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Volume:4 Issue:3 Number:3 ISSN#:2563-559X
OE Original

COVID-19 Vaccines: Failure Is Not An Option

Authored By: OrthoEvidence

March 15, 2021

How to Cite

OrthoEvidence. COVID-19 Vaccines: Failure Is Not An Option. OE Original. 2021;4(3):3. Available from: https://myorthoevidene.com/Blog/Show/119


  • - The success of a vaccine program relies on a number of factors other than having an effective vaccine alone. To avoid vaccination failure for COVID-19, vaccine coverage in the population and non-pharmaceutical interventions (NPIs) during the vaccine rollout are crucial
  • - Low COVID-19 vaccine coverage is prevalent around the world. Other than insufficient production capacity, vaccine nationalism and vaccine hesitancy are grave threats. Equitable and coordinated global cooperation, promoting evidence-based information among the public, and re-establishing public trust are necessary solutions.
  • - NPIs, such as social distancing and mask wearing, have helped us to control the spread of COVID-19 before vaccines were available. Remaining unknowns about current COVID-19 vaccines and evidence from model simulation studies have warranted the necessity and essence of the continuation of NPIs as the COVID-19 vaccines roll out.
  • - The Centers for Disease Control and Prevention (CDC) released an interim guidance for fully vaccinated people to emphasize the importance and necessities of continuing NPIs when in public or in contact with unvaccinated people.

So, we really need to continue these precautions [Non-pharmaceutical interventions] while we're still learning about what the vaccines can do. … The vaccines are in short supply, so we don't have enough vaccines yet out in the community to protect everybody. … We have to continue the precautions [Non-pharmaceutical interventions] , especially the masking, the physical distancing, the hand washing and not gathering in big groups. For how long [do] we need to continue those interventions? Time is going to tell...

--Professor Katherine O'Brien, Interview with World Health Organization

March 11th, 2021 marked the one-year anniversary since the World Health Organization (WHO) declared COVID-19 a global pandemic. To date, COVID-19 has resulted in over 120 million cases and claimed more than 2.65 million lives all over the world (Johns Hopkins Coronavirus Resource Center). 

Vaccines against COVID-19 offer us the best chance to end the pandemic. In the past few months, several vaccines, such as the mRNA vaccine developed by Pfizer/BioNTech (BNT162b2) and the replication-deficient chimpanzee adenoviral vector-based vaccine developed by Oxford/AstraZeneca (AZD1222), have been tested under optimal and controlled research conditions and also proven effective in the real world settings (See past OE Original: COVID-19: Vaccine Effectiveness in the Real World). 

With the arrival of these effective vaccines and the prospect of vaccination for the general population on the horizon, people have high hopes that the spread of COVID-19 will soon be under control or even eliminated. Some people have even started talking about returning to “normal life” after being fully vaccinated, in which current public health measures such as social distancing, mask wearing, test and trace measures, and personal protective equipment are no longer necessary. 

However, having effective COVID-19 vaccines alone is not sufficient to guarantee the success of COVID-19 vaccination programs. The success of a vaccine program is a multi-factorial issue. In other words, several factors could lead to the failure of a vaccination program. 

Heininger et al. (2012) proposed a general framework for vaccination failure, which could be due to either actual vaccine failure or failure to vaccinate properly. Vaccine failure can be further divided into host-related and vaccine-related issues, while failure to vaccinate can be related to usage and immunization program-related issues (Heininger et al., 2012). 

Given the COVID-19 situation, we identified some possible factors that might result in the failure of the COVID-19 vaccination program in Table 1. As we can see, vaccine effectiveness is only one among many factors. We have addressed some of the factors in our previous OE Originals, such as COVID-19 Variants of Concern: Will There Be A Third Wave? (addressing the vaccine coverage of SARS-CoV-2 variants of concern) and COVID-19 Vaccines: What Does the Evidence Say about Delaying the Second Dose? (addressing recommendations regarding number and time points of vaccinations).

