Reinfection, more frequent serious outcome with the BA.5 variant; virus spike protein toxic to heart cells

By Nancy Lapid

(Reuters) – The following is a summary of some recent studies on COVID-19. They include research that deserves further study to corroborate the findings and that has not yet been certified by peer review.

Reinfections, serious consequences may be more frequent with BA.5

Compared to the earlier Omicron BA.2 subvariant, the currently dominant Omicron BA.5 is linked to a higher likelihood of causing a second SARS-COV-2 infection, regardless of vaccination status, suggests a Portuguese study.

From late April to early June, the researchers studied 15,396 adults infected with the BA.2 variant and 12,306 infected with BA.5. Vaccines and boosters were equally effective against both sublines, according to a report published Monday on medRxiv ahead of peer review. However, 10% of BA.5 cases were reinfections, compared to 5.6% of BA.2 cases, suggesting a reduction in the protection conferred by prior infection against BA.5 compared to BA.2, the researchers said. Additionally, the vaccines appeared to be less effective in reducing the risk of serious outcomes for BA.5 compared to BA.2.

“Among those infected with BA.5, booster vaccination was associated with a 77% and 88% reduction in the risk of hospitalization and death from COVID-19, respectively, while a higher risk reduction was found for BA.2 cases, with 93% and 94%, respectively,” the researchers wrote, while “COVID-19 booster vaccination still provides substantial protection against severe consequences after BA infection. 5,” they said, their findings provide “evidence to adjust public health measures during the BA.5 surge.”

Virus spike protein damages heart muscle cells

The spike protein on its surface that the coronavirus uses to enter heart muscle cells also triggers a damaging immune system attack, new research suggests.

The SARS-CoV-2 spike protein interacts with other proteins in heart myocytes to cause inflammation, researchers said Wednesday during a presentation at the 2022 American Heart Basic Cardiovascular Sciences Scientific Sessions. Association. In experiments with mouse hearts, comparing the effects of SARS-CoV2 spike proteins and spike proteins from a different and relatively harmless coronavirus, researchers found that only the SARS-CoV-2 spike protein caused dysfunction. heart, hypertrophy and inflammation. Additionally, they found that in infected heart muscle cells, only the SARS-CoV-2 spike interacted with so-called TLR4 (Toll-like receptor-4) proteins that recognize invaders and trigger inflammatory responses. In a deceased patient with COVID-19 inflammation, researchers found SARS-CoV-2 spike protein and TLR4 protein in heart muscle cells and other cell types. Both were absent in a biopsy of a healthy human heart.

“This means that once the heart is infected with SARS-CoV-2, it will activate TLR4 signaling,” Zhiqiang Lin of the Masonic Medical Research Institute in Utica, New York, said in a statement. “We have provided direct evidence that spike protein is toxic to heart muscle cells and narrowed down the underlying mechanism, as spike protein directly inflames heart muscle cells,” he told Reuters. “Further work is underway in my lab to test if and how the spike protein kills heart muscle cells.”

Omicron-targeted antibody combo nears human trials

A new combination of monoclonal antibodies can prevent and treat Omicron infections in monkeys, researchers reported Monday in Nature Microbiology.

The antibodies, called P2G3 and P5C3, recognize specific regions of the spike protein that the SARS-CoV-2 virus uses to enter cells. “P5C3 alone can block all SARS-CoV-2 variants that had dominated the pandemic until Omicron BA.2,” said Dr Didier Trono of the Swiss Institute of Technology in Lausanne. “P2G3 then comes to the rescue because it can not only neutralize all previous worrying variants of SARS-CoV-2, but it can also block BA.4 and BA.5,” he said. “P2G3 is even effective against some BA.2 or BA.4/BA.5 mutants able to evade bebtelovimab (Eli Lilly), the only clinically approved antibody still showing activity against BA.4 subvariants /BA.5 currently dominant.”

In laboratory experiments, mutations that could make SARS-CoV-2 variants resistant to P2G3 failed to escape P5C3, and P5C3 escape mutants were still blocked by P2G3, a said Trono. “Essentially, the two antibodies cover each other, with one filling in the gaps of the other and vice versa.”

Aerium Therapeutics plans to start testing the combination in humans next month, said Trono, one of the company’s founders. If larger trials ultimately confirm its effectiveness, the P5C3/P2G3 combination will be given by injection every three to six months to people who are immunocompromised and do not have a strong response to COVID-19 vaccines, the company said.

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(Reporting by Nancy Lapid; Editing by Bill Berkrot)

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