Beginner's Guide to Covid Vaccines

Introduction

As the world totters into its second year of the global pandemic, with over 100 million cases and 2 million deaths, everyone has been looking towards vaccines as the “light at the end of the tunnel”. As the first shipments of the Covid vaccines arrive in Hong Kong and appointments are opened to the public, the question of how the general public can understand, evaluate and make informed decisions based on the performance of Covid vaccines becomes ever more pressing.

Chances are, you have already come across news articles speaking of the results of “Phase III” clinical trials, of the “efficacy” of vaccines, of reports of “serious adverse events”. But what do these widely publicized results mean exactly? This article hopes to provide a guide on how to evaluate the efficacy and safety of vaccines, and to provide a summary and comparison of the characteristics of the two vaccines that are locally available.

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Clarifications on Terminology

The names of vaccines can be genuinely confusing – a vaccine can be referred to by its brand name, trade name, or the name of the companies which developed it, and one might easily confuse one vaccine to be several different vaccines. For clarification, the two vaccines currently available in Hong Kong are:

1) Comirnaty / BNT162b2 / COVID-19 mRNA vaccine / Pfizer-BioNTech vaccine / Fosun-BioNTech vaccine / 復必泰

2) Coronavac / Sinovac vaccine / SARS-CoV-2 Vaccine (Vero Cell)

In the rest of the article, I will mostly be referring to these vaccines as the Pfizer vaccine and the Sinovac vaccine, respectively.

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How the Vaccines Work

The Pfizer vaccine and the Sinovac vaccine are made in very different ways:

- The Pfizer vaccine is an mRNA vaccine. The mRNA in the vaccine instructs our body’s own cells to produce a harmless virus protein (known as the “spike protein”), which is displayed on the cell surface. The protein is recognized by the body’s immune cells, stimulating the production of antibodies and the development of immunity.

- The Sinovac vaccine is an inactivated vaccine. It is occasionally referred to as “Vero Cell” because it is produced by inoculating African green monkey kidney cells, known as Vero cells, with SARS-CoV-2, then harvesting and inactivating the viral particles. These viral particles in turn stimulate the development of immunity.

The noteworthy difference between the two vaccines’ mechanism is that one is more innovative while the other is more traditional.

- mRNA vaccines (which the Pfizer vaccine belongs to) is a relatively new vaccine type. Although scientists have been researching this type of vaccine for decades, Pfizer’s Covid vaccine is the very first one to be approved for use in any disease.

- Inactivated vaccines (which the Sinovac vaccine belongs to) is a more traditional type of vaccine, with around a century of research and usage behind it.

What are the practical implications of this difference? The relative novelty of mRNA vaccines could mean that Pfizer’s vaccine has a greater level of uncertainty in terms of long-term risks compared to Sinovac’s; on the other hand, this novelty could also harbor greater potential for strengths and advantages compared to more traditional vaccines.

At the end of the day, however, all vaccines, new or traditional, are subjected to the same standards of clinical efficacy and safety, and the main criteria for evaluating a vaccine should be the vaccine’s actual, objective safety and efficacy data in large-scale clinical trials, rather than tenuous and subjective inferences based on the vaccine’s nature.

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Efficacy

The “efficacy” of a vaccine in a clinical trial is calculated by comparing the incidence of infection in the experimental group (who receives the vaccine), and the control group (who receives a placebo). For those of you that want a bit of mathematical precision,

Vaccine efficacy = 1 – (incidence in experimental group / incidence in control group)

What this means is that if a vaccine is found to be 90% effective, it theoretically reduces your risk of infection to 1 – 90% = 10% of the previous level.

Although this single number might seem relatively straightforward, there are several caveats to keep in mind:

- The efficacy of a vaccine may vary based on the outcome. For instance, a vaccine may have a higher efficacy in preventing severe diseases compared to mild diseases. In such a case, it is important to not be misled by one single number, and to get a full picture of the vaccine’s performance.

- Efficacy is not the same as effectiveness. Efficacy refers to the vaccine’s performance under the highly controlled conditions of a clinical trial, while effectiveness refers to the vaccine’s ability to prevent disease in real-life situations. In real life, many factors such as vaccine storage and transport, the skill of healthcare workers who administer the vaccine, etc. could all affect its effectiveness.

