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The first detection of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) Omicron variant (B.1.1.529) took place on 24th November 2021 in South Africa, following which it replaced the Delta (B.1.617.2) variant in becoming the predominant SARS-CoV-2 variant throughout the world.
Though the severity of disease caused by Omicron was lower in the UK and South Africa than in Delta, large outbreaks could still have a significant impact. Studies from Qatar and the UK have reported that administering a third (booster) dose of mRNA COVID-19 vaccine can increase the protection against severe disease and SARS‑CoV‑2 Omicron infection. However, data from the US Centers for Disease Control and Prevention VISION network, as well as Israeli research, indicated a waning of protection against infection even after three doses of vaccination.
Study: Analysis of COVID-19 Incidence and Severity Among Adults Vaccinated With 2-Dose mRNA COVID-19 or Inactivated SARS-CoV-2 Vaccines With and Without Boosters in Singapore. Image Credit: Dmitry Demidovich / Shutterstock
Singapore, which is located in Southeast Asia and comprises a population of approximately 5.5 million, implemented stringent COVID-19-containing strategies from January 2020 to around September 2021. The national vaccination program began in Singapore on 30th December 2020 with the BNT162b2 (Pfizer-BioNTech) vaccine, followed by the introduction of mRNA-1273 (Moderna) on 17th March 2021 and CoronaVac (Sinovac) vaccine on 23rd October 2021. Moreover, the BBIBP-CorV (Sinopharm) vaccine was reported to be available at private healthcare providers from 30th August 2021. As a result, 85% of the total population was said to be fully vaccinated by 27th December 2021, while 69% were reported to receive a booster dose by 10th March 2022. However, despite high vaccine coverage, the Omicron wave was larger than the Delta wave.
A new study published in the journal JAMA Network Open aimed to analyze the association of the types of vaccine and their combination with the waning of protection against Omicron in residents of Singapore who were aged 30 years and above and had received at least two doses of a COVID vaccine.
The study involved collecting anonymized data from people living in Singapore, including sex, age, type of residence, vaccination dates, vaccine types, the severity of infection, and dates of detection of all COVID-19-positive cases. Severe disease was defined as death, the requirement of oxygen supplementation, or admission to the intensive care unit (ICU). In addition, the participants had to be 30 years of age or above as of 10th October 2021, as well as administered either 2 or 3 doses of inactivated (Sinovac or Sinopharm) or mRNA (Pfizer-BioNTech or Moderna) vaccines.
Asymptomatic and symptomatic individuals with existing medical conditions were required to undergo confirmatory tests for SARS-CoV-2 infection at quick test centers as well as clinics. Confirmed infections from 27th December 2021 to 10th March 2022 were included in the study since this was the period of Omicron dominance. Finally, confirmed and severe SARS-CoV-2 infection outcomes were examined.
The results indicated that out of the total number of participants included in the study, 90.2% were reported to receive a 3-dose vaccination by 10th March 2022. Out of them, 97.8% were reported to receive three doses of an mRNA vaccine, while 2.2% received three doses of an inactivated vaccine. Additionally, most people with 2-dose vaccination were reported to have received an mRNA vaccine. A higher percentage of women have been observed to receive either 2 or 3 doses of vaccine. The age of participants who received the mRNA vaccine was reported to be approximately 53 years, while those who received the inactivated vaccine were reported to be 49 years.
The rate of incidence of confirmed infection among those who received two doses of an mRNA vaccine was found to be 162 confirmed infections per 100,000 person-days at risk. However, the incidence rate ratio (IRR) for confirmed infection was found to increase from 15 days post-vaccination up to 11 months. The rate of incidence of confirmed infection among those who received three doses of an mRNA vaccine was observed to be 195 confirmed infections per 100,000 person-days at risk. The booster effectiveness was observed to be highest for homologous mRNA-1273 boosting as compared to heterologous boosting as well as homologous BNT162b2 boosting. However, the booster effectiveness was also reported to wane rapidly, approximately four months post-third dose.
The rate of severe COVID-19 among those who received two doses of an mRNA vaccine was reported to be 2 per 100,000 person-days at risk. However, in the case of severe COVID-19, the adjusted IRR was not found to increase from 15 days to 11 months post-vaccination. The rate of severe COVID-19 among those who received three doses of an mRNA vaccine was reported to be 0.5 per 100,000 person-days at risk. Moreover, the booster effectiveness for homologous as well as heterologous vaccine combinations did not show any significant decrease over time.
Furthermore, the incidence rate for those who received 2-dose inactivated SARS-CoV-2 vaccine was observed to be 193 confirmed infections per 100000 person-days at risk, while for those who received 3-dose inactivated vaccine was 213 per 100,000 person-days at risk. For severe COVID-19, the incidence rate among those with 2-dose inactivated vaccine was reported to be 3 per 100,000 person-days at risk, while for 3-dose, it was 0.8 per 100,000 person-days at risk. Additionally, the booster effectiveness against severe COVID-19 was reported to be 69.6%, while it was 12.5% against confirmed infection.
Therefore, the current study demonstrated that the mRNA vaccines effectively protect against severe SARS-CoV-2 infections. However, the protection from 2 and 3-dose vaccinations were observed to wane rapidly against Omicron infection, which suggests the requirement of a fourth vaccine dose. Also, inactivated vaccines were found to be effective in protecting against SARS-CoV-2. Further monitoring of the effectiveness of boosters over longer durations, as their response to future SARS-CoV-2 variants, is required to determine ideal vaccination strategies.
The study has certain limitations. First, the study findings might not apply to those belonging to younger age groups. Second, vaccine mandates could have led to a reduction in infection risk. Third, the study did not contain information on negative COVID-19 results. Fourth, individuals not tested at a registered test site could introduce bias. Fifth, data on COVID-19 symptoms and comorbidity was not available. Finally, confirmed infection by the BA.1 and BA.2 sublineages could not be differentiated.