Omicron variant (B.1.1.529) of SARS-CoV-2: Threat for the elderly?

The evolvement of coronavirus variants is socially unacceptable but understandable in a world that has grown tired of playing defence against “severe acute respiratory syndrome coronavirus, SARS-CoV-2″. The new Omicron variant (B.1.1.529), a heavily mutated variant of SARS-CoV-2, was first detected in South Africa on 24 November 2021 from a specimen collected on 9 November 2021 [1]; it was declared as a variant of concern (VOC) on 26 November 2021. Omicron was detected in over 30 countries in a matter of days, to over 89 countries in a matter of weeks, and had become the predominant variant in most countries globally by year end 2021. According to the CDC director, Dr. Rochelle Walensky, “this is becoming a pandemic of the unvaccinated”; however, by the first week of January 2022 omicron was dominant even in those who were vaccinated. This is attributed to the fact that the omicron viral variant has more than 50 mutations, of which 30 are associated with the viral spike protein - a prime target for vaccine design (Table 1 and Fig. 1 A) [2,3]. A number of mutations have been detected in VOCs, including Alpha, Beta, Gamma, Delta and now the Omicron (Fig. 1B). There are three mutations at the furin cleavage site (P681H, H655Y and N679K) that helps the Omicron variant to replicate as well as increasing its transmissibility. T478K and N501Y mutations of the receptor binding domain (RBD) of the viral spike proteins are associated with an increased binding affinity of the virus. The majority of the mutations are associated with increased pathogenicity and the potential to escape infection-blocking antibodies (Table 1). However, the virus still relies on angiotensin converting enzyme 2 (ACE2) receptors for host cell entry. As such, existing pharmacotherapeutics, such as vaccines, should continue to be effective in reducing incidence, hospitalizations and deaths. To make matters even more complicated, two variants of Omicron have now been identified: the standard one, which is now referred to as BA.1/B.1.1.529.1, and a second variant, known as BA.2/B.1.1.529.2. BA.2 has been nicknamed 'Stealth Omicron' (Fig. 1A) because it differs from the 'standard' variety by not having the characteristic SGTF-causing deletion (Δ69–70) by which many PCR tests were able to detect it as an Omicron, or Alpha, variant [4].

Table 1

Genetic mutations of Omicron variant of SARS-CoV-2.

SARS-CoV-2 genome site	Mutation	Role	Same mutations in other VOCs
Furin cleavage site	P681H	Increases transmissibility andreplication	Alpha
Furin cleavage site	H655Y	Increases transmissibility andreplication	Gamma
Furin cleavage site	N679K	Increases transmissibility andreplication	Gamma
RBD	T478K	Increases the binding affinity of the virus	Delta
RBD	N501Y	Increases the binding affinity of the virus	Alpha, Beta and Gamma
N-terminal domain	T95I, G142D/Δ143–145	Evasion of antibodyneutralization	Delta
Outside of the spike protein	nsp6 deletion Δ105–107	Enhancedtransmissibility	Alpha, Bata and Delta

Fig. 1

(A) Genetic mutations of Omicron (BA.1) and stealth Omicron (BA.2) variant of SARS-CoV-2. Adopted from https://covdb.stanford.edu/page/mutation-viewer/#omicron under a Creative Commons Attribution-ShareAlike 4.0 International License. (B) The schematic diagram showing the spike mutations of five variants of concern (VOCs). Adopted under Creative Commons by 4.0 License from [17].

The potential of antibodies in the blood of 12 fully immunized individuals were assessed to determine their ability to neutralize Omicron [5]. Six of the samples had no prior exposure to COVID-19. The remaining six were diseased with the original Wuhan variant during the first endemic of SARS-CoV-2 in South Africa. The samples demonstrated very strong neutralization against the original SARS-CoV-2 variant, as expected. Antibodies from those who had been immunized with two doses of the mRNA Pfizer vaccine, however, showed a 40-fold decrease in neutralizing ability against Omicron. This evasion of immunity was not complete. Indeed, blood samples from five people revealed relatively high levels of anti-Omicron antibodies. In addition to being vaccinated, all five had originally been afflicted with SARS-CoV-2. This data adds to the body of evidence supporting the value of full vaccination for the prevention of reinfections in those who have already had COVID-19 [5,6].

