United States: Surge in the infections associated to SARS-CoV-2 – the virus responsible for COVID-19 – has been found to be responsible for infections in more types of lung cells. The conclusion has been made by the health experts of scientists at Sanford Burnham Prebys, University of California and their international collaborators.
In addition to this, the research team has for the first time concluded that lung can independently muster the inflammatory antiviral response without any help from the immune system when an individual is suffering from SARS-CoV-2.
The conclusions have been drawn during a time when the risks linked to COVID-19 infection have been increasing due to a surge in cases. It is to be noted that more than half of the US states have been reporting “high” to “very high” levels of COVID infections, according to the reports by the Centers for Disease Control and Prevention, according to the reports by medicalxpress.com.
While addressing the concern, the director of the Center for Stem Cells and Regenerative Medicine and a professor in the Human Genetics Program at Sanford Burnham Prebys, MD, PhD – Evan Snyder said, “Headlines have come and gone, but SARS-CoV-2 and COVID-19 have never left. And neither have the scientists studying it.”
Along with this, a neonatologist at Rady Children’s Hospital-San Diego and an associate professor of Pediatrics at UC San Diego School of Medicine, MD, MSc – Sandra Leibel stated, “While many people experience mild or moderate symptoms, COVID-19 still kills,” adding, “This virus is here to stay, and we need to learn everything we can about it so we can improve treatment and prevention.”
The researchers published their new discoveries about COVID-19 and the SARS-CoV-2 virus in a paper in Proceedings of the National Academy of Sciences.
Researchers employed a methodology to transmute patient-derived cells into entities reminiscent of stem cells. These embryonic cells—termed induced pluripotent stem cells (iPSCs)—possess the potential to differentiate into various human cell types. The researchers orchestrated their development into an assemblage of diverse lung cell phenotypes arranged in a manner that emulates the human pulmonary structure on a diminutive scale.
Snyder, while explaining the same, mentioned, “With most models for studying respiratory infections, you can’t isolate a specific cellular response because you have all the immune system cells rushing in to help deal with the invaders,” as reported by medicalxpress.com.
Along with this, Leibel added, “Using our lung organoids or ‘mini lungs,’ another benefit is that we can choose the sex of the cells, so we’re not just studying male-dominant or female-dominant lung tissue. This is important, as we know that the lung responds differently during disease if you’re a female or a male.”
Furthermore, the research team was able to generate iPSCs from patients of diverse racial and ethnic backgrounds to delve into the disparities observed in this and other diseases, considering infection susceptibility, disease severity, and medication responsiveness.
The scientists discovered that SARS-CoV-2 could acutely infect many previously undocumented cell types within the mini lungs. This was consistent across different SARS-CoV-2 strains, although some strains demonstrated a greater ability to infect specific cell types.
“Historically, it was believed that SARS-CoV-2 primarily infected cells with certain receptors, particularly those featuring the ACE2 receptor known to bind with the notorious spike protein of the virus,” explained Snyder. “Our research showed that when a direct entry pathway was unavailable, the virus could breach the cell membrane directly.”
Leibel added, “Considering the delta variant induced more severe symptoms, and the omicron variant was less lethal but more contagious, we hypothesized that delta might target deeper alveolar cells in the lungs, while omicron would favor the upper airways. Despite all strains being capable of infecting various lung cell types, our observations confirmed these tendencies,” as per the reports by medicalxpress.com.
As the strains evolved, the scientists observed changes reported in patients, reflecting the shifting nature of the pandemic. Earlier strains like delta led to more fatal pneumonia by affecting lower lung cells, while later strains such as omicron targeted upper lung cells, resulting in fewer cases of pneumonia but more airway issues and sore throats. Consequently, the mini-lung model could help predict patient outcomes.
Beyond demonstrating the virus’s ability to infect cells previously considered safe, the researchers identified a method to block this unexpected invasion route. The team found that apilimod—a drug under investigation for cancer, ALS, dementia, and various viral infections—effectively obstructed SARS-CoV-2’s alternative entry into cells lacking traditional receptors.
Snyder stated, “Our data suggest that apilimod could be an early adjunct therapy to slow down infection and boost the effectiveness of other medications and the body’s innate immune response.”
In an additional unexpected finding, Leibel, Snyder, and their team discovered that the mini lungs have an intrinsic “first response” system to detect SARS-CoV-2. Despite lacking an immune system connection, the mini lungs demonstrated the ability to initiate similar biological and cell signaling responses to a viral threat, as seen in the presence of an immune system.
Snyder noted, “We found that lung cells can independently react to infection immediately and subsequently summon reinforcements from the immune system.”
Leibel added, “Our research shows that it’s not only immune cells over-activating and secreting excessive pro-inflammatory cytokines contributing to severe COVID-19 cases, but lung cells also play a significant role,” according to medicalxpress.com.
The scientists identified that this inherent antiviral response in the mini lungs was driven by an unexpected source: one of the four proteins that combine with fats to create a soap-like substance in the lungs’ air sacs, aiding in keeping them open during breathing. This substance, called surfactant, contains the protein surfactant protein B (SP-B), which proved to be crucial in the mini lungs’ defense against SARS-CoV-2. No previous research had suggested SP-B’s involvement in cellular signaling.
“When we tested mini lungs engineered to lack SP-B, we observed a threefold increase in cells infected with SARS-CoV-2,” said Leibel. “However, when we treated these engineered mini lungs with SP-B, similar to how premature infants with surfactant deficiency are treated, we saw a reduction in viral infectivity.”
Snyder concluded, “These findings point to not just one but two potential novel drug applications involving surfactant in early COVID-19 treatment. This is significant, given that we currently only have two proven antiviral drugs—Paxlovid and remdesivir.”
The team plans to continue this research to understand precisely how surfactant protects cells from viral invasion. They are also investigating whether a rapid test for SP-B and certain characteristic pro-inflammatory cytokines could help quickly identify individuals at higher risk for severe COVID-19, as per medicalxpress.com.
Leibel added, “This could assist people in making informed decisions about traveling and attending public events during COVID-19 spikes and help physicians tailor treatments for those at increased risk of serious illness.”