Covid vaccine dilemma curbing the herd immunity in India- Jab or no jab?

After the devastating second wave of COVID-19, with the rapid increase in the number of new cases in many states of India marking the beginning of a probable third wave of COVID-19, our best bet is taking a jab to protect against COVID-19. Currently, licensed vaccines are found to be reasonably safe and effective. The second wave of COVID19 was devastating, but it's a silver lining to note that most of the individuals who had taken the jab recovered with mild infections, and the hospitalization rates among jabbed individuals were meager. Various rumours related to the efficacy, safety, content, and side effects of the vaccine in India had caused a plunge in the vaccine acceptance rate leading to hesitancy and carelessness among the Indian population. This is a critical time for facts, not fear or rumors. This review provides an insight into the myths, pros and cons, and efficacy of the available vaccines.


INTRODUCTION
he Coronavirus disease is an invisible enemy, a lethal single-stranded RNA virus belonging to the family coronaviridae, mimicking severe acute respiratory syndrome. This disease produces a wide range of symptoms from the common cold, diarrhea to fatal illnesses. It first originated in the city of Wuhan in China in 2019, hence coined as covid-19, after which it has rapidly spread to various countries worldwide, rendering it a pandemic (1). This novel virus name was replaced with "SARS-CoV-2" due to the respiratory symptom depicted.
The outbreak of coronavirus disease has played a devastating role, infecting over 206 million people worldwide as of August 13 th , 2021. India, the United States of America (USA), and Brazil (2). The second wave has gripped India, with more than 27 million cases of COVID-19 and more than 300,000 deaths (3).
India has overtaken the USA in this wave and is the hardest hit country globally regarding socioeconomic burden. The government reported an unprecedented surge of 352,991 new infections cases on 25 April 2021. Daily global cases have surpassed 899,755 in a week, breaking a record set in January (4).
In May 2020, 95% of the total COVID-19 positive cases were found in urban spaces. 40% of the total cases in the country were found in the four densely populated cities in India; Delhi, Mumbai, Chennai, and Kolkata. This further spread to rural areas in the second wave. One out of six Indian resides in an urban slum that are situated in close proximity with no proper ventilation. Restraining the spread was an arduous task and nearly impossible in this living condition (5). Precise treatment for this deadly disease is still in progress, and nationwide all countries have diverted their efforts towards curbing this detrimental health hazard. The silver lining was observed around the world when a vaccine was secured, and it relieved the emotional, mental, physical, and economic baggage faced worldwide. India started the largest vaccination drive on January 16 th , 2021, with two vaccines available, Covishield (Serum Institute, Pune, India) and Covaxin (Bharat Biotech, Hyderabad, India) to develop herd immunity. Both are administered in two doses intramuscularly (6). Even though safe and effective vaccines were issued, there was a surge in daily cases in India.
Moreover, vaccination programs, especially in India, have faced significant obstacles. Sporadically 10% of the target population in the country was vaccinated by the end of March, and in the stipulated period, end of June, the remaining 90% needed to be covered. Varied rumours related to the efficacy, safety, content, and side effects of the vaccine in India had caused a plunge in the vaccine acceptance rate leading to hesitancy and carelessness (7). Thus, interfering in curbing the catastrophic spread of this disease.
To identify the scope of this problem, this nonsystematic review aimed to assess the acceptance rates for COVID-19 vaccines in different cities in India and provide insight into the myths, pros and cons, and efficacy of the available vaccines. Thus, eradicating the potential for fallacy which lies behind these vaccines.

II. Vaccine drive phases
Accordingly, these vaccines were allocated in phases by the National Expert Group on Vaccine Administration for COVID-19 (NEGVAC). These vaccines were first offered to healthcare workers, frontline workers, followed by senior citizens above 60 years of age. By 14 th April, more than 111 million people had been vaccinated in the country. However, anticipating vaccine shortage, the government halted the export of Oxford-AstraZeneca vaccine, also known as Covishield (9). India claimed to vaccinate over 300 million of its population, therefore speculated to procure 600 million doses. The next phase vaccinated individuals above 45 years with/without co-morbidities. The following phase vaccinated individuals above 18 years. However, below 18 years are still facing the brunt and eagerly awaiting the green signal.

