COVID-19 has impacted our lives in multiple ways (1, 2). Studies have observed age and comorbidity as strongly associated factors for the disease severity (3–6). Moreover, the long-COVID and post-COVID complications have added another complexity to this disease (7–11). Since this disease is new, information related to it is not very concrete. With the latest research accumulating daily (3), the WHO and government guidelines have changed substantially. These changes have mystified the general population (3, 12, 13). Thus, several local rumors against the vaccination drive have surfaced in the population (14, 15). Since the flow of information in Indian society heavily depends upon oral transmission, i.e., word-of-mouth, many people are afraid to visit vaccination centers (16).

India began the vaccination drive on January 16 2021. Only ~200,000 cases were active during this time, and most Indians had overcome the trauma of the first wave (17). With repeated encouragement from the Government, India has achieved 22 million doses per day by the end of March 2021 (18). This number increased exponentially during the first week of April 2021, when the Government decided to vaccinate everyone above 45 years of age (19). However, this was also the time of the beginning of the second wave (20, 21). Due to the severe second wave, the daily vaccine doses administered, which were more than 35 million a day till April 13 2021, have been reduced to < 15 million a day just after a month (18).

Moreover, leaders from several political parties have released public statements against vaccination (22). Those mentioned above appear to significantly contribute to the reduced vaccination rate after the second wave (10). Recent studies on vaccine hesitancy have highlighted the significant reasons and rigorous vaccination campaigns to overcome the problem (14, 23–29). The concern about the side effects was highlighted, and it has been shown that at the global level, females are more hesitant than males (28). Indian society is segregated into various castes and tribal populations. Our recent study has reported that the susceptibility of several smaller tribal populations is significantly higher than the other populations (30). A study on social affiliation and vaccine hesitancy has suggested 3.5 times higher vaccine hesitancy among Scheduled caste populations (31). Thus, it is pertinent that low education and lower socioeconomic status is the primary cause of vaccine hesitancy (23, 26, 28, 29).

So far, the Varanasi and adjoining regions have not been surveyed for vaccine hesitancy. Therefore, to understand vaccine hesitancy in North India, we have systematically uncovered the cause. Some empirical evidence is much needed to understand the nature and cause of the vaccine hesitancy to suggest a potential psychosocial intervention to help the North Indian policymakers and immunization staff to overcome this key hurdle in immunization against COVID-19. To understand the nature and causes of vaccine hesitancy among North Indians, we conducted an extensive survey in Varanasi and adjoining regions. We followed a questionnaire-based survey approach to uncover the factors that inculcate vaccine hesitancy (Table 1). We presented structured questions with a predefined set of responses for each question.

In order to understand the vaccination drive in a region, it is necessary to focus on the local hurdles behind vaccine hesitancy. Our questionnaire was designed to reflect the mass feeling about the nature of the virus, the second wave, comments on measures taken by the Government during the second wave, and rumors leading to vaccine hesitancy (Table 1). Apart from the highly infective virus variants during the second wave (32), the role of the public was also concerning. A large proportion of participants (0.75) either relied on rumors or did not take the virus seriously. Moreover, according to the respondents, when asked what steps would help prevent the coronavirus, most people think that total vaccination and personal consciousness (0.658) will be a better tool than lockdowns (Table 1).

An exciting result that our study yielded is that in some questions, there was a significant difference (two-tailed p-value < 0.001) in the responses between male and female respondents (Supplementary Figure 1). For example, a significantly lower number of females think that the coronavirus is a lab-made or biological weapon. In contrast, more females think COVID-19 is a natural pandemic (two-tailed p-value < 0.001) (Table 1). Similarly, more females followed the health instructions than the males (two-tailed p-value < 0.001).

During the survey, many participants had an impression that the vaccine relates to introducing the second wave. Therefore, we first investigated the vaccine hesitation during the second wave (Table 1 and Supplementary Figure 1). We have looked at the vaccination data during March-June 2021 (18). We found a major vaccination dip during the second wave (two-tailed p < 0.0001).

From our research, we found that a large proportion of people (0.849) prefer to get vaccinated. They are aware of vaccines (0.962) and know that the vaccine for SARS-CoV-2 prevents COVID-19 (0.899). However, a substantial proportion of people reported that they would refrain from vaccinating (0.15) (Figure 1). Remarkably, the vaccine hesitancy ratio was similar for both male and female participants. The vaccine acceptance among the studied cohort in India is significantly (two-tailed p < 0.0001) higher than the global data (28). It is worthwhile to mention here that the trend of vaccine willingness in the Indian community is similar to the data of Bangladesh (29, 33); nevertheless, the educated community in India is significantly (two-tailed p < 0.0001) well aware and is at a greater acceptance.

