COVID-19 vaccines- panacea or delusion: A public health perspective
Arun Kumar Yadav1, Subhadeep Ghosh2, Atul Kotwal3
1 Associate Professor, Department of Community Medicine, AFMC, Pune, India
2 Dir Health, O/o DGAFMS, India
3 MG Med (SW) Comd, Armed Forces Medical Services, India
Assoc Prof (Dr) Arun Kumar Yadav
Department of Community Medicine, AFMC, Pune - 411 040, Maharashtra
Source of Support: None, Conflict of Interest: NoneCheck
The number of COVID-19 cases has crossed 65 million with 1.5 million deaths, and the pandemic has affected more than 200 countries across the globe as of December 05, 2020. One of the tools from the public health armamentarium, which might help in preventing cases of COVID-19 and ending the pandemic with returning to normalcy, is the vaccine. The vaccine development, manufacture, and distribution at such a large scale in a short period have never been carried out in the history of humankind. This paper focuses on the public health aspects of vaccination for prevention and control of COVID-19.
Vaccines have been known to humanity for more than 300 years now. Over a period of time, the technology, availability, and effectiveness of vaccines have increased considerably. However, questions and concerns have been raised regarding the safety of vaccines since the very beginning. Although the communities in few countries are sharply divided into vaccine acceptors and antivaxxers, independent reviews and the World Health Organization (WHO) studies have clearly shown vaccines to be far safer than many therapeutic interventions. The available newer molecular techniques have made the vaccines even safer. The vaccine benefits are not only restricted to individual vaccinees but also extend to the society and the economy. An estimated 2–3 million lives are saved every year by vaccination. The pandemic's relentless march with a significant morbidity and mortality despite various preventive measures forced the world to look toward a safe and effective vaccine. Thus, the development of the vaccine for COVID-19 started at an unprecedented pace to ensure its availability at the earliest.Vaccine Candidates for COVID-19
The WHO launched access to COVID-19 Tools (ACT) Accelerator by the end of April 2020 to accelerate development, production, and equitable access to COVID-19 tests, treatments, and vaccines by bringing various stakeholders on board. The draft landscape of COVID-19 candidate vaccines assembled and released by the WHO on December 02, 2020, has 51 candidate vaccines in clinical evaluation and another 163 in preclinical evaluation. These include live attenuated, inactivated, viral-vector, protein subunit, nucleic acid (DNA and RNA) vaccines, and virus-like particle. Out of these, 13 candidate vaccines have been registered for the phase 3 trial and three out of these have completed phase 3 trials. Most of these vaccines require the administration of two doses at 14–56 days apart. Only two registered vaccine trials are for single dose and one for triple dose. Realizing exceedingly early that even if an effective vaccine is developed, its fair and equitable distribution would remain a challenge led to the development of fair allocation framework to share the product among countries. The framework aims to ensure equitable sharing of successful COVID-19 vaccines and treatment modalities. The COVID-19 vaccines global access (COVAX) pillar is jointly led by the global alliance for vaccines and immunization, coalition for epidemic preparedness innovations, the WHO, and other global partners. The goal of COVAX is to deliver at least 2 billion doses of approved vaccines and end the acute phase of the pandemic by the end of the year 2021 to have a pool of large and diverse vaccines and guaranteed access to participating economies. Simultaneously, a tool for assessment for country readiness for introduction of the vaccine has also been developed to help in their efforts.
Fair allocation mechanism for COVID-19 vaccines provides the value-based framework for prioritizing and allocating vaccines across countries. The overarching goal is to make vaccines a global public good contributing significantly to the equitable protection and promotion of human well-being. At the initial stage, countries would be provided vaccine in tranches to cover 20% of the population. This coverage of 20% of the people would protect health-care workers, persons above 65 years of age, and adults with comorbidity with the simultaneous allocation of essential vaccination to all countries. A total of 3% of the total population would be sufficient to cover health-care workers in all countries. If the first tranche has less than this amount, the vaccine may be prioritized among the health-care workers based on the framework values. In addition, epidemiological settings would determine the prioritization of groups. When supplies are severely constrained, the initial focus will be on reducing morbidity and mortality and maintaining the most critical essential services and reciprocity.National Response
The government of India constituted a high-level task force for vaccine development as early as the 3rd week of April 2020. The ICMR launched its COVID-19 vaccine portal on September 28. There are four vaccines uploaded on the website under the heading COVID-19 vaccines under trials. COVAXIN (indigenous, Whole-Virion inactivated, Bharat Biotech) is undergoing phase III human trial, Covishield (Serum Institute of India) has completed phase III trial, while Sputinik (Gamalaya, Russia) and ZyCov-D (Zydus/Cadilla) are currently in phase II human trials. Covaxin phase III for efficacy has 25 sites with a total sample size of 25,800. Covishield has 15 sites and is being tested for immunogenicity and safety with a sample size of 1600. ZyCov-D is in adaptive phase I and phase II trial for safety and immunogenicity in nine sites with 1048 sample size. Sputnik is in adaptive phase II and III trial conducted in nine centers with a sample size of 1600 for vaccine safety and immunogenicity.
