key: cord-0891326-69o8tkoy authors: Strathdee, Steffanie A; Abramovitz, Daniela; Harvey-Vera, Alicia; Vera, Carlos F; Rangel, Gudelia; Artamonova, Irina; Patterson, Thomas L; Mitchell, Rylie; Bazzi, Angela R title: Correlates of COVID-19 Vaccine Hesitancy among People who Inject Drugs in the San Diego-Tijuana Border Region date: 2021-11-22 journal: Clin Infect Dis DOI: 10.1093/cid/ciab975 sha: 879156218e2c8111e7eee9313fa2dec6c6784639 doc_id: 891326 cord_uid: 69o8tkoy BACKGROUND: People who inject drugs (PWID) are vulnerable to acquiring SARS-CoV-2. We examined correlates of COVID-19 vaccine hesitancy among PWID in the U.S.-Mexico border region, of whom only 7.6% had received ≥one COVID-19 vaccine dose by September, 2021. METHODS: Between October, 2020 and September, 2021, participants aged ≥18 years from San Diego, California, USA and Tijuana, Baja California, Mexico who injected drugs within the last month completed surveys and SARS-CoV-2, HIV, and HCV serologic testing. Logistic regressions with robust standard error estimation via generalized estimating equations identified factors associated with being unsure or unwilling to receive COVID-19 vaccines). RESULTS: Of 393 participants, 266 (67.7%) were willing to receive COVID-19 vaccines and 127 (32.3%) were hesitant (23.4% unwilling and 8.9% unsure). Older participants, those with greater food insecurity, and those with greater concern about acquiring SARS-CoV-2 were more willing to be vaccinated. Higher numbers of chronic health conditions, having access to a smart phone or computer, and citing social media as one’s most important source of COVID-19 information were independently associated with vaccine hesitancy. COVID-19-related disinformation was independently associated with vaccine hesitancy (adjusted odds ratio: 1.51 per additional conspiracy theory endorsed; 95% confidence interval: 1.31-1.74). CONCLUSIONS: Nearly one third of people injecting drugs in the U.S.-Mexico border region were COVID-19 vaccine hesitant, which was significantly associated with exposure to social media, disinformation and co-morbidities and inversely associated with food security and high perceived threat of COVID-19. Interventions that improve accurate knowledge of and trust in COVID-19 vaccines are needed in this vulnerable population. An ongoing contributor to SARS-CoV-2 transmission is low vaccine uptake [1] . In high-income countries, structural issues such as limited transportation and healthcare access disproportionately affect under-represented minorities and those with low socio-economic status [2] . COVID-19 vaccine hesitancy has also emerged as a major problem, due at least in part to an "infodemic" of misinformation and disinformation [3] . Misinformation refers to inaccurate information shared without malicious intent, whereas disinformation is the deliberate spread of false information, for example, through organized social media campaigns [4] . Although both misinformation and disinformation have sowed confusion about the epidemiology of SARS-CoV-2 and illness severity [3] , disinformation campaigns have seriously undermined public confidence in COVID-19 vaccine safety in the U.S. and elsewhere [5, 6] , especially among people who are Black and Latinx [7] . People who use drugs, especially people who inject drugs (PWID), may be especially vulnerable to SARS-CoV-2 infection due to exposures such as using drugs with others, engaging in sex work [8] ), elevated prevalence of chronic diseases [9] , homelessness, incarceration [8, 10] , and other structural factors that limit healthcare engagement such as stigma [11] . We previously reported that over one third of PWID in San Diego County and Tijuana, Mexico had been infected with SARS-CoV-2, and only 9% had received at least one COVID-19 vaccine dose [8] . Herein, we studied COVID-19 vaccine hesitancy in the same population, hypothesizing that sociostructural factors such as homelessness and Latinx ethnicity would be significantly associated with COVID-19 vaccine hesitancy, as well as COVID-19 misinformation. We were also interested in studying whether exposure to COVID-19 disinformation was significantly associated with COVID-19 vaccine hesitancy in a population that has historically had limited access to social media [12] . A c c e p t e d M a n u s c r i p t 5 Participants and Eligibility. Between October 28, 2020 and September 10, 2021, street outreach was used to recruit participants aged ≥18 or older who injected drugs within the last month and reported living in San Diego County or Tijuana, as previously described [8] . Participants were compensated $20 USD for study visits. Protocols were approved by institutional review boards at the University of California San Diego and Xochicalco University. Survey Measures: After providing informed consent, participants underwent interviewer-administered surveys at baseline and approximately one week later using computer assisted personal interviews. Surveys assessed