This cross-sectional study was carried out among former COVID-19 patients in Jianghan District of Wuhan, China, from June 10 to July 25, 2021. According to the electronic medical records of the Health Bureau of Jianghan District and the inclusion criteria, a total of 3059 recovered COVID-19 patients were eligible for the study who had all been infected with the original SARS-CoV-2 strain and were diagnosed between December 10, 2019, and April 20, 2020. Among them, 1601 COVID-19 survivors were invited to complete a questionnaire survey on their vaccine hesitancy status when they were receiving clinical reexamination. If they agreed to participate in this survey, they were invited to the “Survey Room” to complete the questionnaire. Self-administered electronic questionnaires were generated on Research Electronic Data Capture (REDCap), an online survey platform, from which patients could complete by themselves. To ensure the quality of the survey, our trained investigators stayed at the “Survey Room” to promptly answer the participants’ questions.

The following inclusion requirements had to be met by participants: participants must be at least 18 years old, have a COVID-19 infection history, be able to work independently with the researcher to complete several scale assessments, and have access to a mobile communication device such as a cell phone with a WeChat account. People who fit one or more of the following criteria were excluded: (1) having significant cognitive impairment; (2) having life-threatening medical conditions such as heart, lung, kidney, liver diseases or cancers; and (3) finding it challenging to cooperate with the questionnaire study. In total, 1422 of the 1601 invited participants were chosen as the sample for this study based on the aforementioned standards and after discarding any incomplete questionnaires.

Ethics approval for the study was obtained from the Ethics Review Committee of the Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China (IPB-2020-22). All individuals provided digital informed consent to ensure their voluntary participation, which also included consent that the study data could be analyzed when used anonymously. All data were deidentified. All data are stored in an account with a password and cannot be used without consent. All study participants were compensated for transportation to the questionnaire site.

Figure 1 depicts the results of the confirmatory factor analysis for the model built in the sample, including the three dimensions of the 3Cs model. Separate confirmatory factor analysis based on the original structure of the “complacency” dimension (2 items), “confidence” dimension (2 items), and “convenience” dimension (2 items) were performed. The RMSEA value (0.076) indicated a moderate fit, the CFI value (0.994) indicated a good fit, and the TLI value (0.986) indicated a good fit.

Table 1 shows the results of convergent validity and discriminant validity of the model. For convergent validity, the AVE values for all dimensions of the model were greater than 0.50 and the CR values for all three dimensions of the model were greater than 0.70. In addition, the CR values for all factors in the model were greater than the AVE. For discriminant validity, the correlation coefficients for any two dimensions were less than the square root of the corresponding AVE, except for the correlation coefficients for confidence and convenience, which were higher than the square root of the corresponding AVE.

Among the 1422 participants, 538 (37.8%) were not vaccinated against COVID-19. There was a higher proportion of participants aged 41 to 60 years (634/1422, 45.2%), followed by the 61-80 years age group (611/1422, 43%). The great majority of the participants lived in urban areas (1245/1422, 87.6%), and 1197 (84.2%) participants were married. The majority (968/1422, 68.1%) had an education level of senior high school or below. Nearly half of the participants had a household income for 2020 lower than 60,000 Yuan (approximately US $8607) per year. Most participants self-reported that they were not current smokers (1233/1422, 86.7%) or drinkers (1038/1422, 73.0%), and 6.1% (87/1422) of the patients were asymptomatic, 70.8% (1007/1422) had mild symptoms of COVID-19, 10.3% (146/1422) had moderate symptoms, and 12.8% (182/1422) had critically severe symptoms. In the acute phase, 62.7% (891/1422) of patients had fever, 49.9% (709/1422) had respiratory symptoms, 18.2% (259/1422) had gastrointestinal symptoms, 6.4% (91/1422) had cardiovascular symptoms, and 15.5% (221/1422) had other symptoms. Overall, 24.1% (342/1422) were reinfected with COVID-19 after the first discharge, nearly half of the participants (654/1422, 46%) had family members who had been infected with COVID-19, 30.2% (429/1422) had relatives or friends who had been infected with COVID-19, and 17.2% (245/1422) of the participants had received other vaccines within the last 5 years (Table 2).

