COVID-19 Vaccine Boosters Effective and Safe
By Prof. Suranjith L. Seneviratne
In recent months, an increased number of SARS-CoV-2 infections have been observed in several countries and this in spite of hitherto successful vaccination campaigns. This may be due to the greater transmissibility and infectiousness of the SARS-CoV-2 Delta variant and the waning of immunity from COVID-19 vaccines that were administered earlier. The rapid global spread of SARS-CoV-2 variants of concern (VOC), raised several immunological, public health, and ethical questions about the duration and effectiveness of vaccine-induced protection and the need for vaccine boosting. During the past few months, many experts from around the world have recommended the roll out of COVID-19 vaccine booster doses. In the summer of 2021, Israel administered booster doses of the Pfizer vaccine and thus far several countries have put in place COVID-19 vaccine booster programmes. Questions have been asked about the effectiveness of the booster vaccine doses and its potential side effects. This article would outline the current status of COVID-19 booster vaccination in certain regions/countries of the world and discuss what is known so far about its effectiveness and safety.
Status of booster COVID-19 vaccine rollout in selected countries/regions
United Kingdom (UK)
In the UK, the administration of booster doses started in September 2021. This was given to those aged 50 and over, health and social care staff, at risk under 50s, above 16s living with immunosuppressed people, and those in long-stay care settings. They were offered the Pfizer vaccine six months after the second vaccine dose, regardless of which vaccine the person had initially received. The COV-Boost trial had found the Pfizer vaccine to be well tolerated as a third dose and to provide a strong booster response. This finding helped the authorities recommend mixing of vaccine doses. Since15 November 2021, the COVID-19 vaccine booster is being offered to all persons aged 40 years and above. Recently, the British Prime Minister mentioned that to be fully vaccinated no longer meant having two COVID-19 vaccine doses but rather three doses.
United States of America
On 19 November 2021, the United States Food and Drug Administration (US FDA) amended the Emergency Use Authorisations (EUA) for both the Pfizer and Moderna COVID-19 vaccines. They authorised them for use as a single booster dose for all individuals 18 years and older, after they had completed primary vaccination with any FDA-authorised or approved COVID-19 vaccine. For the Pfizer COVID-19 vaccine booster dose, the FDA analysed the immune response from around 200 persons, between 18 and 55 years, who received a single booster dose about six months after their second dose. One month after a booster vaccine dose, the SARS-CoV-2 antibody response, was higher compared to levels found one month after the two-dose primary series. For the Moderna COVID-19 vaccine booster dose, the FDA analysed the immune response from 149 persons, 18 years of age or older from the original clinical studies who received a booster dose at least six months after their second dose. This was compared to the immune responses of 1,055 individuals who had completing their two-dose vaccine series. The antibody response against the SARS-CoV-2 virus 29 days after a booster vaccine dose was higher. The FDA stated that the benefits of a single booster dose of either the Pfizer or Moderna COVID-19 vaccines outweigh the risks of myocarditis and pericarditis in individuals aged 18 years and older, when used following the completion of primary vaccination. They also stated that those who were initially vaccinated with the Johnson & Johnson (J&J) vaccine would benefit the most from a booster dose.
In recent weeks, many European countries have launched their COVID-19 booster vaccine campaigns. Currently, around 3.7 per cent of population in Europe has received a booster vaccine dose. Iceland (where 90 per cent have already received two vaccine doses) leads the way, with nearly 20 per cent of persons already receiving a booster dose. The Icelandic Government announced a booster dose for all over the age of 16 years. In France, the over-65s have been offered a third vaccine dose since September 2021. Those who do not receive the booster dose, risk having their COVID-19 health pass suspended in mid-December 2021. Spain and Sweden have currently limited its booster campaign to those aged 70 and over and 80 and over respectively. In Serbia and Hungary, 16 and 14 out of every 100 persons respectively, have received booster vaccine doses. A few days ago, Austria announced that COVID-19 vaccination would be made compulsory from 1 February 2022. It is the first EU country to issue such a mandate.
