The first COVID-19 vaccines have already been approved by MHRA, FDA, and EMA, as we are writing this blog post. The initial information about the effectiveness of the vaccinations has been very encouraging and the safety data for the vaccinations is very comprehensive due to the trials’ large sample sizes. However, already the first few allergic reactions following the vaccinations are headlining in the news outlets of US and UK [i].

Unique situation for the World and for Pharmacovigilance

2020 and COVID-19 has been a very unique situation in many aspects, and we can expect that 2021 and the safety monitoring and patient support for the vaccines will become a very unique situation for Pharmacovigilance. Never before has the whole world been vaccinated in such a short period of time with a handful of vaccines against one virus.

The attention the vaccinations and their safety are getting is also unheard of. COVID-19 has been the main news of the year and in some ways part of almost every discussion, thought and action in our lives since March. So now that the products are being used, their safety will be monitored following the existing best practices by healthcare professionals but what we can also expect is a close monitoring of billions of people who have been eagerly waiting for the vaccine.

Hopefully, the number of patients vaccinated against COVID-19 next year will be large and also, the collection of safety related information will be on a completely new level. This combined with the vigilant monitoring of COVID-19 cases on national level should lead to a completely new kind of dataset that could benefit the image of vaccines in general.

We hope that when new COVID-19 cases are found, the vaccination status of the patient will be well documented in order to produce reliable information about the vaccines with larger population. The huge amount of attention could mean a large number of reported adverse events because all vaccines have, typically, at least mild side effects.

Below we have described general information about the vaccines that have been already approved or probably will be soon approved. We describe what kind of adverse events are to be expected for the vaccines and how often these appeared in the trials.

Vaccination approval situation

Currently, there are four vaccines undergoing evaluation (or approved) by the EMA[ii] The BioNTech / Pfizer vaccine was approved by the MHRA on December 2, 2020 and it received emergency use authorization from the FDA on December 11, and EMA’s authorization on December 21[iii]. Moderna’s vaccine was approved by the FDA December 18[iv]. The vaccine from China’s Sinopharm is already in use in China and has been approved for use in Bahrain and UAE[v]. Russia’s Sputnik V vaccine has been administered to 200,000 people in the country[vi]. The approval situation is changing daily, and the number of approved products globally will be growing in January to ensure that there are enough approved vaccines to be distributed globally.

Safety and efficacy of the vaccines

BioNTech and Pfizer – BNT162b2 mRNA COVID-19 Vaccine

BNT162b2 was 95% effective in preventing COVID-19 with patients receiving two doses, 21 days apart[vii]. 43,448 people received injections: 21,720 with the vaccine and 21,728 with placebo. In the vaccination group there were 8 cases of COVID-19 with onset at least 7 days after the second dose and 162 cases in the placebo group.

The safety profile of the BioNTech and Pfizer vaccine was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Safety over a median of 2 months was similar to that of other viral vaccines.

The most commonly reported systemic events were fatigue and headache. Other common systematic event was fever (temperature, ≥38°C), that was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients.

Adverse events were reported more by the vaccine group than the placebo group (27% vs. 12%). No deaths were considered by the investigators to be related to the vaccine or placebo. No COVID-19–associated deaths were observed.

AstraZeneca – ChAdOx1 nCoV-19 vaccine (AZD1222)

In participants who received two standard doses, vaccine efficacy was 62.1% and in participants who received a low dose followed by a standard dose, efficacy was 90.0%[viii]. 11,636 participants in these two groups met the inclusion criteria for the primary analysis, 5,807 of whom received two doses of ChAdOx1 nCoV-19 and 5829 of whom received two doses of control product.

Local and systemic reactogenicity of ChAdOx1 nCoV-19 has been shown to be tolerable and the side-effects are less both in intensity and number in older adults, with lower doses, and after the second dose.

