Understanding the Omicron Variant in the COVID-19 Pandemic

Abstract

The proposed chapter aims to provide an overview of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant and its potential effects on public health. The origins of coronavirus disease of 2019 (COVID-19) pandemic and the SARS-CoV-2 virus evolution through time will be briefly covered at the beginning of the chapter with an emphasis on the emergence of new variants. The next section will present an overview of Omicron, outlining where it was first identified, the key mutations that set it apart from prior variants, and how it has spread worldwide. In the following section, we will briefly discuss the evidence regarding Omicron’s rapid spread in comparison to other COVID-19 variants along with any possible implications in disease severity and hospitalization rates. The chapter also explores how Omicron could affect natural immunity and vaccination efficiency and will provide information on recent studies on the effectiveness of COVID-19 vaccines against Omicron. Finally, we will discuss public health responses to Omicron’s emergence and outline the effective strategies that can lessen its effects.

1. Introduction

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is believed to have originated in a seafood market in the city of Wuhan, China, in late 2019. The World Health Organization (WHO) declared the COVID-19 outbreak a global pandemic on March 11, 2020. The exact origin and transmission route of the virus are still under investigation by the scientific community, but it is believed to have originated in bats and may have been transmitted to humans through an intermediate host, possibly a pangolin [1, 2].

The SARS-CoV-2 virus has quickly spread to other parts of China and then to other countries around the world. The rapid and wide expansion of the virus was facilitated by its ability to be transmitted through respiratory droplets [3], and by the fact that infected individuals can exhibit mild symptoms or be entirely asymptomatic, thereby complicating efforts to identify and control its spread [4].

As of May 2023, the virus has infected more than 700 million people and caused almost 7 million deaths worldwide [5]. The pandemic has had a profound impact on the world, resulting in substantial disruptions across social and economic domains. Moreover, it has underscored the critical significance of preparedness in addressing future outbreaks of infectious diseases [6].

Like all viruses, SARS-CoV-2 can mutate as it replicates. Mutations are changes in the virus’s genetic material (RNA) that occur randomly and can result in new variants with different characteristics. Most of these mutations are harmless, but some may make the virus more infectious or resistant to immune responses [7].

Since the beginning of the pandemic, numerous SARS-CoV-2 variants have emerged, including the Alpha, Beta, Gamma, Delta, and Omicron variants [8]. These variants differ from the original strain of the virus in key genetic changes that affect the virus’s Spike (S) protein, which is used by the virus to infect human cells [9].

The Omicron variant was first identified in South Africa in November 2021. It has more than 50 mutations in its S protein, including many in the receptor-binding domain (RBD), which is the part of the S protein that attaches to human cells. Some of these mutations are similar to those seen in other variants, such as Delta, but others are unique to Omicron [10, 11].

These mutations are believed to make the virus more infectious and may also help it evade the immune system, including antibodies generated by vaccination or a previous infection [12]. According to preliminary findings, the Omicron variant has a greater risk of re-infection than the other variants. In South Africa, hospitalization rates are increased, and fewer people who needed oxygen support were presenting less severe symptoms as compared to previous variants [13].

It is important to note that SARS-CoV-2 will continue to evolve and mutate over time, and new variants may continue to emerge. Therefore, ongoing surveillance and research are critical to understand the impact of these variants and to develop effective strategies in order to control the spread of the virus and protect public health [14].

2. Overview of Omicron

Omicron (B.1.1.529) was first identified in Botswana, South Africa, and was classified on November 26, 2021, as a “variant of concern” by the World Health Organization due to its high number of mutations and potential impact on public health [10].

It was reported that Omicron was spreading at a much faster rate than Delta variant, with a basic reproduction number (R0) estimated to be 8.2. This means that each infected person could potentially transmit the virus to eight people [15].

