Hospital Strain During the COVID-19 Pandemic and Outcomes in Older Racial and Ethnic Minority Adults.

Importance: Marginalized populations have been disproportionately affected by the COVID-19 pandemic. Critically ill patients belonging to racial and ethnic minority populations treated in hospitals operating under crisis or near-crisis conditions may have experienced worse outcomes than White individuals. Objective: To examine whether hospital strain was associated with worse outcomes for older patients hospitalized with sepsis and whether these increases in poor outcomes were greater for members of racial and ethnic minority groups compared with White individuals. Design, Setting, and Participants: In this cross-sectional study, multivariable regression analysis was conducted to assess differential changes in all-cause 30-day mortality and major morbidity among older racial and ethnic minoritized individuals hospitalized with sepsis compared with White individuals and changes in hospital strain using Medicare claims data. Data were obtained on patients hospitalized between January 1, 2016, and December 31, 2021, and analyzed between December 16, 2023, and July 11, 2024. Exposure: Time-varying weekly hospital percentage of inpatients with COVID-19. Main Outcomes and Measures: Composite of all-cause 30-day mortality and major morbidity. Results: Among the 5 899 869 hospitalizations for sepsis (51.5% women; mean [SD] age, 78.2 [8.8] years), there were 177 864 (3.0%) Asian, 664 648 (11.3%) Black, 522 964 (8.9%) Hispanic, and 4 534 393 (76.9%) White individuals. During weeks when the hospital COVID-19 burden was greater than 40%, the risk of death or major morbidity increased nearly 2-fold (adjusted odds ratio [AOR], 1.90; 95% CI, 1.80-2.00; P < .001) for White individuals compared with before the pandemic. Asian, Black, and Hispanic individuals experienced 44% (AOR, 1.44; 95% CI, 1.28-1.61; P < .001), 21% (AOR, 1.21; 95% CI, 1.11-1.33; P < .001), and 45% (AOR, 1.45; 95% CI, 1.32-1.59; P < .001) higher risk of death or morbidity, respectively, compared with White individuals when the hospital weekly COVID-19 burden was greater than 40%. Conclusion and Relevance: In this cross-sectional study, older adults hospitalized with sepsis were more likely to die or experience major morbidity as the hospital COVID-19 burden increased. These increases in adverse outcomes were greater in magnitude among members of minority populations than for White individuals.

Post-Acute Care Trends and Disparities After Joint Replacements in the United States, 1991-2018: A Systematic Review.

OBJECTIVE: To review evidence on post-acute care (PAC) use and disparities related to race and ethnicity and rurality in the United States over the past 2 decades among individuals who underwent major joint replacement (MJR). DESIGN: Systematic review. SETTING AND PARTICIPANTS: We included studies that examined US PAC trends and racial and ethnic and/or urban vs rural differences among individuals who are aged ≥18 years with hospitalization after MJR. METHODS: We searched large academic databases (PubMed, CINAHL, Embase, Web of Science, and Scopus) for peer-reviewed, English language articles from January 1, 2000, and January 26, 2022. RESULTS: Seventeen studies were reviewed. Studies (n = 16) consistently demonstrated that discharges post-MJR to skilled nursing facilities (SNFs) or nursing homes (NHs) decreased over time, whereas evidence on discharges to inpatient rehab facilities (IRFs), home health care (HHC), and home without HHC services were mixed. Most studies (n = 12) found that racial and ethnic minority individuals, especially Black individuals, were more frequently discharged to PAC institutions than white individuals. Demographic factors (ie, age, sex, comorbidities) and marital status were not only independently associated with discharges to institutional PAC, but also among racial and ethnic minority individuals. Only one study found urban-rural differences in PAC use, indicating that urban-dwelling individuals were more often discharged to both SNF/NH and HHC than their rural counterparts. CONCLUSIONS AND IMPLICATIONS: Despite declines in institutional PAC use post-MJR over time, racial and minority individuals continue to experience higher rates of institutional PAC discharges compared with white individuals. To address these disparities, policymakers should consider measures that target multimorbidity and the lack of social and structural support among socially vulnerable individuals. Policymakers should also consider initiatives that address the economic and structural barriers experienced in rural areas by expanding access to telehealth and through improved care coordination.

