Despite the end of the pandemic, COVID-19 continues to pose a serious health threat. Most individuals have established robust immune protection and do not develop severe disease but the infection can still lead to marked and sometimes long-lasting disease symptoms.
The researchers discovered that the pirola variant, in contrast the all previously circulating omicron variants, enters lung cells with high efficiency and uses the cellular enzyme TMPRss2 for entry, thereby exhibiting surprising parallels to variants alpha, beta, gamma and delta that circulated during the first years of the pandemic. The improved entry into lung cells might indicate that the virus is more aggressive but production of new, infectious viral particles in infected cells was reduced, which may limit spread and pathogenic potential.
The researchers report in the journal Cell that the pirola variant is resistant against all therapeutic antibodies and efficiently evades antibody responses in vaccinated individuals with and without breakthrough infection. However, the virus was appreciably inhibited by antibodies elicited by the new, XBB.1.5-adpated mRNA vaccine.
In summary, the results show that four years after the start of the pandemic the virus is still capable of profound changes and can reacquire properties that may promote the development of severe disease.
The spread of SARS-CoV-2 is associated with the constant emergence of new viral variants. These variants have acquired mutations in the spike protein, which allow evasion of neutralizing antibodies in vaccinated and convalescent individuals. The emergence of viral variants started with the alpha variant followed by the beta, gamma and delta variants.
At the end of the year 2021 the omicron variant became globally dominant, which, based on genome sequence, differed markedly from previously circulating variants. However, the virus had to pay a price for this massive change. Thus, the omicron variant evades neutralizing antibodies and is transmitted with high efficiency but has lost the ability to efficiently use a host cell enzyme, the protease TMPRSS2, for lung cell entry. As a consequence, the omicron variant induces pneumonia less frequently.
Pirola: A quantum leap in SARS-CoV-2 evolution
Descendants of the omicron variant dominated globally until the end of the year 2023. New variants frequently differed only by few mutations from their predecessors and there was evidence that viruses circulating in 2023 had only limited options to evade antibody pressure in the human population. Therefore, the discovery of a new SARS-CoV-2 omicron subvariant, pirola (BA.2.86), which, based on genome sequence, strongly differed from other circulating viruses drew a lot of attention.
The pirola variant, analogous to the omicron variant, likely arose in immunocompromised patients and presents a quantum leap in SARS-CoV-2 evolution. The spike protein of the pirola variant harbors more than 30 mutations relative to its precursor variant, BA.2, and it is largely unknown how these mutations affect the biological properties of the virus.
A team of researchers from the German Primate Center (DPZ) led by Markus Hoffmann and Stefan Pöhlmann addressed this question jointly with the research groups of Christian Drosten (Charité, Berlin), Georg Behrens (Hannover Medical School), Luka Cicin-Sain (Helmholtz Center for Infection Research, Braunschweig) and Hans-Martin Jäck (Friedrich-Alexander-University Erlangen Nuremberg).
Pirola can infect lung cells more efficiently
The researchers discovered that the pirola variant, in contrast to all previously circulating omicron subvariants, enters lung cells with high efficiency and in a TMPRSS2-dependent manner. Further, they could demonstrate that mutations S50L and K356T in the spike protein of the pirola variant are important for the highly efficient lung cell entry.
“It is noteworthy that two years after the global dominance of the omicron variant, which fails to robustly enter lung cells, now a quite different virus is spreading and that this virus is able to again enter lung cells with high efficiency. If the augmented lung cell entry translates into more severe disease upon infection with the pirola variant remains to be investigated in animal models,” says Pöhlmann, head of the Infection Biology Unity of the German Primate Center.
Pirola replicates less well than its predecessors
SARS-CoV-2 infected cells produce new virus particles many of which, but not all, are able to infect new cells. The researchers provided evidence that cells infected by the pirola variant are less well able than cells infected with previous variants to produce intact viral particles. “The relatively inefficient production of infectious particles by cells infected with the pirola variant was surprising,” says Hoffmann, the lead contact of the study.
“It will be interesting to analyze which mechanism is responsible. Maybe the infected cells produce defective interfering particles, which regulate spread of the pirola variant and contribute to antibody evasion.”
Therapeutic antibodies are ineffective against pirola
Recombinantly produced neutralizing antibodies were successfully used for COVID-19 prophylaxis and therapy. However, due to the emergence of viral variants with mutations in the antibody binding sites most of those antibodies are not active against currently circulating variants. The present study shows that the pirola variant is no exception—none of the tested antibodies was able to neutralize the virus.
“These results show that the development of new, broad spectrum antibodies is an important task,” says Hoffmann.
New, adapted vaccine protects against pirola
The pirola variant was also able to evade antibodies induced by vaccination or infection but with less efficiency than the contemporaneously circulating Eris variant (EG.5.1). However, antibodies induced by vaccination with the new XBB.1.5-adapted vaccine were able to appreciably inhibit both the pirola and the Eris variant.
