Search

Introduction: Oral antiviral medications are important tools for preventing severe COVID-19 outcomes. However, their uptake remains low for reasons that are not entirely understood. Our study aimed to assess the association between perceived risk for severe COVID-19 outcomes and oral antiviral use among those who were eligible for treatment based on Centers for Disease Control and Prevention (CDC) guidelines. Methods: We surveyed 4034 non-institutionalized US adults in April 2023, and report findings from 934 antiviral-eligible participants with at least one confirmed SARS-CoV-2 infection since December 1, 2021 and no current long COVID symptoms. Survey weights were used to yield nationally representative estimates. The primary exposure of interest was whether participants perceived themselves to be "at high risk for severe COVID-19." The primary outcome was use of a COVID-19 oral antiviral within 5 days of suspected SARS-CoV-2 infection. Results: Only 18.5% of antiviral-eligible adults considered themselves to be at high risk for severe COVID-19 and 16.8% and 15.9% took oral antivirals at any time or within 5 days of SARS-CoV-2 infection, respectively. In contrast, 79.8% were aware of antiviral treatments for COVID-19. Perceived high-risk status was associated with being more likely to be aware (adjusted prevalence ratio [aPR]: 1.11 [95% confidence interval (CI) 1.03–1.20]), to be prescribed (aPR 1.47 [95% CI 1.08–2.01]), and to take oral antivirals at any time (aPR 1.61 [95% CI 1.16–2.24]) or within 5 days of infection (aPR 1.72 [95% CI 1.23–2.40]). Conclusions: Despite widespread awareness of the availability of COVID-19 oral antivirals, more than 80% of eligible US adults did not receive them. Our findings suggest that differences between perceived and actual risk for severe COVID-19 (based on current CDC guidelines) may partially explain this low uptake. [ABSTRACT FROM AUTHOR]

Our objective was to examine the influence of COVID-19 vaccination on recent (i.e., past month) moderate or severe symptoms of anxiety (GAD ‐ 7 ≥ 10) or depression (PHQ ‐ 8 ≥ 10) before and after the COVID-19 vaccine became universally available for adults in the U.S. Participants belonged to the Communities, Households, and SARS-CoV-2 Epidemiology Cohort (CHASING COVID), a national longitudinal study. Our analytic population included 4,832 participants who reported vaccination status from December 2020 to December 2021 with follow-up outcomes assessed through March 2022. We emulated a hypothetical randomized experiment, a target trial, to estimate the effect of COVID-19 vaccination on symptoms of anxiety or depression. Before vaccines were universally available, participants who were vaccinated versus not had significantly lower adjusted odds of symptoms of moderate or severe anxiety (aOR: 0.79; 95% CI: 0.70-0.89). In the universal vaccine era, vaccination was associated with marginally higher adjusted odds of symptoms of moderate or severe anxiety (aOR: 1.23; 95% CI: 1.00-1.50). Vaccination did not influence subsequent moderate or severe depressive symptoms in the preuniversal vaccine era (aOR: 0.92; 95% CI: 0.82-1.03) or universal vaccine era (aOR: 1.11; 95% CI: 0.91-1.36). Research into the longitudinal relationship between COVID-19 vaccination and symptoms of depression and anxiety is warranted, with a focus on advancing understanding of potential mediators on the pathway between vaccination and mental health as well as modifiable factors, such as vaccine hesitancy or vaccine beliefs, that may help identify populations for whom vaccination may be particularly beneficial to their mental health. [ABSTRACT FROM AUTHOR]

Background We described the oral nirmatrelvir/ritonavir (NMV/r) and molnupiravir (MOV) uptake among a subgroup of highly vaccinated adults in a US national prospective cohort who were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 12/2021 and 10/2022. Methods We estimate antiviral uptake within 5 days of SARS-CoV-2 infection, as well as age- and gender-adjusted antiviral uptake prevalence ratios by antiviral eligibility (based on age and comorbidities), sociodemographic characteristics, and clinical characteristics including vaccination status and history of long coronavirus disease 2019 (COVID). Results NMV/r uptake was 13.6% (95% CI, 11.9%–15.2%) among 1594 participants, and MOV uptake was 1.4% (95% CI, 0.8%–2.1%) among 1398 participants. NMV/r uptake increased over time (1.9%; 95% CI, 1.0%–2.9%; between 12/2021 and 3/2022; 16.5%; 95% CI, 13.0%–20.0%; between 4/2022 and 7/2022; and 25.3%; 95% CI, 21.6%–29.0%; between 8/2022 and 10/2022). Participants age ≥65 and those who had comorbidities for severe COVID-19 had higher NMV/r uptake. There was lower NMV/r uptake among non-Hispanic Black participants (7.2%; 95% CI, 2.4%–12.0%; relative to other racial/ethnic groups) and among individuals in the lowest income groups (10.6%; 95% CI, 7.3%–13.8%; relative to higher income groups). Among a subset of 278 participants with SARS-CoV-2 infection after 12/2021 who also had a history of prior SARS-CoV-2 infection, those with (vs without) a history of long COVID reported greater NMV/r uptake (22.0% vs 7.9%; P =.001). Among those prescribed NMV/r (n = 216), 137 (63%; 95% CI, 57%–70%) reported that NMV/r was helpful for reducing COVID-19 symptoms. Conclusions Despite proven effectiveness against severe outcomes, COVID-19 antiviral uptake remains low among those with SARS-CoV-2 infection in the United States. Further outreach to providers and patients to improve awareness of COVID-19 oral antivirals and indications is needed. [ABSTRACT FROM AUTHOR]

