In a major scientific study published in the international authoritative journal Cell, scientists from the University of North Carolina School of Medicine and the University of North Carolina Gillins School of Global Public Health characterized the specific ways of infection with SARS-CoV-2, the coronavirus that causes COVID-19. The coronavirus has largely infected the nasal cavity, where it replicates specific cell types and in cells at the lower end of the respiratory tract (including the lungs), the ability to infect and replicate is getting worse. The results of the
study show that the virus tends to be firmly firm in the nasal cavity first, but in some cases the virus is inhaled into the lungs, where it can cause more serious illnesses, including potentially fatal pneumonia.
"If the nasal cavity is the primary starting point that causes lung infection, then widespread use of masks to protect nasal passages and any therapeutic strategies to reduce nasal viruses, such as nasal irrigation or antiviral nasal sprays, are beneficial." said Richard Boucher, MD, Distinguished Professor of Medicine at the United Nations Medical Association School of Medicine and Director of the Massico Institute for Pulmonary Studies at the University of North Carolina School of Medicine.
Another co-senior author of the study is Dr. Ralph Baric, Ph.D., who is the distinguished professor of epidemiology at the University of North Carolina’s Jillins School of Global Public Health.
"This is a landmark study that reveals new and unexpected insights into the mechanisms of disease progression and severity regulation after SARS-CoV-2 infection." Baric said, who also serves as a professor in the Department of Microbiology at the University of North Carolina School of Medicine. "In addition, we describe a new SARS-CoV-2 reverse genetic platform that allows us to obtain key virus indicators that will support vaccine development efforts in various countries aimed at controlling the spread and severity of this terrible disease."
SARS-CoV-2 first broke out in China in late 2019, and then appeared one after another around the world, infecting nearly 6 million people and over 350,000 deaths. Of these infections and deaths, the United States is particularly serious, accounting for nearly one-third.
The team at the University of North Carolina at Chapel Hill in their study tried to better understand some aspects of the virus, including which cells it infects the airway and how it enters the lungs of people with pneumonia.
In a set of laboratory experiments, the researchers used different SARS-CoV-2 isolates to observe how they effectively infect cultured cells in different parts of the human airway. They found a significant pattern of continuous change, from the higher infectivity of SARS-CoV-2 in nasal passage cells, to the lower infectivity of throat and bronchial cells, to the lower infectivity of lung cells.
Scientists also found that ACE2—the cell surface receptor used by the virus to enter cells—is more in nasal mucosal cells and less in the lower respiratory tract cell surface. This difference can explain, at least to some extent, why upper respiratory nasal mucosa cells are more susceptible to infection.
Other experiments focus on TMPRSS2 and furin (furin), two protein lyases found on many human cells. SARS-CoV-2 is believed to use these two enzymes to reshape key viral proteins and enter human cells. Experiments have confirmed that when these human enzymes are more abundant, this special coronavirus can infect cells and replicate itself with enhanced ability.
researchers found that this virus can infect respiratory cells called epithelial cells and to some extent infect all important "pulmonary cells" that help transfer the inhaled oxygen into the blood. However, SARS-CoV-2 hardly infects other respiratory cells.
Interestingly, although these cells express both ACE2 and TMPRSS2, the virus does not infect respiratory cells called secretory cells. In addition, the susceptibility of the same type of airway epithelial cells from different human donors, especially lower airway epithelial cells, tends to differ significantly in their susceptibility to infection.These findings suggest that there are undetected factors in airway cells that help determine the individual’s infection process—from mild or asymptomatic to respiratory failure and death—this process varies greatly.
research team mapped the locations of lung coronavirus infection in several patients who died of COVID-19, and found that these locations exhibited some degree of incompleteness and other characteristics, consistent with the hypothesis that these locations originated from infection in higher parts of the respiratory tract.
Inhalation of oral contents into the lungs is an important cause of COVID-19 pneumonia This hypothesis is consistent with the observation that people at high risk for severe lung disease (older, obese, and diabetics) are more likely to inhale, especially at night.
The team also found that the previously described individual antibodies that neutralize the 2002 SARS coronavirus and the MERS coronavirus that has been slowly spreading in Middle East since 2012 did not neutralize SARS-CoV-2. However, in 2002, 2 of 5 SARS patients had serum levels shown lower levels but significantly neutralizing SARS-CoV-2 infectivity in cells cultured in vitro. These data suggest that people exposed to other coronaviruses may carry some other types of antibodies in their blood that at least partially protect the body from SARS-CoV-2 infection.
"These studies have adopted some novel and innovative approaches to open up new directions for future research on SARS-C0V-2 that can guide the development of therapeutic drugs and practices to reduce the spread and severity of COVID-19." said James Kiley, director of lung disease at the National Institutes of Health, , the Institute of Heart, Lung, and Blood.
Boucher, Baric and colleagues noted that their study, in addition to specific findings on respiratory SARS-CoV-2 infection, also involved the development of key laboratory tools, including a redesigned version of SARS-CoV-2 with fluorescent signals, which should play a role in future viral research.
Compilation/Foresight Economist APP Information Group
Original source:
https://medicalxpress.com/news/2020-06-sars-cov-infection-cells-nasal-cavity.html
https://www.cell.com/cell/pdf/S0092-8674(20)30675-9.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420306759%3Fshowall%3Dtrue
