The FDA Is Needed Now More Than Ever

The FDA was created in 1906, during the administration of Theodore Roosevelt, by the Pure Food and Drug Act to ensure the safety and purity of the American food supply by prohibiting interstate transport of "adulterated" food.1 This resulted from the writing of various contemporary journalists, including Upton Sinclair. Yet, apparently under political pressure, the FDA gave hydroxychloroquine an emergency use authorization, and the US government stockpiled massive quantities of the drug. The history of FDA's fight for consumer protection and public health.

LETTER TO THE READERS

Kariko was eventually demoted in rank at UPenn for lack of grants, but is now a senior vice president at BioNTech, a German biotechnology company that was co-founded by a pair of Turkish married physicians at Mainz University. In particular, a recent letter to the government has asserted the importance of National Institute of Allergy and Infectious Diseases' mRNA-1273 as a critical part of the invention and the contributors to numerous other patents which may have been funded by taxpayers. The key to this approach is translocation of the artificial mRNA coding for proteins of interest to the cytoplasm, transcription by the ribosome, and protein overproduction (as in the anti-spike protein antibodies).

The Unhappy Intersection of Cancer and COVID-19

Distinguished Professor of Medicine, Rutgers Robert Wood Johnson Medical School Associate Director for Clinical Research, Rutgers Cancer Institute of New Jersey Director of Oncology Research, RWJBarnabas Health In this issue of ONCOLOGYR, investigators who were led by John Nakayama, MD, from the Seidman Cancer Center at Case Western Reserve University in Cleveland, have provided a very large sample of patients with cancer and compared cancellation rates of oncology appointments in 2020 and 2019. The authors report on the clinical, lab, radiation, and surgery appointments for these time periods and compare the cancellation rates in the control year versus the experience year presumably by reviewing all their electronic medical record data. [...]some patients may have switched to more local practices.

SARS-CoV-2 Mpro Protease Variants of Concern Display Altered Viral Substrate and Cell Host Target Galectin-8 Processing but Retain Sensitivity toward Antivirals.

The main protease of SARS-CoV-2 (Mpro) is the most promising drug target against coronaviruses due to its essential role in virus replication. With newly emerging variants there is a concern that mutations in Mpro may alter the structural and functional properties of protease and subsequently the potency of existing and potential antivirals. We explored the effect of 31 mutations belonging to 5 variants of concern (VOCs) on catalytic parameters and substrate specificity, which revealed changes in substrate binding and the rate of cleavage of a viral peptide. Crystal structures of 11 Mpro mutants provided structural insight into their altered functionality. Additionally, we show Mpro mutations influence proteolysis of an immunomodulatory host protein Galectin-8 (Gal-8) and a subsequent significant decrease in cytokine secretion, providing evidence for alterations in the escape of host-antiviral mechanisms. Accordingly, mutations associated with the Gamma VOC and highly virulent Delta VOC resulted in a significant increase in Gal-8 cleavage. Importantly, IC50s of nirmatrelvir (Pfizer) and our irreversible inhibitor AVI-8053 demonstrated no changes in potency for both drugs for all mutants, suggesting Mpro will remain a high-priority antiviral drug candidate as SARS-CoV-2 evolves.

Health and economic benefits of achieving contraceptive and maternal health targets in Small Island Developing States in the Pacific and Caribbean.

INTRODUCTION: Reducing unmet need for modern contraception and expanding access to quality maternal health (MH) services are priorities for improving women's health and economic empowerment. To support investment decisions, we estimated the additional cost and expected health and economic benefits of achieving the United Nations targets of zero unmet need for modern contraceptive choices and 95% coverage of MH services by 2030 in select Small Island Developing States. METHODS: Five Pacific (Kiribati, Samoa, Solomon Islands, Tonga and Vanuatu) and four Caribbean (Barbados, Guyana, Jamaica and Saint Lucia) countries were considered based on population survey data availability. For each country, the Lives Saved Tool was used to model costs, health outcomes and economic benefits for two scenarios: business-as-usual (BAU) (coverage maintained) and coverage-targets-achieved, which scaled linearly from 2022 (following COVID-19 disruptions) coverage of evidence-based family planning and MH interventions to reach United Nations targets, including modern contraceptive methods and access to complete antenatal, delivery and emergency care. Unintended pregnancies, maternal deaths, stillbirths and newborn deaths averted by the coverage-targets-achieved scenario were converted to workforce, education and social economic benefits; and benefit-cost ratios were calculated. RESULTS: The coverage-targets-achieved scenario required an additional US$12.6M (US$10.8M-US$15.9M) over 2020-2030 for the five Pacific countries (15% more than US$82.4M to maintain BAU). This additional investment was estimated to avert 126 000 (40%) unintended pregnancies, 2200 (28%) stillbirths and 121 (29%) maternal deaths and lead to a 15-fold economic benefit of US$190.6M (US$67.0M-US$304.5M) by 2050. For the four Caribbean countries, an additional US$17.8M (US$15.3M-US$22.4M) was needed to reach the targets (4% more than US$405.4M to maintain BAU). This was estimated to avert 127 000 (23%) unintended pregnancies, 3600 (23%) stillbirths and 221 (25%) maternal deaths and lead to a 24-fold economic benefit of US$426.2M (US$138.6M-US$745.7M) by 2050. CONCLUSION: Achieving full coverage of contraceptive and MH services in the Pacific and Caribbean is likely to have a high return on investment.

