March 11 2020 will go down in the annals of human history as a day of reckoning. On that day, confronted with an uncontrollably raging novel viral infection sweeping across the world, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) as a pandemic. 1 Since then, the infection has spared virtually no country, claiming over 121 million lives globally and killing over 2.6 million in total. 2 A small piece of RNA has indelibly changed human history.

The global research community, at the time, predicted that it may take at least a year or more before an effective vaccine would be found for the disease, because no vaccine for an infectious disease has ever been invented within a year of the infection’s arrival, and only a sceptic would have dared to suggest that an efficacious COVID-19 vaccine would be discovered, evaluated and administered within 9 months. Nevertheless, due to the remarkable ingenuity of humankind and the recent, explosive technological advances, both in molecular biology and industrial automation, there are currently at least 13 COVID-19 vaccines approved for early or limited use, and a further 27 are in large scale, Phase III, final trials (as of 18 March 2021). 2, 3

At the time of their introduction, the effectiveness of these vaccines in large population groups on a community-wide basis, was unknown. Clearly due to the Phase III trials in limited cohorts, which provide only efficacy data under experimental conditions, (note the differentiation between efficacies versus effectiveness), the larger, looming question was how effective would they be on a global scale once administered on a community-wide basis? Initial comparisons of effectiveness in different vaccine trials, in various countries, has been fraught with difficulties. There are many reasons for this, such as their assessment in populations with or without mild symptoms, testing the vaccine in countries with viral variants, and evaluation of the symptomatology after a single dose. Nevertheless, mass vaccination data tracking repositories that collate and analyse ‘big data’ on a global scale, now indicate the profound effectiveness of almost all of the current COVD-19 vaccines. The most satisfying and comforting result of all is that almost all of the currently approved vaccines are highly effective in halting hospital admissions of the vaccines, meaning that the vaccines stops SARS-CoV-2 in its tracks, totally suppressing its potency to cause severe disease requiring hospitalization, and the associated morbidity and mortality (Table 1).

Over two centuries of vaccine history, since their introduction in early 1800s by Edward Jenner in UK, indicates that they do not need to be extremely effective to save lives, and prevent disease. The popular ‘flu shot’ for seasonal influenza, administered annually for example, has an effectiveness of 40–60% according to the Centres for Disease Control and Prevention (CDC) (Figure 1). 4 For instance, during 2018–2019, it prevented around 4.4 million influenza illnesses, and some 3,500 influenza-associated deaths. 5

It is also noteworthy that the number of doses can also improve the effectiveness of some vaccines. In the case of vaccines against polio and measles, a higher number of doses will confer peak effectiveness. Similarly, a third dose of hepatitis B vaccine (that should be taken by all dental professionals) leads to seroconversion and will provide cover for the very small minority of individuals (5–7%) who may not seroconvert after the first two doses. 6 Of the currently recommended COVID- 19 vaccines, all apart from the Johnson and Johnson vaccine need to be administered as a double dose, and even the latter vaccine appears to confer higher protection after a double dose. A double-dose Johnson and Johnson vaccine trial is currently being conducted in UK (Table 1).

Despite such emerging and striking data on COVID-19 vaccine efficacy, the rate of vaccine uptake appears to be low in most parts of the world. One reason for this may be the so-called ‘vaccine hesitancy’ due to their real or perceived adverse side-effects.

Another could be the ‘vaccine politics’ that has subsumed vaccine uptake, particularly in USA.

Indeed, side-effects of any vaccine are a major concern in general. This is particularly the case when, in the case of COVID-19, a vast majority (approximately 70%) of the whole human populace has to be vaccinated to elicit global herd immunity. Hence, hard data on vaccine side-effects are needed. With the numbers of vaccines in different jurisdictions increasing on a daily basis, these effects can be seen in a much better light. The WHO, the European Medicines Agency (EMA) and the vaccine regulators in the UK keep a tab on such vaccine adverse effects. For instance, in the UK where 10 million doses of each of the AstraZeneca and Pfizer vaccines have been administered to date, it appears that both vaccines cause between three and six adverse effects, all of which are mild, for every 1000 doses of vaccines administered. 7

Although, overall, vaccine-associated severe morbidity seems to be relatively low, a few sporadic reports of major illnesses, such as anaphylaxis that may be likely to be associated with vaccination, appear to be a major concern in some quarters. 8 Another case in point is the AstraZeneca vaccine, which was recently suspended in over 13 European countries due to reports of ‘thromboembolic events,’ and later re-introduced (as we were going to press), 9 and the sporadic reports of facial palsy with the Sinovac vaccine. 10 Yet, it is too early to draw conclusions from these sporadic reports of severe adverse effects, particularly in older people with various comorbidities, until the causality of such adversity is confirmed by detailed analyses, and differentiated from mere association and coincidence.

Yet another headache for the vaccine manufacturers is the efficacy of their vaccines in the face of the intermittent arrival of new viral variants through genetic mutations. 11 There are up to three major viral variants, and their derivatives, in global circulation: B117 (UK), B1351 (South Africa) and P1 (South America/Brazil1). Fortunately, a number of the currently available vaccines appear to be highly effective against these variants (Table 1). Indeed, according to the manufacturers of mRNA vaccines (i.e. Moderna and Pfizer-BionTech) these are amenable to rapid chemical reconfiguration to combat the variants in the event of the emergence of host-susceptible, viral penetrants, which may become the predominant circulating strain/s. RNA viruses mutate frequently, although the frequency of mutation in corona viruses is generally lower than other RNA respiratory viruses, such as influenza viruses. This appears to be a saving grace in the battle against COVID-19; however, the unpredictability of viral mutations in general means that there is a great need to keep a close vigil and be ready for rapid action in such an event.

Returning to the story of COVID-19 vaccine administration, there are still a number of debated issues, such as its administration for those who have contracted the disease, mixed vaccine administrations, timing of the first and second dose, and the necessity for a second dose. Various authorities have now stated their positions on these, and given below are salient excerpts of interest to the dental profession, obtained from the recommendations on various vaccine protocols appertaining to special situations, as promulgated by the UK JCVI, 12 as well as the US ACIP. 13 However, it should be noted that the statements below are based on the currently available data (20 March 2021), and owing to the dynamic nature of the topic, they are subject to constant revision and modification.

Vaccines for COVID-19 are the last great hope for eradicating a ‘once in a century,’ debilitating disease from the face of the earth. Nevertheless, there are many nay-sayers, vaccine doubters, and falsehoods that have led to their rejection by a significant proportion of the community in all regions of the world. Hence, dental professionals have a duty and an obligation to inform their patients, and the local community, of the truth and facts behind the vaccines, and dispel the concerns and fears surrounding this issue. It should not be forgotten that ‘no one is safe until all are safe’ and there is a critical need for global eradication of the virus to return to a post-COVID-19 ‘normalcy.’ For, mutants/variants that may be resistant to the current crop of vaccines, originating from any far corner of the world may lead to further frightening waves of the pandemic.