Review: What do various studies say about the real-world effectiveness of COVID-19 vaccines?
Sai Krishna Muthyanolla
May 21, 2021
The administration of various COVID-19 vaccines has begun in many countries. Parallelly, studies are being undertaken to understand the effectiveness of the vaccines in the real-world. Here is a review of some such studies.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has left no continent untouched. With vaccination being the critical way forward to curb the spread of infections and prevent the virus from mutating further, the unprecedented and concerted efforts of countries resulted in nearly 300 vaccine candidates which are in different stages of development. As observed in one of our earlier stories, 100 vaccines are in clinical development and 184 vaccines were in pre-clinical development stages as of 14 May 2021, according to WHO.
The development and clinical trials of vaccines against the SARS-CoV-2 virus (COVID-19), took place between six to 18 months of the pandemic’s onset. The disease was first detected in December 2019 in Wuhan, China. Within a year, on 02 December 2020, UK became the first country to give emergency authorization to a COVID-19 vaccine and on 08 December 2020, the country became the first in the world to begin its nationwide vaccination drive.
Vaccine manufacturers announced the efficacy results during phase-3 trials
While carrying out clinical trials of the vaccines, the manufacturers made announcements regarding the efficacy of their vaccines. For instance, announcements were made that the efficacy of the vaccines was 95% for the Pfizer–BioNTech, 94% for the Moderna–NIH, 90% for the Gamaleya, 66% for the Johnson & Johnson, and 67% for the AstraZeneca–Oxford vaccines, by the respective manufacturers. The efficacy of a vaccine is different from effectiveness. The efficacy of vaccine indicates the percentage reduction in disease occurrence among those vaccinated or in other words, the percentage decrease in the number of cases that would have been recorded if the vaccine were not introduced. The effectiveness of a vaccine, on the other hand, measures the ability of the vaccine to prevent the disease in the real world, that is, among the general population.
Vaccine effectiveness in real world uncontrolled setting needs to be analysed
In simpler terms, efficacy can be defined as the performance of an intervention under ideal and controlled circumstances, whereas effectiveness refers to its performance under ‘real-world’ conditions. Now that it has been nearly six months since mass vaccination campaigns against COVID-19 have begun worldwide, it is necessary to assess vaccine effectiveness for a range of outcomes across diverse populations in a non-controlled setting. Studies are being undertaken, taking into consideration various population groups such as elderly persons, healthcare workers, etc. to understand how effective the administered vaccines have been, in controlling infection & mortality. It should be remembered that vaccination does not imply 100% protection from the virus but helps in reducing the severity of the infection. Here is a brief review of some of the studies which highlight the efficiency of various vaccines. It has to be noted that these studies are still preprints and not yet peer-reviewed.
Among elderly persons, risk of mortality due to COVID-19 dropped post vaccination
In a first of its kind study, New Public Health England (PHE) conducted an analysis that estimated the risk of death in vaccinated COVID-19 cases compared to the unvaccinated group taking into consideration new symptomatic cases of COVID-19 between December 2020 and April 2021 and people who died within 28 days of their positive test by vaccination status. The analysis covering 48,096 cases aged 70 years and above revealed that protection against death from the Pfizer-BioNTech vaccine increased from approximately 80% after one dose to 97% after 2 doses. Individuals who received a single dose of the AstraZeneca vaccine had approximately 80% lower risk of death with COVID-19 compared with unvaccinated individuals. Furthermore, people who had a single dose of the AstraZeneca vaccine were 55% protected against death and those who had a single dose of Pfizer were 44% protected, compared to unvaccinated people. Protection against mortality from the Pfizer-BioNTech vaccine improved to 69% for cases who had their second dose at least a week before they tested positive. The two-dose effect of the AstraZeneca vaccine is yet to be analysed as the vaccine was rolled out later. The study notes that this is on top of the protection provided against becoming a case.
Risk of hospitalization also reduced for those aged 70+ because of vaccination
Another analysis by PHE covering the risk of hospitalization among older adults in England which included 13,907 hospital admissions aged above 70 years showed that the vaccine was highly effective in reducing the risk of hospitalization, especially in older ages. Among those aged above 80 years, it was estimated that 2 doses of the Pfizer-BioNTech vaccine reduce the risk of hospitalization by 93%. Among those aged above 80 years who had received one dose of the Pfizer vaccine, the risk of hospitalization dropped by 81% and for those who received one dose of the AstraZeneca vaccine, the risk dropped by 73%. In those aged 70-79 years, the effectiveness of the vaccine against hospitalization was 84% and 81% following the first dose of the AstraZeneca and Pfizer vaccines, respectively.
