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COVID-19 is a viral disease caused by SARS-CoV-2. Various variants of SARS-CoV-2 were responsible for causing havoc worldwide resulting in approximately 6.9 million deaths across the globe to date. Since the end of 2021, Omicron (B.1.1.529) has been the recent most variant to be studied and understood to a greater extent. Omicron was found to be the most mutated variant, which enhanced its pathogenic characteristics. Its highly contagious nature and the ability to evade immunity have made it a cause of global concern. The variant also poses a serious risk of reinfection. Furthermore, vaccines developed in response to COVID-19 were found to be less successful with Omicron infections. For the development of targeted vaccines and efficient therapeutic methods, it is necessary to understand the pathogenesis of Omicron. Numerous studies have been conducted to analyze the molecular properties of this variant. This chapter summarizes the biological and molecular properties of this variant and its successive mutations. Further, the clinical traits of the variant, including its pathogenicity, transmissibility and response to body’s immune actions and vaccines are discussed. Precisely examining the mechanisms through which the variant infects and propagates inside the host can aid in preventing the illness and lead to successful management of its global spread.
Amity Institute of Biotechnology, Amity University, Noida, UP, India
*Address all correspondence to: khushigandhi5103@gmail.com
1. Introduction
Coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, China in December 2019. The patients infected with virus showed symptoms similar to severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), including cough, fever and chest discomfort. In January 2020, the whole genome sequence was performed on the novel coronavirus. The outbreak then reached its peak in China in February and later spread worldwide [1, 2]. Since then, there have been 770+ million confirmed cases and 6.9 million deaths globally [3]. Coronaviruses are RNA viruses belonging to the family Coronaviridae and order Nidovirales. Nidovirales are known to have large genomes, high replicative rate and exhibit various enzymatic activities [2].
Mutations are a natural phenomenon commonly seen during the course of replication. SARS-CoV-2 has a great capacity of undergoing mutations and resulting in antigenic changes over time. It is known to evolve at the rate of one substitution approximately every 11 days [4]. New variants of SARS-CoV-2 have hence emerged through accumulation of these mutations. These variations, however, contribute to increased transmissibility, disease progression and reduced treatment efficacy among other concerns [5]. Specific strains of SARS-CoV-2 have been declared as variants of concern (VOC) due to their highly infectious nature and ability to cause re-infections. These VOCs tend to have mutations that lead to alterations in receptor binding, higher transmissibility, reduced antibody neutralization, decreased therapeutic effects and potentially increased disease severity [6].
The first emerged VOC of SARS-CoV-2 is the Alpha (B.1.1.7) variant. It was first detected in the UK in September 2020. It showcased 14 non-synonymous mutations and three deletions. Eight of these were on the spike protein, resulting in increased affinity towards the ACE2 receptors through which the virus entered the host’s cells. The variant also showed higher viral load and mortality [4, 5, 7]. The Beta (B.1.351) variant was the next VOC, emerging in South Africa in October 2020. It too possessed nine mutations on the spike protein, with three being on the receptor binding domain (RBD). It exhibited increased transmissibility; however, similar effects were not seen in terms of disease severity and fatality [7, 8, 9]. The Gamma (P.1 or B.1.1.28), first detected in Brazil in January 2021, showed 10 mutations on the spike protein, with three on the RBD. The gamma variant significantly reduced treatment efficiency with previously used monoclonal antibody (mAb) cocktail showing reduced neutralization [5, 8, 10]. Fourth VOC of SARS-CoV-2—the Delta (B.1.617.2) emerged in India in May 2021. It had several mutations at the spike protein. Interestingly, along with the RBD, N-terminal domain (NTD) region of the spike protein also showed numerous amino acid alterations. This was not seen in the earlier variants. The Delta variant too showed reduced susceptibility to priorly used antibodies and exhibited a high transmissibility rate [8, 11, 12].