III. Current vaccination scenario in India
As of 14 th august 2021, the ministry of health and family welfare reported that India has vaccinated 536188903 of its population amidst a total of 1.3 billion, which is not even half of its population. The second-largest populated country in the world is facing a jolt with vaccination acceptance. State-wise cumulative vaccination rate is shown in table 1 (10). The target of vaccinating 90% of the population by the end of June was not achieved.
The total population in India and the status of the population vaccinated as of August 13 th 2021 are as shown in table 2 (11). The majority of the states have jabbed their population except for Uttar Pradesh, Maharashtra, Bihar, Jharkhand, Madhya Pradesh, Meghalaya, Nagaland, Odisha, Punjab, Rajasthan, Tamil Nadu, Telangana, Chhattisgarh, West Bengal, and Assam. These states have jabbed less than 50% of their population. The preponderance of population among these states and their perplexed attitude are the drawback of their vaccination campaign.
A number of states have been successful in their vaccination campaign and have jabbed the bulk of their population such as Goa, Sikkim, Kerala, Andaman & Nicobar, Tripura, Delhi Daman and Diu, Lakshadweep, and Ladakh. Vaccination in kids and below 18 years is still awaited, and clinical trials are in progress in these age groups. Parents are skeptical and bewildered.   (19). Fully vaccinated individuals had a lower incidence of SARS-CoV-2 infections than partially vaccinated and non-vaccinated individuals. The cumulative vaccine efficiency was determined to be 88.6% in fully vaccinated individual and 44.1% in partially vaccinated individuals (20). Despite these encouraging findings on vaccine effectiveness, few significant severe Adverse Events Following Immunization (AEFI) have been documented in partially and fully vaccinated individuals. BellsPalsy, Anaphylaxis, Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT), pericarditis, myocarditis and rarely deaths have been reported (21,22).
Recently a new-fangled experiment is in progress with the mixing of jab and is found to be more potent than homologous jab either by Covaxin or Covishield. Eighteen individuals received Covishield as the first jab and Covaxin as the second, and the safety and immunogenicity were effectively compared with 40 receiving the same jabs. The heterologous vaccine safety was determined by decreased adverse effects. Antibody titers and levels of IgG antibodies were always better in heterologous group to Alpha, Beta and Delta variant (23).

V. Reasons for hesitancy/ Low vaccination rate in India
• Vaccine development The biggest obstacle across the globe initially related to vaccination stem is that the vaccines have been developed at a rapid pace as vaccines usually take years to develop. Methodically clinical trials and efficacy of these vaccines are monitored meticulously and take a very long duration for the vaccine to be introduced in the market. Moreover, the mechanism, storage, and cold chain of these vaccines in India is an arduous task and tedious work. However, this procedure and mechanism is almost entirely a mystery to the general population (24 ,25).

• Vaccine dose interval/ vaccine efficacy
The second dose of covid vaccine, especially Covishield was initially given at an interval of 4 weeks to all the health care workers, frontline workers, and senior citizens. However, this interval got prolonged to 6weeks, and then the government of India announced the gap to be prolonged to 12 weeks to vaccinate maximum people with the first dose. Some data from global trials of Covishield suggests that extending the duration between doses to 12 weeks increased its efficacy much more (22). Recurrent lifethreatening conditions dropped significantly after 28 days of the second dose. Interim data from the studies in USA, Chile and Peru indicated that the vaccine had 79% effectiveness even when the second dosage was administered four weeks after the first dose (26).
In phase 3 clinical trials in the UK, Brazil, and South Africa, the efficacy of AZD1222 was around 54.9 percent when the second dose was given less than six weeks after the first dose. The efficacy increased to 59.9 percent when the second dose was administered 6-8 weeks after the first dose, and to 63.7 percent when administered 9-11 weeks after the first dose and 82.4% when the dosing interval stretched to 12 weeks or more. Covishield vaccine efficacy increased to 81.3% in > 12 weeks dose interval and 51.1% in short duration. Further claiming that antibodies start fading at 90 days (27). Astrazeneca vaccine efficacy and the various interval between doses is shown in Fig.1 (28). The shortage of vaccine availability was speculated to be one of the reasons for increasing the interval. However, the government of India claimed to have no shortage, as announced by Dr. Harshvardhan. However as per, Dr. N K Arora of NTAGI, one of the groups that looked at present issue, declared that there was "no good scientific evidence" to promote a recommendation to extend the interval beyond eight weeks, especially given that India does not have a vaccine shortage" (29). He also believed that this recommendation was for countries and societies where there is a deficiency of vaccines. This unclear decision by the government of India based on their flexibility has triggered a negative notion related to the vaccine administration. The central government's unsynchronised allocation of the vaccine to various states also created a misconception among the population not ruled by the central party (30).

• Reinfection
Another major obstacle and hesitance in administering the vaccine among the general population of India was the recurrence of infection in several health care workers and frontline workers even when they were fully vaccinated with both doses. This haunted the minds of the public about the vaccines' competence. A similar reason for hesitation in 82.3% of medical students was collected coupled with the real concern regarding adverse events noticed from the vaccine's possible 'long term' effect. This apprehension was conjoint with the vaccines not been tested vigorously to determine all possible adverse events (31).