Table 2 also shows that the age gap between vaccinated and unvaccinated participants was statistically significant; participants aged ≤40 years had a higher hesitancy rate compared to the other three age groups (P<.001). The hesitancy rate of those living in urban areas (485/1245, 39.0%) was significantly higher than that of participants living in a village (53/177, 29.9%). Significantly, participants who were married had a lower hesitancy rate (428/1197, 35.8%) compared to that of participants who were single (23/54, 42.6%) and those with another marital status (87/171, 50.9%). Participants who perceived having an unhealthy status had a higher hesitancy rate than that of participants who self-reported being healthy (P<.001). Patients who had fever in the acute phase had a higher COVID-19 vaccine hesitancy rate (359/891, 40.3%) than those who did not have fever (179/531, 33.7%).

Figure 2 shows the distribution of answers on the COVID-19 vaccine hesitancy scale based on the 3Cs model among all participants. Table 3 shows the univariate analysis results of 3Cs model components and trust in vaccinated and unvaccinated groups. The unvaccinated group scored significantly higher on “complacency” related to COVID-19 vaccination than the vaccinated group. In contrast, participants who had received the COVID-19 vaccine scored higher on “confidence” and “convenience” than those who were not vaccinated. Moreover, the vaccinated group scored significantly higher than the unvaccinated group on trust (all P<.001).

Table 4 shows that participants aged 41-60 years (OR 2.12, 95% CI 1.34-3.36) and 61-80 years (OR 2.59, 95 %CI 1.56-4.30) were more likely to receive a COVID-19 vaccine than participants aged ≤40 years; however, participants aged >80 years (OR 0.14, 95% CI 0.03-0.66) were less likely to receive a COVID-19 vaccine than those aged <40 years. Participants who reported “other” marital status (ie, divorced, widowed) were more likely to be hesitant about receiving the COVID-19 vaccine than those who were single (OR 0.42, 95% CI 0.19-0.91). In addition, patients who perceived having an unhealthy status had more hesitancy about the COVID-19 vaccine than those who were healthy (OR 0.45, 95% CI 0.28-0.71). Compared to the asymptomatic patients, patients with mild symptoms were more likely to receive the COVID-19 vaccine (OR 1.67, 95% CI 1.02-2.82). Regarding the acute-phase symptoms, patients who did not have fever were less likely to receive the COVID-19 vaccine than those who had fever (OR 1.48, 95% CI 1.13-1.94). Not receiving any other vaccination within the last 5 years was negatively associated with receiving the COVID-19 vaccine (OR 0.69, 95% CI 0.50-0.95). Regarding the 3Cs model constructs, complacency was a significant negative factor for getting vaccinated for COVID-19 (OR 0.81, 95% CI 0.71-0.94), whereas convenience was a significant positive factor for COVID-19 vaccination (OR 1.21, 95% CI 1.06-1.37). Participants who had more trust were more likely to receive the COVID-19 vaccine (OR 1.14, 95% CI 1.09-1.19).

Among the reasons for getting vaccinated against COVID-19, “self-needs” was chosen most frequently (n=625), followed by “recommended by health agencies” (n=191) and “free vaccination” (n=149). The reason for “recommended by those who have been vaccinated” was selected 37 times, which was only higher than the “others” response option (n=11). Among the reasons for not getting vaccinated against COVID-19, “antibodies are already in existence and do not require vaccination” was chosen most frequently (n=88), followed by “don’t know how to get reliable information about the COVID-19 vaccine” (n=53) and “others” (n=30). The reason “have had a bad experience with the health clinic or provider” was selected 4 times, which was the least frequently selected option (Table 5).

