Covid-19 vaccine – should I have it?

18th January 2021, Dr Chee L Khoo

Covid-19 vaccine

I am sure many of you have lots of questions about the whole vaccination roll out ranging from questions about safety, efficacy, herd immunity to elimination and “eradication”. It has been a busy 12 months but I thought I better update you on the relevant and important issues on Covid-19 with the vaccines pretty much at our doorstep.

  • What vaccines are we getting?

Covid-19 is a coronavirus and coronaviruses are RNA viruses. The spikey protein sitting on the surface of the virus is used by the virus to gain entry into human respiratory cells. Most of the vaccines available now and those still under development are designed to raise our body’s antibodies (Ab) against this S protein. So, when we meet the virus for the first time, we are primed and ready to fend off the virus.

How the S protein is delivered to the body differs from one vaccine to another. Pfizer has purified the RNA (genetic) code for the S protein and that is what is in their vaccine. Once in the body, it goes into cells and the cells make the S protein. This is recognised by the body’s immune system and because it is a foreign protein, neutralising antibodies are raised against the S protein. These neutralising antibodies reduce the severity of Covid-19 disease and deaths. There is a possibility that the neutralising Ab may also prevent infection. RNA material is very unstable and hence, it has to be stored under  minus 70 degrees Celsius.

The AstraZeneca/Oxford vaccine (AZO) also uses the RNA code for the S Protein but they deliver the RNA using a common cold vector, adenovirus, to do the job. Once inside the body, the adenovirus (with the S protein RNA) infects human cells and make them produce the S protein which then raise neutralising AB like the Pfizer vaccine. Because the RNA is inside a virus, the AZO vaccine just to be stored between 2-8 degrees Celsius. Because it is likely that most humans may already have antibodies against the common cold virus, the vaccine might be deactivated before they deliver the payload. The AZO vaccine uses a chimpanzee adenovirus and not a human adenovirus. The Russian and a few of the Chinese vaccines use the human adenovirus vector. Because we have not seen results of any Phase 3 trials from the Russian and Chinese vaccines, the effectiveness of those vaccines is unclear.

  • What about efficacy?

The gold standard of clinical trials is what we called randomised controlled trials. Participants are divided into two similar groups, one group is given the real vaccine and the other a placebo (“blank”). Neither the participants nor researchers know who was given what until the trial has ended and the data analysed. In both the AZO and Pfizer trials, participants were sent away after the injections and were told to come back if they have symptoms whereby they were swabbed to see whether they were infected with Covid-19. Of note, not everyone was swabbed. In particular, there must have been participants who were asymptomatic and were not detected or swabbed. In a small subgroup of participants in the AZO trial based in UK, all the participants were swabbed weekly, whether they had symptoms or not.

In the Pfizer trial, participants who had the vaccine were 90% less likely to come back with symptoms and when they did come back, the symptoms were only mild. This means the Pfizer vaccine reduce the number of patients with severe disease by 90% (i.e. efficacy rate is ~90%).

The AZO trial was conducted across multiple sites and the results published were a combination of the all the 4 major trials. Overall, the efficacy rate was 60%. However, a subgroup of participants who received the initial dose as a half dose and the second dose as a full dose had an efficacy rate of 90%.  We don’t know whether the AZO vaccine regimen rolled out in Australia will be based on the half dose/full dose protocol.

  • What will vaccination do?

The efficacy rate reported in the two trials is reduction of symptomatic infection. In other words, the vaccine should reduce the number of people with severe disease and the number of people who will die from Covid-19. We don’t know whether it will actually reduce the number of people getting the infection nor whether the vaccine will reduce transmission from one person to another.

There is a lot of discussion comparing one vaccine with the other but we shouldn’t and we can’t. Different trial populations in different countries with different prevalence of Covid-19 and with different rules of social distancing and facemasks makes the trials not comparable. For example, in countries where the infection is rife and there isn’t much social distancing or facemask use, the vaccine might look very effective in reducing disease burden and hence, a better efficacy rate.

It is expected that both vaccines should reduce transmission and hence, reduce new cases. Theoretically, they should both be as effective.

  • Is it safe?

Nothing is 100% safe but so far, nothing out of the ordinary has been uncovered. There were a couple of reports of multiple sclerosis type reactions after vaccination but it is thought that the patient already had those symptoms prior.

There were further reports of some deaths in Norway but it is thought to be related to allergic reactions. Experts are looking into the issue as this article went to air.

  • Is the vaccine approval rushed?

The technology behind RNA vaccines is not new. We have experience with RNA vaccines in the past with Ebola and HIV vaccines with no issues. The AZO, Pfizer and Moderna trials  was started in April 2020 and the regulatory authorities have been kept updated along the way. All safety aspects of the vaccines have been scrutinised like any other new treatments in Europe and US. No, the approvals were not rushed.

  • Will the UK (and SA) strain affect the vaccination?

R number (R0) refers to the effective reproductive number of the virus. It reflects the virus capacity to spread and indicate the average number of people that one infected person can pass the virus to. The R0 is not fixed. It develops over time. It is affected by how a population behaves (social isolation or not), and any immunity already possessed thanks to infection or vaccination. Location is also important – a densely populated city is likely to have a higher R0 than a sparsely peopled rural area. With social distancing and other measures, the generally accepted R0 for Covid-19 is about 2.7. The UK (and possibly South African) strain is said to be more transmissible with the R0 between 3-4. The strategy to attain control is to get the R0 below 1. The higher the R0is, the more coverage with the vaccination is required to achieve herd immunity.

  • How will it be rolled out?

Phase one will target people >65 years old and front-line workers. Phase two will be for the rest. People with underlying medical conditions will probably be ahead of the average person. Because of limitations of manufacturing, Phase 2 will probably commence close to the second half of 2021. Because Australia has a good grip on the situation, we are not desperate and an organised, albeit slower, roll out will not make any meaningful difference.

  • What about facemasks, social distancing and hand hygiene?

We don’t know whether the vaccine can prevent Covid-18 infection or reduce viral transmission or not. So, it is expected social distancing, facemasks and hand hygiene will still be needed for much of 2021.

  • Will Dr Khoo have the vaccine? Should I have the vaccine?

Herd immunity is attained when the entire population is protected either from natural infection or by mass vaccination. When we achieve herd immunity, the number of susceptible individuals is too small for infection to spread. Attempting to achieve herd immunity by letting increasing numbers of people to get the infection means many will die even though the mortality rate with Covid-19 is low. Sweden, Brazil, US and UK found out the wrong way, didn’t they? The only other option is via mass vaccination.

The level of herd immunity depends on the R number of the virus and the efficacy of the vaccine. The higher the R number, the higher the herd immunity required to control spread of the disease. The higher the efficacy of the vaccine, the lower the vaccine coverage need to be to achieve herd immunity. For example, a vaccine with an efficacy of 90% will require vaccine coverage of at least 66%. A vaccine with an efficacy of 60% will require vaccine coverage of 100% which is not achievable.

It’s not about protecting you and me alone. We all have loved ones, neighbours, colleagues or friends that may not fare so well if they get Covid-19. You don’t want to be the one who pass on the infection to someone less fortunate. I will have the jabs because I need to contribute to the herd immunity so that we can all benefit from achieving herd immunity. I don’t want to be the one who pass on the infection to someone else.