI: 10.1038/s41598-020-73777-8

Emory researchers have been observing immune cell activations resembling acute flares of systemic lupus erythematosus (SLE) in severe cases of COVID-19. The study, published in Nature Immunology, compared 10 critically ill patients with COVID-19 admitted to the ICU at Emory hospitals to 7 people with the virus who were treated as outpatients and 37 healthy controls. The critically ill patients tended to have higher levels of antibody-secreting cells early in their infection and the B cells and the antibodies they made displayed characteristics that suggest the cells were being activated in an extrafollicular pathway, which looks very similar to observations in SLE patients. These findings could have implications on which patients should receive immunomodulatory treatments, like dexamethasone and anti-IL-6 drugs. DOI: 10.1038/s41590-020-00814-z

Virologists at KU Leuven Rega Institute used hamsters to test the efficacy of hydroxychloroquine and favipiravir on preventing and treating SARS-CoV-2. The hamsters were given either hydroxychloroquine or favipiravir for four to five days and were infected with the SARS-CoV-2 virus either intranasally or by contact with an infected hamster in the same cage. Four days after infection or exposure, the researchers measured how much of the virus was present in the hamsters. They found that treatment with hydroxychloroquine had no impact, however, a high dose of favipiravir had a significant effect. Hamsters that were infected intranasally and received a high dose of favipiravir had hardly any infectious virus particles detected a few days after infection, and those hamsters that were in a cage with an infected hamster and had received the drug did not develop any infection. The authors of this study, published in PNAS, noted that a low dose of favipiravir did not have the same effect. DOI: 10.1073/pnas.2014441117

A new study published in Science shows further evidence that the two-antibody cocktail, REGN-COV2, offers protection and treatment of COVID-19. The authors reported that when administered three days before viral challenge, treatment almost completely blocked establishment of viral infection in macaques. When the macaques were treated with the cocktail one day after infection, the authors reported faster viral clearance than in controls who had not been treated. Similar results were found in the hamster model. DOI: 10.1126/science.abe2402

Antibodies in serum samples from patients infected with SARS-CoV during the outbreak in 2003 effectively neutralized SARS-CoV-2 infection in cultured cells, according to a new study published in Science Advances. The authors of this study also reported that mice and rabbits immunized with a receptor binding domain (RBD) from a strain of SARS-CoV that infects the Himalayan palm civet provided a stronger antibody response against SARS-CoV-2 than animals immunized with a RBD from a human SARS-CoV strain. The authors suggest that these findings may help in strategies to develop universal vaccines against emerging and future coronaviruses. DOI: 10.1126/sciadv.abc9999

Improving upon a previously developed protein selection lab test called TRAP (transcription-translation coupled with association of puromycin linker), scientists at Nagoya University have identified nine synthetic proteins that bind to the spike protein on SARS-CoV-2’s outer membrane. Upon investigating these proteins, they discovered that some were able to detect SARS-CoV-2 in nasal swabs and one attaches to the virus to prevent it from binding to the receptors in human cells. The researchers believe this could be useful in developing test kits and for finding treatments for COVID-19. The method is published in Science Advances. DOI: 10.1126/sciadv.abd3916

Researchers at John Hopkins Medicine have identified a protein that, when blocked, may prevent deadly inflammatory reactions and severe organ damage. This protein, know as factor D, can accelerate the immune system and cause severe organ damage when infected with SARS-CoV-2. The research team notes that there are a number of drugs in development and testing that can inhibit this protein and may work well with vaccines in the coming years to control the spread of COVID-19 and future viral pandemics. This study is published in the journal Blood. DOI: 10.1182/blood.2020008248

Severe SARS-CoV-2 infection may be linked to an overreaction of the immune system, according to a new study led by Imperial College London researchers. The research team tested samples from the lungs of six patients in China with severe COVID-19 and compared those samples to three moderate COVID-19 patients and three healthy individuals, looking at gene usage in single cells which allowed them to gain fine details on the immune system response. They found that the protein ‘Foxp3’ was inhibited in the lungs of those with severe COVID-19. This protein is responsible for activating the ‘brake mechanism’ in T cells to reduce their activity and calm inflammation. These findings are published in Frontiers of Immunology. DOI: 10.3389/fimmu.2020.589380

A research team at the Institute for the Genetics of Heart Diseases of Munster University has developed a viral expression model using stem cells to better understand the progress of viral infections. This model can be used to simulate and analyze a large number of viral infections, including SARS-CoV-2. This study can be found in the Scientific Reports. DOI: 10.1038/s41598-020-72966-9

Industry News

ViDok, a new app that anyone can download on a smartphone, aims to crowdsource for potential COVID-19 treatments. Users are able to choose from a library of molecules that may bind to target proteins on the SARS-CoV-2 virus and then modify the molecules to find the best fit. The developer notes that out of the top 200 molecules from more than 2,500 drug candidates that have been tested thus far, only five come from the original library and the other 195 have been modified by users of the app. Press Release

Experts in Computer Science and Medicine at the University of Birmingham have partnered with the Institute for Global Innovation to launch an international open-access database for ongoing research activity (COVID CORPUS) that aims to encourage collaboration and reduce duplication of COVID-19 research. This platform is curated by experts across the globe, and users will have the ability to upload their own contributions to COVID-19 research, network with other researchers to create new partnerships, and search for ongoing research across all academic disciplines. Press Release

The Vaccine and Infectious Disease Organization-International Vaccine Center (VIDO-InterVac) at the University of Saskatchewan (USask) has received a nearly $830,000 grant from the COVID-19 Therapeutics Accelerator to expand its testing efforts with several antiviral compounds against COVID-19. Testing for these antiviral compounds will use a hamster model, meant to mimic human SARS-CoV-2 infections. VIDO-InterVac has partnered with more than 80 organizations around the globe to test antivirals, vaccines, and other therapeutics. Press Release

Sandia National Laboratories has collaborated with BioBright to improve security in the fight against cyberattacks. Current security models are outdated, many developed two decades ago, while hackers are taking advantage of the COVID-19 pandemic to exploit sensitive data. Using Emulytics, an initiative developed at Sandia to evaluate threats against critical systems, the teams will develop solutions to safeguard biological data. Press Release

The University of Houston (UH) has partnered with AuraVax Therapeutics in an exclusive license option agreement for development of a COVID-19 vaccine. This new vaccine is in the form of a nasal inhalant, similar to FluMist, and developers believe this new technology will elicit both mucosal and systemic immunity, based on pre-clinical work. The developer, and UH professor, is using the spike protein for virus entry based on its ability to produce a strong immune response and absence of infectious particles. Press Release

Researchers at the Walter and Eliza Hall Institute are leading a new study, named COVID PROFILE study, to help determine immune responses to COVID-19—specifically how people are protected and for how long from a future reinfection of the virus. The study will recruit 300 adult volunteers in Melbourne who have had COVID-19 and those who have been in close contact with someone who has. The participants will then be following for 12 months after their exposure, whether contracting the virus or not, through collecting blood samples and nasal and throat swab testing. They aim to advance vaccine development through their findings and determine risk of reinfection. Press Release