The WHO indicated that antibodies in COVID-19–recovered patients do not guarantee protection against reinfection, making it necessary to receive the COVID-19 vaccine after natural infection [7]. However, diverse and effective preventive measures such as wearing a mask provided an alternative to prevent COVID-19 and might undermine the perceived need for vaccination to the point of developing an attitude of COVID-19 vaccine hesitancy [43,44]. This study revealed that the rate of COVID-19 vaccine hesitancy among patients who recovered from COVID-19 was 37.8%. According to previous research, this vaccine hesitancy rate is higher than that determined in a similar time period among Chinese patients with chronic diseases, including HIV infection (27.5%), cancer (24.1%), and inflammatory bowel disease (27.4%) [45-47]. Even though COVID-19–recovered patients and patients with chronic diseases are both vulnerable to COVID-19 reinfection based on their poor health conditions, COVID-19–recovered patients have a lower perceived risk of COVID-19 reinfection due to their belief that they already have antibodies gained from previous infection compared to patients with chronic diseases. Several studies also suggested lower vaccination intention among COVID-19–recovered individuals compared to uninfected individuals [48,49]. Research has shown that acquired immunity from COVID-19 infection would diminish over 6-8 months and protection against the new variant (Omicron variant) might be inadequate [50]; thus, COVID-19–recovered patients are still at risk of reinfection. The high perceived risk of contracting diseases is an essential determinant in overcoming vaccine hesitancy; that is, individuals who perceived a high risk of COVID-19 infection were assumed to adopt more preventive health behaviors to avoid or minimize health risks [51]. As the threat of reinfection increases due to continuously emerging new mutant strains, raising COVID-19–recovered patients’ awareness of the reinfection risk is essential to reduce their vaccine hesitancy.

In this study, COVID-19 patients with mild symptoms were more likely to receive the COVID-19 vaccine than asymptomatic patients. Similarly, previous studies have shown that people who have experienced severe COVID-19 disease have a lower rate of hesitancy compared to those with less severe disease [17]. Patients who have experienced the negative health effects of COVID-19 infection were willing to be vaccinated because they did not want to experience these symptoms again and would have a greater fear of reinfection. Previous studies also suggested that the severity perception of COVID-19 infection would directly affect the intention to vaccinate against COVID-19; patients who perceived COVID-19 infection to be severe were the most likely to be vaccinated [52,53]. In addition, patients with symptoms may develop sequelae symptoms and thus believe that they are vulnerable and that their perceived risk of COVID-19 infection will be higher, leading to the belief that they need to be vaccinated. Results of a cohort study showed that 61.4% of patients infected with the original SARS-CoV-2 strain had at least one sequelae symptom [54]. The significance of vaccination was not limited to preventing COVID-19 infection, as vaccination in COVID-19–recovered patients was found to also be effective at preventing sequelae symptoms [55]. Several studies have shown that the vaccinated group had a lower risk of developing sequelae symptoms compared to the unvaccinated group [56-58]. Emphasizing the benefits of vaccination among hesitant patients, such as prevention of reinfection and prevention of sequelae, will raise their awareness of the need for vaccination and thus motivate unvaccinated COVID-19–recovered patients to get vaccinated.

Complacency occurs when individuals have a lower perception of the need for a vaccination or a perceived low risk from diseases, which is influenced by general health beliefs [59,60]. Similar to other studies, complacency had a significant effect on increasing COVID-19 vaccine hesitancy in this study [61,62]. The immunity from previous infections might be one of the reasons for the complacency among the patients who recovered from COVID-19 infection. Meanwhile, misconceptions about the efficacy or safety of vaccination, misinformation in popular social media, and the perception that vaccines may not offer better protection than previous infections also could lead to complacency and result in underacceptance of the COVID-19 vaccine [63-65]. Additionally, the belief that vaccination of those around them is sufficient to prevent transmission and protect themselves from COVID-19 reinfection could result in a lower perception of COVID-19 reinfection risk among COVID-19–recovered patients. According to our study, among the reasons why COVID-19 survivors were willing to be vaccinated, most participants chose “self-needs,” which could eventually lead to high vaccine uptake [66]. By reducing their beliefs about complacency, this group of COVID-19 survivors might realize that vaccination is necessary for them. Specifically, health systems and relevant authorities should provide valuable information highlighting the evidence that immunity gained from natural infection would diminish over time and the risks of failure to vaccinate to enhance their “self-needs.” This would increase vaccination rates among COVID-19 survivors and ensure that they have sufficient protection against reinfection.

