Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants.

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity against Delta and Omicron SARS-CoV-2 variants in 259 samples from 128 vaccinated individuals. Following Delta breakthrough infection, titers against WT rose 57-fold and 3.1-fold compared with uninfected boosted and unboosted individuals, respectively, versus only a 5.8-fold increase and 3.1-fold decrease for Omicron breakthrough infection. Among immunocompetent, unboosted patients, Delta breakthrough infections induced 10.8-fold higher titers against WT compared with Omicron (p = 0.037). Decreased antibody responses in Omicron breakthrough infections relative to Delta were potentially related to a higher proportion of asymptomatic or mild breakthrough infections (55.0% versus 28.6%, respectively), which exhibited 12.3-fold lower titers against WT compared with moderate to severe infections (p = 0.020). Following either Delta or Omicron breakthrough infection, limited variant-specific cross-neutralizing immunity was observed. These results suggest that Omicron breakthrough infections are less immunogenic than Delta, thus providing reduced protection against reinfection or infection from future variants.

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant.

We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.

Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination.

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.

The B.1.427/1.429 (epsilon) SARS-CoV-2 variants are more virulent than ancestral B.1 (614G) in Syrian hamsters.

As novel SARS-CoV-2 variants continue to emerge, it is critical that their potential to cause severe disease and evade vaccine-induced immunity is rapidly assessed in humans and studied in animal models. In early January 2021, a novel SARS-CoV-2 variant designated B.1.429 comprising 2 lineages, B.1.427 and B.1.429, was originally detected in California (CA) and it was shown to have enhanced infectivity in vitro and decreased antibody neutralization by plasma from convalescent patients and vaccine recipients. Here we examine the virulence, transmissibility, and susceptibility to pre-existing immunity for B 1.427 and B 1.429 in the Syrian hamster model. We find that both variants exhibit enhanced virulence as measured by increased body weight loss compared to hamsters infected with ancestral B.1 (614G), with B.1.429 causing the most marked body weight loss among the 3 variants. Faster dissemination from airways to parenchyma and more severe lung pathology at both early and late stages were also observed with B.1.429 infections relative to B.1. (614G) and B.1.427 infections. In addition, subgenomic viral RNA (sgRNA) levels were highest in oral swabs of hamsters infected with B.1.429, however sgRNA levels in lungs were similar in all three variants. This demonstrates that B.1.429 replicates to higher levels than ancestral B.1 (614G) or B.1.427 in the oropharynx but not in the lungs. In multi-virus in-vivo competition experiments, we found that B.1. (614G), epsilon (B.1.427/B.1.429) and gamma (P.1) dramatically outcompete alpha (B.1.1.7), beta (B.1.351) and zeta (P.2) in the lungs. In the nasal cavity, B.1. (614G), gamma, and epsilon dominate, but the highly infectious alpha variant also maintains a moderate size niche. We did not observe significant differences in airborne transmission efficiency among the B.1.427, B.1.429 and ancestral B.1 (614G) and WA-1 variants in hamsters. These results demonstrate enhanced virulence and high relative oropharyngeal replication of the epsilon (B.1.427/B.1.429) variant in Syrian hamsters compared to an ancestral B.1 (614G) variant.

Converting non-neutralizing SARS-CoV-2 antibodies into broad-spectrum inhibitors.

Omicron and its subvariants have rendered most authorized monoclonal antibody-based treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ineffective, highlighting the need for biologics capable of overcoming SARS-CoV-2 evolution. These mostly ineffective antibodies target variable epitopes. Here we describe broad-spectrum SARS-CoV-2 inhibitors developed by tethering the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), to known non-neutralizing antibodies that target highly conserved epitopes in the viral spike protein. These inhibitors, called receptor-blocking conserved non-neutralizing antibodies (ReconnAbs), potently neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron. Neutralization potency is lost when the linker joining the binding and inhibitory ReconnAb components is severed. In addition, a bi-functional ReconnAb, made by linking ACE2 to a bi-specific antibody targeting two non-overlapping conserved epitopes, defined here, shows sub-nanomolar neutralizing activity against all VOCs, including Omicron and BA.2. Given their conserved targets and modular nature, ReconnAbs have the potential to act as broad-spectrum therapeutics against SARS-CoV-2 and other emerging pandemic diseases.