The emergence of the Omicron variant has caused a new wave of infections with high hospitalization rates worldwide. This wave is distinct from those caused by earlier variants, and its peak is significantly higher [16]. Apart from B.1.1.529, multiple sub-lineages have been identified and studied, with over 100 subvariants estimated to exist. Among these subvariants are BA.1 and its sister-variant BA.2, and other diverse Omicron variants, such as BA.4, BA.5, BA.2.12.1, BA.2.75, BA.2.75.2, BQ.1, BQ.1.1, and BF.7. Additionally, several recombinant subvariants of Omicron, including XBB, XBB.1.5, and XBB.1.16, have emerged [17]. These subvariants exhibit unique characteristics and have been linked to diverse epidemiological patterns [18].

Sequencing analysis revealed that Omicron variant harbors several key mutations that differentiate it from earlier variants like Delta. BA.1 is a variant of concern due to its high number of mutations in the S gene, particularly in the receptor-binding domain and the N-terminal domain. These mutations can impact ACE2 binding and antibody recognition. The variant shares the deletion at positions S:H69- and S:V70- with Alpha and Eta, among others. It is noteworthy that del69-70 in the S protein is being explored as a diagnostic marker for Omicron, as the TaqPath PCR test yields negative results for the S gene in this variant but positive results for other SARS-CoV-2 variants [19]. There is a 3 amino-acid insertion (‘EPE’) at position 214 in the S protein, which is located in an area known as an “insertion hotspot” [20, 21, 22, 23]. A cluster of mutations at the S1-S2 furin cleavage site (S:H655Y, S:N679K, S:P681H) may be associated with increased transmissibility. The mutation at S:E484A is also present in other variants and mutations at this position have been linked to immune escape. The combination of mutations S:Q498R and S:N501Y has been shown to significantly enhance the binding affinity to ACE2 in in-vitro evolution studies [24, 25]. Additionally, there is a three amino-acid deletion in ORF1a at ORF1a:L3674-, ORF1a:S3675-, and ORF1a:G3676-. This deletion may affect innate immune evasion by compromising cells’ ability to degrade viral components [26]. The accessory protein ORF9b has a three amino-acid deletion at ORF9b:E27-, ORF9b:N28-, and ORF9b:A29-. ORF9b is believed to suppress the innate immune response by interacting with TOM70 and NEMO, ultimately impacting interferon production [27, 28, 29]. Lastly, two ancestral mutations in the Nucleocapsid protein, N:R203K and N:G204R, have been associated with increased subgenomic RNA expression and higher viral loads [30, 31]. Moreover, BA.2 and BA.1 share 38 mutations in both nucleotides and amino acids. However, BA.2 has an additional 27 unique mutations, while BA.1 has an additional 20 unique mutations. In the S protein alone, both variants share 21 amino acid mutations. BA.1 has 12 additional unique amino acid mutations, while BA.2 has six additional unique amino acid mutations, along with a deletion/mutation. It is important to note that BA.2 lacks the deletion del69-70. The six additional Spike mutations in BA.2 are S:T19I, S:V213G, S:S371F, S:T376A, S:D405N, and S:R408S. Additionally, there is a nine-nucleotide deletion (position 21,633–21,641) that leads to the deletions and mutation S:L24-, S:P25-, S:P26-, and S:A27S. The ORF1a:L3201F mutation has emerged multiple times within BA.2. In South Africa, where the variant is suspected to have originated, it is mostly present in its wild-type form. However, outside of South Africa, the ORF1a:L3201F mutation is more common. Therefore, sub-clades of BA.2 may or may not have the ORF1a:L3201F mutation depending on their lineage. The variant BA.4 appears to have arisen in late 2021, while BA.5 likely arose in early 2022. Both variant sequences were predominantly from South Africa, though now are detected globally. BA.4 and BA.5 have identical Spike proteins, leading researchers to group them together in studies focusing on Spike alone, such as antibody research. These variants share several Spike mutations with BA.1 and even more Spike mutations with BA.2. In fact, the Spike mutations in BA.2, BA.4, and BA.5 are mostly identical. The only difference is that BA.4 and BA.5 lack the S:Q493R mutation found in BA.2 and instead have S:L452R and S:F486V mutations. Furthermore, they share the deletion del69-70 with BA.1, which allows BA.4 and BA.5 to be detected through “S gene drop out” or “S gene target failure (SGTF)” in certain qPCR assays [32]. It is noteworthy that BA.4 and BA.5 formed >50% of the subvariants during June–July 2022 [33].

