Injectable hydrogels for personalized cancer immunotherapies.

The field of cancer immunotherapy has shown significant growth, and researchers are now focusing on effective strategies to enhance and prolong local immunomodulation. Injectable hydrogels (IHs) have emerged as versatile platforms for encapsulating and controlling the release of small molecules and cells, drawing significant attention for their potential to enhance antitumor immune responses while inhibiting metastasis and recurrence. IHs delivering natural killer (NK) cells, T cells, and antigen-presenting cells (APCs) offer a viable method for treating cancer. Indeed, it can bypass the extracellular matrix and gradually release small molecules or cells into the tumor microenvironment, thereby boosting immune responses against cancer cells. This review provides an overview of the recent advancements in cancer immunotherapy using IHs for delivering NK cells, T cells, APCs, chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. First, we introduce IHs as a delivery matrix, then summarize their applications for the local delivery of small molecules and immune cells to elicit robust anticancer immune responses. Additionally, we discuss recent progress in IHs systems used for local combination therapy, including chemoimmunotherapy, radio-immunotherapy, photothermal-immunotherapy, photodynamic-immunotherapy, and gene-immunotherapy. By comprehensively examining the utilization of IHs in cancer immunotherapy, this review aims to highlight the potential of IHs as effective carriers for immunotherapy delivery, facilitating the development of innovative strategies for cancer treatment. In addition, we demonstrate that using hydrogel-based platforms for the targeted delivery of immune cells, such as NK cells, T cells, and dendritic cells (DCs), has remarkable potential in cancer therapy. These innovative approaches have yielded substantial reductions in tumor growth, showcasing the ability of hydrogels to enhance the efficacy of immune-based treatments. STATEMENT OF SIGNIFICANCE: As cancer immunotherapy continues to expand, the mode of therapeutic agent delivery becomes increasingly critical. This review spotlights the forward-looking progress of IHs, emphasizing their potential to revolutionize localized immunotherapy delivery. By efficiently encapsulating and controlling the release of essential immune components such as T cells, NK cells, APCs, and various therapeutic agents, IHs offer a pioneering pathway to amplify immune reactions, moderate metastasis, and reduce recurrence. Their adaptability further shines when considering their role in emerging combination therapies, including chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. Understanding IHs' significance in cancer therapy is essential, suggesting a shift in cancer treatment dynamics and heralding a novel period of focused, enduring, and powerful therapeutic strategies.

Experiences of Health Departments on Community Engagement and Implementation of a COVID-19 Self-testing Program.

CONTEXT: Health departments (HDs) work on the front lines to ensure the health of their communities, providing a unique perspective to public health response activities. Say Yes! COVID Test (SYCT) is a US federally funded program providing free COVID-19 self-tests to communities with high COVID-19 transmission, low vaccination rates, and high social vulnerability. The collaboration with 9 HDs was key for the program distribution of 5.8 million COVID-19 self-tests between March 31 and November 30, 2021. OBJECTIVE: The objective of this study was to gather qualitative in-depth information on the experiences of HDs with the SYCT program to better understand the successes and barriers to implementing community-focused self-testing programs. DESIGN: Key informant (KI) interviews. SETTING: Online interviews conducted between November and December 2021. PARTICIPANTS: Sixteen program leads representing 9 HDs were purposefully sampled as KIs. KIs completed 60-minute structured interviews conducted by one trained facilitator and recorded. MAIN OUTCOME MEASURES: Key themes and lessons learned were identified using grounded theory. RESULTS: Based on perceptions of KIs, HDs that maximized community partnerships for test distribution were more certain that populations at a higher risk for COVID-19 were reached. Where the HD relied predominantly on direct-to-consumer distribution, KIs were less certain that communities at higher risk were served. Privacy and anonymity in testing were themes linked to higher perceived community acceptance. KIs reported that self-test demand and distribution levels increased during higher COVID-19 transmission levels. CONCLUSION: HDs that build bridges and engage with community partners and trusted leaders are better prepared to identify and link high-risk populations with health services and resources. When collaborating with trusted community organizations, KIs perceived that the SYCT program overcame barriers such as mistrust of government intervention and desire for privacy and motivated community members to utilize this resource to protect themselves against COVID-19.

The Impact of Community-Based Testing Sites and Gift Incentives on COVID-19 Testing Uptake in Maryland, April 29 - May 9, 2021.