Omicron (B.1.1.529) is the recent most VOC of SARS-CoV-2. It was first reported in South Africa in November 2021. Omicron exhibited far more mutations than any other variant that emerged before it. It also demonstrated a very high transmission rate and by the beginning of December, it had spread worldwide, becoming the dominant variant of SARS-CoV-2. It contributed to 99.7% of the confirmed cases in the months of February and March 2022. Omicron could not only successfully escape immunological responses but also alter them. Antibodies formed from previous infections or vaccines offered little to no protection against the variant. Moreover, Omicron posed a high risk of reinfection. The only relief was the reduced severity of illness and hence reduced mortality. Over time, sub-variants of Omicron too emerged [4, 13, 14, 15, 16]. Specific mutations on structural proteins enabled Omicron to exhibit such attributes. Omicron’s molecular structure, mutations and pathogenic traits are discussed in detail later (Figure 1).
Figure 1.
Evolution of the VoCs of SARS-CoV-2. Mutations in the structural proteins, especially S protein of the SARS-CoV-2 led to the emergence of different variants, which because of their threatening nature, were titled variants of concern. SARS-C0V-2, severe acute respiratory syndrome [17].
The novel Beta coronavirus, SARS-CoV-2, is an enveloped virus with a single-stranded RNA as the genetic material [18, 19]. It primarily consists of four structural proteins—the membrane (M) protein, the envelope (E) protein, the spike (S) protein and the nucleocapsid (N) protein [20, 21]. The E protein aids in the formation of pentameric ion channels in the virus’s body while the M protein acts as the fundamental structural protein [20, 22]. The N protein plays an essential role in the packaging of the viral RNA in the helical nucleocapsid and formation of the liquid enveloped. It further interacts with the other structural proteins during virion assembly and aids in the virus’s replication [21]. S protein is made up of two subunits—S1 (head) and S2 (stem) [20, 22].
It is the S protein that plays the central role in the binding of the virus with the host’s ACE2 receptors, causing the integration of the membranes of the virus and the host cell [20]. The M protein, through the association with the host’s endoplasmic reticulum, aids in the formation of viral particles, which is performed by the virus’s RNA by using the host’s resources [23]. Thus, the structural proteins (found in the spike, membrane, envelope and the nucleocapsid) contribute to the virulence of SARS-CoV-2 and aid in higher pathogenicity and infectivity [5]. Other than this, the viral genome codes for 16 non-structural and 9 accessory proteins. The non-structural proteins (NSPs) are involved in the replication and translation of the viral RNA while the accessory proteins (ORFs 3a, 3b, 6, 7a, 7b, 8, 9b, 9c and 10) regulate the virus’s interaction with the host and aid in immunity evasion and virulence enhancement [20, 24].
The Omicron variant (B.1.1.529) of SARS-CoV-2, upon genome sequence analysis, was found to have numerous synonymous and non-synonymous mutations [25]. It has been the most mutated variant reported to date, with more than 60 substitutions, deletions and insertions [5, 26]. Most of the mutations were observed in the S protein—with 28 amino acid substitutions, 3 deletions and 1 insertion in the Omicron 21 K lineage [16, 26, 27]. The key mutations in the spike protein are: A67V, del69–70, T95I, del142–144, Y145D, del211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F [16, 25]. Figure 2 illustrates the mutations observed in the proteins of the Omicron variant.
Figure 2.
Omicron (B.1.1.529) mutation profile. S protein was found to be heavily mutated. Mutations depicted in red are known to enhance the binding affinity with ACE2 receptors, resulting in an increase in the infectivity of the variant. Mutations in green aid in immune evasion while mutations in blue promote viral replication leading to a high viral load and virulence. ORF, open reading frame; NTD, N-terminal domain; RBD, receptor binding domain; RBM, receptor binding motif; SD 1 and 2, sub-domains 1 and 2; S1/S2, Furin cleavage site; E, envelope; M, membrane; N, Nucleocapsid proteins [25].