The BA.2.12.1 variant shares many Spike mutations with both BA.1 and BA.2 variants. Specifically, the Spike mutations of BA.2 and BA.2.12.1 are identical, except that BA.2.12.1 has two additional mutations at S:L452Q and S:S704L. In terms of amino-acid mutations outside of Spike, BA.2.12.1 does not have any additional mutations compared to BA.2. In South Africa, where this variant is believed to have originated, the wild type is most prevalent. Outside of South Africa, the ORF1a:L3201F mutation is more common. Therefore, sub-clades of BA.2 may or may not have the ORF1a:L3201F mutation, depending on whether they are descended from a part of BA.2 carrying this mutation. It is worth noting that the BA.4 and BA.5 variants, thought to have emerged in South Africa, do not possess this mutation, whereas BA.2.12.1, believed to have originated in North America, does have it. It is noteworthy that neutralizing titers against BA.2.12.1 were lower in vaccinated individuals who received the CoronaVac vaccine compared to BA.2. Additionally, BA.2.12.1 showed an increased affinity for binding to ACE2 receptors compared to BA.1 and other variants [34].

The variant BA.2.75 seems to have emerged in late spring 2022, potentially originating in India. By July 2022, most of the identified sequences of this lineage were found in India, but it has also been detected in various countries globally. BA.2.75 shares many Spike mutations with BA.1 and BA.2. It has the same Spike mutations as its parent, BA.2, except for S:G446S and S:R493Q , and it has additional mutations: S:K147E, S:W152R, S:F157L, S:I210V, S:G257S, S:G339H, and S:N460K. It does not have the MutationS:H69- and S:V70-deletion found in BA.4 and BA.2.12.1. Adintrevimab, bamlanivimab, casirivimab, and etesevimab were not effective against BA.2.75, but ragdanvimab, sotrovimab, and tixagevimab were effective. However, BA.2.75 showed higher resistance against cilgavimab and bebtelovimab compared to BA.2 [35]. BA.2.75 is more immune-evasive than BA.4/BA.5 in areas with previous Delta infection and may escape BA.2-induced immunity. It may also have higher ACE-2 binding affinity than BA.4/ BA.5 [36]. A study using donated blood from Sweden did not find greater immune evasion by BA.2.75 compared to BA.5 [37]. BA.2.75 subvariant was undergoing further mutations and forming a new subvariant known as BA.2.75.2, it comprises specific substitutions such as R346T, F486S, and D1199N, along with S:K444T and S:N460K [38].

BQ.1 variant probably emerged in mid-2022, potentially in central or western Africa. It gained attention in August as a notable variant and has since spread worldwide. BQ.1 shares all the mutations found in BA.5 but also has additional mutations. Within Spike, it has mutations at S:K444T and S:N460K, and the S:Q493R mutation found in its ancestor, BA.2, is reverted to S:Q493Q in BQ.1. Outside of Spike, it has mutations at ORF1a:Q556K, ORF1a:L3829F, ORF1b:Y264H, ORF1b:M1156I, ORF9b:P10F, and N:E136D. There is concern that BQ.1 may have an increased ability to evade existing immunity. Studies have shown a significant reduction in neutralization titers against BQ.1, especially in sublineage BQ.1.1, indicating the potential for immune escape. It can also escape certain monoclonal antibodies, making them likely ineffective against the variant. The mutation S:N460K is associated with neutralizing antibody evasion and is driving enhanced neutralization resistance and fusogenicity in BQ.1 and BQ.1.1 lineages [39, 40, 41]. Since late September 2022, China has been experiencing a continuous increase in COVID-19 cases, and this resurgence can be attributed to the emergence of a subvariant known as SARS-CoV-2 Omicron BF.7 (BA.5.2.1.7), which is a subtype of BA.5. This particular subvariant has been detected in several countries, including Belgium, China, Denmark, Norway, France, Germany, India, Mongolia, the United Kingdom (UK), and the United States (US) [42, 43]. The heightened transmission rate of the BF.7 subvariant can be attributed to the presence of novel mutations in its spike protein. Molecular modeling studies have shed light on how these mutations, namely K444T, F486S, and D1199N, affect the RBD of the spike protein, enabling antibody-mediated immune evasion. Additionally, BF.7 carries an additional mutation, R346T, in the spike protein, which is derived from the BA.4/5 subvariant. This specific mutation contributes to a 4.4-fold increase in resistance to neutralization compared to the original D614G variant. Notably, the R346T mutation in the BF.7 variant’s spike glycoprotein, especially within the RBD, has been associated with a heightened ability to evade neutralizing antibodies generated by vaccines or previous infections [43].