State- and Territory-Level Nursing Home and Home Health Care COVID-19 Policies and Disease Burden.

This cross-sectional study creates a dataset and dashboard of US state- and territory-level COVID-19 policies specific to nursing homes and home health care agencies.

Health Information Technology Adoption at U.S. Home Health Care Agencies: Results from a Multi-Methods Study.

Health information technology (HIT) holds potential to transform Home Health Care (HHC), yet, little is known about its adoption in this setting. In the context of infection prevention and control, we aimed to: (1) describe challenges associated with the adoption of HIT, for example, electronic health records (EHR) and telehealth and (2) examine HHC agency characteristics associated with HIT adoption. We conducted in-depth interviews with 41 staff from 13 U.S. HHC agencies (May-October 2018), then surveyed a stratified random sample of 1506 agencies (November 2018-December 2019), of which 35.6% participated (N = 536 HHC agencies). We applied analytic weights, generating nationally-representative estimates, and computed descriptive statistics, bivariate and multivariable analyses. Four themes were identified: (1) Reflections on providing HHC without EHR; (2) Benefits of EHR; (3) Benefits of other HIT; (4) Challenges with HIT and EHR. Overall, 10% of the agencies did not have an EHR; an additional 2% were in the process of acquiring one. Sixteen percent offered telehealth, and another 4% were in the process of acquiring telehealth services. In multivariable analysis, EHR use varied significantly by geographic location and ownership, and telehealth use varied by geographic location, ownership, and size. Although HIT use has increased, our results indicate that many HHC agencies still lack the HIT needed to implement technological solutions to improve workflow and quality of care. Future research should examine the impact of HIT on patient outcomes and the impact of the COVID-19 pandemic on HIT use in HHC.

Systematic Review of Rural and Urban Differences in Care Provided by Home Health Agencies in the United States.

OBJECTIVE: Home health care agencies (HHAs) are skilled care providers for Medicare home health beneficiaries in the United States. Rural HHAs face different challenges from their urban counterparts in delivering care (eg, longer distances to travel to patient homes leading to higher fuel/travel costs and fewer number of visits in a day, impacting the quality of home health care for rural beneficiaries). We review evidence on differences in care outcomes provided by urban and rural HHAs. DESIGN: Systematic review guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and using the Newcastle-Ottawa Scale (NOS) for quality appraisal. SETTING: Care provided by urban and rural HHAs. METHODS: We conducted a systematic search for English-language peer-reviewed articles after 2010 on differences in urban and rural care provided by U.S. HHAs. We screened 876 studies, conducted full-text abstraction and NOS quality review on 36 articles and excluded 2 for poor study quality. RESULTS: Twelve studies were included; 7 focused on patient-level analyses and 5 were HHA-level. Nine studies were cross-sectional and 3 used cohorts. Urban and rural differences were measured primarily using a binary variable. All studies controlled for agency-level characteristics, and two-thirds also controlled for patient characteristics. Rural beneficiaries, compared with urban, had lower home health care utilization (4 of 5 studies) and fewer visits for physical therapy and/or rehabilitation (3 of 5 studies). Rural agencies had lower quality of HHA services (3 of 4 studies). Rural patients, compared with urban, visited the emergency room more often (2 of 2 studies) and were more likely to be hospitalized (2 of 2 studies), whereas urban patients with heart failure were more likely to have 30-day preventable hospitalizations (1 study). CONCLUSION AND IMPLICATIONS: This review highlights similar urban/rural disparities in home health care quality and utilization as identified in previous decades. Variables used to measure the access to and quality of care by HHAs varied, so consensus was limited. Articles that used more granular measures of rurality (rather than binary measures) revealed additional differences. These findings point to the need for consistent and refined measures of rurality in studies examining urban and rural differences in care from HHAs.

