More Immunological Updates for SARS-CoV-2 Infection, Modeling New Drugs: COVID-19 Updates
February 26, 2021 | More insights into how the immune system reacts to SARS-CoV-2 infection, docking analysis predicts new COVID-19 drugs, and impacts of temperature and humidity. Plus: correlating COVID-19 symptoms and genetic profiles.
A new analysis of B cells and more than 1,000 different monoclonal antibodies from 8 patients with COVID-19 shows that, contrary to previous hypotheses, protective B cell responses to the SARS-CoV-2 spike protein remain stable and continue to evolve over a 5-month period, many months after the initial period of active viral replication. However, the neutralizing antibody response was dominated by public clonotypes that displayed significantly reduced activity against SARS-CoV-2 variants emerging in Brazil and South Africa that harbor mutations at positions 501, 484 and 417 in the S protein. The work is published in Science Immunology. DOI: 10.1126/sciimmunol.abg6916
A team of German researchers have pinpointed a helper T cell population in the lungs of patients with severe COVID-19 that may be central to the development of hyperinflammation, lung injury, and subsequent acute respiratory distress syndrome (ARDS) during disease. Their data, published in Science Immunology, support the ongoing investigation of anti-cytokine therapies that target this cell subset, called tissue-resident memory-like Th17 cells (Trm17). DOI: 10.1126/sciimmunol.abf6692
An important manifestation of severe COVID-19 is the ARDS-like lung injury that is associated with vascular endothelialitis, thrombosis, and angiogenesis. The intravascular innate immune system (IIIS) is likely to be involved in the pathogenesis of COVID-19 ARDS. A team from Uppsala University published findings in Frontiers in Immunology suggesting that critically ill COVID-19 patients display a conjunct activation of the IIIS that is linked to organ damage of the lung, heart, kidneys, and death. We present evidence that the complement and in particular the kallikrein/kinin system is strongly activated and that both systems are prognostic markers of the outcome of the patients suggesting their role in driving the inflammation. DOI: 10.3389/fimmu.2021.627579
Guided by a computational docking analysis, a research team from Texas A&M University and The University of Texas Medical Branch (UTMB) experimentally characterized about 30 FDA/EMA-approved drugs on their inhibition of essential main protease of SARS-CoV-2, the pathogen of COVID-19. From this study, the team discovered that bepridil, an FDA-approved antianginal medication, is potent against SARS-CoV-2. The antiviral analysis of bepridil indicated that it had low micromolar EC50 values in inhibiting SARS-CoV-2 in two highly permissive mammalian cell lines. The work is published in PNAS. DOI: 10.1073/pnas.2012201118
University of Warwick scientists have modeled the movements of nearly 300 protein structures in SARS-CoV-2 from the Protein Databank and have publicly released data on all the protein structures to aid efforts to find potential drug targets. They plan to use the simulations to identify potential targets to test with existing drugs, and even check effectiveness with future SARS-CoV-2 variants. They have published their work in Scientific Reports. DOI: 10.1038/s41598-021-82849-2
In a review in Science Advances, researchers from Cornell outline the immunogenicity profiles of several leading SARS-CoV-2 vaccine candidates, including several developed under the auspices of the U.S. Government's "Operation Warp Speed" program, as well as leading candidates from China and Russia. The authors review data from evaluations in non-human primates as well as human clinical trials, summarizing what is known about antibody and T cell immunogenicity for roughly a dozen leading candidates. Noting the variability in the methods used to assess each vaccine, which makes direct comparisons challenging, they nonetheless attempt to qualitatively compare and contrast the vaccines' performance. DOI: 10.1126/sciadv.abe8065
A researcher team including researchers from the University of Louisville, Johns Hopkins, and the U.S. Department of Defense Joint Artificial Intelligence Center, theorized that SARS-CoV-2 would be impacted by temperature and humidity like other coronaviruses. They tracked infections from January to April 2020. The data analysis showed that between 30 and 100 degrees Fahrenheit, a 1-degree Fahrenheit increase in daily low temperature was associated with a 1% decrease in the rate of increase in COVID-19 cases, and a 1-degree decrease in temperature was associated with an increase in that rate by 3.7%. By analyzing data from early in the pandemic, the results were obtained without significant influence by lockdowns, masking or other social efforts to contain the virus. They published their findings in PLOS One. DOI: 10.1371/journal.pone.0246167
Veos Digital signed an agreement with the University of Siena to correlate COVID-19 symptoms and genetic profile. Veos Digital’s research Lab works closely with the group of academics involved in this project to create advanced machine learning algorithms able to work on datasets composed of few but very high-dimensional samples (e.g., Whole Exome Sequencing, WES). These models will allow the group of geneticists and MDs that actively collected the data to determine which and how expressed genes interact nonlinearly, regulating (at least partially) the infection’s severity. Press release.