XBB is a recombinant variant composed of genetic material from two different parent variants, lineage BJ.1 and BM.1.1.1, parts of BA.2 and BA.2.75, respectively, with a breakpoint in the S1 region of the Spike subunit. The initial sequences were identified in August 2022 and originated from India. Since then, it has experienced significant global expansion. It has unique mutations S:V445P from BJ.1 and S:N460K from BM.1.1.1. This recombination likely occurred within a short region containing these mutations. Before the breakpoint, XBB carries all the mutations of its BJ.1 parent, and after the breakpoint, it carries all the mutations of its BM.1.1.1 parent. It also shares common mutations with the broader BA.2 lineage. Additional mutations found in XBB include S:V83A, S:Y144-, S:H146Q , S:Q183E, S:V213E, S:G339H, S:R346T, S:L386I, S:G446S, S:F486S, and S:F490S. It also has a unique synonymous mutation at A19326G.

Certain sublineages within XBB, such as XBB.1, have acquired additional amino acid mutations S:G252V and ORF8:G8*, which raise concerns about its ability to evade existing immunity.

Preliminary laboratory results indicate that XBB may have a higher potential to evade immune responses. A study showed a significant reduction in neutralization titers against XBB in vaccinated individuals while maintaining ACE2 binding affinity. It was also found that clinically available monoclonal antibodies Evusheld and Bebtelovimab are likely ineffective against XBB, and sublineage XBB.1 escaped all NTD-targeting neutralizing antibodies tested [39].

XBB.1.5 is a recombinant variant that descends from XBB, likely arose by October 2022, possibly in North America. As a result, XBB.1.5 shares the same mutations as XBB, along with a few additional mutations, including S:G252V and ORF8:G8*. Additionally, XBB.1.5 has a nucleotide mutation at position T23018C, which causes the S:F486S mutation in XBB to change to S:F486P. This change from S to P in the Spike protein has implications for ACE2 binding. Based on the Spike protein mutations in XBB.1.5, it is expected to have similar immune evasion properties as its parental lineages, XBB.1 and XBB, but with the potential for enhanced transmission due to the new S:F486P mutation. Studies have shown that neutralizing titers in vaccinated individuals with breakthrough infections were comparable between XBB.1 and XBB.1.5, but ACE2 binding was significantly stronger in XBB.1.5, suggesting a potential growth advantage for XBB.1.5 over XBB and XBB.1 [44]. Another study found minimal differences in neutralizing titers and fusogenicity among XBB, XBB.1, and 23A XBB.1.5 in vaccinated/infected individuals [45]. Furthermore, neutralizing antibody titers were similar between XBB.1.5 and XBB.1 in a study involving bivalently-boosted mRNA vaccine recipients [46].

The variant XBB.1.16 is descended from variant XBB. It likely emerged towards the end of 2022 or the beginning of 2023, possibly in Asia. XBB.1.16 shares the same mutations as XBB, with additional mutations including S:G252V and ORF8:G8*, as well as ORF1a:L3829F, ORF1b:D1746Y, ORF9b:I5T, and ORF9b:N55S.