These mutations in the S protein have been correlated with disease severity, infectivity and immune evasion [5]. Two mutations have been associated with S protein’s enhanced affinity to ACE2 receptors, thus improving the virus’s attachment to the host cell. Three mutations near the cleavage site may aid in boosting Omicron’s transmissibility [16, 28]. Moreover, 15 of these mutations have been discovered to be in the RBD (residues 319–541), which is the key target of the neutralizing antibodies (nAb) [16, 25, 29]. However, some studies showed that the current nAb will still bind with the mutated spike protein and the mutated RBD of Omicron had a low predisposition towards the antibodies. Hence, antibodies produced by previous SARS-CoV-2 infections or vaccines may still offer some protection against the Omicron variant [16, 30]. Interestingly Omicron exhibited no mutations in the accessory proteins, which are immunological regulators and are often heavily altered. This indicated the selection pressures on Omicron [31]. Further, while comparing the nucleotide changes in Omicron with other variants, Alpha variant was found to be the closest with an identity percentage of 99.63% [16, 32].
2.1 Subvariants of Omicron
Omicron is further classified into four sub-strains by WHO—BA.1, BA.1.1, BA.2 and BA.3. Each sub-strain has different properties with respect to their transmissibility, pathogenicity, growth and infectivity. BA.1 and BA.2 have significant differences in their mutations contributing to virulent attributes. Out of the two, BA.2 is the more transmittable (33% higher rate) and has a significant growth advantage. Five different mutations in the RBD of the spike protein are responsible for this enhancement [5, 33, 34]. Table 1 summarizes and compares the key characteristics of BA.1 and BA.2 sub-variants.
Comparative analysis between the Omicron sub-variants BA.1 and BA.2.
Certain differences in the mutations on the S protein of the sub-variants were observed, which resulted in differences in specific characteristics. This included a higher infectivity rate and pathogenicity in BA.2 sub-variant. However, both the sub-variants resulted in similar severity in cases and had a similar response against various vaccines and treatments [35, 36, 37, 38].
Even though all the sub-variants emerged around the same time, BA.1 dominated the cases worldwide. The reason still remains unclear, although some researchers attribute this to the spike protein variations, which regulate the virus’s entry into the host cell and its further propagation [39]. BA.3 has been predominantly observed in hospitalized patients, indicating higher disease severity. However, it caused the lowest number of cases out of the three [40]. BA.4 and BA.5 have also been identified as Omicron sub-variants [41]. All these variants are under study to understand the immunological resilience of Omicron [5].
SARS-CoV-2 transmits primarily through two methods—direct viral spread or droplet infection [5]. Omicron, similar to the other variants, infects the host cells in the similar fashion. However, it has a greater infectivity rate [27]. Numerous studies reported its high transmissibility, for instance, a study from South Africa reported doubling times of 3.38 d, while a study from the UK reported doubling times of 2–2.5 d, with the basic reproduction number more than 3 [42, 43, 44]. With respect to the Delta variant, Omicron is reported to have a 3.2 times higher transmission rate, with an average of 3 days as the doubling time [35, 45]. The mutations in the spike protein have been thought to contribute in making Omicron extremely contagious [16].
Various pieces of evidence have been provided by different studies to substantiate the above-made claim. For instance, an in vitro Chinese study used an AI model to show that the mutations at locations N440K, N501Y and T478K directly contributed to increased infectivity, with tenfold increase in Omicron with respect to the original SARS-CoV-2 variation and a double increase with respect to the Delta variant [46]. Another study found the combination of mutations N501Y and Q498R significantly enhance the S protein’s binding affinity to the ACE2 receptors [47]. Other mutations such as the N679K, D614G and P681H have also been associated with higher infectivity [16, 48].