Convenience was a significant factor affecting vaccine hesitancy. Previous vaccination programs have shown that obstacles to vaccination include limited access to information, difficulties obtaining vaccines, unaffordable vaccine prices, and the long time (or distance) required to receive a vaccine [67-69]. Our results showed that “long waiting time for vaccination” and “have had a bad experience with the health clinic or provider” were among the convenience-related reasons participants stated for not receiving the COVID-19 vaccine. “Free vaccination” was among the reasons why participants received a COVID-19 vaccine, which is related to high convenience. Hence, to enhance COVID-19–recovered patients’ convenience in getting vaccinated for COVID-19, relevant health facilities should optimize the vaccination process to shorten waiting or queueing times, further improve the vaccination environment, and train vaccination-related workers to make them knowledgeable about the vaccine and to be more patient when answering questions [65]. In addition, targeting COVID-19–recovered patients with mobility issues and offering door-to-door vaccinations to address accessibility barriers would be very effective measures to increase vaccination rates.

Trust is a strong driver in reducing vaccine hesitancy. People with a higher level of trust in health authorities would have a more positive perception of the COVID-19 vaccine [70,71]. This study utilized two questions to evaluate participants’ trust, and the results also showed that trust was a motivating factor for patients who recovered from COVID-19 to get immunized. However, a crisis of trust in the COVID-19 vaccine, vaccine manufacturers, and health facilities unavoidably arose as a result of vaccine safety–related events and the dissemination of false information since the COVID-19 outbreak. Trust would build when people feel that health authorities possess knowledge and expertise; that the authorities take into account all relevant opinions; and that the authorities are transparent, honest, and open [72]. To assist in fostering trust and boosting confidence in the COVID-19 vaccine, identifying the concerns of patients who recovered from COVID-19, providing accurate information, and establishing communication channels with the health authorities are necessary. Ensuring appropriate, effective, and more specific education targeted at patients who recovered from COVID-19, while expressing the overall benefits and risks of the vaccine would also be beneficial to build trust to promote vaccination.

Since the availability of COVID-19 vaccines, we have dependable, high-quality evidence attesting to their safety, effectiveness, and value of protecting people from COVID-19 infection. However, our research has shown that patients are likely to be hesitant to receive vaccines because of complacency, convenience, trust, and other issues. In December 2022, a large-scale outbreak of COVID-19 infection occurred in China that lasted for 2-3 months, resulting in a high proportion of the population being in the category of COVID-19–recovered patients. These individuals will inevitably have to decide whether to get another dose (booster shot) if the COVID-19 epidemic persists and new variants continue to emerge. The study team conducted an online survey between January 5, 2023, and February 9, 2023, among people in seven geographic subdivisions of China regarding their willingness to receive a booster shot. A total of 7070 valid questionnaires were collected among these COVID-19–recovered patients and the COVID-19 vaccine hesitancy rate was 43.54% (data not shown). This high rate indicates that vaccine hesitancy still exists among COVID-19–recovered patients in China since the latest surge of the COVID-19 pandemic. The findings of this study may contribute to providing a research base and support for interventions to reduce future hesitancy related to COVID-19 booster shots among COVID-19–recovered patients, since future booster shots and the COVID-19 vaccination services and procedures that are currently in progress may converge.

This study has several limitations. First, the study was conducted in Wuhan, China, and a convenience sampling approach was employed for the survey, which may result in potentially biased estimates and selection bias. Therefore, the generalizability of our results will still be limited in certain aspects. Second, this was a cross-sectional study using a self-report questionnaire, leading to the presence of information bias. Third, since these data were collected between June and July 2021, the investigation was carried out in a very dynamic and ever-changing context, and it is possible that current perceptions of vaccines have changed both in terms of the perceived disease threat to study participants and the development of the COVID-19 vaccine itself.

COVID-19–recovered patients may have a low perception of the risk of reinfection because they already have immunity acquired through natural infection, and this may lead to complacency, ultimately leading to COVID-19 vaccine hesitancy. Advocacy strategies based on scientific evidence to raise public awareness of the risk of reinfection and the superiority of immunity gained from vaccination over that gained from infection can be effective in reducing complacency and thus overcoming vaccine hesitancy. Improving convenience-related factors such as time, transportation, and environment to get vaccinated is also necessary to address accessibility barriers and facilitate vaccination uptake. Furthermore, education efforts targeted at individuals who recovered from COVID-19 based on solid and adequate knowledge are needed to address their concerns about vaccination, which could foster greater trust and promote their vaccination acceptance.