Parent perspectives on young children's changing digital practices: Insights from Covid-19

Young children's use of digital technologies has presented challenges for parents, particularly in response to an increased reliance on digital resources during the Covid-19 pandemic. This mixed-methods study explored young children's digital practices within the context of their families and homes. Although this study was originally planned, the timing of data collection meant that it was uniquely positioned to capture parent perspectives as the pandemic and first lockdown was unfolding in Australia. Data was collected through questionnaire (N = 101) and semistructured interview (n = 20) about status and change in children's digital practices, and parents' rules and flexibility in governing these experiences. Quantitative findings suggested children's frequency and duration of digital device use trended upwards during lockdown, and parents were more flexible in their rules about the amount of screen time, as well as when and where children could use digital devices. Qualitative results suggested that, more than a temporary and situational change, for many parents, exposure to new ways of engaging with digital technologies facilitated a shift in their perceptions, leading to greater consideration of quality in their choices for their children. This study highlights the influential role of parents in shaping children's digital experiences. Understanding their perceptions, as well as children's current and shifting digital practices in the home, is important for informing efforts and guidance for supporting young children's safe and effective use of digital technologies.

SARS-CoV-2 Mpro protease variants of concern display altered viral and host target processing but retain potency towards antivirals (preprint)

Main protease of SARS-CoV-2 (Mpro) is the most promising drug target against coronaviruses due to its essential role in virus replication. With newly emerging variants there is a concern that mutations in Mpro may alter structural and functional properties of protease and subsequently the potency of existing and potential antivirals. We explored the effect of 31 mutations belonging to 5 variants of concern (VOC) on catalytic parameters and substrate specificity, which revealed changes in substrate binding and rate of cleavage of a viral peptide. Crystal structures of 11 Mpro mutants provided structural insight into their altered functionality. Additionally, we show Mpro mutations influence proteolysis of an immunomodulatory host protein Galectin-8 (Gal-8) and subsequent significant decrease in cytokine secretion, providing evidence for alterations in escape of host-antiviral mechanisms. Accordingly, mutations associated with the highly virulent Delta VOC resulted in significant increase in Gal-8 cleavage. Importantly, IC50s of nirmatrelvir (Pfizer) and our irreversible inhibitor AVI-8053 demonstrated no changes in potency for both drugs for all mutants, suggesting Mpro will remain a high-priority antiviral drug candidate as SARS-CoV-2 evolves.

Hospital Readmissions Among Veterans Within 90 Days of Discharge Following Initial Hospitalization for COVID-19.

INTRODUCTION: Some patients experience ongoing sequelae after discharge, including rehospitalization; therefore, outcomes following COVID-19 hospitalization are of continued interest. We examined readmissions within 90 days of hospital discharge for veterans hospitalized with COVID-19 during the first 10 months of the pandemic in the US. METHODS: Veterans hospitalized with COVID-19 at a Veterans Health Administration (VA) hospital from March 1, 2020, through December 31, 2020 were followed for 90 days after discharge to determine readmission rates. RESULTS: Of 20,414 veterans hospitalized with COVID-19 during this time period, 13% (n = 2,643) died in the hospital. Among survivors (n = 17,771), 16% (n = 2,764) were readmitted within 90 days of discharge, with a mean time to readmission of 21.6 days (SD = 21.1). Characteristics of the initial COVID-19 hospitalization associated with readmission included length of stay, mechanical ventilator use, higher comorbidity index score, current smoking, urban residence, discharged against medical advice, and hospitalized from September through December 2020 versus March through August 2020 (all P values <.02). Veterans readmitted from September through December 2020 were more often White, lived in a rural or highly rural area, and had shorter initial hospitalizations than veterans hospitalized earlier in the year. CONCLUSION: Approximately 1 of 6 veterans discharged alive following a COVID-19 hospitalization from March 1 through December 31, 2020, were readmitted within 90 days. The longer the hospital stay, the greater the likelihood of readmission. Readmissions also were more likely when the initial admission required mechanical ventilation, or when the veteran had multiple comorbidities, smoked, or lived in an urban area. COVID-19 hospitalizations were shorter from September through December 2020, suggesting that hospital over-capacity may have resulted in earlier discharges and increased readmissions. Efforts to monitor and provide support for patients discharged in high bed-capacity situations may help avoid readmissions.