Similar to XBB.1.5, XBB.1.16 has an additional nucleotide mutation resulting in the S:F486S mutation in XBB becoming S:F486P. This change affects ACE2 binding. Additionally, XBB.1.16 has unique synonymous mutations at T12730A, A14856G, and C29386T.

Based on the Spike protein mutations, XBB.1.16 is expected to have immune evasion properties similar to its parental lineages, XBB.1 and XBB, potentially enhanced by the S:F486P mutation and the RBD mutation S:T478R. The impact of the Spike mutation S:E180V is less certain.

Preliminary studies suggest that XBB.1.16 may evade immunity, similar to XBB.1.5, based on neutralizing titers against mRNA-vaccinated individuals with breakthrough BA.2/BA.5 infections. XBB.1.16 shows resistance to most monoclonal antibodies, except strovimab [47]. Binding affinity to the ACE2 receptor may be lower than XBB.1.5 but higher than XBB.1. It is estimated to have a higher reproductive number compared to XBB.1.5 and XBB.1 [47]. Early reports from India have indicated changing demographic and clinical associations with XBB.1.16 infections, including cases of conjunctivitis [48]. The WHO designated XBB.1.16 as a Variant of Interest (VOI) on April 17, 2023 [49].

3. Clinical characteristics and severity

The burden of COVID-19 on hospital services is determined by the prevalence and severity of SARS-CoV-2 variants, and modified by individual factors such as age, frailty, and vaccination status [50, 51].

Despite Omicron displaying only mild severity, its 3.31 times greater transmission rate than the Delta variant represents a global epidemic threat [52]. The clinical presentation of the Omicron variant differs from previous SARS-CoV-2 variants. The most common symptoms are a cough, runny nose, congestion, and fatigue. A sore throat and a hoarse voice were more prevalent during the Omicron outbreak. Individuals infected with Omicron are less likely to show at least one of the three classic symptoms of COVID-19: the loss of smell, a fever, and a persistent cough, which are associated with individuals infected with the Delta variant [53]. The Omicron variant outbreak has also resulted in a large number of asymptomatic carriers, which may have resulted in milder symptoms. In all age groups, respiratory discomfort is a typical sign. Vomiting is the most typical gastroenterological symptom, and children with Omicron infection aged 5–9 years old also frequently experience diarrhea and abdominal pains [54]. Children in the age group of 9–11 show less severe symptoms than infants do, which is valid for both Delta and Omicron variants [55]. The Omicron variant exhibited a lower replication rate in lung and gut cell lines but replicated faster in primary cultures of human nasal epithelial cells. Omicron has been reported to multiply faster in human airway organoids and ex vivo bronchus explant cultures, but less efficiently in human alveoli organoids and ex vivo lung explant cultures [56, 57]. These findings indicated that Omicron infected the upper respiratory system rather than the lungs, which might result in enhanced transmissibility and a better prognosis.

Across multiple studies, it has been consistently observed that Omicron-infected patients have lower hospital admission rates compared to other variants, regardless of their vaccination status or number of vaccine doses. Specifically, lower ICU admission rates have been reported among Omicron-infected patients compared to other variants, irrespective of vaccination status or vaccine doses. Moreover, Omicron-infected patients exhibit lower rates of oxygen therapies [58].

Empirical evidence from real-world scenarios indicates that vaccine effectiveness against symptomatic disease caused by the Omicron variant is lower and tends to deteriorate faster over time than with the Delta variant [59, 60]. However, Omicron infection still resulted in substantial patient and public health burden and an increased hospital admission rate of older patients with Omicron, which counteracts some of the benefit arising from less severe disease [61, 62, 63, 64, 65].

