At a time when few genetic changes of SARS-CoV-2 had been described, researchers from Duke-NUS, A*STAR and the National Centre for Infectious Diseases, published two papers describing a new variant of the SARS-CoV-2 virus detected in Singapore, which resulted in milder infections compared with wild-type or ancestral virus infections.
The studies, which were published in the journals mBio and The Lancet, showed that out of the 92 patients with the wild-type virus, 26 required supplementary oxygen, 15 needed admitting to the intensive care unit, and 10 were placed on mechanical ventilation.
None of the 29 patients infected with the new variant, however, needed these interventions. Not only that, they also experienced a lower degree of fever, had more effective T-cell responses and better platelet regulation during the early phase of infection. Only when it came to sore throats did those infected with the new variant fare less well when compared with the group which was infected with the wild-type virus.
This variant had been identified by its deletion of 382 nucleotides, or RNA building blocks, in a section of the viral genome known as open reading frame (ORF) 7b and ORF8. A similar deletion of 29 nucleotides in ORF8 of the original SARS virus had been observed during the 2003 outbreak, resulting in a less infectious SARS-CoV-1 variant, though its severity had not been not examined.
However, evidence suggested that the ORF8 gene, a mystery protein of unclear function, could help the virus evade the immune system and its deletion may have helped to uncloak the virus to the immune system.
The researchers, Professors Gavin Smith and Wang Linfa, and then-Assistant Professor Yvonne Su from the Emerging Infectious Diseases Programme at Duke-NUS among them, noted that patients infected with the variant also had lower concentrations of widely released pro-inflammatory cytokines, chemokines and growth factors that are strongly associated with severe SARS-CoV-2 infections.
“These studies provide the first convincing data showing that an observed genetic change (mutation) in SARS-CoV-2 has affected the severity of disease in patients,” said Smith at the time.
“This further highlights the importance of tracking the genetic diversity of SARS-CoV-2 as the virus continues to evolve,” he added.
Elaborating on the significance of deletion such as this, Smith explains, “Strains like this — which make the virus less dangerous — have the potential to be used for human challenge studies”, referencing a type of study where healthy volunteers are deliberately infected with a virus to test vaccines and treatments.