Measuring Palliative Care-Related Knowledge, Attitudes, and Confidence in Home Health Care Clinicians, Patients, and Caregivers: A Systematic Review.

Background: Integrating palliative care services in the home health care (HHC) setting is an important strategy to provide care for seriously ill adults and improve symptom burden, quality of life, and caregiver burden. Routine palliative care in HHC is only possible if clinicians who provide this care are prepared and patients and caregivers are well equipped with the knowledge to receive this care. A key first step in integrating palliative care services within HHC is to measure preparedness of clinicians and readiness of patients and caregivers to receive it. Objective: The objective of this systematic review was to review existing literature related to the measurement of palliative care-related knowledge, attitudes, and confidence among HHC clinicians, patients, and caregivers. Methods: We searched PubMed, CINAHL, Web of Science, and Cochrane for relevant articles between 2000 and 2021. Articles were included in the final analysis if they (1) reported specifically on palliative care knowledge, attitudes, or confidence, (2) presented measurement tools, instruments, scales, or questionnaires, (3) were conducted in the HHC setting, (4) and included HHC clinicians, patients, or caregivers. Results: Seventeen articles were included. While knowledge, attitudes, and confidence have been studied in HHC clinicians, patients, and caregivers, results varied significantly across countries and health care systems. No study captured knowledge, attitudes, and confidence of the full HHC workforce; notably, home health aides were not included in the studies. Conclusion: Existing instruments did not comprehensively contain elements of the eight domains of palliative care outlined by the National Consensus Project (NCP) for Quality Palliative Care. A comprehensive psychometrically tested instrument to measure palliative care-related knowledge, attitudes, and confidence in the HHC setting is needed.

Influenza vaccination of home health care staff and the impact on patient hospitalizations.

BACKGROUND: Influenza is associated with significant morbidity and mortality for adults aged 65 years and older. Influenza vaccination of health care workers is recommended. There is limited evidence regarding influenza vaccinations among health care workers in the home health care (HHC) setting and their impact on HHC patient outcomes. METHODS: A national survey of HHC agencies was conducted in 2018-2019 and linked with patient data from the Centers for Medicare and Medicaid Services. Adjusted logistic regression models were used to estimate the association between hospital transfers due to respiratory infection during a 60 day HHC episode and staff vaccination policies. RESULTS: Only 26.2% of HHC agencies had staff vaccination requirements and 71.2% agencies had staff vaccination rates higher than 75%. Agency policies for staff influenza vaccination were associated with reduced hospital transfers due to respiratory infection among HHC patients. DISCUSSION: Influenza vaccination rates among HHC staff were low during the 2017-2018 influenza season. Policymakers may consider vaccination mandates to improve health care worker vaccination rates and protect patient safety. CONCLUSIONS: This study sheds light on the potential impact of COVID-19 vaccination among HHC workers on patient outcomes. COVID-19 vaccination mandates could prove to be a vital tool in the fight against COVID-19 variants and infection outbreaks.

The Effects of Home Health Value-Based Purchasing on Home Health Care Quality in For-Profit and Nonprofit Agencies: A Comparative Interrupted Time-Series Analysis, 2012-2018.

Beginning in 2016, the Home Health Value-Based Purchasing (HHVBP) model incentivized U.S. Medicare-certified home health agencies (HHAs) in nine states to improve quality of patient care and patient experience. Here, we quantified HHVBP effects upon quality over time (2012-2018) by HHA ownership (i.e., for-profit vs. nonprofit) using a comparative interrupted time-series design. Our outcome measures were Care Quality and Patient Experience indices composed of 10 quality of patient care measures and five patient experience measures, respectively. Overall, 17.7% of HHAs participated in the HHVBP model of which 81.4% were for-profit ownership. Each year after implementation, HHVBP was associated with a 1.59 (p < .001) percentage point increase in the Care Quality index among for-profit HHAs and a 0.71 (p = .024) percentage point increase in the Patient Experience index among nonprofits. The differences of quality improvement under the HHVBP model by ownership indicate variations in HHA leadership responses to HHVBP.