POLLINATOR-FLOWER INTERACTIONS IN GARDENS DURING THE COVID-19 PANDEMIC LOCKDOWN OF 2020

During the main COVID-19 global pandemic lockdown period of 2020 an impromptu set of pollination ecologists came together via social media and personal contacts to carry out standardised surveys of the flower visits and plants in gardens. The surveys involved 67 rural, suburban and urban gardens, of various sizes, ranging from 61.18° North in Norway to 37.96° South in Australia, resulting in a data set of 25,174 rows, with each row being a unique interaction record for that date/site/plant species, and comprising almost 47,000 visits to flowers, as well as records of flowers that were not visited by pollinators, for over 1,000 species and varieties belonging to more than 460 genera and 96 plant families. The more than 650 species of flower visitors belong to 12 orders of invertebrates and four of vertebrates. In this first publication from the project, we present a brief description of the data and make it freely available for any researchers to use in the future, the only restriction being that they cite this paper in the first instance. The data generated from these global surveys will provide scientific evidence to help us understand the role that private gardens (in urban, rural and suburban areas) can play in conserving insect pollinators and identify management actions to enhance their potential. © 2022 The authors.

The Impact of COVID-19 Pandemic on Spine Surgeons Worldwide: A One Year Prospective Comparative Study.

STUDY DESIGN: Survey. OBJECTIVE: In March of 2020, an original study by Louie et al investigated the impact of COVID-19 on 902 spine surgeons internationally. Since then, due to varying government responses and public health initiatives to the pandemic, individual countries and regions of the world have been affected differently. Therefore, this follow-up study aimed to assess how the COVID-19 impact on spine surgeons has changed 1 year later. METHODS: A repeat, multi-dimensional, 90-item survey written in English was distributed to spine surgeons worldwide via email to the AO Spine membership who agreed to receive surveys. Questions were categorized into the following domains: demographics, COVID-19 observations, preparedness, personal impact, patient care, and future perceptions. RESULTS: Basic respondent demographics, such as gender, age, home demographics, medical comorbidities, practice type, and years since training completion, were similar to those of the original 2020 survey. Significant differences between groups included reasons for COVID testing, opinions of media coverage, hospital unemployment, likelihood to be performing elective surgery, percentage of cases cancelled, percentage of personal income, sick leave, personal time allocation, stress coping mechanisms, and the belief that future guidelines were needed (P<.05). CONCLUSION: Compared to baseline results collected at the beginning of the COVID-19 pandemic in 2020, significant differences in various domains related to COVID-19 perceptions, hospital preparedness, practice impact, personal impact, and future perceptions have developed. Follow-up assessment of spine surgeons has further indicated that telemedicine and virtual education are mainstays. Such findings may help to inform and manage expectations and responses to any future outbreaks.

MIXEDMETHODS EVALUATIONOF THE INITIAL IMPLEMENTATION OF A MEDICAID ACCOUNTABLE CARE ORGANIZATION PROGRAM TO ADDRESS FOOD AND HOUSING INSECURITY