SARS-CoV-2 infects humans through different cell types of the respiratory system such as the airway and alveolar epithelium cells, the vascular endothelial cells, etc. by binding to the ACE2 receptor [5, 49]. This binding, as discussed earlier, is facilitated by the spike protein. Studies even found high Omicron infection in cells possessing high number of ACE2 receptors [50]. However, Omicron has been found to follow a different route. Omicron enters through the endosomal pathway, instead of the plasma membrane followed by the other variants. This pathway is enhanced by cathepsins instead of TMPRSS2 [51, 52].
A study found that the infection by Omicron was more significant in the cells, which exhibited a lower TMPRSS2 expression. This further indicated that Omicron followed the endosomal entry pathway [53]. This altered entry pathway has been associated with better success in the virus’s replication in the upper respiratory tract [54]. Omicron has also been observed to have a lower cleavage efficiency in comparison to the other emerged variants such as the Gamma and the Alpha variant. Mutations like the N679K and H655Y are the primary cause of the same [35, 55].
Other mutations in the N and S proteins have been linked to the variant’s enhanced cellular permeability. These mutations also aid in more efficient capsid assembly, found to be three-fold better than the Delta variant [56]. The sub-variants of Omicron (BA.1 and BA.2) do not form syncytia (normally produced at the boundary of S1 and S2 during the processing of the S protein), owing to the numerous changes in the S protein. These alterations, combined with the altered entry pathway result in different cellular tropism [35, 54].
Viral load may also be associated with Omicron’s high transmissibility and growth rate. A higher viral load was reported in the upper airway (specifically the nose, trachea and throat). This aggregation of the viral particles in the upper respiratory tract may result from higher growth and increased viral load [35]. Figure 3 illustrates the difference in observed viral load in Omicron in comparison to the other variants.
Figure 3.
Comparison of observed viral load in omicron with the SARS-CoV-2 wild type. The Omicron variant tends to accumulate in the upper respiratory tract, exhibiting higher viral load in the nasal region and larynx. While, the SARS-Cov-2 wild type as well as the other variants settle in the lower respiratory tract, resulting in a higher viral load in the lungs. SARS-CoV-2, severe acute respiratory syndrome [35].
Omicron also has the ability to cause reinfection [42]. Data from South Africa showed that the reinfection rates increased significantly during the Omicron wave in comparison to the Beta and Delta waves [57]. In the UK, it was reported that there was 6 times higher risk of reinfection with Omicron with respect to the Delta variant. A prior COVID-19 infection provided 80% protection against the Delta variant, however, only 19% protection was observed against the Omicron variant [44]. The good news is that fewer cases of Omicron infections required hospitalization, while the frequency of severe cases was more in Alpha and Delta infections [25].
Upon infection with SARS-CoV-2, the innate immune cells, primarily consisting of the neutrophils and the macrophages, identify the virus and activate the immune response. Cytokines and chemokines such as Interleukin-6 (IL-6), monocyte chemoattractant protein-1 and Interferon γ (IFN-γ) are then secreted by these immune cells. Monocytes, neutrophils and macrophages, attracted by the released chemicals, reach the site of infection and release cytotoxic chemicals to kill the virus. The virus is fought by cytotoxic CDB+ T cells, CD4+ T helper cells and B cells. The CDB+ T cells eradicate the virus through cytotoxins while the B cells produce nAb. The cellular reaction is efficient and long-lasting and also triggers immuno-protective memory [5, 58, 59, 60, 61]. A study identified the 14 neutralizing IgG antibodies from SARS-CoV-2 infected patients, with BD-368-2 being the most potent [62]. Other antibodies recovered were IgI and IgM. These antibodies were specific to RBD suggesting that anti-RBD antibodies can be used as clinical interventions against SARS-CoV-2 infections [63].
The Omicron variant triggers exactly the same immune reactions as that seen in the wild type of SARS-CoV-2 variant. The infection results in the production of cytotoxic and follicular T helper cells, along with RBD and spike-related IgG+ B cells and memory B cells. The cytotoxic T cells - CDB+ T cells produce proteases and induce apoptosis in infected cells. On the other hand, the B cells derived from the pool of live memory cells interact with the spike protein [5, 35, 53, 64].
