Yale’s Akiko Iwasaki shows SARS-CoV-2 invades neurons
C$24.6M from Canadian government for translational studies on COVID-19 immunity, incidence; and Merck starts vaccine study
SARS-CoV-2 in neurons
Scientists led by Yale University’s Akiko Iwasaki showed in bioRxiv that SARS-CoV-2 can infect neurons and that brain infection is associated with stroke. In post-mortem brain tissue from patients who’d had severe COVID-19 complications, the researchers found SARS-CoV-2 spike protein in cortical neurons, around microvasculature and at the edges of ischemic infarct sites.
Though neurons express low levels of ACE2 mRNA, the virus’ host cell receptor, the team demonstrated that the cells express ACE2 protein, using both post-mortem brain samples and human induced pluripotent stem (iPS) cell-derived brain organoids. The virus was able to infect human iPS cell-derived forebrain cells, and mature neurons and neural stem cells in the organoids.
Infection led to cell death mainly in uninfected neighboring cells. Single-cell sequencing of the brain organoids showed that SARS-CoV-2 induced gene expression changes including metabolic alterations and induction of hyperoxia genes in infected cells. Uninfected, bystander neurons responded by upregulating hypoxia genes.
Canada funding 22 COVID-19 studies
Canada’s COVID-19 Immunity Task Force has partnered with the Canadian Institutes of Health Research (CIHR) to provide C$24.6 million ($18.7 million), of which C$12.4 million comes from the task force, to support 22 studies. The projects cover translational research on SARS-CoV-2 immunity and studies to determine the incidence of infection in various populations.
Merck starts vaccine trial
Merck & Co. Inc. (NYSE:MRK) has begun recruiting volunteers in Belgium for a Phase I/II trial evaluating the safety and immunogenicity of COVID-19 vaccine candidate V591. According to ClinicalTrials.gov, the double-blind study will enroll about 260 subjects ages 18-55 or ages 60 and older; and assess ascending doses of single and prime-boost regimens of the measles virus vector vaccine. The estimated primary completion date is April 26, 2022.
Updates on AstraZeneca vaccine trials
Multiple media outlets have reported that AstraZeneca plc (LSE:AZN; NYSE:AZN) CEO Pascal Soriot said in a Tortoise media event that it is still feasible for AZD1222 to gain approval by year-end despite the hold on the COVID-19 vaccine’s Phase III trial. AZ voluntarily paused the study Tuesday to investigate a single safety event. A similar safety event led to a brief trial pause in July that was not deemed vaccine-related, nor have been reports of demyelinating events in past trials of other vaccines (see “Demyelinating Syndromes Back in Spotlight”).
Separate media reports citing a statement from the Serum Institute of India said the vaccine manufacturer has paused trials in India, as directed by the Drugs Controller General of India, while AZ investigates the safety event.
AZ and Serum Institute did not respond to BioCentury in time for comment.
ACE2 – Angiotensin-converting enzyme 2