- A vaccine doesn’t need to be 90% effective to be useful. According to CDC data from the past decade, the effectiveness of flu vaccines is generally less than 50%, yet it is still regularly given during flu seasons. While such a vaccine may not be capable of eradicating an infectious disease, it can still be helpful in limiting its spread. That being said, the WHO Target Product Profiles for COVID-19 Vaccines states that an efficacy of 70% is preferred, with a minimum efficacy requirement of 50%.

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Safety

A vaccine’s safety profile is mainly indicated by the increase in occurrence of adverse events after administration. Important points to note include:

- Just because certain adverse events occurred in vaccinated populations, does not mean that the vaccine puts you at increased risk of those adverse events.

- Temporal correlation does not equate to causation. Simply put, just because an adverse event occurs after vaccination, does not mean that the vaccine caused the adverse event.

- Cases of severe adverse events (e.g. death) are often heavily reported in the media, which can easily lead to misguided fears. So far, most cases of death after vaccination occurred in elderly people with multiple comorbidities; in these cases, it is quite likely that their underlying disease, rather than the vaccine itself, was the true cause of death. While it is important to pay attention to these reports, it is equally important not to draw premature conclusions before a thorough investigation has been completed.

- Vaccines (and drugs in general) may have long-term adverse effects that are not immediately evident. Follow-up studies of vaccinated individuals would be needed to ascertain these effects, and it is possible that we might not know about them until years later.

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Pfizer versus Sinovac

Since the vaccine rollout has begun, I have been asked several times for my recommendation on which vaccine to get. While I cannot provide a clear-cut assertion as to which vaccine is superior, I do hope to provide a basic comparison of the two vaccines on several areas of performance, based on currently available information (as of March 12, 2021), which will hopefully stimulate the reader to gather more information and make their own decisions.

Efficacy

In terms of efficacy, the Pfizer vaccine reports a higher overall efficacy (95%) compared to the Sinovac vaccine, although it does not distinguish between mild and severe infections. The Sinovac vaccine’s efficacy results from different trials vary greatly, possibly because of the small sample size, and because some trials only have preliminary results. A trial from Brazil also shows that the Sinovac vaccine is more effective in preventing moderate to severe infections, compared to mild infections.

- The Pfizer vaccine had an overall 95% in its Phase III clinical trials (from ~30,000 subjects), with similar results in different ages, races and sexes.

- The Sinovac vaccine reported varying efficacies from its Phase III trials conducted in various countries. A trial in Turkey reported a final result of 83.5% efficacy (from ~10,000 subjects); a trial in Indonesia reported 65.3% efficacy (from ~1600 subjects), and a trial in Brazil reported 100% efficacy in preventing moderate to severe disease (which was, however, not statistically significant), 78% efficacy in preventing mild to severe disease, and 50.38% efficacy in preventing very mild to severe disease.

Adverse Events

In terms of safety, the Pfizer vaccine reports a higher incidence of many side effects compared to the Sinovac vaccine. However, it is important to note that while the safety data of the Pfizer vaccine comes from a large Phase III trial involving over 30,000 subjects, the best available scientific data on the safety of the Sinovac vaccine comes from a Phase II trial of 600 subjects. Below is a rough summary of the most common reported adverse events in Pfizer and Sinovac’s clinical trials (Note that the original data is stratified according to many factors such as dosage, administration schedule, etc.)

Injection Site PainFatigueHeadacheMuscle PainPfizer~80%~50%~30-50%~20-30% Any Side EffectPainLocal Reactions (e.g. rash, swelling)Systemic Symptoms (e.g. fatigue, headache)Sinovac~30-35%~10-25%~10-25%~10-15%

Severe Adverse Events

Both Pfizer’s and Sinovac’s vaccines have seen reports of severe adverse events, including deaths, after administration, but so far there has been little to no evidence showing that these events were directly caused by the vaccine. It would be impossible to describe all reported cases of severe adverse events in this article, but some more notable cases include:

- On Pfizer’s side, 30 elderly people in Norway died after receiving the vaccine; while it is possible that vaccine side effects aggravated their underlying conditions, the WHO reports no evidence that the vaccines were the cause of death. Additionally, over 40 cases of severe allergic reaction were reported among the first 9.9 million doses, leading to recommendations for a 30-50 minute monitoring period after vaccination.

