key: cord-1044356-z3ab5ek6 authors: Chenchula, Santenna; Karunakaran, Padmavathi; Sharma, Sushil; Chavan, Madhavrao title: Current evidence on efficacy of COVID‐19 booster dose vaccination against the Omicron variant: A systematic review date: 2022-03-14 journal: J Med Virol DOI: 10.1002/jmv.27697 sha: 5d60b735e51ca8ab9c88795068a175b1a66f2fc0 doc_id: 1044356 cord_uid: z3ab5ek6 Coronavirus disease 2019 (COVID‐19) is an ongoing pandemic, which affected around 45 million confirmed cases of COVID‐19, including more than 6 million deaths. However, on November 24, 2021, the World Health Organization announced a new severe acute respiratory syndrome coronavirus 2 variant designated as the B.1.1.529, a variant of concern (VOC), and the variant has been named as “Omicron.” Available preliminary evidence suggests that, as compared with previous VOCs, it has an increased risk of infectivity. Studies have shown that protection from various vaccines effectiveness against hospitalization and death from severe COVID‐19 disease is decreasing slowly after a two‐dose schedule of COVID‐19 vaccines. In response to experiencing a new COVID‐19 variant and ongoing resurgence of cases, the importance of COVID‐19 vaccine booster dose and durability of the effect of the third dose of vaccine against COVID‐19 Omicron variant is controversial yet. To address this, we conducted a systematic literature survey on effectiveness of the third or booster dose of COVID‐19 vaccine against the Omicron variant. We have performed a systematic search in PubMed (Medline), Google Scholar, and MedRXiv database, from inception to January 2022 using the MeSH terms and keywords “Corona Virus Disease‐2019 OR COVID‐19 AND Omicron AND COVID‐19 Booster Vaccine.” We have identified a total of 27 published studies. We have reviewed all the eligible available studies on the effectiveness of the COVID‐19 vaccine booster shots against the Omicron variant. This review may be helpful in accelerating the COVID‐19 booster dose vaccination. transmissibility and increased resistance to vaccine-induced immunity. 3 The Omicron variant was initially confirmed from a specimen collected on November 9, 2021, and has a large number of mutations (>50 mutations), some of which are highly concerning; it has a high capacity for immune escape and the T cells, which destroy infected cells, also appear to not recognize the Omicron variant, which helps in preventing the severity of the disease, hospitalization, and deaths. 3 It was first to come into attention by an outbreak in the South African younger adults <30 years age at the province of Gauteng, an area of high infection-acquired immunity following a third Delta wave with low vaccine coverage in this age group, where only 44% of the adult populations have received at least one dose of COVID-19 vaccine. Till now, the new variant has been identified in almost more than 57 countries. 3 The most common symptoms shown by Omicronaffected patients were fever, severe fatigue, a scratchy throat, wet cough, runny nose, diarrhoea, headache, and other body aches. Current SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (RT-PCR) diagnostics continue to detect this variant. 4 However, it was also found that, with a usual RT-PCR test, one of the three target genes called S gene is not detected (S gene dropout or S gene target failure) and this test can therefore be used as a marker for this variant, pending sequencing confirmation. 5 The first report from a hospital in Tshwane, the epicentre of the Omicron outbreak in South Africa, had shown that 42 patients in the ward on December 2, 2021, revealed that 29 (70%) patients were not on oxygen therapy, whereas 13 patients were dependent on supplemental oxygen, of which 9 (21%) had a diagnosis of COVID-19 pneumonia based on a combination of symptoms, clinical signs, chest X-ray, and inflammatory markers. The remaining four patients were on oxygen for other medical reasons (two previously on home oxygen, one for heart failure, and one with a confirmed diagnosis of pneumocystis pneumonia). There were only four patients in high care and one in the intensive care unit (ICU). The number of patients in high care on double oxygen, high-flow nasal oxygen, or on noninvasive ventilation was noticeably less in the present wave. All are being prescribed steroids as the mainstay of therapy. Of 38 adults in the COVID wards on December 2, 2021, 6 were vaccinated, 24 were unvaccinated, and 8 had unknown vaccination status. Of the nine patients with COVID pneumonia, eight were unvaccinated and one was a child. Only a single patient on oxygen was fully vaccinated but the reason for the oxygen was chronic obstructive pulmonary disease. 6 A total of 27 eligible studies were identified (in vitro studies: 5; prospective observational studies: 20; case series: 2) and were included for analysis. All 27 review studies' findings are summarized in Table 1 . A preliminary analysis by insurer Discovery, the largest private health insurance administrator, from the first 3 weeks of the Omicron wave in 211,000 positive PCR tests from adults covered by the insurer (41% of these adults had received two doses of the Pfizer vaccine), and 78,000 results were attributed to Omicron infections reported that the two-dose Pfizer-BioNTech vaccination provides 70% protection against hospitalization for those who have received the two-dose series compared with the unvaccinated. Protection against hospitalization was maintained across all people aged 18-79 years, with slightly lower levels of protection for those aged 60-69 (67%) and 70-79 (59%) years. Overall protection against infection fell to 33% for the two-dose series, down from the 80% seen during the Delta wave. The report also revealed that a total of 16% of ICU admissions were among the vaccinated individuals only. Additionally, the risk of reinfection with Omicron was significantly higher compared with prior variants. The insurer's data have shown that those who had been infected with the Delta variant had a 40% relative risk of reinfection with Omicron, those infected during the Beta wave had a 60% risk of reinfection, and those infected with the original viral strain identified in Wuhan during the first wave had a 73% risk of reinfection. The data suggest