socio-demographics, substance use, chronic health conditions (e.g., diabetes, asthma, hypertension), food insecurity [13] and COVID-19 experiences, exposures, and protective behaviors (e.g., social distancing, masking). To assess COVID-19 misinformation, we presented participants with seven statements about SARS-CoV-2 transmission, severity, immunity, symptoms, treatments, and vaccines, and asked them to classify each statement as "True", "False," or "Unsure". We then created a binary variable for each statement indicating whether the participant was misinformed or not. We assessed COVID-19 disinformation through endorsement of six conspiracy theory items, three of which were based on work by Romer and Jamison (e.g., "COVID-19 was created by the pharmaceutical industry" or "the Chinese government"; "childhood vaccines cause autism" [7] ). Based on field experience and the media, we added three new items: "COVID-19 vaccines include a tracking device", "alter DNA", or are being offered to communities differentially (i.e., "COVID-19 vaccines offered to "people like me" are not as safe"). We dichotomized responses to indicate endorsement of disinformation ("True" and "Unsure") or not ("False") and summed them into a total score ranging from 0 to 6. The mean inter-item correlation value was 0.31, which indicates optimal internal consistency [14] . A c c e p t e d M a n u s c r i p t 6 Our primary outcome of interest, COVID-19 vaccine hesitancy, was assessed by asking participants whether they would agree to receive a free COVID-19 vaccine. This question was introduced on November 5, 2020. However, items on COVID-19 knowledge and beliefs were not introduced until May 14, 2021. SARS-CoV-2 Antibody Detection. Serology was conducted by Genalyte® (San Diego, CA), using their Maverick™ Multi-Antigen Serology Panel [15] that detects IgG and IgM antibodies to five SARS-CoV-2 antigens (Nucleocapsid, Spike S1-S2, Spike S1, Spike S1-RBD, Spike S2) within a multiplex format based on photonic ring resonance. A machine learning algorithm was used to call results using the Random Forest Ensemble method with 3000 decision trees. [16] HIV and HCV Serology. Rapid HIV and HCV tests were conducted using the Miriad ® HIV/HCV Antibody InTec Rapid Anti-HCV Test (Avantor, Radnor, PA). Reactive and indeterminate tests underwent a second rapid test with Oraquick ® HIV or Oraquick ® HCV, respectively (Orasure, Bethlehem, PA). Statistical Analysis: Participants who responded that they were unsure or would not agree to receive a free COVID-19 vaccine were coded as vaccine hesitant. Characteristics of participants who were and were not COVID-19 vaccine hesitant were compared using Mann-Whitney U tests for continuous variables and Chi-square or Fisher"s Exact tests for categorical variables. Univariate and multivariable logistic regressions with robust standard error estimation via generalized estimating equations were performed to identify factors associated with vaccine hesitancy. Following Hosmer and Lemeshow"s "purposeful selection of variables" approach to model building [17] , variables attaining significance at a level of α=0.10 in the univariate regressions, were considered for inclusion in multivariable models. The final model was selected based on subject matter significance, relationships among potential predictors (e.g., correlations, confounding, and interactions) and statistical significance.retaining Only variables retaining significance levels at α=0.05 level were included in the final model.. The multivariable model also controlled for time using a linear and A c c e p t e d M a n u s c r i p t 7 quadratic term, which were highly significant but did not change the parameter estimates or their significance. We checked the final multivariable model for integrity by assessing relationships between the predictors (e.g., correlations, confounding, interactions). Multi-collinearity was assessed and ruled out by appropriate values of the largest condition index and variance inflation factors. All statistical analyses were conducted using SAS, version 9.4. were more likely to be vaccine-hesitant (16.5% vs. 6%, p<0.001). Almost all participants endorsed at least one statement that reflected COVID-19 misinformation (99%), such as thinking that COVID-19 is about as dangerous as having the flu (63.9%). Respondents who thought COVID-19 vaccines were unsafe for pregnant women or believed they could tell if someone had COVID-19 by looking at them were significantly more likely to be vaccine hesitant. A majority of participants also endorsed at least one conspiracy theory related to COVID-19 or vaccines (85%). COVID-19 disinformation scores were higher among those who were vaccine hesitant (mean number of COVID-19 conspiracy theories endorsed out of six total: 3.7 vs. 2.4, p<.001). Vaccine-hesitant participants were more likely to identify social media as their primary source of COVID-19-related information (21.1% vs. 8%, p<.001). There were no differences observed in