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Populations With Unique Enzymes More Susceptible To COVID-19, Other News



July 16, 2020 | Researchers from Cleveland Clinic have found unique genetic susceptibility to COVID-19 across populations in ACE2 and TMPRSS2. Elsewhere, the University of California Health has developed a unified, secure data set for use in COVID-19 research. This, plus more, is included in this week’s COVID-19 news from the biotech and research industries.

Literature Updates

Researchers from Cleveland Clinic considered how polymorphisms in ACE2 or TMPRSS2 were likely to be associated with genetic susceptibility of COVID-19. In a study of 81,000 human genomes, they found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. For instance, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. The group calls for a human genetics initiative for fighting the COVID-19 pandemic. Their work was published in BMC Medicine. DOI: 10.1186/s12916-020-01673-z

Korean researchers conducted a new single-cell RNA sequencing analysis of cells from COVID-19, healthy, and severe flu patients, revealing a detailed look at patients' immune responses to severe cases of COVID-19. Their findings were published in Science Immunology. The results suggest that patients with severe COVID-19 experience increased regulation of the type I interferon (IFN-I) inflammation-triggering pathway—a signature that the researchers also observed in patients hospitalized with severe cases of influenza. Their findings suggest that anti-inflammatory treatment strategies for COVID-19 should also be aimed toward the IFN-I signaling pathway, in addition to targeting inflammatory molecules such as TNF, IL-1beta, and IL-6 that have been implicated in COVID-19. DOI: 10.1126/sciimmunol.abd1554

Researchers at the University of Pennsylvania proposed three distinct immune profiles—or immunotypes—that could help predict the trajectory of disease in severe COVID-19 patients and may ultimately inform how to best treat them. The first immunotype had robust CD4+ T cell activity, with modest activation of CD8+ T cells and peripheral blood lymphocytes. CD4+ and CD8+ act as the main inflammatory immune cells that work to clear viruses. The second immunotype was characterized mainly by a subset of CD8+ T cells known as EM and EMRA and a modest activation of CD8+ T cells, memory B cells, and peripheral blood lymphocytes. The third immunotype showed little to no evidence of an immune response to the infection. The work was published in Science. DOI: 10.1126/science.abc8511

By studying fifty COVID-19 patients, researchers in France identified a unique signature—a combination of deficiency in a response of a particular interferon, as well as exacerbated inflammation—in the most critically ill. They published their findings in Science. These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches, the authors argue. DOI: 10.1126/science.abc6027

Early results on the Moderna vaccine, mRNA-1273, show that it was generally well tolerated and prompted neutralizing antibody activity in healthy adults. mRNA-1273 is designed to induce neutralizing antibodies directed at a portion of the coronavirus "spike" protein, which the virus uses to bind to and enter human cells. Results were published in The New England Journal of Medicine. The interim analysis includes results of tests measuring levels of vaccine-induced neutralizing activity through day 43 after the second injection. Two doses of vaccine prompted high levels of neutralizing antibody activity that were above the average values seen in convalescent sera obtained from persons with confirmed COVID-19 disease. DOI: 10.1056/NEJMoa2022483

By surveying 114 patients who were diagnosed with COVID-19 over a six-week period at in Switzerland, researchers assessed severity of the loss of smell or taste, nasal obstruction, excessive mucus production, fever, cough and shortness of breath during COVID-19. They found that depressed mood or anxiety in COVID-19 patients are most closely associated with a loss of smell and taste rather than the more severe indicators of the novel coronavirus such as shortness of breath, cough or fever. They published their findings in The Laryngoscope. The authors suggest the novel possibility of emotional disturbance as a central nervous system manifestation of COVID‐19 given trans‐olfactory tract penetration of the central nervous system (CNS) by coronaviruses. DOI: 10.1002/lary.28964

To assess levels of human angiotensin-converting enzyme 2 (ACE2) in different patient populations researchers from the Masonic Medical Research Institute, the Broad Institute, the University of Pennsylvania, and Bayer US, used single nucleus sequencing technologies on human heart samples. They published their findings in Circulation. From these studies, they were able to conclude that the amount of the viral receptor is increased in patients with pre-existing cardiac conditions, but only in the beating cells of the heart, termed cardiomyocytes. The researchers found that the effect of anti-hypertension medications, termed ACE inhibitors, do not appreciably affect the levels of ACE2 in a way that would support any changes in clinical use of these medications. These data suggest that prior cardiovascular disease is a predominant driver of cardiomyocyte-specific increased transcription of ACE2, and may provide a pathological link for SARS-CoV-associated viral myocarditis. DOI: 10.1161/CIRCULATIONAHA.120.047911

University of Cambridge researchers introduced a SARS-CoV-2 infection screening program for hospital staff to investigate clusters of COVID-19 infections, informing infection control measures and breaking chains of transmission. The repeat testing has helped reduce the number of hospital-acquired infections, ensuring maximum safety for patients and staff as the NHS aims to re-start other services. Researchers have published details of these investigations in two peer-reviewed journals, Lancet Infectious Diseases and eLife. DOI: 10.1016/S1473-3099(20)30562-4

Industry Updates

Drawing on electronic health records from across its academic health system, University of California Health has developed a unified, secure data set for use in COVID-19 research. The HIPAA Limited Data Set consisting of clinical information with more than 460 million data points is accessible to researchers across the entire UC system, enabling them to rapidly compare treatment options from previous patients to help future patients. The University of California COVID Research Data Set (UC CORDS) simplifies the process a researcher would otherwise have to go through to have a critical mass of detailed clinical data and patient variables to make meaningful comparisons. Once the request is validated, researchers gain access to the systemwide data from UC Health’s five academic health centers. UC CORDS follows the U.S. Department of Health & Human Services definition of a HIPAA Limited Data Set and excludes key direct identifiers of the individual or of relatives, employers, or household members of the individual. Press release.

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