Urinary catheter policies in home healthcare agencies and hospital transfers due to urinary tract infection.

BACKGROUND: Urinary tract infections (UTIs) are a frequent cause of hospital transfer for home healthcare (HHC) patients, particularly among patients with urinary catheters. METHODS: We conducted a cross-sectional, nationally representative HHC agency-level survey (2018-2019) and combined it with patient-level data from the Outcome and Assessment Information Set (OASIS) and Medicare inpatient data (2016-2018) to evaluate the association between HHC agencies' urinary catheter policies and hospital transfers due to UTI. Our sample included 28,205 patients with urinary catheters who received HHC from 473 Medicare-certified agencies between 2016-2018. Our survey assessed whether agencies had written policies in place for (1) replacement of indwelling catheters at fixed intervals, and (2) emptying the drainage bag. We used adjusted logistic regression to estimate the association of these policies with probability of hospital transfer due to UTI during a 60-day HHC episode. RESULTS: Probability of hospital transfer due to UTI during a HHC episode ranged from 5.62% among agencies with neither urinary catheter policy to 4.43% among agencies with both policies. Relative to agencies with neither policy, having both policies was associated with 21% lower probability of hospital transfer due to UTI (P < .05). CONCLUSION: Our findings suggest implementation of policies in HHC to promote best practices for care of patients with urinary catheters may be an effective strategy to prevent hospital transfers due to UTI.

The state of infection prevention and control at home health agencies in the United States prior to COVID-19: A cross-sectional study.

BACKGROUND: Home health care is a rapidly growing healthcare sector worldwide. Home health professionals face unique challenges related to preventing and controlling infections, which are likely to amplify during an infectious disease outbreak (e.g. SARS-CoV-2). Little is known about the current state of infection prevention and control-related policies and outbreak preparedness at U.S. home health agencies. OBJECTIVES: In this study, we conducted a national survey to assess infection prevention and control-related policies, infrastructure, and procedures prior to the SARS-CoV-2 pandemic. DESIGN: Cross-sectional study. SETTING/PARTICIPANTS: Using a stratified random sample of 1506 U.S. home health agencies, we conducted a 61-item survey (paper and online) from November 9, 2018 to December 31, 2019. METHODS: Survey data were linked to publicly-available data on the quality of patient care, patient satisfaction, and other agency characteristics. Probability weights were developed to account for sample design and nonresponse; Pearson's χ2, Fisher's exact, t-tests or linear regression were used to compare the universe of agencies/respondents and urban/rural agencies. RESULTS: 35.6% of agencies responded (n = 536). Most home health personnel in charge of infection prevention and control have other responsibilities; one-third have no formal infection prevention and control training. Rural agencies are more likely to not have anyone in charge of infection prevention and control compared to those in urban areas. About 22% of agencies implement recommended guidelines when administering antibiotics. Less than a third (26.4%) report that their staff vaccination rates were higher than 95% during the last flu season. Only 48.1% of agencies accept patients requiring ventilation, and of those, 40.9% located in rural areas do not have specific infection prevention and control policies for ventilated patients, compared to 20.8% in urban areas (p < 0.001). Only 39.7% of agencies provide N95 respirators to their clinical staff; rural agencies are significantly more likely to provide those supplies than urban agencies (50.7% vs. 37.7%, p = 0.004). Lastly, agencies report their greatest challenges with infection prevention and control are collecting/reporting infection data and adherence to/monitoring of nursing bag technique. CONCLUSIONS: Prior to the SARS-CoV-2 pandemic, we found that infection prevention and control was suboptimal among U.S. home health care agencies. Consequently, most agencies have limited capacity to respond to infectious disease outbreaks. Staff and personal protective equipment shortages remain major concerns, and agencies will need to quickly adjust their existing infection prevention and control policies and potentially create new ones. In the long-term, agencies also need to improve influenza vaccination coverage among their staff. Tweetable abstract: Infection prevention and control infrastructure, policies and procedures and outbreak preparedness at U.S. home health agencies was found to be suboptimal in nationally-representative survey conducted just prior to the COVID-19 pandemic.