4. Immunity and vaccination

Vaccine effectiveness against severe diseases is a matter of concern. The vaccine’s effectiveness is not largely affected by the variants. This is because of the mutations of the variants, which hinder the neutralization potency of any vaccine. In the Omicron case, several mutations have been noted in the nAb binding region of the S protein, especially in RBD and NTD, which cause the nAb escape phenomenon. Therefore, we can say that the Omicron variant possesses a partial vaccine escape ability [23, 66].

Recent studies elucidate that the Omicron sub-lineages, BA.1, BA.2, and BA.3, are very competent in escaping the immune system. The subjects who have taken one or two doses of the vaccine cannot protect against these variants significantly, thus, the neutralization efficiency of the vaccines is gradually decreasing. Most surprisingly, people who had received three shots of the vaccine only have partial protection from the infection of these variants [41, 67, 68]. Moreover, certain Omicron subvariants such as BA.4.6, BF.7, BQ.1, BQ.1.1, and BA.2.75.2 displayed some level of enhanced neutralization resistance compared to their parental subvariants. Among them, BQ.1, BQ.1.1, and BA.2.75.2 demonstrated the strongest resistance [69]. These findings are consistent with another research where the sensitivity of BA.2.75.2, BA.4.6, and BQ.1.1 to six therapeutic monoclonal antibodies (mAbs) and 72 sera samples from individuals vaccinated with Pfizer BNT162b2 was investigated. It was observed that Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost their antiviral effectiveness against BA.2.75.2 and BQ.1.1 subvariants, while Xevudy (Sotrovimab) exhibited limited activity. Additionally, BQ.1.1 showed resistance to Bebtelovimab. The neutralizing titers in individuals who received three vaccine doses were either low or undetectable against BQ.1.1 and BA.2.75.2, four months after the booster shot. However, a breakthrough infection with BA.1/BA.2 led to an increase in these titers, albeit remaining about 18-fold lower against BA.2.75.2 and BQ.1.1 compared to BA.1. Conversely, a breakthrough infection with BA.5 resulted in a more efficient increase in neutralization against BA.5 and BQ.1.1 than against BA.2.75.2 [38]. Importantly, it was observed that the neutralization resistance of BQ.1 and BQ.1.1 was primarily driven by the N460K mutation, while the resistance of the BA.2.75.2 subvariant was determined by the F486S mutation. The N460K mutation was identified to enhance ACE2 interactions, potentially leading to increased cell-cell fusion and neutralization resistance when introduced into BA.4/5-derived subvariants [69]. Furthermore, it has been shown that the mutations R346T, K444T, and F486S play a crucial role in antibody recognition and potentially contribute to immune evasion through these specific alterations. Significantly, these mutations not only conferred resistance to sera induced by 3-dose mRNA vaccines but also to sera from individuals previously infected with BA.1 and BA.4/5 variants [70].

Vaccine escape is a common phenomenon. Several researchers urge the development of new vaccines against the Omicron variant. The study conducted by Pérez-Then et al. evaluated the effect of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of individuals who had previously received two doses of CoronaVac vaccine. The results showed that the heterologous CoronaVac prime followed by BNT162b2 booster induced high levels of virus-specific antibodies and potent neutralization activity against the SARS-CoV-2 Wuhan virus and Delta variant. However, neutralization activity against the Omicron variant was undetectable in those who had received two doses of CoronaVac. Following the BNT162b2 booster, neutralization activity against Omicron increased by 1.4-fold compared to two doses of mRNA vaccine, but the neutralizing antibody titers were still lower for Omicron compared to Wuhan virus and Delta variant. These findings suggest that countries using CoronaVac vaccines should consider mRNA vaccine boosters to combat the spread of Omicron and future emerging variants [71].

Rössler et al. conducted a study to evaluate the effectiveness of COVID-19 vaccines (mRNA-1273, ChAdOx1-S, and BNT162b2) against the Omicron variant. The results showed that individuals vaccinated with these vaccines had much lower neutralization levels against the Omicron variant compared to other variants (Alpha, Beta, or Delta). However, cross-neutralization persisted in individuals who had received the BNT162b2 vaccine or a heterologous ChAdOx1-S-BNT162b2 vaccine but not in those who had received the homologous ChAdOx1-S vaccine. Serum samples obtained from individuals who had received the mRNA-1273 vaccine 4–6 months after the second dose did not show any neutralizing antibodies against the omicron variant, but the interval between the second dose and sample collection was longer than for other vaccination-regimen groups [72].