PURPOSE: Information on incentives for COVID-19 testing is needed to understand effective practices that encourage testing uptake. We describe characteristics of those who received an incentive after performing a rapid antigen test. DESIGN: Cross-sectional descriptive analysis of survey data. SETTING: During April 29-May 9, 2021, COVID-19 rapid antigen testing was offered in 2 Maryland cities. SAMPLE: Convenience sample of 553 adults (≥18 years) who tested and received an incentive; 93% consented to survey. MEASURES: Survey questions assessed reasons for testing, testing history, barriers, and demographics. ANALYSIS: Robust Poisson regressions were used to determine characteristic differences based on testing history and between participants who would re-test in the future without an incentive vs participants who would not. RESULTS: The most common reasons for testing were the desire to be tested (n = 280; 54%) and convenience of location (n = 146; 28%). Those motivated by an incentive to test (n = 110; 21%) were 5.83 times as likely to state they would not test again without an incentive, compared to those with other reasons for testing (95% CI: 2.67-12.72, P < .001). CRITICAL LIMITATIONS: No comparative study group. CONCLUSION: Results indicate internal motivation and convenience were prominent factors supporting testing uptake. Incentives may increase community testing participation, particularly among people who have never tested. Keywords COVID-19, pandemic, incentives, health behavior, community testing.

COVID-19 Outbreaks Linked to Workplaces, 23 US Jurisdictions, August-October 2021.

OBJECTIVES: Early in the COVID-19 pandemic, several outbreaks were linked with facilities employing essential workers, such as long-term care facilities and meat and poultry processing facilities. However, timely national data on which workplace settings were experiencing COVID-19 outbreaks were unavailable through routine surveillance systems. We estimated the number of US workplace outbreaks of COVID-19 and identified the types of workplace settings in which they occurred during August-October 2021. METHODS: The Centers for Disease Control and Prevention collected data from health departments on workplace COVID-19 outbreaks from August through October 2021: the number of workplace outbreaks, by workplace setting, and the total number of cases among workers linked to these outbreaks. Health departments also reported the number of workplaces they assisted for outbreak response, COVID-19 testing, vaccine distribution, or consultation on mitigation strategies. RESULTS: Twenty-three health departments reported a total of 12 660 workplace COVID-19 outbreaks. Among the 12 470 workplace types that were documented, 35.9% (n = 4474) of outbreaks occurred in health care settings, 33.4% (n = 4170) in educational settings, and 30.7% (n = 3826) in other work settings, including non-food manufacturing, correctional facilities, social services, retail trade, and food and beverage stores. Eleven health departments that reported 3859 workplace outbreaks provided information about workplace assistance: 3090 (80.1%) instances of assistance involved consultation on COVID-19 mitigation strategies, 1912 (49.5%) involved outbreak response, 436 (11.3%) involved COVID-19 testing, and 185 (4.8%) involved COVID-19 vaccine distribution. CONCLUSIONS: These findings underscore the continued impact of COVID-19 among workers, the potential for work-related transmission, and the need to apply layered prevention strategies recommended by public health officials.

Incidence of COVID-19 Among Persons Experiencing Homelessness in the US From January 2020 to November 2021.

Importance: A lack of timely and high-quality data is an ongoing challenge for public health responses to COVID-19 among people experiencing homelessness (PEH). Little is known about the total number of cases of COVID-19 among PEH. Objective: To estimate the number of COVID-19 cases among PEH and compare the incidence rate among PEH with that in the general population. Design, Setting, and Participants: This cross-sectional study used data from a survey distributed by the Centers for Disease Control and Prevention to all US state, district, and territorial health departments that requested aggregated COVID-19 data among PEH from January 1, 2020, to September 30, 2021. Jurisdictions were encouraged to share the survey with local health departments. Main Outcomes and Measures: The primary study outcome was the number of cases of COVID-19 identified among PEH. COVID-19 cases and incidence rates among PEH were compared with those in the general population in the same geographic areas. Results: Participants included a population-based sample of all 64 US jurisdictional health departments. Overall, 25 states, districts, and territories completed the survey, among which 18 states (72.0%) and 27 localities reported COVID-19 data among PEH. A total of 26 349 cases of COVID-19 among PEH were reported at the state level and 20 487 at the local level. The annual incidence rate of COVID-19 among PEH at the state level was 567.9 per 10 000 person-years (95% CI, 560.5-575.4 per 10 000 person-years) compared with 715.0 per 10 000 person-years (95% CI, 714.5-715.5 per 10 000 person-years) in the general population. At the local level, the incidence rate of COVID-19 among PEH was 799.2 per 10 000 person-years (95% CI, 765.5-834.0 per 10 000 person-years) vs 812.5 per 10 000 person-years (95% CI, 810.7-814.3 per 10 000 person-years) in the general population. Conclusions and Relevance: These results provide an estimate of COVID-19 incidence rates among PEH in multiple US jurisdictions; however, a national estimate and the extent of under- or overestimation remain unknown. The findings suggest that opportunities exist for incorporating housing and homelessness status in infectious disease reporting to inform public health decision-making.

Symptoms of Mental Health Conditions and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers - United States, March 14-25, 2022.