On 30 July 2021, Israel approved the administration of a booster dose of the Pfizer vaccine for persons 60 years or older and who had received a second dose of vaccine at least 5 months earlier. In Israel, a person needs to have received a booster COVID-19 vaccine dose to become eligible for a green pass, unless they have only received the second dose within the last six months. Such a pass is needed for persons to enter gyms, restaurants, and other venues.
From 9 November 2021, Australia’s Department of Health started offering booster vaccine doses to the public. The Pfizer COVID-19 vaccine was approved by the Therapeutic Goods Administration (TGA) and recommended as the booster dose. A person is eligible for a COVID-19 booster dose if they are 18 years and older and have had the second dose of their COVID-19 vaccination at least 6 months ago.
The Health Ministry started administering booster vaccines, six months after the second dose for people aged 30 to 59, and five months for those aged 60 and above. This was decided as waning of antibodies can clearly occur by around six months after the second dose and may occur earlier in the older age groups. From 24 November 2021, all eligible individuals would be able to receive their COVID-19 booster vaccine, five months after completing their second dose. The expert committee on COVID-19 vaccination recommended a standardised interval of five months to pre-empt waning of antibodies for all eligible persons. It is mentioned that 1.5 million booster vaccine doses would be given by the end of December 2021, and this would raise Singapore’s booster vaccination coverage from 21 to 50 per cent.
As vaccine supplies have increased, some public health experts in India have urged the Government to start a booster vaccine programme for the most vulnerable. Currently, India has still not considered authorising a COVID-19 vaccine booster dose. The authorities are concentrating on getting most of India’s 944 million adults to complete two-dose vaccination by January 2022. So far, 81 and 43 per cent of India’s adults have received at least one and two vaccine doses respectively. Vaccination for those under 18 is still to commence. It has been stated that once most adults have had two vaccine doses, the Government may make vaccine boosters optional.
Findings from studies on COVID-19 booster vaccines
Data from 728,321 individuals aged 12 or above who had received the booster dose of the Pfizer vaccine between July 2020 and September 2021 were obtained from Israel’s largest healthcare organisation (Clalit Health Services) and analysed. They were matched 1:1 with individuals who had received only two doses of the Pfizer vaccine at least five months before. The matching was based on an extensive set of demographic, geographic and health-related attributes associated with risk of infection, risk of severe disease, health status and health seeking behaviour. The primary outcomes included hospital admission related to COVID-19, severe disease, and mortality. Compared with individuals who received only two doses five months prior, individuals who received three doses of the vaccine had 93% lower risk of COVID-19-related hospitalisation, 92% lower risk of severe COVID-19, and 81% lower risk of COVID-19-related death. Effectiveness was assessed starting from day 7 after the third dose. The estimated effectiveness of the third dose against hospital stays and severe complications were similar for males and females, and between individuals aged 40–69 years and over 70 years.
The study’s large size allowed a more precise assessment of the vaccine’s effectiveness across different time periods, different sub-populations (for example sex, age and number of comorbidities), and different severe outcomes (which are rarer and thus need a bigger sample size). However, in this study, reliable estimates could only be obtained about secondary outcomes such as infection and symptomatic infection. Furthermore, as it was an observational study, it could not account for every factor that may have influenced the outcomes. Due to the relative scarcity of events in individuals younger than 40 years, it was not possible to evaluate vaccine effectiveness in this age group. Furthermore, this study did not explore potential adverse clinical events and excess healthcare utilisation associated with the administration of a third dose.
UK Health Security Agency study
This study found that at least 20 weeks after being vaccinated with two doses of the Pfizer vaccine, effectiveness against symptomatic disease was 62.5%. For the Oxford-AstraZeneca vaccine it was 44.1%. It was apparent that protection from the first two vaccine doses was beginning to wear off in the older age groups. Two weeks after receiving a vaccine booster dose, protection against symptomatic infection increased to 94% and 93.1% in those who had initially received two doses of the Pfizer or Oxford-AstraZeneca vaccines respectively. A booster dose of the Pfizer COVID-19 vaccine provided significant increased protection against symptomatic disease in those aged 50 and over, irrespective of whether the person had the Oxford-AstraZeneca or Pfizer vaccines as their first doses. This is real world evidence of the effectiveness of the booster in an UK setting and confirms the findings from Israel. It is too early to know how effective the booster will be at reducing the risk of hospital admissions in the UK. However, from the Israeli experience we can expect the booster to be even more effective at preventing severe disease than at preventing symptomatic infection.