Serious adverse events in 79 participants in the ChAdOx1 nCoV-19 group and 89 of whom received MenACWY or saline control. There were 175 events (84 in the ChAdOx1 nCoV-19 group and 91 in the control group), three of which were considered possibly related to either the experimental or a control vaccine. Although there were many serious adverse events reported in the study in view of the size and health status of the population included, there was no pattern of these events that provided a safety signal in the study.

There were four non-COVID-19 deaths reported across the studies (three in the control arm and one in the ChAdOx1 nCoV-19 arm) that were all considered unrelated to the vaccine.

Janssen – COVID-19 vaccine Ad26.COV2.S

Janssen’s vaccine is under rolling review from EMA since December 1, 2020. Janssen is conducting trials in people to assess safety and immunogenicity, and effectiveness[ix].

In July, Janssen published information about their results rhesus macaques[x]. The results demonstrated protection against SARS-CoV-2 with single-shot vaccine in non-human primates.

Moderna – mRNA-1273

EMA has started the assessment for Moderna’s vaccine for conditional marketing authorisation [xi]. The assessment is proceeding under an accelerated timeline. CHMP concludes its assessment latest January 12. EMA has already reviewed some data on the vaccine during a rolling review.

Moderna has reported preliminary safety and efficacy results from the study in two articles[xii].

Gamaleya National Center – Sputnik V

The vaccine from Russian government research centre has recently published safety and efficacy results from their trials[xiii]. Evaluation of efficacy was carried out among 22,714 volunteers (17,032 vaccine, 5,682 placebo) 21 days after receiving the first dose of the vaccine or placebo. The data analysis at the final control point of the trials demonstrated a 91.4% efficacy rate.

The analysis of the Sputnik V vaccine efficacy at the final control point was carried out on the basis of 78 confirmed cases identified in the placebo group (62 cases) and in the vaccine group (16 cases).

Sinopharm – CoronaVac

The safety information for the vaccine from Chinese government owned Sinopharm has been published[xiv]. 743 participants received at least one dose of the investigational product (143 for phase 1 and 600 for phase 2).

Two doses of CoronaVac at different concentrations and using different dosing schedules were well tolerated and moderately immunogenic in healthy adults aged 18–59 years. The incidence of adverse reactions in the 3 μg and 6 μg group were similar, indicating no dose-related safety concerns. Most adverse reactions were mild, with the most common symptom being injection-site pain, which is in accordance with previous findings for another inactivated COVID-19 vaccine from Sinopharm. Compared with other COVID-19 vaccine candidates, such as viral-vectored vaccines or DNA or RNA vaccines, the occurrence of fever after vaccination with CoronaVac was relatively low.

These results supported the approval of emergency use of CoronaVac in China and in three phase 3 studies. The protective efficacy of CoronaVac remains to be determined. Results for the phase 3 studies are yet to be published.

Discussion

It could be expected that the total number of adverse event reporting has increased in 2020 due to COVID-19 because people’s attention to their health has been on unprecedented level. However, it can also be seen that the COVID-19 situation has had a negative effect on the reporting and monitoring of other illnesses such as influenza[xv].

In 2009 and 2010, almost 40 million people (only 10% of the European population) were vaccinated against influenza A/H1N1 and 16,000 reports were received to EudraVigilance on three different vaccinations. It remains to be seen how well these adverse events will be collected.

Now hopefully close to 400 million people in Europe will be vaccinated. Will this lead to 10 times more ICSRs? Or more because of the increased attention? It remains to be seen.

IQVIA is planning to create 170 new jobs just for monitoring the safety of the Covid-19 vaccines[xvi]. The company is recruiting in the areas of medical information and pharmacovigilance, with a focus on delivering these services in support of the commercial launch of Covid-19 vaccines.

What if the worst-case scenario happens and the vaccines are not safe in the long-term and the worst possible negative image falls upon the pharmaceutical industry and drug safety? What kind of implications will this have for the future of the Pharmacovigilance industry?