BACKGROUND: States and health systems are investing in programs to address patients' unmet social needs, such as food and housing insecurity, but there has been limited evaluation of the implementation of these programs. In 2020, Massachusetts initiated the Flexible Services (Flex) program to provide funding to Medicaid accountable care organizations (ACOs) to address food and housing insecurity through community resources. The study objective was to examine initial implementation of Flex (March 2020-July 2021), using the Reach, Efficacy, Adoption, Implementation, Maintenance (RE-AIM) framework. METHODS: This mixed-methods evaluation was part of LiveWell, a longitudinal study assessing the impact of Flex on community health center patients aligned with two large hospitals within Mass General Brigham (MGB) in Boston, MA. ACO participants were screened annually for food and housing insecurity. To assess reach, we examined Flex enrollment using electronic health record data of enrollees ≥21 years old. Eligibility criteria for Flex included: 1) enrollment in MGB Medicaid ACO, 2) food or housing insecurity identified by screening or clinical encounter, and 3) a complex health condition (e.g., uncontrolled diabetes, depression). To assess implementation, adoption, and effectiveness, we conducted qualitative interviews with Flex enrollees (N=16) and health system staff (N=15). Interviews were analyzed using the Framework Method. RESULTS: Of 44,417 ACO enrollees, 693 (2%) were enrolled in Flex in the first 17 months. A total of 19,275 (43%) of ACO enrollees and 521 (75%) of Flex enrollees completed annual screening for food/housing insecurity. Mean ACO participant age was 40 years (SD: 14);62% were female;32% were Hispanic. Mean Flex enrollee age was 46 years (SD: 13);81% were female;54% were Hispanic. Implementation challenges included complex eligibility requirements, administrative burden (e.g., tracking, documentation), COVID- 19 factors (e.g., reduced clinic visits), and coordinating with community organizations. Facilitators included raising staff awareness to increase referrals, administrative funding for enrollment staff, adaptive strategies to identify eligible patients, and streamlined communication with community organizations. Flex enrollees reported improvements in healthy eating and food security. Patients who were able to select food or meals based on their preferences reported higher satisfaction. Patient-reported housing support included assistance with utility bills and affordable housing applications. CONCLUSIONS: To improve reach, adoption, and effectiveness in diverse populations, states and health systems implementing programs to address social needs should consider expanding screening for food and housing insecurity, minimizing administrative burden, providing funding for enrollment staff, and tailoring programs to patient preferences.

TIMELY FOLLOW-UP OF ABNORMAL CANCER SCREENING TEST RESULTS IN TWO LARGE PRIMARY CARE PRACTICE NETWORKS

BACKGROUND: Timely follow-up of abnormal cancer screening test results (“abnormal screens”) is critical but often not achieved. As part of an NCI funded intervention trial (mFOCUS: multilevel Follow-up of Cancer Screening, ClinicalTrials.gov NCT03979495), we report on abnormal screens that were identified and tracked to identify eligible patients overdue for study inclusion. While not anticipated when this study was conceived, the COVID-19 pandemic resulted in a larger than anticipated backlog of patients in need of follow-up of abnormal screens. METHODS: Patients in two primary care practice networks affiliated with Mass General Brigham who had an abnormal screen for breast, cervical or lung cancer were identified using computerized algorithms and then tracked for completion of appropriate follow-up based upon the cancer type and the severity of the abnormal result. Since the intervention was designed as a “fail safe” system, additional time (2-6 months depending on the severity of the abnormal screen) was added after the recommended follow-up interval. We report the number of abnormal screens by cancer type and severity of the abnormality and the number of patients who completed follow-up based upon guideline and expert recommendations. RESULTS: Patient tracking and enrollment started with abnormal screens for breast and lung on 8/24/2020 and cervical cancer on 10/16/2020. Enrollment ended for all abnormal screens on December 15, 2021. Over the study period, 4003 abnormal breast, 5214 abnormal cervical, and 478 abnormal lung screens were identified. High risk abnormalities were most common for cervical (51.7%, recommended colposcopy or endometrial biopsy), lung (22.6%, LRADS 4B, 4X or 5), and lowest for breast (0.4%, BIRADS 5). Rates of completing recommended follow-up of abnormal screens by cancer type and severity of the result are shown in the table. CONCLUSIONS: Maximizing the benefits of cancer screening requires the timely follow-up of abnormal screening results. Though likely exacerbated by the COVID-19 pandemic, we identified that timely completion of abnormal screens is often not achieved. Rates of completion varied by cancer type and the severity of the abnormal result but highlight the need for systems based, multi-level interventions to identify, report and track abnormal results.

