Covid-19 vaccines: efficacy and safety

Photo by Lisa Ferdinando. licensed by creative commons

As more data come along, we will be able to refine our vaccination strategy

Three Covid-19 vaccines have received an authorization for emergency use in the UK: they are produced from Pfizer, Moderna and Astra Zeneca. The first two are mRNA vaccines, whilst the Astra Zeneca one has an adenovirus vector.

The two mRNA vaccines have been authorised in several countries, whereas the Astra Zeneca one has not been yet authorised by the EU or the US. The European medicines agency website states that additional information has been requested. The US regulator has announced that they will probably not authorise this vaccine until April because of the limited data on this vaccine available at this stage.

Astra Zeneca has been criticised for combining data from four separate trials as opposed to using a single study protocol as Pfizer and Moderna did.

Russia has also produced a vaccine similar to the Astra Zeneca one, known as Sputnik V, but with a different adenovirus vector. Sputnik V is already used in Russia, despite having been tested only on a small scale. Conversely, China has developed some conventional inactivated-virus vaccines.

In terms of efficacy, the 2 mRNA vaccines (Pfizer and Moderna) appear to have a higher efficacy than the Astra Zeneca one (see Table) and, currently, there is better evidence of efficacy in older individuals with the mRNA vaccines. Astra Zeneca is looking at ways of increasing the efficacy of their vaccine, including a possible combination with the Russian Sputnik V (one dose of each one).

It is too early to say what is the most effective vaccine. None of the vaccine studies have yet been completed and we do not know what the efficacy is in the long-term or in relation to virus variants or in specific sub-groups such as immunocompromised patients.

A subgroup of Astra Zeneca volunteers received a reduced dose in the first jab by mistake, but had a higher level of protection (90% efficacy instead of 62.1%). It is not known whether the apparent higher efficacy after the initial lower dose is genuine and what is the explanation.

There have been no deaths attributable to vaccination in the three vaccine trials. The alternative to vaccination is having the infection: in those aged 45 and above 5 every 1,000 patients with the infection die. Above the age of 75 the Covid-19 mortality is 12% (12 out of one hundred die).

Most vaccines, including the three authorised Covid-19 vaccines, cause mild transient side-effects such as pain at the injection site, fatigue and headache.

Severe allergic reactions with any vaccine are possible but infrequent. The allergic reaction risk might be higher with the mRNA vaccines, possibly because they contain polyethylene glycol (PEG). Thus, the Astra Zeneca vaccine is preferable in individuals with either a history of severe allergy or known allergy to PEG. Recipients of either the Pfizer or the Moderna vaccines should remain under observation in the vaccination centre for at least 15 minutes after the administration, as this is common the time scale for severe allergic reactions.

The US CDC recommends that Covid-19 vaccines should be administered in centres with access to the medications used to treat allergic reactions. 

There has been a small number of facial paralysis cases amongst the recipients of all three vaccines. Facial paralysis is unpleasant, but usually resolves over 2-3 months. The US Food and Drug Administration believes that the low number of facial paralysis cases is what would be expected in the general population, regardless of vaccination. The authors of the Moderna trial do not exclude a slight increase in the risk of facial palsy and have recommended monitoring.

One case of transverse myelitis (a severe neurological condition) has been reported in one of the 11,636 recipients of the Astra Zeneca vaccine: there is no certainty, but the investigators could not exclude that the transverse myelitis was triggered by the vaccine. However, without vaccination there is a significant risk of getting the Covid-19 infection, which can be followed not just by death but also by a range of complications including severe neurological complications like transverse myelitis.

As the authors of the Pfizer study have put it: we can be highly confident that these vaccines do not cause severe side-effects at a frequency of more than 1 in 10,000 vaccines. It would be rare for vaccines to cause significant side-effects at a frequency of less than that, but these infrequent events can only be detected after large-scale vaccination has started through phase 4 post-marketing surveillance.


More data will be available in a few months’ time from completion of the trials and from post-marketing surveillance. More vaccines are also likely to be authorised. We may eventually be able to identify what are the best vaccines.

However, the benefit-risk balance is already heavily tilted in favour of vaccination and particularly so in those aged 45 and above facing a much greater risk of death from Cocid-19. By the time we start vaccinating those below the age of 45, we will have even more data on efficacy and safety. Large scale vaccination would facilitate the much-desired return to “normality”.

*Efficacy in the group receiving 2 standard doses: this is the protocol currently used for vaccination in the UK.
**The UK government has decided to administer the two doses at intervals of up to 12 weeks.

Sources can be found below

Pfizer BNT162b2
Moderna mRNA-1273
Astra Zeneca AZD1222

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