QBRI Insights: COVID-19 Vaccination - To boost or not to boost

Entity: Qatar Biomedical Research Institute

QBRI Insights presents expert-led opinions about current vaccination practices

Two years ago, the world was shaken by a surge of patients with an illness of unknown cause that rapidly affected nearly every country. The culprit causing the outbreak was identified as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a newly described human beta coronavirus, and hence the associated disease was termed the Coronavirus Disease 2019 (COVID-19) [1]. Since the pandemic began, there have been over 371M confirmed infected cases and around 5.6M deaths [2].

COVID-19 treatment options

When COVID-19 was declared a pandemic, it became apparent that there was an urgent need to prevent further spread of the virus and to alleviate severe illness from COVID-19. Researchers around the globe began working to find treatments to reduce the risk of severe disease and support patients with critical illness. These treatments now include the use of corticosteroids, antiviral drugs, cytokine inhibitors, anti-malarial agents, convalescent plasma [3].

On December 14, 2021, Pfizer announced the results of a new experimental treatment (NCT04960202) for the treatment of COVID-19 that combines two antiviral drugs (nirmatrelvir and ritonavir) in one pill [4]. When taken within the first three days of symptoms, the treatment reduced the risk of hospitalization or death by 89% in high-risk unvaccinated adults. However, the United States Food and Drug Administration (FDA) is yet to review the data to consider the drug for emergency use authorization. Although the data looks very promising in reducing hospitalization, vaccination remains the top priority against COVID-19 as it offers protection against contracting COVID-19, and risk of severity and death.

COVID-19 vaccination effectiveness

As of December 16,, 2021, the World Health Organization (WHO) notes that there are currently 137 vaccines in clinical and 194 in pre-clinical development [5]. The majority of the vaccines in clinical trials use either a harmless fragment (virus spike protein) or related RNA of the SARS-CoV-2 virus to activate our natural immune response to produce antibodies that recognize the virus as a foreign object and eliminate the threat. Once produced, the antibodies remain in our body even after the virus has been eliminated so that the immune system can quickly respond the next time it encounters the same virus. Thus, vaccination is key to priming our immune system to quickly recognize the virus during infection and mark it for destruction before it can cause serious illness.

In Qatar, the vaccination program was initiated in December 2020 and to date approximately 90% of the adult population has received two doses of a mRNA-based vaccine (BNT162b2 from Pfizer-BioNTech or mRNA-1273 from Moderna) or, to a lesser extent, the viral vector vaccine (AZD1222 from AstraZeneca) [6]. Early on, both Ministry of Public Health (MOPH)-approved mRNA vaccines showed 94% efficacy for preventing severe COVID-19 disease [7].

However, as we gather more data, the question arises whether the two-dose vaccination strategy confers sufficient protection against COVID-19 in the long term. Emerging data demonstrates that the vaccine effectiveness against SARS-CoV-2 infection gradually declines to approximately 70-80% by six months after the second dose [8,9], which is likely due to waning immunity.

Whereas overall vaccine effectiveness against infection declined to 20-30% after the second dose, the effectiveness against severe disease and hospitalization was only reduced by 10% [10]. Strikingly, a report from Qatar showed a dramatic decline in effectiveness of the Pfizer-BioNTech vaccine against infection, going from 77.5% one month after the second dose to 20% at five months after the second dose [11]. These findings alerted researchers and healthcare professionals to the need for booster vaccinations to counteract waning of our immunity against SARS-CoV-2.

The holy grail of booster vaccinations: long-term immunity

A study in the US analyzed antibody responses after administration of the third dose of Pfizer-BioNTech and reported a significant increase in neutralizing antibodies that can recognize the wild type of SARS-CoV-2 as well as the beta and delta variant [12]. This is very encouraging news as SARS-CoV-2 has been shown to continuously adapt and evolve to increase the rate of spread and to evade our immune system, which may negatively affect vaccine effectiveness.

To date, WHO has identified five variants of concern (Alpha, Beta, Gamma, Delta and Omicron), which are associated with an increased rate of transmission or detrimental change in COVID-19 epidemiology, increase in virulence or change in clinical disease presentation, or decrease in effectiveness of public health and social measures or available diagnostics, vaccines, and therapeutics [13].

The most recent variant of concern is named Omicron and was first identified in November 2021. The Omicron variant of the virus carries a high number of alterations which may make it more likely to escape our immune response and to spread more easily. To date, there is limited data available to support these assumptions. Preliminary data demonstrates that a third dose of the Pfizer-BioNTech vaccine increases the levels of antibodies that recognize the Omicron variant by 25-fold, up to levels similar as observed against the wild type virus after two doses [14]. As the virus continues to evolve, these findings strongly advocate for booster vaccinations as the best option for two-dose vaccinated individuals to remain protected against COVID-19.

Living in a world with COVID-19

As activities around the world are starting to resume with reduced restrictions, many questions remain about life with SARS-CoV-2 and COVID-19. Is COVID-19 here to stay and will SARS-CoV-2 become part of our normal life with annual vaccinations like annual flu shots? Will the virus start evolving or will we need a single vaccine that can protect us from numerous variants of the virus? Are these specific demographic or professional populations that are more vulnerable and will require more frequent booster vaccinations than others? Time will tell but the recent events have shown that humanity can adapt quickly to be better prepared in the future.

Contributed by: Dr. Julie V. Decock (Scientist), Dr. Amany S. Dahir (Head of Clinical Research)
Arabic text validation: Rowaida Z. Taha (Research Associate)

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