Do healthcare providers consider the social determinants of health? Results from a nationwide cross-sectional study in the United States.

BACKGROUND: While the social determinants of health (SDOH) have a greater impact on individual health outcomes than the healthcare services a person receives, healthcare providers face barriers to addressing these factors in clinical settings. Previous studies have shown that providers often lack the necessary knowledge and resources to adequately screen for and otherwise assist patients with unmet social needs. This study explores the perceptions and behaviors related to SDOH among healthcare providers in the United States (US). METHODS: This cross-sectional study analyzed data from a 22-item online survey using Reaction Data's research platform of healthcare professionals in the US. Survey items included demographic questions as well as Likert scale questions about healthcare providers' perceptions and behaviors related to SDOH. Descriptive statistics were calculated, and further analyses were conducted using t-tests and analysis of variance. RESULTS: A total of 563 respondents completed the survey, with the majority being male (72.6%), White (81%), and located in urban areas (82.2%). In terms of perceptions, most providers agreed or strongly agreed that SDOH affect the health outcomes of all patients (68.5%), while only 24.1% agreed or strongly agreed that their healthcare setting was set up to address SDOH. In terms of behavior, fewer than half currently screened for SDOH (48.6%) or addressed (42.7%) SDOH in other ways. Most providers (55.7%) wanted additional resources to focus on SDOH. Statistical analyses showed significant differences by gender, with females being more likely than males to prioritize SDOH, and by specialty, with psychiatrists, pediatricians, and family/general medicine practitioners being more likely to prioritize SDOH. CONCLUSION: Most healthcare providers understand the connection between unmet social needs and their patients' health, but they also feel limited in their ability to address these issues. Ongoing efforts to improve medical education and shift the healthcare system to allow for payment and delivery of more holistic care that considers SDOH will likely provide new opportunities for healthcare providers. In addition to what they can do at the institutional and patient levels, providers have the potential to advocate for policy and system changes at the societal level that can better address the root causes of social issues.

The effects of COVID-19 stressors and family life on anxiety and depression one-year into the COVID-19 pandemic.

The purpose of this study was to examine the effects of Coronavirus (COVID-19)-related stressors and family health on adult anxiety and depressive symptoms 1 year into the pandemic. The sample consisted of 442 adults living in the United States who were recruited via Amazon Mechanical Turk. Data were analyzed using multiple logistic regression. Results indicated that compared to a sample 1 month into the pandemic, participants in the current sample reported worse family health and increases in both positive and negative perceptions of the pandemic on family life and routines. COVID-19 stressors and perceived negative effects of the pandemic on family life increased the odds for moderate-to-severe depression and anxiety while having more family health resources decreased the odds for depression and anxiety symptoms. Participants reported lower odds for worse depression and anxiety since the beginning of the pandemic when they reported more positive family meaning due to the pandemic. The results suggest a need to consider the impact of family life on mental health in pandemics and other disasters.

Neutralizing Immunity Induced Against the Omicron BA.1 and BA.2 Variants in Vaccine Breakthrough Infections.

BACKGROUND: As of early 2022, the Omicron variants are the predominant circulating lineages globally. Understanding neutralizing antibody responses against Omicron BA.1 and BA.2 after vaccine breakthrough infections will provide insights into BA.2 infectivity and susceptibility to subsequent reinfection. METHODS: Live virus neutralization assays were used to study immunity against Delta and Omicron BA.1 and BA.2 variants in samples from 86 individuals, 24 unvaccinated (27.9%) and 62 vaccinated (72.1%), who were infected with Delta (n = 42, 48.8%) or BA.1 (n = 44, 51.2%). Among the 62 vaccinated individuals, 39 were unboosted (62.9%), whereas 23 were boosted (37.1%). RESULTS: In unvaccinated infections, neutralizing antibodies (nAbs) against the three variants were weak or undetectable, except against Delta for Delta-infected individuals. Both Delta and BA.1 breakthrough infections resulted in strong nAb responses against ancestral wild-type and Delta lineages, but moderate nAb responses against BA.1 and BA.2, with similar titers between unboosted and boosted individuals. Antibody titers against BA.2 were generally higher than those against BA.1 in breakthrough infections. CONCLUSIONS: These results underscore the decreased immunogenicity of BA.1 compared to BA.2, insufficient neutralizing immunity against BA.2 in unvaccinated individuals, and moderate to strong neutralizing immunity induced against BA.2 in Delta and BA.1 breakthrough infections.