An increase in adverse mental health symptoms occurred in the general population at the onset of the COVID-19 pandemic, which peaked in 2020 and subsequently decreased (1-3). The pandemic exacerbated existing stress and fatigue among public health workers responding to the public health crisis.* During March-April 2021, a survey of state, tribal, local, and territorial (STLT) public health workers found that 52.8% of respondents experienced symptoms of at least one of the following mental health conditions: depression, anxiety, or posttraumatic stress disorder (PTSD) (4); however, more recent estimates of mental health symptoms among this population are limited. To evaluate trends in these conditions from the previous year, the prevalence of symptoms of mental health conditions and suicidal ideation, a convenience sample of STLT public health workers was surveyed during March 14-25, 2022. In total, 26,069 STLT public health workers responded to the survey. Among respondents,† 6,090 (27.7%) reported symptoms of depression, 6,467 (27.9%) anxiety, 6,324 (28.4%) PTSD, and 1,853 (8.1%) suicidal ideation. Although the prevalences of depression, anxiety, and PTSD among public health workers were lower (p<0.001)§ among 2022 survey respondents compared with those of 2021 survey respondents (4), the prevalences of symptoms of suicidal ideation, anxiety, depression, and PTSD remained high among those who worked >60 hours per week (range = 11.3%-45.9%) and those who spent ≥76% of their work time on COVID-19 response activities (range = 9.0%-37.6%). Respondents were less likely to report mental health symptoms if they could take time off (prevalence ratio [PR] range = 0.48-0.55), or if they perceived an increase in mental health resources from their employer (PR range = 0.58-0.84). To support the mental health of public health workers, public health agencies can modify work-related factors, including making organizational changes for emergency responses and facilitating access to mental health resources and services.¶.

The impact of traumatic experiences, coping mechanisms, and workplace benefits on the mental health of U.S. public health workers during the COVID-19 pandemic.

PURPOSE: To evaluate the association between risk factors, mitigating factors, and adverse mental health outcomes among United States public health workers. METHODS: Cross-sectional online survey data were collected March to April 2021. The survey was distributed to public health workers who worked in a state, tribal, local, or territorial public health department since March 2020. RESULTS: In total, 26,174 United States state and local public health workers completed the survey. Feeling isolated was a risk factor for anxiety (PR, 1.84; 95% CI, 1.74-1.95), depression (PR, 1.84; 95% CI, 1.75-1.94), post-traumatic stress disorder (PR, 1.50; 95% CI, 1.43-1.57), and suicidal ideation (PR, 3.23; 95% CI, 2.82-3.69). The ability to take time off was linked to fewer reported symptoms of anxiety (PR, 0.87; 95% CI, 0.83-0.90), depression (PR, 0.86; 95% CI, 0.83-0.89), post-traumatic stress disorder (PR, 0.84; 95% CI, 0.81-0.88), and suicidal ideation (PR, 0.84; 95% CI, 0.77-0.92). CONCLUSIONS: Since COVID-19 was declared a pandemic, respondents who felt isolated and alone were at an increased risk for adverse mental health outcomes. Findings from this study call for public health organizations to provide their workforce with services and resources to mitigate adverse mental health outcomes.

Change in unemployment by social vulnerability among United States counties with rapid increases in COVID-19 incidence-July 1-October 31, 2020.

OBJECTIVE: During the COVID-19 pandemic, the unemployment rate in the United States peaked at 14.8% in April 2020. We examined patterns in unemployment following this peak in counties with rapid increases in COVID-19 incidence. METHOD: We used CDC aggregate county data to identify counties with rapid increases in COVID-19 incidence (rapid riser counties) during July 1-October 31, 2020. We used a linear regression model with fixed effect to calculate the change of unemployment rate difference in these counties, stratified by the county's social vulnerability (an indicator compiled by CDC) in the two months before the rapid riser index month compared to the index month plus one month after the index month. RESULTS: Among the 585 (19% of U.S. counties) rapid riser counties identified, the unemployment rate gap between the most and least socially vulnerable counties widened by 0.40 percentage point (p<0.01) after experiencing a rapid rise in COVID-19 incidence. Driving the gap were counties with lower socioeconomic status, with a higher percentage of people in racial and ethnic minority groups, and with limited English proficiency. CONCLUSION: The widened unemployment gap after COVID-19 incidence rapid rise between the most and least socially vulnerable counties suggests that it may take longer for socially and economically disadvantaged communities to recover. Loss of income and benefits due to unemployment could hinder behaviors that prevent spread of COVID-19 (e.g., seeking healthcare) and could impede response efforts including testing and vaccination. Addressing the social needs within these vulnerable communities could help support public health response measures.

Investigation of SARS-CoV-2 Transmission Associated With a Large Indoor Convention - New York City, November-December 2021.