In light of the continuing progression of the COVID-19 pandemic, we discuss two other factors that are critical to the success of the COVID-19 vaccination campaign, which are vaccine coverage in the population and non-pharmaceutical interventions (NPIs) during COVID-19 vaccine rollout.

Table 1: Factors that may cause failure in the COVID-19 vaccine program

Vaccine Failure

Failure to Vaccinate Appropriately

Host-related issues

Vaccine-related issues

Usage issues

Immunization program-related issues

Waning immunity

Low vaccine effectiveness

Administration error (wrong or suboptimal route, inadequate dose, wrong diluent)

Suboptimal recommendations regarding number and time points of vaccinations

Suboptimal health status (e.g., underlying disease, nutrition)

Incomplete coverage of variants of concern

Vaccination series incomplete, non-compliance with recommended schedule

Low vaccine coverage in the population (due to vaccine supply issues, vaccine nationalism, or vaccine hesitancy)

Pre-existing infection with pathogen or immunization during incubation period (after exposure to pathogen)

Manufacturing- related failure (e.g. batch variations, quality defect)

Transportation and storage failure

Suboptimal recommendations regarding non-pharmaceutical interventions during COVID-19 vaccine rollout

adapted from Heininger et al. (2012) and modified according to COVID-19 situation

1. COVID-19 vaccine coverage in the population

1.1 Current state of COVID-19 vaccine coverage 

The picture of COVID-19 vaccine coverage is worrying. According to the data from Johns Hopkins Coronavirus Resource Center, globally, only Gibraltar and Israel have fully vaccinated more than 40% of their total population, followed by Seychelles (25.44%), United Arab Emirates (22.72%), and Cayman Islands (13.83%). 

For the United States of America (USA), less than 10% of its population has been fully vaccinated, although in absolute number, the USA has vaccinated the most individuals -- over 30 million, compared to other countries around the globe (Johns Hopkins Coronavirus Resource Center). 

Canada sits just above the world average for the percentage of fully vaccinated people in the population -- about 1.5% (over half a million people) (Johns Hopkins Coronavirus Resource Center). Every day in Canada, only 0.2 doses of COVID-19 vaccine is administered per 100 people in the total population, much smaller than the numbers of other countries such as Israel (1.06) and the USA (0.64) (Our World in Data, a collaborative effort between the Global Change Data Lab and the University of Oxford).

1.2 Vaccine nationalism

The major reason for this low coverage is without doubt the limited supply of COVID-19 vaccines. However, with pharmaceutical companies racing to increase their manufacturing capacity, the resolution of the limited supply problem can be expected. At the moment, the more concerning issue is the rise of vaccine nationalism (Fidler, 2020). Vaccine nationalism occurs when a country with the resources to obtain vaccines prioritizes securing doses of vaccines from manufacturers only for its own citizens or residents (Fidler, 2020). Vaccine nationalism not only puts developing countries with less resources and power at disadvantage, but also affects developed countries such as Canada, which has no control over COVID-19 production. 

Vaccine nationalism is a dangerous short-sighted policy, which may lead to vaccination failure. For countries that refuse to share COVID-19 vaccines, the pandemic might be under control for them in the short term with increasing numbers of people getting vaccinated. However, for countries with vaccine shortages, allowing COVID-19 to continue to rage means that we are allowing the virus to keep mutating, and it is likely that a SARS-CoV-2 variant which may resist or escape the vaccine will surface. As Dr. Bruce Aylward, the senior adviser to the director general of the WHO, pointed out, “Anything that restricts the ability to get these products out will affect our ability to control this disease and prevent variants emerging” (Eaton, 2021).

Countries with the power to obtain COVID-19 vaccines need to realize that none of us are safe until all of us are safe (Hurley, 2021). An equitable and coordinated global approach, which requires a “genuine commitment to ensuring equitable access to vaccines both between and within countries”, is urgently needed (Middleton et al., 2021). 