A test-negative case-control study found that receiving three doses of mRNA COVID-19 vaccine was associated with protection against symptomatic infection caused by the SARS-CoV-2 Omicron and Delta variants. The study analyzed 70,155 tests from symptomatic adults and concluded that a third dose of the mRNA vaccine can increase the vaccine’s protective efficacy against both variants [73].

Lee and colleagues showed that previous infection in octogenarians followed by two doses of BNT162b2 resulted in strong neutralization of the omicron variant when compared to subjects who had only received two BNT162b2 doses [74]. In addition, a separate study measured the neutralization potency of serum from individuals who received two doses of mRNA-1273 or BNT162b2 vaccines or one dose of Ad26.COV2.S vaccine against Wuhan virus, Delta, and Omicron pseudoviruses [75].

Currently, several researchers or pharmacological companies have developed new vaccines against the Omicron variant [76]. ModernaTX has developed two mRNA-based bivalent vaccines, notably mRNA-1273.214 [77] and mRNA-1273.222. The safety and efficacy of the vaccine have been evaluated through a total of seven clinical trials and was approved in 38 and 33 countries, respectively. In addition to ModernaTX’s bivalent vaccine, Pfizer-BioNTech has also created a bivalent COVID-19 vaccine. Pfizer-BioNTech has developed the BNT162b2 (B.1.1.529) and BNT162b2 Bivalent (covid19.trackvaccines.org). A total of seven clinical trials have been conducted to understand these vaccines’ safety profile, ultimately, they were approved in more than 35 and 33 countries, respectively. These two bivalent vaccines’ safety profiles have also been assessed in kidney transplant recipients [78].

These findings highlight the worrisome evolutionary path of the Omicron subvariants, enabling their transmission in vaccinated populations, and raise concerns about the efficacy of most available monoclonal antibodies.

5. Public health responses

The continuous emergence of new variants of SARS-CoV-2 has consistently raised significant global public health concerns, leading to waves of the COVID-19 pandemic. This ongoing crisis has obliged countries to establish and maintain comprehensive public health measures aimed at detecting and managing emerging infectious threats. The unprecedented magnitude and duration of the pandemic have appropriately sparked inquiries into the key elements necessary for a strong and sustainable public health response [79]. The extent of the threat posed by the Omicron variant is primarily determined by four crucial inquiries: (i) the level of transmissibility exhibited by the variant, (ii) the effectiveness of vaccines and previous infection in preventing a new infection, transmission, clinical illness, and mortality, (iii) the virulence of the variant in comparison to other variants, and (iv) the population’s comprehension of these dynamics, their perception of risk, and adherence to control measures, including public health and social measures [80].

In order to mitigate the transmission of Omicron and other emerging variants, it is crucial to implement proposed preventive measures diligently, taking into account the lessons learned from previous waves of the COVID-19 pandemic. This includes conducting widespread confirmatory diagnosis, as well as global genomic surveillance and sequencing of a larger number of SARS-CoV-2 isolates. In-depth studies are needed to understand the higher transmissibility and pathogenicity acquired by emerging variants, focusing on SARS-CoV-2-host interactions, adaptation, evolutionary dynamics, and mechanisms of genomic mutation or variation. Strengthening medical research facilities and trained staff for gene sequencing, variant identification, and characterization is essential, along with a collaborative global approach to update genomic and epidemiological data repositories. These efforts will contribute to a more effective response to emerging variants [11, 81, 82, 83, 84, 85].