• Vaccination cost
High cost of the vaccine, which is not favourable to the low-income group of people. This problem was resolved by providing vaccines in government hospitals free of cost. However, private sectors/ hospitals charged a minimum of Rs 250/-. A study done in West Bengal revealed that 40% of their subjects wanted a cheap vaccine, and 58% preferred an Indian vaccine (32).

• Vaccination centres
In government centres the wait was long, approximately 10-12h, and was overcrowded. A working-class or a daily wage labourer was in a dilemma regarding the above-mentioned reason. However, the scare of acquiring the infection in these sectors made the public psychologically panic and avoid the vaccine administration. In both places, minimum vaccines were available daily, and people returned home empty-handed after visiting 2-3 times, which lead to hesitancy.

• Adverse events after vaccination
Due to multiple factors other than the vaccines themselves, minimum adverse events, allergies, anaphylactic reactions, or some other life-threatening events occurred post-vaccination. But even rare events, like the post-vaccination clotting incidents in Europe, were enough to create massive doubt in people's minds (33).

• Religion/Rumours related to the make of vaccine
Some religious groups opposed the vaccine based on rumours. Muslims and Jews aborted or declined the vaccination due to fictitious claims that vaccines contain infertility agents or spread the human immunodeficiency virus (HIV). Vaccine mutating the DNA and erectile dysfunction in males was the paramount concern in the population. Rumours related to COVID-19 vaccine reagents flawed the vaccination strategy among Christians and Buddhists, claiming that the COVID-19 vaccines were being produced with cells from aborted foetuses. Nevertheless, rumours also claimed vaccine production with genes from monkeys and pigs (25). A déjà vu was experienced earlier, and rubella and measles vaccines were boycotted due to similar beliefs, and the world had to face the brunt (34,35). The aluminium present in these vaccines is claimed to cause Alzheimer's disease. A pharma gimmick was another conspiracy for the hesitancy. Misbelief in people regarding these rumours has led to a decline in immunization.

VI. Truth behind Covid Vaccines
In India, 700 severe and severe adverse events were reported from across the country over the unusual type of blood clots after receiving the AstraZeneca-Oxford University vaccine. This was rare, and the probability was 0.0001%, with the majority complaining of fever, myalgia, injection site pain, headache, and joint pain after the first dose (36,37). Both vaccines, Covishield and Covaxin elicited a good immune response in health care workers across India after two doses of vaccination despite the fact that seropositivity rates and the median anti-spike antibody titer were significantly higher in Covishield (38). Protective levels of anti-SARS CoV-2 Ig G antibodies were in the majority after 14 days of the second dose (39).  (41). The efficacy and safety of these vaccines were mentioned and discussed in detail earlier (26)(27)(28). The government of India has procured Moderna vaccine Pfizer bio Ntec, Sputnik V in order to speed up the vaccine drive. The mRNA vaccine has been reported to have an efficacy of 95% (Pfizer), whereas Moderna represented 94% efficacy, and these are currently in vogue in several countries (42). Natural immunity by COVID-19 may not last long, and evidence suggests reinfection. Therefore, vaccination is necessary for boosting immunity (43). There is also no difference in the doses, schedule, or platform. However, the vaccine is given to such subjects after 90 days. These suggest the rumours about the contents of the vaccine as fabricated.
All development programs in this short period aimed at synthesizing S-protein neutralizing antibodies in the bodies of vaccinated COVID-19 individuals. Researchers identified the presence of restricted or zero cross-neutralization in serum of both SARS-CoV and SARS-CoV-2. Thus, indicating that successful recovery from one disease is not guaranteed and can develop an infectious disease in the future. Therefore, these vaccines aim to either incite or weaken viruses' live -conditions. A vaccine that provides 100% protection and eradicates corona completely is not developed and scientists around the globe are aiming to develop such vaccines shortly.

CONCLUSION
Indian population is still in a dilemma regarding covid 19 vaccination. Fewer than half of the Indian population are vaccinated six months down the lane, as of August 13 th 2021. Uttar Pradesh, Maharashtra, Bihar, Jharkhand, Madhya Pradesh, Meghalaya, Nagaland, Odisha, Punjab, Rajasthan, Tamil Nadu, Telangana, Chhattisgarh, West Bengal, and Assam have vaccinated less than half of their population due to an apprehension related to vaccines. This review concludes that all the current covid vaccines face paradox as they are safe and efficient but abolishes 100% protection. Pfizer provides 95% and Moderna 94% with higher rates of side effects. However, Indian vaccines have lower efficacy rates with 81% in Covaxin and 70% efficacy in Covishield with more potency at 12 weeks intervals between doses. Thus, with these findings, we conjectured that in India, Covaxin is a potent vaccine to shield against the mutant variants of covid 19 and is the only way to develop herd immunity amongst the Indian population.

Data Availability
Data for the study is taken from the Ministry of Health and Family Welfare, Government of India site: https://www.mohfw.gov.in/.