Omicron is a strain of coronavirus that appeared in early October 2021. Omicron is unusual because it has over 30 mutations in the spike protein that SARS-CoV-2 uses to attach and fuse with cells. These mutations affect the neutralizing activity of antibodies to coronavirus and, therefore, may reduce the effectiveness of vaccines.

Specific spike protein mutations increase Omicron’s ability to bind to the ACE2 receptor protein on the cell surface or help it evade the body’s immune system.

Omicron can evade the immune system that explains its rapid spread and poses a risk of reinfection after infection with other coronavirus strains.

Omicron captures ACE2 more strongly than previous strains. The N501Y and Q498R mutations found in Omicron increase the ability of the virus to bind to the ACE2 protein by almost 20-fold.

Other changes in the spike protein affect how Omicron enters the cell. Typically, the SARS-CoV-2 virus particle uses the cell membrane protein TMPRSS2. However, Omicron can enter cells without using TMPRSS2. Instead, it enters the cell after absorption by the endosome, the membrane vesicle. Omicron can infect more cells in the respiratory epithelium, making the virus more infectious at lower doses.

However, Omicron causes less severe disease. The data of South African scientists confirm this:

  • The number of patients treated in the hospital during the same early pandemic waves was 6342 in the third and 2351 in the fourth.
  • In the first three waves, 68-69% of patients with COVID-19 are hospitalized. In the fourth wave – 41.3%.
  • Significantly fewer patients with comorbidities were admitted to the fourth wave, and the proportion of patients with the acute respiratory disease was lower: 91.2% in the third wave and 31.6% in the fourth.
  • The proportion of patients requiring oxygen therapy has decreased significantly: 74% in the third wave and 17.6% in the fourth. The percentage of patients receiving mechanical ventilation has also reduced.
  • Admission to the intensive care unit was 29.9% in the third wave and 18.5% in the fourth.
  • The length of stay in the hospital has decreased: 7-8 days in previous waves and up to 3 days in the fourth wave.
  • The death rate has decreased: 19.7% in the first wave, 29.1% in the third wave, and 2.7% in the fourth.

Of the 971 patients admitted to the hospital during the fourth wave, 24.2% were vaccinated, 66.4% were not vaccinated, and 9.4% had an unknown vaccination status.

One of the reasons for the milder form of COVID-19 is that Omicron suppresses the interferon signaling pathway less. German scientists have shown that, unlike the Delta strain, Omicron activates interferon signaling, which may contribute to the lower pathogenicity of the virus.

Mutations that have appeared in the Omicron strain affect the effectiveness of the treatment of COVID-19. One of the methods of treatment is the introduction of monoclonal antibodies. French scientists examined 9 monoclonal antibodies and found that Omicron is entirely or partially resistant to neutralization by all tested antibodies.

Testing of antiviral drugs has shown that Omicron and Delta strains are equally sensitive to remdesivir, favipravir, ribavirin, nafamostat, camostat, aprotinin, molnupiravir, and nirmatrelvir. It shows that mutations in the Omicron strain do not significantly affect the effectiveness of drug therapy.

Conclusions

Mutations in the Omicron spike protein make it easier for the virus to enter the cell, making it more contagious.

Omicron can evade neutralizing antibodies. Therefore, vaccines and natural immunity are less effective. In addition, Omicron is resistant to treatment with monoclonal antibodies. However, Omicron mutations do not affect the effectiveness of drug therapy.

To a lesser extent than Delta, Omicron suppresses the interferon response. Therefore, COVID-19 occurs in a milder form.

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