Sylvatic Transmission of Chikungunya Virus among Nonhuman Primates in Myanmar.

Nonhuman primates living in proximity to humans increase risks for sylvatic arbovirus transmission. We collected serum samples from nonhuman primates in Hlawga National Park near Yangon, Myanmar, and detected antibodies against chikungunya (33%) and Japanese encephalitis (4%) viruses. Buffer zones between primate and human communities might reduce cross-species arbovirus transmission.

Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.

BACKGROUND: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption. METHODS: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter). RESULTS: A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy. CONCLUSIONS: UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).

Effectiveness of Abbott BinaxNOW Rapid Antigen Test for Detection of SARS-CoV-2 Infections in Outbreak among Horse Racetrack Workers, California, USA.

The Abbott BinaxNOW rapid antigen test is cheaper and faster than real-time reverse transcription PCR (rRT-PCR) for detecting severe acute respiratory syndrome coronavirus 2. We compared BinaxNOW with rRT-PCR in 769 paired specimens from 342 persons during a coronavirus disease outbreak among horse racetrack workers in California, USA. We found positive percent agreement was 43.3% (95% CI 34.6%-52.4%), negative percent agreement 100% (95% CI 99.4%-100%), positive predictive value 100% (95% CI 93.5%-100%), and negative predictive value 89.9% (95% CI 87.5%-92.0%). Among 127 rRT-PCR-positive specimens, the 55 with paired BinaxNOW-positive results had a lower mean cycle threshold than the 72 with paired BinaxNOW-negative results (17.8 vs. 28.5; p<0.001). Of 100 specimens with cycle threshold <30, a total of 51 resulted in positive virus isolation; 45 (88.2%) of those were BinaxNOW-positive. Our comparison supports immediate isolation for BinaxNOW-positive persons and confirmatory testing for negative persons.

Engineering of a Lectibody Targeting High-Mannose-Type Glycans of the HIV Envelope.

High-mannose-type glycans (HMGs) are aberrantly enriched on HIV envelope glycoproteins. However, there is currently no drug selectively targeting HIV-associated HMGs. Here, we describe a novel HMG-targeting "lectibody," a recombinant Fc-fusion protein comprising human IgG1 Fc and a novel actinohivin lectin variant (Avaren) obtained by structure-guided modifications for improved overall surface charge properties (AvFc). AvFc was engineered and produced using a rapid and scalable plant-based transient overexpression system. The lectibody exhibited potent antiviral activity against HIV-1 groups M and O primary viruses, as well as HIV-2 and simian immunodeficiency virus (SIV) strains, without affecting normal human blood cells. Furthermore, the lectibody induced Fc-mediated cell killing activity against HIV-1-infected cells and selectively recognized SIVmac239-infected macaque mesenteric lymph node cells in vitro. AvFc showed an extended serum half-life in rats and rhesus macaques, while no discernible toxicity was observed upon repeated systemic dosing in mice. These results highlight AvFc's potential as a biotherapeutic targeting HIV-associated HMGs of cell-free virions, as well as productively infected cells, providing a foundation for new anti-HIV strategies. Efficient and cost-effective bioproduction in greenhouse facilities may open unique possibilities for further development of AvFc.

The longitudinal association between cognitive control capacities, suicidality, and depression during late adolescence and young adulthood.

This study examined the association between cognitive control capacities, suicidal thoughts and attempts, and depressive symptoms during late adolescence and young adulthood. The sample included 4192 participants (55.5% female) from the United States who participated in Waves III (2001-2002; respondent age 18-26 years) and IV (2007-2008; respondent age 24-33 years) of the National Longitudinal Study of Adolescent to Adult Health. Data were analyzed using structural equation modeling. Suicidality in late adolescence predicted depressive symptoms in young adulthood. Depressive symptoms were not predictive of later suicide ideation nor attempts. Working memory was associated with lower depressive symptoms. Higher verbal ability was associated with more suicidal thoughts but not attempts. Internal locus of control was associated with decreased depressive symptoms and suicidal thoughts/attempts in young adulthood. Findings suggest that cognitive control capacities developed in adolescence differentially predict depressive symptoms, suicidal thoughts, and suicide attempts in young adulthood.