- As for Sinovac, since the vaccine’s rollout in Hong Kong, there have been four reported cases of death following vaccination. Most of these deaths involved elderly people (mostly in their 60s-70s), who had multiple preexisting comorbidities, such as diabetes, hypertension, high cholesterol, etc. Among the four deaths, an expert panel has determined that the first two deaths were not related to the vaccine, while the latest two deaths are still under investigation. Additionally, there have so far been around 70 cases of adverse events reported to the Department of Health, which included 47 cases of hospitalization.

The details of the four deaths are summarized below:

#AgePreexisting ConditionsCause of Death as Determined by Expert Committee163Diabetes, hypertension, chronic bronchitisNot related to vaccine Acute heart attack and pulmonary edema, leading to respiratory failure 255Hypertension, high cholesterol Not related to vaccine Rupture of the aorta leading to rupturing of arteries in the neck, which caused a stroke attack 371No significant medical history Had thyroid problems a few years agoUnder investigation Entered coma 4 days after vaccination, died after being sent to hospital. 470Hypertension, osteoarthritisUnder investigation

So far, there have not been many local reports of adverse events following administration of the BioNTech vaccine, which is likely due to the low number of doses administered in Hong Kong. As administration of the BioNTech vaccine picks up speed locally, we may likely see more reports of its adverse effects.

Data Availability and Transparency

Finally, apart from efficacy and safety, the availability and transparency of data is another aspect that should be considered. While detailed results from Pfizer’s Phase III clinical trial was published in the New England Journal of Medicine last December, Sinovac has only published results from its Phase II trial, which is much smaller in size and may be a less accurate reflection of its actual performance. While we have received some of the results from Sinovac’s Phase III trials, they were mostly revealed in a piecemeal manner to the public by public health officials in various countries, and none of them have been published in a medical journal (the Hong Kong government waived the requirement that the vaccine’s late-stage clinical trials be published in a medical journal, instead having Sinovac send the results from the Brazil trials directly to an expert panel of the Food and Health Bureau). According to Sinovac, this was due to difficulties collating the necessary information for publication. Thus, until more comprehensive data is published or publicized, it may be difficult for the public to accurately evaluate the vaccine’s profile.

Booking the Vaccine for SJC students

Currently, the vaccines are only available for priority groups in Hong Kong. (https://www.covidvaccine.gov.hk/en/programme) Most SJC students would have to wait until further announcements on when they will be eligible to book for the vaccination.

Vaccination at community centers

- Students can get vaccinated in community centres that provide either the Sinovac vaccine or the Pfizer vaccine

- The homepage for the HK government organized vaccination program is https://www.covidvaccine.gov.hk/en/

- You can book for vaccination at a community center at the government website https://booking.covidvaccine.gov.hk/forms/index.jsp

- Before booking, you can check for availability of quotas at https://booking.covidvaccine.gov.hk/centre/index.html

- Youtube video guide to vaccination booking: https://www.youtube.com/watch?v=bsT2XmOpIc0

Vaccination at private clinics

Starting from March 1, the government has been distributing the first batch of the Sinovac vaccines to certain private doctors and clinics that have signed up for participating in the COVID-19 Vaccination Programme (Pfizer vaccines have not been distributed to private clinics due to their stricter storage requirements). These private doctors and clinics have started providing vaccination to members of the public from March 2. As of March 3, around 1 350 private doctors (around 1 860 clinic locations) have joined the programme. You can see the list of private doctors and clinics who have placed orders for the vaccines at https://www.covidvaccine.gov.hk/en/VSS. This list is updated in a timely manner.

Apart from community centers and private clinics, students the public can also receive the Sinovac vaccine at designated general outpatient clinics (GOPCs) of the Hospital Authority, For details, go to

https://www.covidvaccine.gov.hk/en/programme

DISCLAIMER: The contents of this website are solely owned by the author of each article and does not represent the views of the Awareness Committee or the Editorial team.