1.3 Vaccine hesitancy

Even with enough supply of COVID-19 vaccines, another factor, namely vaccine hesitancy, could still affect the coverage of COVID-19 in the population -- “a real threat” to the success of the COVID-19 vaccine campaign (Coustasse et al., 2021). We have previously addressed vaccine hesitancy in one of our OE Insight -- Vaccine Hesitancy: A Top 10 Threat to Global Health

Briefly, the success of any COVID-19 vaccine rollout relies on maximizing uptake in the population. However, surveys showed that even health care workers and medical students were hesitant to receive COVID-19 vaccines. For instance, Lucia et al. (2020) found that one in six health care workers surveyed expressed hesitance to get the COVID-19 vaccine; Roy et al. (2020) found that one in five medical students surveyed were unwilling to receive a COVID-19 vaccine immediately upon FDA approval. 

A majority of health care workers cited one of the following reasons for the vaccine hesitancy: wanting long-term (> 1 year) follow-up results of COVID-19 vaccines (29.19%), wanting medium-term (= 1 year) results (12.15%), and nothing would make them feel comfortable to get the vaccine (10.96%) (Lucia et al., 2020). A more recent study done by Dodd et al., (2021) identified two common reasons for unwillingness to receive the COVID-19 among regular people -- concern about the safety of the vaccine in its development (36%) and potential side effects (10%). 

Promoting and encouraging factual and scientific information would be a solution to solving the vaccine hesitancy issue among the general public (Coustasse et al., 2021). Vergara et al. (2021) proposed that the fundamental issue behind the vaccine hesitancy is lacking public trust, which could be built and strengthened by effective and specific public education as well as the role-modelling from public authorities. Guidry et al. (2021) shared a similar point of view and argued that efforts to increase people’s willingness should “go beyond just communications campaigns correcting misinformation about a COVID-19 vaccine to also focus on re-establishing public trust in government agencies.”

2. Non-pharmaceutical interventions (NPIs) during COVID-19 vaccine rollout

2.1 The necessity of NPIs 

Non-pharmaceutical interventions (NPIs), defined by the US Centers for Disease and Prevention (CDC), refer to “actions, apart from getting vaccinated and taking medicine, that people and communities can take to help slow the spread of illnesses. … NPIs are also known as community mitigation strategies” (US CDC). 

The COVID-19 is a new disease in human history; therefore, the human population has little immunity against it. That is why the disease has been spread at an unimaginable speed. To control the disease, NPIs have played a key role before the vaccine is available. A study, investigating the impacts of major NPIs in 11 European countries between February 2020 and May 2020, showed that NPIs including canceling public events and schools, self-isolating, and social distancing are effective ways to curb the spread of COVID-19 (Flaxman et al., 2020). A recent study, examining daily data from 175 countries, found that NPIs such as canceling public events, enforcing restrictions on private gatherings, and closing schools and workplaces made a great deal of contribution to controlling the pandemic worldwide (Askitas et al., 2021). 

Now that we have started the mass COVID-19 vaccination programs, a key question we need to ask is do we still need NPIs as COVID-19 vaccine rolls out? The answer is YES (Galanti et al., 2021; Spinelli et al., 2021).

As COVID-19 vaccination campaigns progress all over the world, we are facing unprecedented challenges and uncertainties. All these unknowns warrant the continuation of NPIs during the COVID-19 vaccine rollout. For instance, in addition to the issues in production, transportation, storage, and distribution of COVID-19 vaccines, we also have very limited data and evidence on many other things which are key to our success of the COVID-19 vaccination campaigns, such as the vaccine efficacy and safety for risk groups (e.g., older people, children, pregnant and lactating women), whether the vaccine could prevent asymptomatic transmission, how long the protection will last, and the effects of partial vaccination on controlling the disease (Bleier et al., 2021; Cohen et al., 2020; Opel et al., 2021; Soiza et al., 2021; Stafford et al., 2021; Past OE Original: COVID-19 Vaccines: What Does the Evidence Say about Delaying the Second Dose?). 

Evidence from mathematical model simulations also supports the adoption of NPIs during the vaccine rollout. For example, the model done by Galanti et al. (2020) examined the US data and suggested that relaxation before comprehensive population-scale vaccination would cause tremendous loss of the benefits brought by vaccination and result in the increase of CVOID-19 cases, hospitalizations and mortality, which in turn would increase the threshold for herd immunity.