Furthermore, booster (3rd) vaccine doses increase the vaccine's efficacy to around 80% as compared to insufficient protection against infection and mild disease caused by the Omicron variant. It might not be as significant as for Delta, but it is still a favourable outcome. Again, such findings suggest that reactivating the immune system after a pause results in increased resistance to new viral variants, and the booster is derived from the original virus. The immune system is extremely intelligent, and individuals gain both quantitative and qualitative advantages [7]. It is also worth mentioning that the Omicron variant lacks genetic changes in parts of its genetic code that are the focus of other elements of vaccine-induced immunity, such as T cells. T cells cannot prevent disease, but they can protect against more serious illness and death [6]. The existing vaccines produce lower levels of neutralizing antibodies against the Omicron variant, which suggests that elderly people are more susceptible to this variant, even those who are fully vaccinated, and a third booster dose may help [8].

The Omicron variant of SARS-CoV-2 represents a new threat to humans, resulting in a new pandemic. Youngsters who have not yet been immunized and aged individuals with chronic health conditions are more vulnerable to the infectious viral variants [9]. The clinical manifestations of the Omicron infectious disease are myalgia (muscle pain) and tiredness, accompanied by fever, sore throat, and cough. As these are prevalent health issues that patients mostly neglect, they give the virus ample incubation time, enabling them to become virulent enough to invade other parts of the body.

Three months ago most double-vaccinated elderly people were enjoying the lifting of restrictions and return to socializing and seeing family; however, with the Omicron surge it has been recommended to seniors that they adjust their plans and avoid large gatherings and public places. Omicron poses high risk to the elderly and booster shots are highly advisable. Even though Omicron has milder symptoms compared to the Delta variant, the elderly are still at high risk of serious complications given their immune system is not as robust and many have underlying disorders. Elderly people with comorbidities such as diabetes, hypertension, chronic heart failure or chronic obstructive pulmonary disease are more prone to serious disease, as their antibody levels usually become inadequate to fight such mutant viruses [10], [11], [12], hence the recommendation for booster vaccines. In the meantime, researchers are working on booster doses to improve efficacy against disseminated variants. Pfizer intends to seek FDA approval for its booster dose, which is believed to result in better neutralization of the Delta and Omicron variants. Antibodies, on the other hand, do not provide a complete picture of protective immunity. How other vaccine-elicited immune components, such as T cells, respond when challenged by the Delta variant is still unknown [13,14]. According to Andrew and colleagues [7], 2 doses of BNT162b2 (Pfizer) or ChAdOx1 (AstraZeneca) vaccines are not sufficient to provide adequate protection against infection with the Omicron variant; a booster dose of BNT162b2 provides a significant increase in protection against mild disease and is likely to offer greater protection against severe disease. According to NIH director, Dr. Francis Collins, the third booster dose will provide 25 times more protection against Omicron infection [6]. It is worth noting that researchers are keeping a close eye on lethality of this VOC. Though the Omicron variant would seem to be extremely transmissible, and it is still too early to draw firm conclusions, it is believed that breakthrough infections cause milder disease than Delta. However, there is still much ongoing research that may change our perception of the Omicron VOC and its pathogenic impact. Since the beginning of 2022, there has been an almost eight-fold increase of the global Omicron cases even after booster dosing for the elderly. A recent research study demonstrated that there are 88% changes of the viral escape from the USFDA-approved monoclonal antibodies for COVID-19 management [15]. Moderna has created two multivalent immunotherapies: mRNA1273.211, which is thought to contain several genetic changes found in both the Omicron and Beta variants; and mRNA1273.213, which is thought to contain a genetic variation found in the Omicron, Beta, and Delta variants [16,17]. There is surely a need for mutation-proof SARS-CoV-2 vaccines and monoclonal antibodies.

Contributors

All authors contributed to the conceptualization, design, writing, and editing of the article. All authors read, reviewed, and approved the final paper. All authors have read and agreed to the published version.

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Declaration of competing interest

The authors declare they have no competing interests with respect to the authorship and publication of this article.