Vaccine was 90% effective in US among healthcare personnel
Another study by USA’s CDC assessing the effectiveness of Pfizer-BioNTech and Moderna vaccines in preventing SARS-CoV-2 infections among 3,950 health care personnel, first responders, and other essential workers in six states over a 13-week period from December 2020 to March 2021 indicated that vaccine effectiveness of full immunization with two doses of the vaccines was 90% after two or more weeks of vaccination. It was also seen that following a single dose of either vaccine, the participants’ risk of infection was reduced by 80%, after two or more weeks after vaccination. The vaccine effectiveness in preventing the infection after one dose of Pfizer vaccine in the US was 80% which was consistent with the studies conducted in the UK and Israel where the effectiveness of a single dose of Pfizer vaccine was 72% and 60% respectively.
Vaccine effectiveness was 91% for those who were infected three months before vaccination, in Sweden
Research by Lund University in Sweden evaluating the effectiveness of the Pfizer-BioNTech vaccine in preventing COVID-19 covering 805,741 study participants revealed that two weeks after the first dose, the vaccine was only about 42% effective and was about 86% effective in preventing COVID-19 in people who had no prior infection, seven days after the second dose. According to the study, people who had been infected earlier showed a 91% vaccine effectiveness. The effectiveness was still high when people had been infected more than three months before vaccination. After a week of the second dose, vaccine effectiveness was 60%, similar to the results from a study in Israel.
Efficacy of vaccines against new variants was lower in Qatar
While vaccine development was underway in 2020, new lineages of the virus were identified globally including the B.1.1.7 variant first discovered in UK and B.1.351 variant first discovered in South Africa.
A study by John Hopkins on the effectiveness of the Pfizer-BioNTech vaccine in Qatar’s national vaccination campaign including a sample of individuals who received vaccine shots in February and March 2021 also considered the variant of SARS-CoV-2 behind infection among the study population. Viral genome sequencing conducted from 23 February 2021 to 18 March 2021 indicated that 50% of cases of COVID-19 in Qatar were caused by B.1.351 and 44.5% by B.1.1.7. Almost all the cases in which the virus was sequenced after 07 March 2021 were caused by either B.1.351 or B.1.1.7.
The study found that the Pfizer vaccine’s effectiveness against the B.1.1.7 (UK) variant was estimated to be 89.5%, and that against the B.1.351 (South African) variant was 75%. Further, it was found that vaccine effectiveness against severe, critical, or fatal disease due to infection was 97.4%, though B.1.1.7 and B.1.351 variants were predominant. Comparison of incidences of infection between vaccinated individuals and those who were antibody negative, vaccine effectiveness was 87% against the B.1.1.7 variant and 72.1% against the B.1.351. Effectiveness against the B.1.351 variant specifically was approximately 20% lower than the 90% effectiveness seen in clinical trials and real-world conditions in Israel and the US.
Vaccines did not show protection against mild to moderate infection in South Africa
In another assessment of the efficacy of the AstraZeneca vaccine (also known as Covishield in India) against B.1.351 variant published in New England Journal of Medicine, 2026 HIV-negative adults from South Africa were part of vaccine trials between June to November 2020. It was seen that 23 of 717 placebo recipients (3.2%) and 19 of 750 vaccine recipients (2.5%) developed mild-to-moderate COVID-19 giving an efficacy of 21.9%. Of the 42 participants with the infection, 39 were due to B.1.351 variant giving a vaccine efficacy of only 10.4% against this variant. Thus, it was concluded that a two-dose regimen of the AstraZeneca vaccine did not show protection against mild-to-moderate COVID-19 due to the B.1.351 variant.
WHO cited study showing COVAXIN as being largely effective against Double mutant discovered in India
Preliminary laboratory studies awaiting peer review of the vaccines by Pfizer and Moderna have shown decreased effectiveness against the double mutant variants discovered in India according to WHO.  WHO has classified B.1.617 as a “variant of concern”, meaning that the mutant strain and its sub-lineages (B.1.617.1, B.1.617.2, and B.1.617.3) appear to have higher rates of transmission and prevalence in 44 countries. WHO also cited another non-peer-reviewed study that showed that Covaxin was largely effective against the double mutant strain of the virus.
Vaccination is key to reduce infection severity
To sum it up, it can be inferred that most of the COVID-19 vaccines appear to be effective and largely safe. Though a single dose can help in preventing the infection, a double dose is recommended as it would further reduce the chances of infection, and severity. Providing a large section of the population with at least one dose of vaccine is necessary to reduce infection rates till second doses are manufactured. However, there is not enough information on the long-term effectiveness or safety of the vaccines in terms of the duration of protection these can offer. For now, the only way forward is to vaccinate as much population as possible and develop herd immunity. Though some studies show reduced efficacy of vaccines, especially against the new variants, it needs to be seen if the effectiveness will be the same in the real world. Many such studies are still ongoing. Furthermore, trials are underway to study the efficacy of vaccines on children and pregnant women. Recently, the FDA gave approval for the Pfizer vaccine to be used in kids aged 12 to 15 years.
Featured Image: Effectiveness of COVID-19 Vaccines