During November 19-21, 2021, an indoor convention (event) in New York City (NYC), was attended by approximately 53,000 persons from 52 U.S. jurisdictions and 30 foreign countries. In-person registration for the event began on November 18, 2021. The venue was equipped with high efficiency particulate air (HEPA) filtration, and attendees were required to wear a mask indoors and have documented receipt of at least 1 dose of a COVID-19 vaccine.* On December 2, 2021, the Minnesota Department of Health reported the first case of community-acquired COVID-19 in the United States caused by the SARS-CoV-2 B.1.1.529 (Omicron) variant in a person who had attended the event (1). CDC collaborated with state and local health departments to assess event-associated COVID-19 cases and potential exposures among U.S.-based attendees using data from COVID-19 surveillance systems and an anonymous online attendee survey. Among 34,541 attendees with available contact information, surveillance data identified test results for 4,560, including 119 (2.6%) persons from 16 jurisdictions with positive SARS-CoV-2 test results. Most (4,041 [95.2%]), survey respondents reported always wearing a mask while indoors at the event. Compared with test-negative respondents, test-positive respondents were more likely to report attending bars, karaoke, or nightclubs, and eating or drinking indoors near others for at least 15 minutes. Among 4,560 attendees who received testing, evidence of widespread transmission during the event was not identified. Genomic sequencing of 20 specimens identified the SARS-CoV-2 B.1.617.2 (Delta) variant (AY.25 and AY.103 sublineages) in 15 (75%) cases, and the Omicron variant (BA.1 sublineage) in five (25%) cases. These findings reinforce the importance of implementing multiple, simultaneous prevention measures, such as ensuring up-to-date vaccination, mask use, physical distancing, and improved ventilation in limiting SARS-CoV-2 transmission, during large, indoor events.†.

Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic - United States, March-April 2021.

Increases in mental health conditions have been documented among the general population and health care workers since the start of the COVID-19 pandemic (1-3). Public health workers might be at similar risk for negative mental health consequences because of the prolonged demand for responding to the pandemic and for implementing an unprecedented vaccination campaign. The extent of mental health conditions among public health workers during the COVID-19 pandemic, however, is uncertain. A 2014 survey estimated that there were nearly 250,000 state and local public health workers in the United States (4). To evaluate mental health conditions among these workers, a nonprobability-based online survey was conducted during March 29-April 16, 2021, to assess symptoms of depression, anxiety, post-traumatic stress disorder (PTSD), and suicidal ideation among public health workers in state, tribal, local, and territorial public health departments. Among 26,174 respondents, 52.8% reported symptoms of at least one mental health condition in the preceding 2 weeks, including depression (30.8%), anxiety (30.3%), PTSD (36.8%), or suicidal ideation (8.4%). The highest prevalence of symptoms of a mental health condition was among respondents aged ≤29 years (range = 13.6%-47.4%) and transgender or nonbinary persons (i.e., those who identified as neither male nor female) of all ages (range = 30.4%-65.5%). Public health workers who reported being unable to take time off from work were more likely to report adverse mental health symptoms. Severity of symptoms increased with increasing weekly work hours and percentage of work time dedicated to COVID-19 response activities. Implementing prevention and control practices that eliminate, reduce, and manage factors that cause or contribute to public health workers' poor mental health might improve mental health outcomes during emergencies.

Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic - United States, March-April 2021.

Increases in mental health conditions have been documented among the general population and health care workers since the start of the COVID-19 pandemic (1-3). Public health workers might be at similar risk for negative mental health consequences because of the prolonged demand for responding to the pandemic and for implementing an unprecedented vaccination campaign. The extent of mental health conditions among public health workers during the COVID-19 pandemic, however, is uncertain. A 2014 survey estimated that there were nearly 250,000 state and local public health workers in the United States (4). To evaluate mental health conditions among these workers, a nonprobability-based online survey was conducted during March 29-April 16, 2021, to assess symptoms of depression, anxiety, post-traumatic stress disorder (PTSD), and suicidal ideation among public health workers in state, tribal, local, and territorial public health departments. Among 26,174 respondents, 53.0% reported symptoms of at least one mental health condition in the preceding 2 weeks, including depression (32.0%), anxiety (30.3%), PTSD (36.8%), or suicidal ideation (8.4%). The highest prevalence of symptoms of a mental health condition was among respondents aged ≤29 years (range = 13.6%-47.4%) and transgender or nonbinary persons (i.e., those who identified as neither male nor female) of all ages (range = 30.4%-65.5%). Public health workers who reported being unable to take time off from work were more likely to report adverse mental health symptoms. Severity of symptoms increased with increasing weekly work hours and percentage of work time dedicated to COVID-19 response activities. Implementing prevention and control practices that eliminate, reduce, and manage factors that cause or contribute to public health workers' poor mental health might improve mental health outcomes during emergencies.