To safeguard the health of the global population and achieve herd immunity, it is important to enhance COVID-19 vaccination drives with equitable global access, wider acceptance, and reduced vaccine hesitancy. However, long-term protection and the attainment of herd immunity still face threats from the adverse effects of emerging variants on vaccine efficacy and protective immunity. The evaluation and adequate addressing of these challenges are necessary. COVID-19 vaccines, such as BNT162b2, mRNA-1273, CoronaVac, Sputnik V, and AZD1222, have demonstrated varying levels of prevention and protection against severe COVID-19 caused by VOCs. Strategic planning should prioritize the strengthening of vaccination efforts with highly effective vaccines and booster doses to limit the virus’s ability to acquire mutations. This is particularly important in low-income countries, where slow or delayed vaccination approaches could leave a larger susceptible population [86, 87, 88].

Strict adherence to recommended public health measures, including COVID-19-appropriate behaviors such as social distancing, wearing face masks, practicing hand hygiene, restricting movements, and avoiding mass gatherings, is crucial in preventing SARS-CoV-2 infection and the spread of variants. Special attention should be given to vulnerable groups, including the unvaccinated, elderly individuals, and those with underlying illnesses, to minimize the risk of infection and disease transmission. Making vaccination compulsory and emphasizing the importance of vaccination/immunization certificates for travel and crossing international borders can act as a protective measure against community transmission of emerging variants and mutants of SARS-CoV-2. Evaluating the transmissibility, severity, diagnostic test sensitivity and specificity, vaccine efficacy, and treatment effectiveness will aid in effectively addressing Omicron and future variant outbreaks [89, 90].

In response to the Omicron variant, many countries have implemented travel restrictions and other measures to limit the importation of new cases. The WHO and other health organizations are closely monitoring the situation and have established a global surveillance network to track the spread of the variant and coordinate efforts to contain the virus. Ongoing research is being conducted to understand the characteristics of the Omicron variant and develop new strategies to prevent and treat COVID-19, including new vaccines and treatments specifically designed for the variant. To support these efforts, the WHO has established a global task force to ensure equitable distribution of vaccines and treatments to all countries, particularly those with limited resources. Overall, the response to the Omicron variant has been a coordinated global effort to protect public health [91].

6. Conclusion

In conclusion, the emergence of the Omicron variant in the ongoing COVID-19 pandemic has presented us with new challenges and uncertainties. Throughout this chapter, we have explored the key aspects of Omicron, including its overview, severity, transmissibility, vaccination, immunity, and public health responses.

Omicron has demonstrated a higher degree of transmissibility compared to previous variants, leading to rapid surges in infection rates across the globe. The concerns surrounding the Omicron variant stem from its potential to evade specific immune responses and potentially diminish the efficacy of current vaccines. Nevertheless, it is important to emphasize the necessity of ongoing research and analysis in order to comprehensively grasp the implications of this variant.

The development and administration of effective vaccines remain crucial tools in our fight against COVID-19, including the Omicron variant. Vaccination efforts should be prioritized, focusing on optimizing booster doses and adapting existing vaccines to enhance their efficacy against emerging variants. Continued research and development will be essential in this pursuit, ensuring our ability to adapt and counter future challenges.

Public health responses have played a pivotal role in mitigating the impact of the pandemic, and this remains true for Omicron. Enhanced surveillance, testing, and contact tracing efforts are essential for early detection and containment. Swift and evidence-based policy decisions, including targeted restrictions and public health messaging, can help prevent further spread and protect vulnerable populations.

Despite the challenges posed by the Omicron variant, it is important to maintain a balanced perspective. Scientific advancements, global collaboration, and lessons learned from previous waves of the pandemic have equipped us with valuable tools and knowledge. By applying these insights, we can navigate this new phase of the pandemic with resilience and resolve.

In conclusion, our understanding of the Omicron variant is still evolving. Vigilance, flexibility, and a commitment to evidence-based decision-making will be crucial in managing its impact.

Acknowledgments

The author would like to acknowledge the support received from the National Center for Scientific and Technical Research in Morocco through the Scholarship of Excellence.

Conflict of interest

The authors declare no conflict of interest.