Home Health Staff Perspectives on Infection Prevention and Control: Implications for Coronavirus Disease 2019.

OBJECTIVES: The role of home healthcare (HHC) services in providing care to vulnerable, often frail individuals with chronic conditions is critical. Effective infection prevention and control (IPC) in HHC is essential to keeping both healthcare workers and patients safe, especially in the event of an emerging infectious disease outbreak. Prior to the coronavirus disease 2019 pandemic, we explored successes and challenges with IPC from the perspectives of HHC staff. DESIGN: Qualitative descriptive study. SETTING AND PARTICIPANTS: From May to November 2018, we conducted in-depth telephone interviews with 41 staff from 13 agencies across the nation. METHODS: Transcripts were coded by a multidisciplinary coding team, and several primary and subcategories were identified using directed content analysis. RESULTS: Four primary categories were generated including (1) uniqueness of HHC; (2) IPC as a priority; (3) importance of education; and (4) keys to success and innovation. Participants perceived that IPC plays a big part in patient safety and reducing rehospitalizations, and protection of patients and staff was a major motivator for compliance with IPC. The identified challenges included the unpredictability of the home environment, patient/family dynamics, the intermittent nature of HHC, and staffing issues. Education was seen as a tool to improve staff, patient, caregiver and families' compliance with IPC. Keys to success and innovation included a leadership focus on quality, using agency infection data to improve quality, and a coordinated approach to patient care. CONCLUSIONS AND IMPLICATIONS: This qualitative work identified barriers to effective IPC in HHC, as well as important facilitators that HHC agencies can use to implement policies and procedures to improve patient care and keep staff safe. Leadership prioritization of IPC is key to implementing appropriate IPC policies and may be especially important in midst of a crisis such as coronavirus disease 2019.

COVID-19 Preparedness in US Home Health Care Agencies.

OBJECTIVES: In the United States, home health agencies (HHAs) provide essential services for patients recovering from post-acute care and older adults who are aging in place. During the COVID-19 pandemic, HHAs may face additional challenges caring for these vulnerable patients. Our objective was to explore COVID-19 preparedness of US HHAs and compare results by urban/rural location. DESIGN: Cross-sectional study. SETTING/PARTICIPANTS: Using a stratified random sample of 978 HHAs, we conducted a 22-item online survey from April 10 to 17, 2020. METHODS: Summary statistics were computed; open-ended narrative responses were synthesized using qualitative methods. RESULTS: Similar to national data, most responding HHAs (n = 121, 12% response rate) were for-profit and located in the South. Most HHAs had infectious disease outbreaks included in their emergency preparedness plan (76%), a staff member in charge of outbreak/disaster preparedness (84%), and had provided their staff with COVID-19 education and training (97%). More urban HHAs had cared for confirmed and recovered COVID-19 patients than rural HHAs, but urban HHAs had less capacity to test for COVID-19 than rural HHAs (9% vs 21%). Most (69%) experienced patient census declines and had a current and/or anticipated supply shortage. Rural agencies were affected less than urban agencies. HHAs have already rationed (69%) or implemented extended use (55%) or limited reuse (61%) of personal protective equipment (PPE). Many HHAs reported accessing supplemental PPE from state/local resources, donations, and do-it-yourself efforts; more rural HHAs had accessed these additional resources compared with urban HHAs. CONCLUSIONS/IMPLICATIONS: This survey reveals challenges that HHAs are having in responding to the COVID-19 pandemic, particularly among urban agencies. Of greatest concern are the declines in patient census, which drastically affect agency revenue, and the shortages of PPE and disinfectants. Without proper protection, HHA clinicians are at risk of self-exposure and viral transmission to patients and vulnerable family members.

