Study Finds COVID-19 Attack On Brain, Not Lungs, Triggers Severe Disease In Micehttps://medicalxpress.com/news/2021-01-covid-brain-lungs-triggers-severe.htmlGeorgia State University biology researchers have found that infecting the nasal passages of mice with the virus that causes COVID-19 led to a rapid, escalating attack on the brain that triggered severe illness, even after the lungs were successfully clearing themselves of the virus
Assistant professor Mukesh Kumar, the study's lead researcher, said the findings have implications for understanding the wide range in symptoms and severity of illness among humans who are infected by SARS-CoV-2, the virus that causes COVID-19.
"Our thinking that it's more of a respiratory disease is not necessarily true," Kumar said. "
Once it infects the brain it can affect anything because the brain is controlling your lungs, the heart, everything. The brain is a very sensitive organ. It's the central processor for everything."
Kumar said that early in the pandemic, studies involving mice focused on the animals' lungs and did not assess whether the virus had invaded the brain. Kumars' team found that virus levels in the lungs of infected mice peaked three days after infection, then began to decline. However, very high levels of infectious virus were found in the brains of all the affected mice on the fifth and sixth days, which is when symptoms of severe disease became obvious, including labored breathing, disorientation and weakness.
The study found virus levels in the brain were about 1,000 times higher than in other parts of the body.Kumar said the findings could help explain why some COVID-19 patients seem to be on the road to recovery, with improved lung function, only to rapidly relapse and die.
His research and other studies suggest the severity of illness and the types of symptoms that different people experience could depend not only on how much virus a person was exposed to, but how it entered their body.The nasal passages, he said, provide a more direct path to the brain than the mouth. And while the lungs of mice and humans are designed to fend off infections, the brain is ill equipped to do so, Kumar said.
Once viral infections reach the brain, they trigger an inflammatory response that can persist indefinitely, causing ongoing damage."The brain is one of the regions where virus likes to hide," he said, because it cannot mount the kind of immune response that can clear viruses from other parts of the body.
"That's why we're seeing severe disease and all these multiple symptoms like heart disease, stroke and all these long-haulers with loss of smell, loss of taste," Kumar said. "All of this has to do with the brain rather than with the lungs."
Kumar said that
COVID-19 survivors whose infections reached their brain are also at increased risk of future health problems, including auto-immune diseases, Parkinson's, multiple sclerosis and general cognitive decline."It's scary," Kumar said. "A lot of people think they got COVID and they recovered and now they're out of the woods. Now I feel like that's never going to be true. You may never be out of the woods."
Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice.
Viruses (2021)
https://www.biorxiv.org/content/10.1101/2020.12.14.422714v1.full--------------------------------------------------
COVID-19 Virus Triggers Antibodies From Previous Coronavirus Infections: Studyhttps://medicalxpress.com/news/2021-01-covid-virus-triggers-antibodies-previous.htmlThe results of a study led by Northern Arizona University and the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest the immune systems of people infected with COVID-19 may rely on antibodies created during infections from earlier coronaviruses to help fight the disease. The published findings appear today in the journal
Cell Reports Medicine.
... The researchers used a tool called PepSeq to finely map antibody responses to all human-infecting coronaviruses. PepSeq is a novel technology being developed at TGen and NAU that allows for the construction of highly diverse pools of peptides (short chains of amino acids) bound to DNA tags. When combined with high-throughput sequencing, these PepSeq molecule pools allow for deep interrogation of the antibody response to viruses.
"The data generated using PepSeq allowed for broad characterization of the antibody response in individuals recently infected with SARS-CoV-2 compared with those of individuals exposed only to previous coronaviruses that now are widespread in human populations," ...
In addition to characterizing antibodies that recognize SARS-CoV-2, they also examined the antibody responses of four older coronaviruses: alphacoronavirus 229E; alphacoronavirus NL63; betacoronavirus OC43; and betacoronavirus HKU1. These so called "common" coronaviruses are endemic throughout human populations, but usually are not deadly and cause mild upper respiratory infections similar to those of the common cold.
By comparing patterns of reactivity against these different coronaviruses, the researchers demonstrated that SARS-CoV-2 could summon immune system antibodies originally generated in response to past coronavirus infections. This cross-reactivity occurred at two sites in the SARS-CoV-2 Spike protein; the protein on the surface of virus particles that attaches to ACE2 proteins on human cells to facilitate cell entry and infection.
"Our findings highlight sites at which the SARS-CoV-2 response appears to be shaped by previous coronavirus exposures, and which have potential to raise broadly-neutralizing antibodies. We further demonstrate that these cross-reactive antibodies preferentially bind to endemic coronavirus peptides, suggesting that the response to SARS-CoV-2 at these regions may be constrained by previous coronavirus exposure," said Dr. Altin, adding that more research is needed to understand the implications of these findings.
... "Our findings raise the possibility that the nature of an individual's antibody response to prior endemic coronavirus infection may impact the course of COVID-19 disease," Dr. Ladner said.
Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with endemic human coronaviruses, Cell Reports Medicine, (2020)
https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(20)30244-5 ----------------------------------------