Mutational Pattern, Impacts and Potential Preventive Strategies of Omicron SARS-CoV-2 Variant Infection

Figures & data

Figure 1 The schematic illustration of the mutational pattern of Omicron SARS-CoV-2 variant. Omicron variant harbors 60 mutations that can be substitution, deletion and insertion of amino acids. Most (thirty-four) of these mutations are concentrated in the S protein; of which nearly half of mutations (fifteen) are localized in RBD (a key part of S protein) and three mutations are found in S1/S2-cleavage site (required for viral entry). These mutations are linked with increased transmission potential, reinfection risk, immune or vaccine evasion, and diagnostic problem. The remaining Omicron mutations, which are less likely associated with the impacts of Omicron variant, are found in other non-S protein genomic region, including other structural proteins (E-, M-, and N-protein) and non-structural proteins (nsp) in ORF1ab region, as well as in ORF9b.

Abbreviations: E protein, envelope protein; M protein, membrane protein; N protein, nucleocapsid protein; nsp, non-structural protein; ORF, open reading frame; RBD, receptor binding domain; S protein, spike protein.

Table 1 Summary on the Efficacy of Different COVID 19 Vaccines Against Omicron SARS-CoV-2 Variant

Studies	Investigated Vaccine	Findings
Liu et al, 2021.^Citation10	YS-SC2-010 vaccine	The neutralization effect of immune serum from YS-SC2-010 vaccine on Omicron decreased by 6.29 folds as compared to D614G and other strains. But the immunization achieved high and long lasting (up to 20 months) neutralization against Omicron.
Collie et al, 2021.^Citation80	BNT162b2 vaccine	The vaccine efficacy against Omicron after two doses of BNT162b2 vaccine was 50–70%, which is lower than Delta variant (90–95%)
Arien et al, 2021^Citation84	BNT162b2 vaccine	A substantial reduction in neutralizing activity of human serum against Omicron in fully BNT162b2 vaccinated people when compared to the original Wuhan strain and Delta variants. The third dose of BNT162b2 vaccine confers effective neutralizing activity against Omicron. Vaccine-induced responses surpass naturally-acquired immunity but hybrid immunity (infection followed by vaccination) results in higher neutralization levels against Wuhan and Delta, but not against Omicron.
Rössler et al, 2021.^Citation54	Spikevax (Moderna, ChAdOx1 and BNT162b2 (Comirnaty, Pfizer/BioNTech)	Sera from vaccinated people neutralize the Omicron variant to a much lesser extent than other variants. Neutralization capacity against this variant was best maintained by the sera of super immune individuals (infected and vaccinated or vaccinated and infected), but to lesser than other variants
Hansen et al, 2021.^Citation83	BNT162b2 and mRNA-1273	Vaccine efficacy against Omicron variant is 55.2% and 36.7% within a month from primary vaccination with BNT162b2 and mRNA-1273 vaccines, respectively. The efficacy is greatly lowered against Omicron than Delta infection and declines rapidly just within a few months. But the efficacy is restored (54.6%) by booster BNT162b2 vaccine.
Nemet et al, 2021.^Citation55	BNT162b2 vaccine	Only limited neutralization activity is shown after two doses of BNT162b2 vaccine. But individuals who received the third dose shows considerable improvement in neutralizing the omicron variant.
Haveri et al, 2021.^Citation116	mRNA (Comirnaty) vaccine	High level of neutralizing antibody was detected after 6–9 months of booster vaccination. Subsequent administration of a single mRNA (Comirnaty) vaccine dose for previously infected persons induces strong antibody comparable to the levels following a Comirnaty booster dose.
Wilhelm et al, 2021.^Citation52	ChAdOx1, mRNA1273 and BNT162b2 vaccines	Little or no vaccine efficacy against Omicron was observed using sera from heterologous ChAdOx1 and BNT162b2 vaccinated individuals. The neutralization capacity of Omicron was 20-fold and 32.8-fold reduced using sera from double mRNA1273-vaccinated and double BNT162b2-vaccinated individuals, respectively. The BNT162b2-booster after primary vaccination showed a significant increase of neutralization titers albeit with a 27.1-fold reduction in neutralization against Omicron.
Schubert et al, 2021.^Citation63	BNT162b2 vaccine	A highly reduced RBD binding and neutralization of Omicron by the sera from BNT162b2 vaccinated persons. But no change has been observed in RBD binding and immune response by the BNT162b2 booster as compared to fully vaccinated people.
Dejnirattisai et al, 2021.^Citation44	ChAdOx1 and BNT162b2 vaccine	Vaccination with two homologous BNT162b2 or ChAdOx1 doses provides no or limited protection against Omicron. The neutralizing titers on sera from homologous ChAdOx1 were reduced below the detectable level, while neutralizing titers on sera from homologous BNT162b2 was above the detection threshold but reduced by 29.8-fold.
Andrews et al, 2021.^Citation71	ChAdOx1 and BNT162b2 vaccine	Two doses of BNT162b2 or ChAdOx1 vaccinations are inadequate to protect against the Omicron variant. The vaccine efficacy after two BNT162b2 doses was 88.0% after 2–9 weeks of the second dose, lowering to 34–37% from 15 weeks after second dose. But there was no observed effect against Omicron from 15 weeks after double doses of ChAdOx1 vaccine. After two weeks of boosting with BNT162b2, the vaccine efficacy against Omicron increased to 71.4% and 75.5% for ChAdOx1 and BNT162b2 primary course recipients, respectively.
Basile et al, 2021.^Citation81	BNT162b2 vaccine	Two doses of BNT162b2 have limited ability to neutralize SARS-CoV-2 but the neutralization titers are boosted by third dose (but at reduced level).
Schmidt et al, 2022.^Citation53	Ad26 and mRNA (BNT162b2 or Moderna) vaccine	Neutralizing antibody titers against Omicron were significantly low in Ad26 vaccine or two dose mRNA vaccine recipients. Sera from recipients of two mRNA vaccine doses were reported to be 30–180-fold less potent against Omicron than Wuhan-hu-1. The vaccine boosters significantly ameliorate SARS CoV-2 neutralization titers. Administering an extra mRNA (BNT162b2 or Moderna) vaccine booster dose to previously infected or two-mRNA dose vaccinated individuals increases neutralizing activity against Omicron by 38–154-fold.
Gruell et al, 2021.^Citation82	BNT162b2 vaccine	Lack of neutralizing activity against Omicron in polyclonal sera from persons vaccinated with two doses of BNT162b2 vaccine but mRNA booster immunizations improve serum neutralization against Omicron
Hoffmann et al, 2021.^Citation85	ChAdOx1 and BNT162b2 vaccines	Omicron evades antibody neutralization from BNT162b2-vaccination with 10–44-fold higher efficiency than the Delta variant. Neutralization of Omicron by antibodies induced by heterologous ChAdOx1/BNT162b2-vaccine or three doses of BNT162b2 was more efficient, but less than the Delta variant.
Yu et al, 2021.^Citation88	BBIBP-CorV	The neutralization activity against Omicron after two BBIBP-CorV doses declined quickly and could hardly be detected. The booster BBIBP-CorV vaccine enhances the neutralization titer by 6.1-folds after 28 days of the second dose, albeit with 20.1-fold reduction relative to the wild-type strain.
Cele et al, 2021.^Citation73	Pfizer BNT162b2	Vaccine efficacy for preventing Omicron infection is 73% for vaccinated and previously infected individuals and 35% for vaccinated only. Efficacy against severe disease is estimated to be 95% for vaccinated and previously infected individuals and 77% for vaccinated only.

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