Our statistical tests have yielded a highly significant association between vaccine hesitancy and the economic status of the participants (χ² = 307.6, p = 0.000). Nevertheless, the gender-biased association of vaccine hesitancy has not been observed in our survey (χ² = 0.007, p = 0.933) (Table 2). The logistic regression analysis supported the strong association of vaccine hesitancy with the economic status of the respondents (Table 3).

The present study effectively contributes to the vaccine hesitancy in district Varanasi and adjoining regions of India. We focused primarily on the educated people with a list of a questionnaire. Our findings show a significant (two-tailed p < 0.0001) hesitancy among males and females (Figure 1). Strikingly, the Indian cohort studies here had lower vaccine hesitancy than the global data, likely due to our cohort structure. Our cohort in the present study was overwhelmed by people with higher education.

India's vaccine drive fluctuated with a significant drop during the second wave significantly (two-tailed p-value < 0.0001). The most crucial reason for this fall was vaccine hesitancy rumors. Our interview and observation found that people ran for the vaccine as soon as the second wave started to spread. It resulted in enormous rush to the vaccination centers. Many have been infected due to large gatherings at the vaccination centers. This has created confusion in society that the people are being infected after taking vaccines (Table 1 and Supplementary Figure 1). Thus, vaccines are not helping to stop the infection. The spread of this rumor through word-of-mouth has reduced the vaccinations significantly (two-tailed p-value < 0.0001) (18). During the second wave, the daily immunization was low when the positive test rate was at its peak. However, it must be understood that it takes 3–4 weeks to develop the effective antibodies after the vaccination (34).

So far, in the SARS-CoV-2 evolution, we have seen that this virus can create more hazardous variants with time (32). Moreover, we are fortunate that no variant has been found that completely evades vaccine-induced immunity. Still, with a large number of vaccination, a non-vaccinated pool may provide a reservoir for the virus to multiply and mutate. Thus, it may offer the opportunity to emerge new variants. Moreover, the selection pressure on the virus against the background of a primarily vaccinated population may favor a variant that will be resistant to the vaccine. Therefore, the real danger is from those who have never been vaccinated or infected before. Such people will provide ground for a new variant of the virus. If it develops immunity to the vaccine, it will be a major setback in controlling the epidemic. The progress we have made against this pandemic will be lost.

Consistent with the previous observations, our multiple statistical analyses confirmed the strong correlation of vaccine hesitancy with the economic status of the participants (Tables 2, 3). Whilst, the gender-specific difference has not been observed, which is likely due to the nature of our cohort, where most of the respondents are well educated.

We caution that the cohort used in our study is overwhelmed by educated people. Therefore, the hesitancy frequency observed in this study may capture the lower bound data of vaccine hesitancy in North India. Further, we add that a retrospective study following face-to-face or structured telephonic interviews with a qualitative approach such as thematic analysis may bring further insight into the dynamics of vaccine hesitancy among Indians. Similarly, post-second wave vaccine hesitancy status also needs to be explored using the same interview format and contrasted with the retrospective data to understand the extent of vaccine hesitancy and changing factors. Since we have used a structured questionnaire with a predefined response format, the study is fraught with the danger of the researchers' subjective biases as the researchers' proposed factors for vaccine hesitancy were limited. The open-ended questions for listing the reasons for vaccine hesitancy may bring newer insights and additional aspects of vaccine hesitancy that could not be foreseen by us while framing the response to the question of vaccine hesitancy.

In conclusion, our study adds systematic knowledge on various potential factors related to the COVID-19 vaccine hesitancy among North Indians. During the second wave, most people in North India relied on fake news. > 65% population opposed total lockdown. A significant number of females were better at following the official health instructions. Vaccine hesitancy is found among 15% of the studied cohort. Consistent with the previous studies, we have also observed a significant correlation between vaccine hesitancy and socioeconomic status. In contrast, we did not find any correlation between vaccine hesitancy and gender. Thus, a region-specific policy is needed for COVID-19 vaccination in North India.

The datasets presented in this study is provided in Table 1 and Supplementary File.

The studies involving human participants were reviewed and approved by VBS Purvanchal University Jaunpur and Banaras Hindu University, Varanasi, India. The patients/participants provided their written informed consent to participate in this study.

GC conceived and designed this study. US, AT, JK, SD, SV, VS, DD, PPS, RM, NK, VM, PK, VR, RT, PS, and RP collected the data and also conducted the online and offline surveys. US, AT, PPS, GC, DD, PK, RT, PS, and VR analyzed the data. GC, US, AT, JK, SD, SV, RT, PS, and RP wrote the manuscript from the inputs of other co-authors. All authors contributed to the article and approved the submitted version.

This work was supported by the ICMR ad-hoc grant (2021-6389). GC and VM are supported by Faculty IOE grant BHU (6031). PPS was supported by CSIR fellowship, Govt. of India.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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