COVID-19 Vaccine Hesitancy Among Patients with Inflammatory Bowel Diseases at a Diverse Safety Net Hospital.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) and underrepresented minorities (URMs) historically have below average vaccination rates. URMs have increased morbidity and mortality from COVID-19. We surveyed IBD patients to assess COVID vaccination attitudes, particularly among URMs. METHODS: In May and June 2021, all 822 adult patients with IBD, medically homed at a tertiary IBD referral center and safety net hospital, and with access to the electronic patient portal, were sent an electronic survey assessing their attitudes regarding COVID-19 vaccination. An additional 115 without access to the patient portal were contacted by phone. Demographic and clinical data were recorded. The primary outcome was vaccination hesitancy, defined as: likely will become vaccinated later this year, but not immediately; unsure if they will get the vaccine; or do not want the vaccine. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) of factors associated with vaccination intent. RESULTS: The mean age was 46.6 years (SD 15.1). 210/1029 patients responded to the survey: 150/822 (18.2%) electronically and 60/115 (52.2%) by phone. Overall vaccine hesitancy rate was 11.9%, significantly higher in younger (aOR for 10-year increments, 0.64; 95% confidence interval [CI], 0.46-0.90, p = 0.011), Hispanic (aOR, 7.67; 95% CI, 2.99-21.3, p < 0.0002), and Black patients (aOR, 3.52; 95% CI 1.11-11.1, p = 0.050). Safety concerns were the most cited reasons for vaccine hesitancy. CONCLUSIONS: URM patients were more vaccine hesitant. Future studies should further explore factors leading to lower vaccination rates among these groups and strategies to improve COVID-19 vaccination rates.

Development of an aerosol intervention for COVID-19 disease: Tolerability of soluble ACE2 (APN01) administered via nebulizer.

As ACE2 is the critical SARS-CoV-2 receptor, we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung, and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here, after demonstrating in vitro neutralization of SARS-CoV-2 by APN01, and after obtaining preliminary evidence of its tolerability and preventive efficacy in a mouse model, we pursued development of an aerosol formulation. As a prerequisite to a clinical trial, we evaluated both virus binding activity and enzymatic activity for cleavage of Ang II following aerosolization. We report successful aerosolization for APN01, retaining viral binding as well as catalytic RAS activity. Dose range-finding and IND-enabling repeat-dose aerosol toxicology testing were conducted in dogs. Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers has now been initiated (NCT05065645), with subsequent Phase II testing planned for individuals with SARS-CoV-2 infection.

Impact of the COVID pandemic on emergency department CT utilization: where do we go from here?

PURPOSE: To analyze the impact of the coronavirus disease (COVID) pandemic on emergency department (ED) computed tomography (CT) utilization. METHODS: A retrospective observational study was conducted assessing seven hospitals' ED imaging volumes between Jan. 6, 2019, and Feb. 27, 2021. Weekly CT utilization is reported as CTs ordered per 100 ED visits. Utilization was ascertained in aggregate and by body area. Interrupted time series analysis was performed to assess significance of utilization change. Prespecified sensitivity analysis was performed for influenza-like or COVID-like illness (ILI/CLI). RESULTS: Weekly ED CT utilization increased from 35.9 CTs per 100 visits (95% confidence interval [95% CI] 35.8-36.1) to 41.8 per 100 visits (95% CI 41.7-42.0) in pre- and post-pandemic periods. Weekly ED CT chest utilization increased immediately following the pandemic declaration (+ 0.52 chest CTs per 100 ED visits, 95% CI 0.01-1.03, p < 0.05) and compared to pre-pandemic period (+ 0.02 per 100 ED visits, 95% CI 0.02-0.05, p < 0.02). For both CT abdomen/pelvis and CT head, there was neither an immediate effect (+ 0.34 CT-AP per 100 ED visits, 95% CI - 0.74 to 1.44, p = 0.89; - 0.42 CT-H per 100 ED visits, 95% CI - 1.53 to 0.70, p = 0.46) nor a change in weekly CT utilization (+ 0.03 CT-AP per 100 ED visits, 95% CI - 0.01 to 0.05, p = 0.09; + 0.03 CT-H per 100 ED visits, 95% CI - 0.01 to 0.06, p = 0.10).  CONCLUSION: These data may help formulate future strategies for resource utilization and imaging operations as we envision a future with COVID and other federal mandates affecting imaging utilization and appropriateness.

Diminishing returns, increasing risks: Impact of antibiotic duration of therapy on respiratory bacterial isolates in hospitalized patients during the coronavirus disease 2019 (COVID-19) pandemic.

In 829 hospital encounters for patients with COVID-19, 73.2% included orders for antibiotics; however, only 1.8% had respiratory cultures during the first 3 hospital days isolating bacteria. Case-control analysis of 30 patients and 96 controls found that each antibiotic day increased the risk of isolating multidrug-resistant gram-negative bacteria (MDR-GNB) in respiratory cultures by 6.5%.

Psychiatric disorders newly diagnosed among veterans subsequent to hospitalization for COVID-19.