that, after adjusting for vaccination status, the risk of hospitalization among adults with a COVID-19 diagnosis was 29% lower with Omicron than it was during the first wave in early 2020. In addition, the analysis found that, Garcia-Beltran et al. 19 8. An increased estimates of vaccine effectiveness against the COVID-19associated emergency and/or urgent care department encounter or hospitalizations during both Delta-and Omicron-predominant time duration among adults who have been administered with a third or booster-dose vaccination (mRNA vaccine). Thompson et al. 20 Persons who had received the booster dose of mRNA COVID-19 vaccine (compared with unvaccinated and those who received of two doses) were less likely among cases with symptomatic SARS-CoV-2 infection compared with test-negative controls. Accorsi et al. 21 10. Booster doses with BNT162b2 (Pfizer BioNTech) in those with two doses of either BNT162b2 or CoronaVac provided acceptable neutralizing immunity against Omicron variant at 1 month postbooster dose. However, three doses of BNT162b2 (Pfizer BioNTech) elicited higher levels of PRNT 50 antibody to Omicron variant, suggesting longer duration of protection. Peiris et al. 22 11. Antibody titers against Omicron were low or undetectable after two immunizations and in most convalescent sera. A booster vaccination significantly increased titers against Omicron to levels comparable to those seen against the ancestral (D614G) variant after two immunizations. Neither age nor sexes were associated with differences in postvaccination antibody responses. Lusvarghi et al. 23 12. Neutralization of Omicron was undetectable in participants that had received a two-dose regimen of CoronaVac vaccine, BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron, compared with a two-dose mRNA vaccine. Pérez-Then et al. 24 13. mRNA booster immunizations in vaccinated and convalescent individuals resulted in a significant increase of serum-neutralizing activity against Omicron. Gruell et al. 25 14. Immune boosting through three vaccine shots significantly improved the convalescents' immunity against the Omicron variants. Ma et al. 26 T A B L E 1 (Continued) Booster vaccination increased the nAb NT 50 titer against all variants. Zeng et al. 27 16. Booster recipients exhibited dramatically increased nAb titers and generation of a stronger and much broader neutralization against the Omicron variant after the booster vaccination. Zeng et al. 28 A booster dose of BBIBP-CorV (Sinopharm Beijing Institute of Biological Products COVID-19 vaccine) led to a significant rebound in neutralizing immune response against SARS-CoV-2, while the Omicron variant showed extensive but incomplete escape from booster-enhanced neutralization. Yu et al. 29 A homologous inactivated vaccine booster or a heterologous booster with a protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Wang et al. 30 19. Comparing with those who received a booster and those who received two doses, there was an estimated odds ratio of 0.14 (95% CI: 0.13-0.15) 28-65 days following receipt of the booster (86% reduction in the odds of testing positive for SARS-CoV-2). Patalon et al. 31 A booster dose of mRNA-1273 vaccine was associated with neutralization titers against the Omicron variant that were 20.0 times higher than those assessed after the second dose of vaccine. Pajon et al. 32 A 50 μg of mRNA-1273 (Moderna) boost increased Omicron neutralization titers and may substantially reduce the risk of symptomatic vaccine breakthrough infections. Doria-Rose et al. 33 22. At all four time intervals after the second mRNA vaccine dose, very minimal neutralizing antibody titers were detected against Omicron, including for a majority of patients who had SARS-CoV-2 breakthrough infections. Neutralizing antibody titers against all other variant spike protein-bearing pseudoviruses declined dramatically from 1 to 6 months. Evans et al. 34 23. Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. Atmar et al. 35 24. Heterologous boosting with Convidecia elicited significantly increased GMTs of neutralizing antibody against SARS-CoV-2 than homologous boosting with CoronaVac in participants who had previously received one or two doses of CoronaVac. Costa Clemens et al. 36 25. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S), an mRNA vaccine (BNT162b2, Pfizer BioNTech), or a recombinant adenoviral-vectored ChAdOx1 (Oxford-AstraZeneca) nCoV-19 vaccine, compared with a third homologous dose of CoronaVac. All four vaccines administered as a third dose induced a significant increase in binding and neutralizing antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. Li et al. 37 Heterologous ChAdOx1 (Oxford-AstraZeneca):mRNA-1273 (Moderna) primeboost immunization induces significantly broader and more potent serumneutralizing antibody and MBC responses against WT SARS-CoV-2 and VOCs relative to homologous ChAdOx1 vaccination, and this difference appears to be driven by both the magnitude and quality of the early secondary B-cell response. Kaku et al. 38 27. Recipients of both vaccine types had a ∼9to 10-fold increase in IgG and neutralizing titers within 2 weeks of vaccination, and an 8-fold increase in live Omicron VOC neutralization, restoring titers to those measured after the third vaccine dose. Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019; GMTs, geometric mean titers; mRNA, messenger RNA; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; VOCs, variants of concern; WT, wild type. The authors declare no conflicts of interest. Santenna Chenchula conducted the literature search and data extraction, and drafted the manuscript. Padmavathi Karunakaran, Sushil Sharma, and Madhavrao Chavan revised the final manuscript. All authors reviewed and approved the final version of the manuscript. The data used in this systematic review are available from the corresponding author with a reasonable request. COVID-19) Dashboard Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern European Centre for Disease Prevention and Control. Epidemiological Update. Omicron Variant of Concern-Data as of 16 What are the symptoms of Omicron and has anyone died from it? European Centre for Disease Prevention and Control. 2021. 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