“These results suggest that the XBB.1.5-adpated vaccine might induce a robust, although likely short-lived, protection against infection with the pirola variant,” says Hoffmann.
“In this context it is interesting that subvariants of pirola are currently globally on the rise that harbor an additional mutation in the spike protein, which may increase antibody evasion. The virus is in the process of optimizing itself and the consequences of this optimization should be studied,” adds Lu Zhang, first author of the study.
More information: Lu Zhang et al, SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency, Cell (2024). DOI: 10.1016/j.cell.2023.12.025
News
Completely New Use Discovered – This Traditional Herb Has Remarkable Nerve Regenerative Properties
Blessed thistle (Cnicus benedictus), a member of the Asteraceae family, thrives in our climate. This plant has been utilized for centuries as a medicinal herb, often consumed as an extract or tea to support [...]
Scientists study lipids cell by cell, making new cancer research possible
Imagine being able to look inside a single cancer cell and see how it communicates with its neighbors. Scientists are celebrating a new technique that lets them study the fatty contents of cancer cells, [...]
Antibiotic Breakthrough: Revolutionary Chinese Study Paves Way for Superbug Defeating Drugs
New research reveals that fluorous lipopetides act as highly effective antibiotics. Bacterial infections resistant to multiple drugs, which no existing antibiotics can treat, represent a significant worldwide challenge. A research group from China has [...]
Signs of Multiple Sclerosis Show Up in Blood Years Before Symptoms Appear
UCSF scientists clear a potential path toward earlier treatment for a disease that affects nearly 1,000,000 people in the United States. By Levi Gadye In a discovery that could hasten treatment for patients with multiple [...]
Advanced RNA Sequencing Reveals the Drivers of New COVID Variants
A study reveals that a new sequencing technique, tARC-seq, can accurately track mutations in SARS-CoV-2, providing insights into the rapid evolution and variant development of the virus. The SARS-CoV-2 virus that causes COVID has the unsettling [...]
No More Endless Boosters? Scientists Develop One-for-All Virus Vaccine
End of the line for endless boosters? Researchers at UC Riverside have developed a new vaccine approach using RNA that is effective against any strain of a virus and can be used safely even by babies or the immunocompromised. Every [...]
How Are Hydrogels Shaping the Future of Biomedicine?
Hydrogels have gained widespread recognition and utilization in biomedical engineering, with their applications dating back to the 1960s when they were first used in contact lens production. Hydrogels are distinguished from other biomaterials in [...]
Nanovials method for immune cell screening uncovers receptors that target prostate cancer
A recent UCLA study demonstrates a new process for screening T cells, part of the body's natural defenses, for characteristics vital to the success of cell-based treatments. The method filters T cells based on [...]
New Research Reveals That Your Sense of Smell May Be Smarter Than You Think
A new study published in the Journal of Neuroscience indicates that the sense of smell is significantly influenced by cues from other senses, whereas the senses of sight and hearing are much less affected. A popular [...]
Deadly bacteria show thirst for human blood: the phenomenon of bacterial vampirism
Some of the world's deadliest bacteria seek out and feed on human blood, a newly-discovered phenomenon researchers are calling "bacterial vampirism." A team led by Washington State University researchers has found the bacteria are [...]
Organ Architects: The Remarkable Cells Shaping Our Development
Finding your way through the winding streets of certain cities can be a real challenge without a map. To orient ourselves, we rely on a variety of information, including digital maps on our phones, [...]
Novel hydrogel removes microplastics from water
Microplastics pose a great threat to human health. These tiny plastic debris can enter our bodies through the water we drink and increase the risk of illnesses. They are also an environmental hazard; found [...]
Researchers Discover New Origin of Deep Brain Waves
Understanding hippocampal activity could improve sleep and cognition therapies. Researchers from the University of California, Irvine’s biomedical engineering department have discovered a new origin for two essential brain waves—slow waves and sleep spindles—that are critical for [...]
The Lifelong Cost of Surviving COVID: Scientists Uncover Long-Term Effects
Many of the individuals released to long-term acute care facilities suffered from conditions that lasted for over a year. Researchers at UC San Francisco studied COVID-19 patients in the United States who survived some of the longest and [...]
Previously Unknown Rogue Immune Key to Chronic Viral Infections Discovered
Scientists discovered a previously unidentified rogue immune cell linked to poor antibody responses in chronic viral infections. Australian researchers have discovered a previously unknown rogue immune cell that can cause poor antibody responses in [...]
Nature’s Betrayal: Unmasking Lead Lurking in Herbal Medicine
A case of lead poisoning due to Ayurvedic medicine use demonstrates the importance of patient history in diagnosis and the need for public health collaboration to prevent similar risks. An article in CMAJ (Canadian Medical Association [...]