OBJECTIVE: The goal of our study was to evaluate the development of new mental health diagnoses up to 6-months following COVID-19 hospitalization for in a large, national sample. METHOD: Data were extracted for all Veterans hospitalized at Veterans Health Administration hospitals for COVID-19 from March through August of 2020 utilizing national administrative data. After identifying the cohort, follow-up data were linked through six months post-hospitalization. Data were analyzed using logistic regression. RESULTS: Eight percent of patients developed a new mental health diagnosis following hospitalization. The most common new mental health diagnoses involved depressive, anxiety, and adjustment disorders. Younger and rural patients were more likely to develop new mental health diagnoses. Women and those with more comorbidities were less likely to develop new diagnoses. CONCLUSION: A subpopulation of patients hospitalized for COVID-19 developed new mental health diagnoses. Unique demographics predictors indicate the potential need for additional outreach and screening to groups at elevated risk of post-hospitalization, mental health sequelae.

Effectiveness of COVID-19 mRNA Vaccination in Preventing COVID-19-Associated Hospitalization Among Adults with Previous SARS-CoV-2 Infection - United States, June 2021-February 2022.

Previous infection with SARS-CoV-2, the virus that causes COVID-19, has been estimated to confer up to 90% protection against reinfection, although this protection was lower against the Omicron variant compared with that against other SARS-CoV-2 variants (1-3). A test-negative design was used to estimate effectiveness of COVID-19 mRNA vaccines in preventing subsequent COVID-19-associated hospitalization among adults aged ≥18 years with a previous positive nucleic acid amplification test (NAAT) or diagnosis of COVID-19.† The analysis used data from Cosmos, an electronic health record (EHR)-aggregated data set (4), and compared vaccination status of 3,761 case-patients (positive NAAT result associated with hospitalization) with 7,522 matched control-patients (negative NAAT result). After previous SARS-CoV-2 infection, estimated vaccine effectiveness (VE) against COVID-19-associated hospitalization was 47.5% (95% CI = 38.8%-54.9%) after 2 vaccine doses and 57.8% (95% CI = 32.1%-73.8%) after a booster dose during the Delta-predominant period (June 20-December 18, 2021), and 34.6% (95% CI = 25.5%-42.5%) after 2 doses and 67.6% (95% CI = 61.4%-72.8%) after a booster dose during the Omicron-predominant period (December 19, 2021-February 24, 2022). Vaccination provides protection against COVID-19-associated hospitalization among adults with previous SARS-CoV-2 infection, with the highest level of protection conferred by a booster dose. All eligible persons, including those with previous SARS-CoV-2 infection, should stay up to date with vaccination to prevent COVID-19-associated hospitalization.

An assessment of Veterans attitudes and willingness to receiving the COVID-19 vaccine: a mixed methods study.

BACKGROUND: While several safe and effective COVID-19 vaccines have been available since December 2020, many eligible individuals choose to remain unvaccinated. This vaccine hesitancy is an important factor affecting our ability to combat the COVID-19 pandemic. METHODS: The objective of the study was to examine the attitudes and willingness among US Veterans toward receiving COVID-19 vaccination. The study used a quantitative qualitative mixed methods design with a telephone survey and then in-depth interviews in a subset of those surveyed. Participants were unvaccinated Veterans (N = 184) selected randomly from a registry of patients who had received VA healthcare during the pandemic and had a diagnostic test for COVID-19. The primary outcome was willingness to accept COVID-19 vaccination. Survey data collection and in-depth interviews were conducted by telephone. Analyses of the survey data compared the primary outcome with demographics, clinical data, and survey responses using bivariate and multiple regression analyses. A subset (N = 10) of those surveyed, participated in an in-depth interview. Interview transcripts were analyzed to derive themes using qualitative content analysis. RESULTS: Almost 40% of participants disagreed they would receive a COVID-19 vaccine. Participants who were younger, female, and had fewer comorbid conditions were more likely (P < 0.05) to disagree with COVID-19 vaccination. In multiple regression analysis, willingness to accept vaccination was associated with reliance on a doctor or family member's recommendation and with a belief that vaccines are effective. In-depth interviews revealed several barriers to COVID-19 vaccination, including lack of trust in the government and vaccine manufacturers, concerns about the speed of vaccine development, fear of side effects, and fear the vaccine was a tool of racism. CONCLUSIONS: This study illustrates the complexity of patients' deliberation about COVID-19 vaccination and may help physicians and other health care providers understand patients' perspectives about COVID-19 vaccination. The results highlight the importance of patients' trust in physicians, healthcare organizations, pharmaceutical manufacturers and the government when making health decisions.