Reply to the letter ‘Effectiveness of COVID-19 vaccines against Omicron variant’

This is about the Letter to the Editor entitled ‘Effectiveness of COVID-19 vaccines against Omicron variant’ [1] in response to the published review ‘A global picture: therapeutic perspectives for COVID-19’ [2]. Since the publication of the review, we submitted a commentary article entitled ‘Therapeutics to tackle Omicron outbreak’, which was recently accepted in Immunotherapy [3]. This commentary article covers various therapeutics required to manage the Omicron outbreak. Following the worldwide dissemination of the SARS-CoV-2 Omicron BA.2 lineage, various BA.2-related variations with mutations in the L452 residue of the spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q) and BA.2.11, BA.4 and BA.5 (L452R), appeared in several nations [4]. The World Health Organization (WHO) designated B.1.1.529 as a variant of concern and it was named the Omicron variant. Omicron is different, highly transmissible, and potent new variant of SARS-CoV-2 due to the high number of mutations. Omicron was first identified in South Africa in November 2021 [5].

As of 31 May 2022, 1.1 million Omicron variant cases in the UK alone have been reported, which accounts for the highest number of cases for a variant worldwide. Following the UK, the USA is the second country to report close to 1 million cases and India is third with 55,000 Omicron cases [6].

We now provide the Omicron management strategies and research outcomes as diagnostics, therapeutics and vaccine.

Diagnostics for Omicron

Reverse transcription PCR testing

Following a nasopharyngeal swab, a reverse transcription PCR test is conducted to determine the presence of SARS-CoV-2 variants, including Omicron [7]. Reverse transcription PCR identifies the envelope protein, RNA-dependent RNA polymerase and nucleocapsid protein genes of SARS-CoV-2. Since Omicron (and other variants) mutations are on the spike (S) gene Omicron is able to be detected [8]. The amplicon sequence provides clear detection using Nextclade, since the Omicron variant includes several mutations in the S gene. Phan et al. developed a qualitative reverse transcription PCR assay with genomic analysis to rapidly detect the Omicron variant in nasal specimens [9]. Furthermore, combining clinical–epidemiological data with supplementary examinations would reduce the number of false-positive and false-negative outcomes [10]. Similarly, Puvar et al. have developed an Omicron-specific duplex PCR test that has a 250-base pair-specific band that efficiently detects and distinguishes Omicron from the other variants of SARS-CoV-2 [11].

Rapid antigen testing

Although rapid antigen tests (RATs) don't usually differentiate between each variant, a new RAT has been developed that can detect Omicron within 20–30 min [12]. Stanley and colleagues demonstrated that RATs are successful at detecting Omicron [13]. The Omicron variant contains 32 mutations in the S protein, which is twice as many mutations as the Delta variant [14,15]. It has been shown that RATs can detect Omicron but with reduced sensitivity [13]. The alterations that influence the nucleocapsid's ability to be recognized by RATs are dependent on the kind of capture antibody utilized in each assay. As a result, viral mutations cannot completely anticipate RATs' effectiveness. It would be necessary to know the viral epitopes identified by the capture antibodies utilized by each commercial test to offer predicted effectiveness [16,17].

Therapeutics against Omicron

Small molecules used in the treatment for Omicron variant

People with confirmed mild to moderate COVID-19 with Omicron variant who are at risk of severe sickness are given one of two antiviral pills [18,19]: (1) nirmatrelvir and ritonavir in combination and (2) mulnupiravir. These drugs have equivalent antiviral activity against all variants of concern for SARS-CoV-2 [20,21]. Remdesivir, another antiviral medication, is also administered intravenously [22].

Monoclonal antibody therapy

Monoclonal antibody therapies are administered to persons with mild to moderate COVID-19 who are at a high risk of serious disease. Similar to other monoclonal antibodies that have been approved for the treatment of high-risk individuals with mild to moderate COVID-19 and having shown a benefit in reducing the risk of hospitalization or death, bebtelovimab (175 mg/2 ml injection; Eli Lilly, IN, USA) acts by binding to the spike protein of the virus that causes COVID-19 [23].

Bebtelovimab retains action against both the Omicron variant and the BA.2 Omicron subvariant, according to laboratory tests [24]. However, according to the US FDA approval, it is stated the following medications are not indicated for the treatment of COVID-19, since they are ineffective against Omicron [23]:

1. Casirivimab plus imdevimab from Regeneron;

2. Bamlanivimab plus etesevimab from Eli Lilly;

3. Sotrovimab from GSK.

A single dosage of AZD7442 (tixagevimab and cilgavimab) was effective in preventing COVID-19 without causing any apparent side effects (NCT04625725) [25].

Vaccination strategy against Omicron

There are 32 mutations in the viral spike protein of the Omicron variant, 15 of which are in the receptor-binding domain, that affect viral transmission, immune evasion and vaccination tolerance. SARS-CoV-2 has a lot of mutations, and each one impacts the virus's protein binding site differently [26]. Moderna developed two multivalent immunotherapies: mRNA1273.211, which has many genetic variations seen in both the Omicron and Beta variants, and mRNA1273.213, which contains a genetic variation found in the Omicron, Beta and Delta forms [5]. To combat Omicron endemics, more than 130 countries in the world have launched booster dosage programs. Despite preliminary evidence that booster may increase Omicron protection, while additional studies are required to determine vaccine effectiveness [27,28]. Vaccination with BNT162b2 decreased the probability of Omicron-related hospitalizations in children aged 5–11 years by two-third. Even though two doses of immunization gave less protection against Omicron-associated hospitalization than Delta-associated hospitalizations in adolescents aged 12–18, vaccination prevented serious illness caused by either type [29]. Following complete immunization, mild to moderate Delta and Omicron breakthrough infections are minimally immunogenic, resulting in diminished immunity toward reinfection and infection from new variations [30]. However, in areas where immunizations are scarce, this may be insufficient to avoid illness and death (NCT05328479). According to Lee and colleagues [31], “Omicron-specific mRNA vaccine can induce potent neutralizing antibody responses against Omicron, but the inclusion of epitopes from other variants may be required for eliciting cross-protection.”

Conclusion

Some drugs and vaccines have been tested in human clinical trials against SARS-CoV-2 that are effective against the variants of concern. As a result, the severity of the disease has decreased, the number of hospitalizations has been reduced and there are fewer deaths. The authors of the Letter to the Editor introduced updated information related to the efficacy of COVID-19 vaccines against Omicron. Herein, we provide additional updates on diagnostics, therapeutics, and vaccines that work against the Omicron variant.