vaccine hesitancy related to identifying friends as a primary source of COVID-19 information (50.8% overall) or ever having had a flu vaccine (45.5% overall). COVID-19-Related Correlates of Vaccine Hesitancy: Participants who engaged in at least one protective behavior (e.g., social distancing, isolating oneself, wearing masks, increasing handwashing), were significantly less likely to be vaccine hesitant (unadjusted odds ratio [OR]: 0.43; 95% confidence interval [CI]: 0.23-0.81; Table 2 ). Those who were more worried about getting COVID-19 were also less likely to be vaccine hesitant (OR: 0.86 per point increase; 95% CI: 0.79-0.93). Conversely, those who thought they had had COVID-19 or had been tested for COVID-19 outside of this study were significantly more likely to be vaccine hesitant, and having been exposed to somebody testing positive for COVID-19 was marginally associated with higher unadjusted odds of In a sub-analysis that included the 42 participants who reported having had at least one COVID-19 vaccine dose and coded them as willing, parameter estimates in our final model were essentially unchanged, with the exception of primarily obtaining COVID-19 information from social media, which became highly significant. Vaccine hesitancy is a critical challenge to COVID-19 pandemic control efforts, especially for vulnerable populations including people who use and inject drugs. In our community-based sample of PWID in the San Diego-Tijuana border region, nearly one third of participants were hesitant about COVID-19 vaccines and almost all endorsed statements reflecting COVID-19 misinformation or disinformation. While the dissemination of COVID-19 disinformation on social media has been reported as undermining vaccine uptake in the general population [3] , we found that it was also independently associated with COVID-19 vaccine hesitancy in a disadvantaged population with A c c e p t e d M a n u s c r i p t 10 limited access to the Internet. Our analysis also suggests specific intervention targets that provide avenues for improving vaccine trust and uptake in this socially marginalized population. We found that COVID-19 disinformation, operationalized as endorsement of specific COVID-19 related conspiracy theories, was independently associated with vaccine hesitancy, while COVID-19 misinformation was not. While research on COVID-19 vaccination hesitancy among substance using populations remain scarce, a study conducted with substance use disorder treatment patients also failed to link COVID-19 knowledge with trust in vaccines [18] . These findings imply that disinformation may be a stronger driver of COVID-19 vaccine hesitancy than misinformation among PWID. The significant role of COVID-19 disinformation in influencing vaccine hesitancy extends a longestablished foundation of medical mistrust among PWID who often avoid traditional clinical settings, preferring to receive prevention information and services in community-based settings [11] . This distrust, along with preferences for alternative sources of information, may lead some individuals to seek health advice online or through social media, where more false information may exist than factual, evidence-based information [19] , and where COVID-19-related disinformation has been perpetuated [3] . Having access to smart phones or computers was strongly associated with COVID-19 vaccine hesitancy in our sample. PWID in other community-based studies increasingly report having regular access to mobile phones and the Internet, particularly within public spaces [12, 20, 21] . Although only 22% had access to either in our study, it is possible that these individuals had more resources and were influencers in their communities, sharing COVID disinformation within their networks. Citing social media as one"s most important source of COVID-19 information was marginally associated with vaccine hesitancy, even after controlling for phone/computer access. When we repeated our analysis to include participants who had received at least one COVID-19 vaccine dose by September 10, 2021, the association between citing social media as one"s most important source of COVID-19 information and vaccine hesitancy was even stronger. Concerns about vaccine safety were also apparent in our sample, confirming previous research among the general population [22] and those receiving substance abuse treatment [18] which reported concerns that COVID-19 vaccines are unsafe and have been tested insufficiently [23] . These findings suggest that interventions to promote COVID-19 vaccine uptake will need to address safety concerns [24] . At the same time, the majority of our sample engaged in at least one protective measure during the COVID-19 pandemic, suggesting that many individuals already consider the severity of COVID-19, suggesting that perceived threat could be leveraged as an intervention target for this population. Increasing confidence in vaccine safety and efficacy may be particularly important for