Recent data from the REal-time Assessment of Community Transmission (REACT) study showed that SARS-CoV-2 infections in the UK are now at rates similar to that seen in January 2021. Home swab tests were taken by 100,112 people in England between 19 October and 5 November 2021. Of them, 1,399 (1.6%) or 1 in 64 were infected (that is had a positive SARS-CoV-2 PCR test result). Of the positive samples, 841 were sequenced and the Delta variant was identified in all. Almost 12% were of the AY.4.2 sub-lineage, and these individuals were less likely to have any symptoms or the ‘classic’ symptoms (such as loss or change of sense of taste or smell, fever, new persistent cough). This study also looked at the effectiveness of booster doses at preventing infection. The risk of infection was around three times lower in those who had received a third dose, compared to those who got two doses. For those aged 50 and above, having a third dose reduced the infection risk by around half compared to two doses.
According to a study that was recently published in the journal ‘Lancet Microbe’, in order to keep vaccine efficacy above 50 per cent, a booster vaccine dose would be necessary within one year of receiving the initial two doses. The authors found a major loss of protection from symptomatic infection with the current variants of concern, during the first year after vaccination. They suggest this would be reversed by a third booster vaccine.
Side effects of COVID-19 vaccine boosters
The side effects of booster vaccine doses are similar for the three (Pfizer, Moderna, J&J) studied vaccines. They include muscle and joint pain, swelling or soreness at the injection site, fatigue, headache, chills or fever, and swollen lymph nodes. Most people have effects that are similar to the initial doses and severe reactions are rare. Swollen axillary lymph nodes are more likely to occur following a Pfizer vaccine booster than from the others. Data released in September 2021, shows that 74.9% of people who received a third dose of the COVID-19 vaccine reported local reactions such as pain or swelling at the injection site. Nearly 70% reported systemic reactions like fever or loss of appetite. This mostly occurred on the day following their vaccination. The most common specific reactions were: pain at the injection site (71%), fatigue (56%), and headache (43%). For most, the side effects were mild or moderate in severity and transient. Of the 6,200 participants who received three doses of the Moderna vaccine, local reactions were marginally more common after the booster (84.7%) than after the second dose (83.5%). Systemic reactions were less common.
Among the 6,300 three-time Pfizer vaccine dose recipients, a similar trend was noted. Local reactions increased slightly (from 71.7% to 74.1%), and systemic reactions reduced marginally (from 71.7% to 69.2%). In its Phase III clinical trial data, J&J noted that recipients of its booster had fewer local and systemic side effects than seen in its Phase I/II study. A National Institutes of Health study found that people who received the Moderna vaccine booster were slightly more likely to experience an adverse reaction such as vomiting, fatigue, or insomnia at 15.6% than those who received Pfizer (14.3%) or J&J (12%). A small number of cases of myocarditis and pericarditis have also been reported in relation to both the Pfizer and Moderna vaccines, mostly in young men. In a recent Israeli study of 5.4 million people over the age of 16, both vaccinated and unvaccinated, 283 people reported ‘probable or definite’ myocarditis. Of those, 142 cases were related to the Pfizer vaccine, and 95% were mild. After medical treatment, most of those who experienced the myocardial inflammation, recovered quickly.
World Health Organisation (WHO) perspective
The WHO position is that it makes no sense to give boosters to healthy adults, or to vaccinate children, when health workers, older people and other high-risk groups around the world are still waiting for their first dose. They state that six times more booster doses are being administered around the world on a daily basis than primary doses in low-income countries. According to the WHO’s special envoy on COVID-19, relying only on a full vaccination strategy is a gamble for rich countries. A call has been made for a combined approach consisting of masks and other health interventions so that people could avoid being infected by the virus.
Because of the observed waning of immune responses following two doses of the COVID-19 vaccine, booster vaccine doses have started to be given in several regions and countries. Different countries follow varying regimes and the currently available data points to the effectiveness and safety of the COVID-19 booster vaccine programme.