In addition, in this entire schema, three issues to be addressed are the mass production capacity to cater to at least two doses of the vaccine for priority category; transport of the vaccine in potent form to the end user; and the vaccine's timing. As a country, India has already prioritized the target population to receive the vaccine based on the value framework of the WHO and maximum benefit to the public health. The priorities are being accorded to health-care providers and workers, frontline workers, population aged 50 years or above and less than 50 years with co-morbidities. India has an estimated 2.2 million health-care workforce spread over a vast area, which needs to be vaccinated on priority. Since there is no national database available for persons with noncommunicable diseases, sociodemographic attributes may be used for prioritization.
As most regulatory agencies would accord expedited authorization for use, monitoring of adverse events should be robust. India has one of the most successful child immunization programs and can utilize its experience of mass vaccination campaigns and routine immunization and cold chain management. India also has a robust electronic vaccine intelligence network. On similar lines, the COVIN app has been developed to compile priority lists and track the vaccine from manufacturer to user in its potent form, maintaining cold chain.Effectiveness and Safety of Vaccines
One of the major concerns is the effectiveness of these vaccines. As of December 05, 2020, no public or peer-reviewed published data are available on the effectiveness of COVID-19 vaccines. Two vaccines, Pfizer/BioNTech, and Moderna have organized press release of interim analysis of efficacy of the vaccine and claim to be 90% and 94% efficacious, respectively., However, both these are mRNA vaccines and require strict temperature control. Oxford/AstraZeneca on the other hand revealed conflicting reports regarding the range of efficacy depending on the initial dose. Certainly, more data on efficacy, immunogenicity, and long-term safety of the vaccines are required.
Notably, the current ongoing/completed trials of all candidate vaccines have been designed only to assess the efficacy in reducing the severity of disease and not for estimating the effectiveness against risk of infection and transmission of infection. The claim of reduction in transmission in the media is only being postulated based on protection by vaccine toward reduction in severity of the disease and has not been proven.
The trials of several vaccine candidates are being conducted at numerous sites involving many small establishments without any prior experience in vaccine trials. This coupled with the lack of transparency in data sharing all over the world, raises an important concern of quality assurance at each site and its impact on the eventual results. Another area of concern is the side effects, especially in the long term.Mass or Target Vaccination?
It is almost a year since the first case of COVID-19 was reported. Around 95% of the cases are either asymptomatic, mild, or moderate. The overall case fatality rate from SARS-CoV-2 infection is 1%. The serosurveys from various parts of the country have estimated the prevalence of seropositivity as 25%–75%. The immune response and the re-infection among COVID-19 remain yet to be fully understood. None of the trials have assessed the utility of vaccination among already infected persons. The purpose of vaccination at initial stage as per the value framework of WHO will be to reduce mortality among high-risk group (those above 65 years of age and with comorbidity) and preserve the health work force.
Thus, mass vaccination to reduce transmission or elimination of disease may not be warranted at this stage when the long-term effects and safety of the vaccines are not known. One of the reasons given for mass vaccination is to return to normal societal and economic activity. However, since it would take at least end of 2021 for vaccine to become available to everyone, most of the societal and economic activity would have been as such started by then. The opportunity cost for the purchase of the vaccine, its distribution, and impact on other national health programs also needs to be seriously considered before undertaking a huge exercise of mass vaccination.Way Forward
The unprecedented human suffering and the pandemic's unfathomable effect on social, economic, and cultural paradigms of the entire world has forced us to look for magic bullets in the form of a vaccine. It is extremely heartening to see the scientific community and organizations rising to the challenge, resulting in numerous candidate vaccines utilizing various approaches in such a short span. However, to make the vaccination efforts safe, effective, and result oriented with acceptance by all, the concerns of, transparency, effectiveness, and safety need to be addressed on priority. It needs to be ensured by the WHO and licensing authorities that the hubris of the large organizations involved in vaccine manufacture and trials should not undermine the vaccine efforts. Governments worldwide need to allay the anxiety and all concerns of the community as already a strong vaccine hesitancy and antivaccine movement is building up. We need to also emphasize the need for continuing preventive measures as hitherto fore for several more months even after the availability of vaccine. Otherwise, we may run the risk of continued transmission and human suffering. The stakes are high as any unwarranted excess risks, perceived or otherwise, or actual failures may potentially threaten the entire vaccination strategy for COVID-19 with repercussions on the routine immunizations for other communicable diseases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.