SARS-CoV-2 z-bio 2021-02-15 326

　　Recently, a team led by Cambridge researchers published an article in the journal Nature, reporting how they observed SARS-CoV-2 mutations in immunocompromised patients receiving restorative plasma therapy. In particular, they saw that the key mutations that led to another large-scale “blockade” of the United Kingdom also appeared in the new variant.

　　The  research team used a variant of the virus created in the laboratory and discovered specific changes in its genetic code that made the virus twice as infectious on cells as ordinary strains.

　　The spike protein structure on the surface of the virus gives it a characteristic coronal shape. The virus uses this protein to attach to the ACE2 receptor on the surface of the host cell, allowing it to enter the cell, hijacking its machinery, and making it replicate and spread in the human body. Most vaccines currently in use or being tried target spike proteins, and there is concern that mutations may affect the efficacy of these vaccines.

　　British researchers in the COVID-19 Genomics UK (COG-UK) Consortium led by Cambridge, UK have identified a special variant of the virus, including an important change that may make it more infectious: part of the spike protein The ΔH69/ΔV70 amino acid deletion in ΔH69/ΔV70 is one of the key changes of this variant.

　　Although ΔH69/ΔV70 deletions have been detected many times, until now, scientists have not seen them appear in patients. However, in a study published today in the journal Nature, researchers at the University of Cambridge documented how these mutations appeared in COVID-19 patients.

　　The related patient is a man in his 70s. He was previously diagnosed with borderline B-cell lymphoma and recently received chemotherapy, which means that his immune system is severely damaged. After admission, the patient was provided with a variety of treatments, including the antiviral drug remdesivir and convalescent plasma (plasma containing antibodies extracted from the blood of patients who successfully cleared the virus from the system). Although his condition initially stabilized, it began to deteriorate later. He was admitted to the intensive care unit for further treatment and eventually died.

　　During the patient’s hospitalization, a total of 23 virus samples were isolated, most of which came from his nose and throat. It was in these sequences that the researchers observed viral genome mutations.

　　Between the 66th day and the 82nd day after the initial two recuperation serums, the research team observed a significant change in the virus population. The variant with the ΔH69/ΔV70 deletion and the mutation of the spike protein called D796H became Advantage. Although this mutation initially seemed to have disappeared, it reappeared after the third remdesivir and convalescent plasma treatment. .

　　"The virus that ultimately won (with the D796H mutation and the ΔH69/ΔV70 deletion) initially prevailed in the rehabilitation plasma therapy, and was then replaced by other strains, but reappeared after resuming treatment."

　　Under strictly controlled conditions, the researchers created and individually tested viruses with ΔH69/ΔV70 deletions and D796H mutations. The combined mutations make the virus less sensitive to the neutralization of convalescent plasma, although it appears that the D796H mutation alone is responsible for the decreased sensitivity of antibodies in plasma. In the absence of plasma, only the D796H mutation can cause loss of infection, which is a typical mutation acquired by the virus to escape immune pressure.

　　The researchers found that the deletion of ΔH69/ΔV70 itself makes the virus twice as infectious as the previous superior variant. Researchers believe that the role of the deletion is to compensate for the loss of infectivity caused by the D796H mutation.

　　Professor Gupta added: “Given that both vaccines and treatments target the spike protein that we have mutated in our patients, our study raises the worrying possibility that viral mutations may defeat our vaccine.”