5.1 Clinical manifestations of Omicron
Clinical symptoms of the Omicron infection were different from the earlier variants. Most prevalent symptoms included a cough, nasal congestion, sore throat and fatigue. Loss of smell and taste, fever, dizziness, headaches, etc. were less prevalent with respect to the Delta variant [65, 66]. The virus also affects the organs, which extensively express ACE2 such as glandular cells of the gastric, duodenal and rectal epithelium [67]. A study found that the acute symptoms lasted for fewer days in the Omicron outbreak with an average of 6.87 days, while during the Delta wave, they lasted for an average of 8.89 days [68]. Omicron infection was also suggested to exhibit milder symptoms with a lot of the cases being asymptomatic and majority requiring no hospitalization. In total, 2.6% of the Delta variant infected patients were admitted to hospitals while only 1.9% of Omicron-infected patients required hospitalization [35, 68, 69]. A study found that out of the Omicron-infected individuals, 36.1% did not exhibit any antibody response, while 62.7% produced IgG and only 1.2% produced IgM along with IgG [70]. Omicron-infected patients exhibited various hematological disorders such as lymphocytopenia, neutrophilia, anemia, erythrocytopenia, thrombocytopenia etc. These can be used as biomarkers in Omicron infections for a better prognosis [71].
5.2 Severe cases of Omicron infection
In vivo investigations revealed that lower viral load, smaller lung damage and lower mortality rates were observed in Omicron infections in comparison to the other variants [72, 73]. As discussed earlier, the viral load tends to settle in the upper respiratory tract and not so much in the lungs [74]. However, severe cases of Omicron can result in pneumonia and respiratory failure and can even be fatal [75, 76]. Significant comorbidities, including hypertension, bronchitis and diabetes, have been observed in Omicron infections [35].
The major damage to the tissues in COVID-19, however, is caused majorly by the host’s immune reactions and not directly by the virus itself. The host’s immune reactions are crucial in the pathophysiology of COVID-19 and are directly connected with the disease’s progression. Severe SARS-CoV-2 infections have been shown to dysregulate the host’s normal immune responses. As discussed earlier, the infection leads to numerous hematological disorders such as leukocytosis, lymphocytopenia and a high neutrophil-lymphocyte ratio (NLR). This is the first sign of immunological dysregulation, resulting in uncontrolled inflammatory reactions. These processes lead to immune cells’ damage and exaggerated responses by macrophages, eventually resulting in cell death and tissue damage due to the release of cytotoxic substances. Its manifestations are also seen as cytokine storms and organ failures [5, 71, 77, 78, 79].
Cytokine release syndrome (CRS) is often observed in severe cases of COVID-19. CRS is a hyperinflammatory condition resulting from augmented release of inflammatory cytokines such as tumor necrosis factor (TNF), IL -1, −6, −12, −18, − 33 and IFN -I and -II, along with certain chemokines, including CCL -2, −3, −5 and CXCL -8, −9, 10 [77, 80, 81]. CRS results in acute respiratory distress syndrome, characterized by alveolar epithelial and endothelial destruction in lungs followed by breathing difficulty, hypoxemia and pulmonary oedema. This causes organ failure and also becomes fatal in severe cases [5, 82, 83].
5.3 Immune evasion by Omicron
Omicron has exhibited the ability to alter the host’s immune responses. Some mutations enable the variant to weaken the T cells’ capacity to identify and destroy the infected cells. In some instances, Omicron has also been observed to escape the nAb produced from previous infections or vaccines. However, the existing nAb still provides protection against severe illnesses [16, 84, 85]. Certain viral proteins such as the Orf3 and Orf6 were also observed to alter the T cell responses, which affected the IFN activations. Omicron also brought on T cell immunity decline through immunological fatigue and memory deficits. All this resulted in easier reproduction and propagation of the variant [16, 86, 87].