subgroups of PWID with higher levels of skepticism or susceptibility to confirmation bias (i.e., the tendency to believe information that aligns with one"s existing beliefs or experiences) [25] . As others have argued [26], interventions may be more acceptable to PWID if they are delivered by trusted sources of health information and support, such as harm reduction outreach workers, street medicine providers, recovery coaches, peers, or staff of other community-based organizations that are frequented and trusted by this population, like shelters, community centers, hostels, libraries, and other public spaces. Interestingly, we found no evidence to support our hypothesis that Latinx participants were more likely to be vaccine hesitant, as others have reported [2, 7] . In fact, our unadjusted analysis found that PWID who were White and those born or living in San Diego were more likely to be vaccine hesitant than those who were Latinx, or born or living in Mexico. Contrary to general population-based samples in the U.S. [27], we did not find educational attainment to be independently associated with vaccine hesitancy. PWID reporting food insecurity and those with higher levels of concern about SARS-CoV-2 were less hesitant about COVID-19 vaccines. However, two thirds of our sample reported willingness to get vaccinated, but only 7.6% had received at least one dose by September 10, 2021, highlighting the urgent need to increase uptake. Of concern, participants who had a greater number of comorbidities such as diabetes and hypertension were more vaccine hesitant than others. This is worrisome since these individuals could be more vulnerable to severe COVID-19 complications and would most A c c e p t e d M a n u s c r i p t 12 benefit from protection. Furthermore, a recent study found that compared to other patients, people with substance use disorders were more likely to experience breakthrough infections following COVID-19 vaccination, which was partly attributed to their high prevalence of comorbid conditions [9] . Our findings suggest that structural supports including financial incentives for vaccination that have been successful with other vulnerable populations could also be beneficial for PWID [28] . These Limitations of this study include the cross-sectional nature of the analysis, which precludes our ability to determine causal associations. Although this was a binational study, sampling was non-random and results may not generalize to other samples of PWID. We also relied on self-report and recall for many behaviors, which may have been subject to socially desirable responding. In conclusion, we identified a concerning level of COVID-19 vaccine hesitancy among communityrecruited PWID in the San Diego-Tijuana border region, which was associated with COVID-19 related disinformation, reliance on social media as a source health information, younger age and comorbidities. Interventions that increase accurate COVID-19 vaccine knowledge, trust and motivation, while also reducing structural barriers to COVID-19 vaccine access are urgently needed to reduce morbidity and mortality in this vulnerable population. A c c e p t e d M a n u s c r i p t 24 A c c e p t e d M a n u s c r i p t Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status -13 U.S. Jurisdictions COVID-19 Vaccine Decisionmaking Factors in Racial and Ethnic Minority Communities Susceptibility to misinformation about COVID-19 around the world Public Health and Online Misinformation: Challenges and Recommendations Understanding COVID-19 misinformation and vaccine hesitancy in context: Findings from a qualitative study involving citizens in Bradford Understanding misinformation infodemic during public health emergencies due to large-scale disease outbreaks: a rapid review Conspiracy theories as barriers to controlling the spread of COVID-19 in the U Prevalence and correlates of SARS-CoV-2 seropositivity among people who inject drugs in the San Diego-Tijuana border region COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States Challenges posed by COVID-19 to people who inject drugs and lessons from other outbreaks Strategies used by people who inject drugs to avoid stigma in healthcare settings Factors associated with patterns of mobile technology use among persons who inject drugs The role of factor analysis in the development and evaluation of personality scales Maverick™ SARS-CoV-2 Multi-Antigen Serology Panel v2 01030ART-01 Target specific serologic analysis of COVID-19 convalescent plasma Applied survival analysis: regression modeling of time to event data COVID-19 vaccine trust among clients in a sample of California residential substance use treatment programs The authors gratefully acknowledge the La Frontera study team and participants in San Diego and Tijuana and staff at Genalyte and Fluxergy for assistance interpreting laboratory results, laboratory staff at the Center for AIDS Research and Sharon Park for assistance with manuscript preparation.