Self-reported National Healthcare Safety Network knowledge and enrollment: A national survey of nursing homes.

Predictors of nursing home staff knowledge of the National Healthcare Safety Network (NHSN) and facility enrollment were explored in a national survey. Facility participation in Quality Innovation Network-Quality Improvement Organization initiatives was positively associated with both knowledge and enrollment. In addition, engaging clinical personnel in decision making on NHSN enrollment was positively associated with staff knowledge of NHSN.

Measuring Quality in Home Healthcare.

BACKGROUND/OBJECTIVES: Improving quality performance in home health is an increasingly high priority. The objective of this study was to examine trends in industry performance over time using three quality measures: a composite quality metric (Q index), an infection prevention measure (vaccination verification), and an outcome measure (hospital avoidance). DESIGN/SETTING/PARTICIPANTS/MEASURES: We linked Home Health Compare and Provider of Services data from 2012 to 2016, which included 39 211 observations during the 5-year study period and 7670 agencies in 2016. The Q index was developed to allow comparability over time, equally weighting the contributions of each element. After examining summary statistics, we developed three regression models stratified by ownership (for-profit/nonprofit agency) and included two constructs of nurse staffing, in addition to controlling for known confounders. RESULTS: Most agencies (80.4%) were for-profit agencies. The Q index and vaccination verification improved substantially over time, but there was no change in hospital avoidance. Ownership status was associated with all three measures (P < .001). Registered nurse staffing (relative to licensed practical nurses and home health aides) was associated with higher Q index and vaccination verification (P < .001). CONCLUSION: The Q index allows for assessment of trends over time in home healthcare. Ownership and nurse staffing are important factors in the quality of care. The overall home care market is driven by for-profit agencies, but their characteristics and outcomes differ from nonprofit agencies. J Am Geriatr Soc 67:1859-1865, 2019.

The expansion of National Healthcare Safety Network enrollment and reporting in nursing homes: Lessons learned from a national qualitative study.

BACKGROUND: This study explored nursing home (NH) personnel perceptions of the National Healthcare Safety Network (NHSN). METHODS: NHs were purposively sampled based on NHSN enrollment and reporting status, and other facility characteristics. We recruited NH personnel knowledgeable about the facility's decision-making processes and infection prevention program. Interviews were conducted over-the-phone and audio-recorded; transcripts were analyzed using conventional content analysis. RESULTS: We enrolled 14 NHs across the United States and interviewed 42 personnel. Six themes emerged: Benefits of NHSN, External Support and Motivation, Need for a Champion, Barriers, Risk Adjustment, and Data Integrity. We did not find substantive differences in perceptions of NHSN value related to participants' professional roles or enrollment category. Some participants from newly enrolled NHs felt well supported through the NHSN enrollment process, while participants from earlier enrolled NHs perceived the process to be burdensome. Among participants from non-enrolled NHs, as well as some from enrolled NHs, there was a lack of knowledge of NHSN. CONCLUSIONS: This qualitative study helps fill a gap in our understanding of barriers and facilitators to NHSN enrollment and reporting in NHs. Improved understanding of factors influencing decision-making processes to enroll in and maintain reporting to NHSN is an important first step towards strengthening infection surveillance in NHs.

Nursing home adoption of the National Healthcare Safety Network Long-term Care Facility Component.