Risk and protective factors associated with being bullied on school property compared with cyberbullied.

BACKGROUND: We identified bullying victimization (bullied on school property versus cyberbullied) by selected demographic, personal characteristic, and behavior variables. METHODS: A cross-sectional analysis was conducted on adolescents (n = 13,583) completing the 2013 Youth Risk Behavior Survey (YRBS) in grades 9 through 12. RESULTS: Being bullied on school property in the past 12 months was significantly more common in females than males, in earlier school grades, and in Whites and other racial groups compared with Blacks and Hispanics. Being bullied on school property generally decreased with later school grades, but cyberbullying in the past 12 months remained constant. Being bullied on school property or cyberbullied was significantly positively associated with mental health problems, substance use, being overweight, playing video games for 3 or more hours per day, and having asthma. The association was greatest with having mental health problems. Cyberbullying was generally more strongly associated with these conditions and behaviors. Protective behaviors against bullying victimization included eating breakfast every day, being physically active, and playing on sports teams. Those experiencing victimization on school property and cyberbullying were significantly more likely to experience mental health problems compared with just one of these types of bullying or neither. CONCLUSIONS: Cyberbullying victimization is generally more strongly associated with mental health problems, substance use, being overweight, playing video games for 3 or more hours per day, and having asthma than bullying victimization on school property. However, because bullying on school property is more common in grades 9-11, this form of bullying has a greater burden on these conditions and behaviors in these school grades.

Health Education Specialists' Knowledge, Attitudes, and Perceptions of the Patient Protection and Affordable Care Act.

The changing landscape of health care as a result of the Patient Protection and Affordable Care Act (ACA) may provide new opportunities for health education specialists (HES). The purpose of this study was to survey HES in the United States on their knowledge and attitudes of the ACA and assess their perceptions of job growth under the law. A random sample of 220 (36% response rate) certified HES completed a 53-item cross sectional survey administered online through Qualtrics. Findings were compared to public opinion on health care reform. HES are highly favorable of the law (70%) compared to the general public (23%). A total of 85% of respondents were able to list a provision of the ACA, and most (81%) thought the ACA would be successful at increasing insured Americans. Over half (64.6%) believe job opportunities will increase. Those who viewed the law favorably were significantly more likely to score better on a knowledge scale related to the ACA. HES understand publicized provisions but are uncertain about common myths and specific provisions related to Title IV, "Prevention of Chronic Disease and Improving Public Health." Directed and continuing education to HES regarding the ACA is warranted.

The Laugh Model: Reframing and Rebranding Public Health Through Social Media.

OBJECTIVES: We examined the use of low-cost social media platforms in communicating public health messages and outline the laugh model, a framework through which public health organizations can reach and engage communities. METHODS: In August 2014, we developed an online campaign (Web site and social media) to help promote healthy family meals in Utah in conjunction with the state and local health departments. RESULTS: By the end of September 2014, a total of 3641 individuals had visited the Utahfamilymeals.org Web site. Facebook ads reached a total of 29 078 people, and 56 900 people were reached through Twitter ads. The per-person price of the campaign was 0.2 cents, and the total estimated target population reach was between 10% and 12%. CONCLUSIONS: There are 3 key takeaways from our campaign: use of empowering and engaging techniques may be more effective than use of educational techniques; use of social media Web sites and online marketing tactics can enhance collaboration, interdisciplinary strategies, and campaign effectiveness; and use of social media as a communication platform is often preferable to use of mass media in terms of cost-effectiveness, more precise evaluations of campaign success, and increased sustainability.

Antibodies to a superantigenic glycoprotein 120 epitope as the basis for developing an HIV vaccine.

