Mutation Making SARS-CoV-2 Milder Identified

The ∆382 mutation in the open reading frame 8 region of the SARS-CoV-2 genome leads to less severe infections and could possibly be used as a live attenuated vaccine.

AsianScientist (Aug. 22, 2020) – In a study published in The Lancet, scientists in Singapore identify a mutation in the SARS-CoV-2 genome linked to milder clinical outcomes. These findings have implications for the development of vaccines and therapies against COVID-19.

Like all viruses, SARS-CoV-2 is evolving over time. Previous studies have shown that the roughly 30,000 base pairs of the SARS-CoV-2 genome are accumulating mutations at a rate expected of RNA viruses; but instead of making the virus more dangerous as many fear, most of these mutations either do not change the resulting proteins or are even harmful to the virus. In fact, scientists have now found that patients infected with a strain with a specific mutation called ∆382 had milder symptoms than other patients infected with SARS-CoV-2.

The researchers, led by Professor Lisa Ng at Singapore’s Agency for Science, Technology and Research (A*STAR), identified this strain while screening patients admitted to public hospitals. They focused on a region of the virus genome known as open reading frame 8 (ORF8), since a deletion in the corresponding region of the SARS-CoV virus resulted in a variant that was not as efficient at replicating during the 2002-2003 outbreak.

“ORF8 is a hotspot for genetic variation in coronaviruses,” Ng told Asian Scientist Magazine. “However, the effects are different for different variants.”

Of the 131 patients screened, 22 percent were found to carry the ∆382 mutant virus, while a further eight percent carried both ∆382 and wild-type SARS-CoV-2. Patients with the ∆382 variant were not only less likely to need supplemental oxygen, but were also less likely to develop a severe symptom of COVID-19 known as hypoxia, where the body becomes oxygen-deprived.

Furthermore, patients infected with ∆382 had a more robust immune response, as judged by the levels of T-cell activation-associated cytokines such as IFN-γ, particularly during the early phase of the infection. This strong and early involvement of T-cell mediated immunity could help the body develop an effective antibody response, the authors suggested.

While the ∆382 variant was able to trigger a protective immune response, it crucially did not appear to lead to over-inflammation in the form of the ‘cytokine storm’ experienced by patients with severe COVID-19, where a high level of pro-inflammatory cytokines in the blood end up harming the patient. Accordingly, patients with the ∆382 variant had lower levels of growth factors associated with lung injury and regeneration, suggesting that the lungs of those patients were not severely damaged.

These results, which were obtained in collaboration with researchers at the National Centre for Infectious Diseases, Singapores Ministry of Health, Duke-NUS Medical School and the A*STAR’s Bioinformatics Institute, could lead to the development of a vaccine against COVID-19.

“This natural variant could be modified further into a live attenuated vaccine,” Ng said.

The article can be found at: Young et al. (2020) Effects of a Major Deletion in the SARS-CoV-2 Genome on the Severity of Infection and the Inflammatory Response: an Observational Cohort Study.


Copyright: Asian Scientist Magazine; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Rebecca did her PhD at the National University of Singapore where she studied how macrophages integrate multiple signals from the toll-like receptor system. She was formerly the editor-in-chief of Asian Scientist Magazine.

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