BACKGROUND: Health care-associated infections pose a significant problem in nursing homes (NHs). The Long-term Care Facility Component of the National Healthcare Safety Network (NHSN) was launched in 2012, and since then, enrollment of NHs into NHSN has been deemed a national priority. Our goal was to understand the characteristics of NHs reporting to the NHSN compared to other NHs across the country. METHODS: To meet this goal, we quantified the characteristics of NHs by NHSN enrollment status and reporting consistency using the Certification and Survey Provider Enhanced Reporting (CASPER) data linked to NHSN enrollment and reporting data. RESULTS: Of the 16,081 NHs in our sample, 262 (or 1.6% of NHs) had enrolled in NHSN by the end of 2015; these early adopting facilities were more likely to be for-profit and had a higher percentage of Medicare residents. By the end of 2016, enrollment expanded by more than 5-fold to 1,956 facilities (or 12.2% of NHs). In our analysis, the characteristics of those later adopting NHs were more similar to NHs nationally than the early adopters. Specifically, bed size and hospital-based facilities were related to both early and late adoption of NHSN. CONCLUSIONS: The types of NHs that have enrolled in NHSN have changed substantially since the program began. The increased enrollment was likely due to the Centers for Medicare & Medicaid (CMS)-funded "C. difficile Infection (CDI) Reporting and Reduction Project" that incentivized Quality Innovation Network-Quality Improvement Organizations (QIN-QIOs) to support NH enrollment and participation in NHSN. Further understanding of a facility's ability to enroll in and maintain reporting to NHSN, and how this relates to infection prevention staffing and infrastructure in NHs and infection rates among NH residents, is needed.

HIV-1 targets L-selectin for adhesion and induces its shedding for viral release.

CD4 and chemokine receptors mediate HIV-1 attachment and entry. They are, however, insufficient to explain the preferential viral infection of central memory T cells. Here, we identify L-selectin (CD62L) as a viral adhesion receptor on CD4+ T cells. The binding of viral envelope glycans to L-selectin facilitates HIV entry and infection, and L-selectin expression on central memory CD4+ T cells supports their preferential infection by HIV. Upon infection, the virus downregulates L-selectin expression through shedding, resulting in an apparent loss of central memory CD4+ T cells. Infected effector memory CD4+ T cells, however, remain competent in cytokine production. Surprisingly, inhibition of L-selectin shedding markedly reduces HIV-1 infection and suppresses viral release, suggesting that L-selectin shedding is required for HIV-1 release. These findings highlight a critical role for cell surface sheddase in HIV-1 pathogenesis and reveal new antiretroviral strategies based on small molecular inhibitors targeted at metalloproteinases for viral release.

Siglecs facilitate HIV-1 infection of macrophages through adhesion with viral sialic acids.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) infects macrophages effectively, despite relatively low levels of cell surface-expressed CD4. Although HIV-1 infections are defined by viral tropisms according to chemokine receptor usage (R5 and X4), variations in infection are common within both R5- and X4-tropic viruses, indicating additional factors may contribute to viral tropism. METHODOLOGY AND PRINCIPAL FINDINGS: Using both solution and cell surface binding experiments, we showed that R5- and X4-tropic HIV-1 gp120 proteins recognized a family of I-type lectin receptors, the Sialic acid-binding immunoglobulin-like lectins (Siglec). The recognition was through envelope-associated sialic acids that promoted viral adhesion to macrophages. The sialic acid-mediated viral-host interaction facilitated both R5-tropic pseudovirus and HIV-1(BaL) infection of macrophages. The high affinity Siglec-1 contributed the most to HIV-1 infection and the variation in Siglec-1 expression on primary macrophages from different donors was associated statistically with sialic acid-facilitated viral infection. Furthermore, envelope-associated sialoglycan variations on various strains of R5-tropic viruses also affected infection. CONCLUSIONS AND SIGNIFICANCE OF THE FINDINGS: Our study showed that sialic acids on the viral envelope facilitated HIV-1 infection of macrophages through interacting with Siglec receptors, and the expression of Siglec-1 correlated with viral sialic acid-mediated host attachment. This glycan-mediated viral adhesion underscores the importance of viral sialic acids in HIV infection and pathogenesis, and suggests a novel class of antiviral compounds targeting Siglec receptors.