Failure to induce synthesis of neutralizing Abs to the CD4 binding determinant (CD4BD) of gp120, a central objective in HIV vaccine research, has been alternately ascribed to insufficient immunogen binding to Abs in their germline V region configuration expressed as BCRs, insufficient adaptive mutations in Ab V regions, and conformational instability of gp120. We employed peptide analogs of gp120 residues 421-433 within the CD4BD (CD4BD(core)) to identify Abs produced without prior exposure to HIV (constitutive Abs). The CD4BD(core) peptide was recognized by single-chain Fv fragments from noninfected humans with lupus that neutralized genetically diverse strains belonging to various HIV subtypes. Replacing the framework region (FR) of a V(H)4-family single-chain Fv with the corresponding V(H)3-family FRs from single-chain Fv JL427 improved the CD4BD(core) peptide-binding activity, suggesting a CD4BD(core) binding site outside the pocket formed by the CDRs. Replacement mutations in the FR site vicinity suggested the potential for adaptive improvement. A very small subset of serum CD4BD(core)-specific serum IgAs from noninfected humans without autoimmune disease isolated by epitope-specific chromatography neutralized the virus potently. A CD4BD(core)-specific, HIV neutralizing murine IgM with H and L chain V regions (V(H) and V(L) regions) free of immunogen-driven somatic mutations was induced by immunization with a CD4BD(core) peptide analog containing an electrophilic group that binds B cells covalently. The studies indicate broad and potent HIV neutralization by constitutive Abs as an innate, germline-encoded activity directed to the superantigenic CD4BD(core) epitope that is available for amplification for vaccination against HIV.

Understanding and predicting social media use among community health center patients: a cross-sectional survey.

BACKGROUND: The use of social media by health care organizations is growing and provides Web-based tools to connect patients, caregivers, and providers. OBJECTIVE: The aim was to determine the use and factors predicting the use of social media for health care-related purposes among medically underserved primary care patients. METHODS: A cross-sectional survey was administered to 444 patients of a federally qualified community health center. RESULTS: Community health center patients preferred that their providers use email, cell phones for texting, and Facebook and cell phone apps for sharing health information. Significantly more Hispanic than white patients believed their providers should use Facebook (P=.001), YouTube (P=.01), and Twitter (P=.04) for sharing health information. Use and intentions to use social media for health-related purposes were significantly higher for those patients with higher subjective norm scores. CONCLUSIONS: Understanding use and factors predicting use can increase adoption and utilization of social media for health care-related purposes among underserved patients in community health centers.

Psychometric Evaluation of the Trauma-Informed Care Provider Assessment Tool.

The increasing recognition of adverse childhood experiences as a significant factor in adult health outcomes underscores the need for trauma-informed care (TIC) in healthcare settings. The purpose of this study was to assess the psychometric properties of the TIC Provider Assessment Tool (TIC-PAT) designed for primary care providers. The TIC-PAT aligns with the TIC Pyramid framework and assesses both universal trauma precautions and trauma-specific care. A total of 176 primary care providers in the United States completed the TIC-PAT through an anonymous online survey. Findings through exploratory and confirmatory factor analyses revealed a unidimensional (one-factor) model, consolidating questions into a concise 10-item measure. This study contributes an efficient assessment tool for the provision of TIC by primary care providers in healthcare settings, promoting better patient-provider interactions and enhancing provider awareness of trauma's impact on health.

U.S. Physicians' Training and Experience in Providing Trauma-Informed Care in Clinical Settings.

Trauma-informed care (TIC) is a comprehensive approach that focuses on the whole individual. It acknowledges the experiences and symptoms of trauma and their impact on health. TIC prioritizes physical and emotional safety through a relationship of trust that supports patient choice and empowerment. It provides a safe and respectful healing environment that considers specific needs while promoting a greater sense of well-being, patient engagement, and partnership in the treatment process. Given the prevalence of trauma, this descriptive cross-sectional study examined the attitudes and perspectives of U.S. physicians (N = 179; 67% males; 84% White; 43% aged 56-65) in providing trauma-informed care using an anonymous 29-item online survey administered by Reaction Data. Findings showed that 16% (n = 18) of physicians estimated that >50% of their patients have a history of trauma. Commonly perceived barriers to providing TIC were resource/time/administrative constraints, provider stress, limited awareness of the right provider to refer patients who experienced trauma, and inadequate TIC emphasis in medical education/training. Expanding physicians' knowledge base of trauma through training and organizational policy/support is crucial in enhancing their TIC competence, particularly in caring for patients with complex care needs whose social determinants increase their risk of exposure to adverse experiences that carry lasting physical and psychological effects.