The understanding of the immunopathogenesis of SARS-CoV-2 aided in developing efficient treatment therapies. However, the precise mechanisms through which the Omicron infection progresses are unclear. For the development of Omicron-specific immunological therapies, it is necessary to analyze the distinct pathophysiology during Omicron infections [5, 88].
Provisionally, the infection can be diagnosed according to the symptoms. It is confirmed using reverse transcription polymerase chain reaction (RT-PCR) or other nucleic acid tests. Serological assays can be used to detect a past infection. They detect the antibodies that were produced by the body in response to the infection. Other laboratory tests can further help in detecting the severity of the infection such as lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin and IL-6 levels. Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection [89, 90].
For the Omicron variant, RT-PCR still remains the gold standard. The RT-PCR diagnostics kits primarily focus on the E, Rp, Rd. and N genes. The S gene mutation observed in the case of Omicron variant may or may not cause a positive test [5, 91, 92]. To identify and classify the variant, next generation sequencing (NGS) is required. NGS also aids in determining the origin of SARS-CoV-2. It also has the opportunity to rebuild whole viral genomes. However, unlike PCR, NGS is expensive, time-consuming and requires expertise for interpretation [5, 93, 94]. Serological assays use S or N protein-specific antibodies. These assays also provide insights into the disease severity—with higher amounts of IgG, IgM and IgI antibodies being reported in severe cases [95].
Important therapeutics for SARS-CoV-2 infection were mAb cocktails such as casirivimab-imdevimab, bamlanivimab-etesevimab that aided in preventing severe disease or hospitalization. These antibodies target the spike protein for neutralization because, as stated before, it is the spike protein that is responsible for the virus’s entry into the host cells by binding to the ACE2 receptors. However, 15 key mutations in the RBD area on the S protein in the Omicron variant may prevent the antibodies from binding with the virus [16, 42]. RBS-A, RBS-B, RBS-C, CR302 and S309 are some of the key targets of the nAb which were replaced in the Omicron variant [96]. This caused scientists worldwide to question the efficacy of such antibodies. In vitro studies too suggested that the Omicron variant is successful in completely escaping neutralization by these antibodies. Nevertheless, mAbs that target sites beyond the RBD, such as sotrovimab and cilgavimab/tixagevimab, have been reported to still remain effective against Omicron in similar studies. Another authorized mAb—bebtelovimab too retained its in vitro activity against the Omicron sub-strains BA.1 and BA.2 [16, 42, 97, 98, 99].
Other antiviral options have also been inspected for emergency use in severe Omicron cases to reduce mortality. Some antivirals proposed are Molnupiravir, Remdesivir, Ensovibep and Camostat. Upon assessment of the above-mentioned and other antiviral molecules against Omicron and its sub-variants, three compounds were found to be particularly efficient. They were Remdesivir, Lufotrelvir and Molnupiravir. Currently, the best antiviral option against omicron is a combination of Nirmatrelvir-Ritonavir. Numerous studies have corroborated the same by analyzing its activity against the variant [35, 100].
7.1 Booster vaccines
The proposal of using booster vaccines was first suggested when in vitro studies found an increase of neutralizing antibody titers against omicron in the serum of individuals provided with the booster dose. Vaccines like BNT162B2/mRNA-1273 (Moderna) and Ad26.COV2.S vaccines were given as boosters which resulted in increase of the nAb titers from 122-fold/44-fold lower against omicron to 4−/sixfold lower. Simultaneously, half of the population in the UK were also given booster doses. These booster doses aided in increasing the vaccine’s effectiveness against symptomatic infections. They also helped in bringing down severe cases, which required hospitalization. Usually, the nAb response used to wane after a couple of months after the second does. This was restored by the booster vaccine [35, 101, 102].
The Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) advised on globalized access of existing COVID-19 vaccines for booster doses, in light of the transmission of Omicron Variant of Concern (VOC). They suggested the vaccine makers to generate and share data on the vaccine’s efficacy against the Omicron variant specifically, along with the other variants. To make the booster doses effective and timely available, the TAG-CO-VAC authorities collaborated with WHO and its expert groups [16].
7.2 Need for new vaccines
As discussed earlier, the Omicron variant is known to escape the mAb, which was effective against the previous variants. Individuals without the booster dose were not able to protect themselves against the variant. Moreover, the booster vaccine also only provided partial protection against it. This indicated the decreasing efficacy of the existing vaccines. Prevalent mutations in Omicron such as Q498R, S477N, Y505H, G496H, T478K, N501Y and E484K are primarily responsible for altering the antigenicity and providing the variant with the capability to evade immune responses. The extensive alterations on the S protein induce stearic hindrance, which in turn affect the antigen–antibody binding. Further, these alterations are unprecedented, making antigen recognition difficult for the antibodies [35, 103, 104, 105].
Hence, several researchers advocated the need for development of novel vaccines, particularly targeting the Omicron variant. Numerous vaccines, predominantly bivalent and RNA vaccines, have since been developed by different researchers or pharmacological companies [17, 35]. A few of the clinical trials working on Omicron vaccines are summarized in Table 2.
Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine
Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above
A Study to Evaluate the Immunogenicity and Safety of Two Recombinant Protein COVID-19 Vaccines in Population Aged ≥18 Years as Booster Vaccines
7
ABO1020 Placebo
Indonesia
II / III
NCT05636319
A Study to Evaluate the Efficacy, Safety, and Immunogenicity of SARS-CoV-2 Variant (BA.4 /5) mRNA Vaccine
8
BNT162b2 vaccine
Israel
IV
NCT05231005
Fourth BNT162b2 COVID-19 Vaccine Dose
9
mRNA1273 vaccine
Israel
III
NCT05230953
Fourth COVID-19 Vaccine Dose- mRNA1273
10
mRNA-1273 Placebo mRNA-1273.222
USA
II /III
NCT04649151
A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19
Table 2.
Phase III and IV clinical trials studying novel vaccines against the omicron variant. All of these studies are currently active and not recruiting [106].
These vaccines show potential in providing protection against Omicron and its sub-variants. Currently, they are under clinical trials for safety and efficacy testing. Numerous studies are under different phases of trials to create a potent vaccine which not only offers protection against the omicron variant but also prevents the need for booster doses [16, 35].
The COVID-19 pandemic resulted in a global public health emergency. The virus’s capability to mutate and evolve rapidly became a threatening concern. To keep up with the pace of the virus, the scientific community had to work round the clock for better diagnosis, precise vaccines and treatment methods. While the new Omicron variant exhibited a reduced disease severity, it posed its own set of challenges. Higher transmissibility, increased infectious rate, immune evasion and partial resistance to monoclonal as well as vaccine-induced antibodies are the key challenges that were to be faced. These complications necessitated the development of new technology and alternate approaches to eradicate the virus.
New variants of SARS-CoV-2 were expected to emerge and the virus is still mutating, each time presenting new risks and challenges. Only traditional approaches are not enough to face this challenge, alternate methods have to be incorporated such as the use of bioinformatics and nanotechnology for development of better drugs and/or vaccines. New data are being generated every day by numerous ongoing studies; however, data interpretation and application require time. Persistent and continued research is necessary for a better understanding of the pathogenesis of the new variants, which will eventually lead to the development of efficient preventive and treatment methods.
I would like to acknowledge my professors and mentors, especially Dr. Gayatri Sharma at Amity Institute of Biotechnology, Amity University, Noida, India for their guidance and counsel that helped in completing this chapter.
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Written By
Khushi Gandhi
Submitted: 10 September 2023Reviewed: 10 September 2023Published: 08 November 2023
Open access peer-reviewed chapter