A model which was based on data from several Chinese major cities and published in Nature Human Behaviour found that a gradual COVID-19 vaccination rollout alone could not contain the resurgence of COVID-19 without relying on the stay-at-home restrictions; however, combing vaccination with physical distancing could (Huang et al., 2021). 

A preprint published in MedRxiv established a model to evaluate the vaccine-behaviour Interplay using data from the United Kingdom, Italy, and France (Gozzi et al., 2021). The model ascertained the importance of NPIs and suggested that relaxing NPIs could jeopardize the benefits brought by the vaccine (Gozzi et al., 2021). 

Another preprint also built a model to investigate the integrated vaccination-NPIs based strategies in Ontario, Canada (Betti et al., 2021). The model showed that early relaxation of NPIs during the vaccine rollout would cause the increase of new cases and put our vaccination achievements at risk of being lost (Betti et al., 2021). Betti et al., (2021) recommended that delaying the relaxation of NPIs until 75% Ontarians have received vaccination by the end of 2021 is a relatively safe way to re-open.

2.2 Recommendations for NPIs during the COVID-19 vaccine rollout

There should be no doubt when it comes to the necessity of NPIs during the COVID-19 vaccine rollout. 

On March 8th, 2021, the US CDC released its interim guidance with regard to NPIs for people who received full vaccination against COVID-19 (defined as people who are two weeks after the second dose of the Pfizer/BioNtech and Moderna vaccines or two weeks after a single dose of the Johnson & Johnson vaccine) (CDC, 2021). 

The guidance focuses on “how fully vaccinated people can safely visit with each other or with unvaccinated people in private settings and how fully vaccinated people should approach isolation, quarantine, and testing” (CDC, 2021). 

Although permitting fully vaccinated people not to use NPIs under some conditions (e.g., visiting other fully vaccinated people indoors), the CDC guideline emphasized the importance of the compliance of fully vaccinated individuals with NPIs in the public or visiting unvaccinated people. The CDC recommended NPIs include wearing well-fitted masks, practicing physical distancing at least 6 feet, avoiding crowds and poorly ventilated spaces, washing hands often, covering coughs and sneezes, etc. (CDC, 2021)

The full guidance can be accessed here.

Closing Remark

The success of a vaccination campaign depends on multifactor in addition to having an effective vaccine available alone. In the context of the unprecedented COVID-19 pandemic, the vaccine coverage in the population and non-pharmaceutical interventions (NPI)s during the vaccine rollout are of extreme importance. 

Currently, low COVID-19 vaccine coverage is prevalent around the world. Low coverage may allow the SARS-CoV-2 to keep mutating among the unvaccinated population and increase the risk of emergence of a SARS-CoV-2 variant resisting or escaping current vaccines. To increase the COVID-19 vaccine coverage, expanding the manufacturing capacity is essential but not sufficient. Vaccine nationalism and vaccine hesitancy are real threats to the vaccine coverage in the population. Equitable and coordinated global cooperation, promoting factual and scientific information among the public, and re-establishing public trust could be the solutions.

NPIs, such as social distancing and mask wearing, had greatly benefited us to curb the COVID-19 pandemic and save thousands of lives before effective vaccines were available. As the COVID-19 vaccination campaigns progress, NPIs are still necessary and essential due to several reasons, such as vaccine shortage and unknown about the vaccine’s effects on preventing asymptomatic transmission. Mathematical model simulations have indicated the risk of resurgence of COVID-19 cases and the increase of threshold for herd immunity if we allow relaxation of NPIs too early. The relatively safe way is to wait until a high percentage (such as 75%) of people are fully vaccinated. The US CDC also released interim guidance for fully vaccinated individuals to stress the importance of continuing NPIs in public or when in contact with unvaccinated people.

Shall we defeat COVID-19? Yes, we will. Will vaccination failure happen for COVID-19? No, most likely not. But all of these depend on whether we collaborate with and trust each other, have patience, resist misinformation, and strictly adhere to guidance built upon science and evidence. 


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