This study used repeat serologic testing to estimate infection rates and risk factors in two overlapping cohorts of SARS-CoV-2 N protein seronegative U.S. adults. One mostly unvaccinated sub-cohort was tracked from April 2020 to March 2021 (pre-vaccine/wild-type era, n = 3421), and the other, mostly vaccinated cohort, from March 2021 to June 2022 (vaccine/variant era, n = 2735). Vaccine uptake was 0.53% and 91.3% in the pre-vaccine and vaccine/variant cohorts, respectively. Corresponding seroconversion rates were 9.6 and 25.7 per 100 person-years. In both cohorts, sociodemographic and epidemiologic risk factors for infection were similar, though new risk factors emerged in the vaccine/variant era, such as having a child in the household. Despite higher incidence rates in the vaccine/variant cohort, vaccine boosters, masking, and social distancing were associated with substantially reduced infection risk, even through major variant surges. [ABSTRACT FROM AUTHOR]

We draw on the experience of the COVID-19 pandemic in the United States to identify important gaps in the surveillance of protracted health emergencies that require rapid and reliable monitoring and active dissemination of dynamic health indicators on key sociodemographic, behavioral, and immunological dimensions. In addition, a dynamic and poorly characterized backdrop of underlying hybrid immunity has further complicated efforts to monitor transmission and disease severity.[6] The COVID-19 pandemic response has focused primarily on increasing uptake of vaccines and antiviral treatments, largely in an untargeted way. Keywords: COVID-19; Surveillance; Bias; Population-based surveys; Infectious disease; Disease burden EN COVID-19 Surveillance Bias Population-based surveys Infectious disease Disease burden S47 S55 9 09/29/23 20230902 NES 230902 Introduction I Good surveillance does not necessarily ensure the making of the right decisions, but it reduces the chances of [making the] wrong ones. i - Alex Langmuir, 1963 Emerging or reemerging infections, as well as other pathogens of public health significance, require robust surveillance systems. Apart from sentinel surveillance or special studies,[48] there is a lack of timely, routinely collected information that incorporates medical vulnerability to severe COVID-19, history of previous SARS-CoV-2 infection, and vaccination. [Extracted from the article]

Background We estimated the prevalence of long COVID and impact on daily living among a representative sample of adults in the United States. Methods We conducted a population-representative survey, 30 June–2 July 2022, of a random sample of 3042 US adults aged 18 years or older and weighted to the 2020 US population. Using questions developed by the UK's Office of National Statistics, we estimated the prevalence of long COVID, by sociodemographics, adjusting for gender and age. Results An estimated 7.3% (95% confidence interval: 6.1–8.5%) of all respondents reported long COVID, corresponding to approximately 18 828 696 adults. One-quarter (25.3% [18.2–32.4%]) of respondents with long COVID reported their day-to-day activities were impacted "a lot" and 28.9% had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection more than 12 months ago. The prevalence of long COVID was higher among respondents who were female (adjusted prevalence ratio [aPR]: 1.84 [1.40–2.42]), had comorbidities (aPR: 1.55 [1.19–2.00]), or were not (vs were) boosted (aPR: 1.67 [1.19–2.34]) or not vaccinated (vs boosted) (aPR: 1.41 [1.05–1.91]). Conclusions We observed a high burden of long COVID, substantial variability in prevalence of SARS-CoV-2, and risk factors unique from SARS-CoV-2 risk, suggesting areas for future research. Population-based surveys are an important surveillance tool and supplement to ongoing efforts to monitor long COVID. [ABSTRACT FROM AUTHOR]

In a population-based survey of adults in New York City, we assessed positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests (including via exclusive at-home testing) and possible cases among untested respondents. An estimated 27.4% (95% confidence interval [CI]: 22.8%–32.0%) or 1.8 million adults (95% CI: 1.6–2.1 million) had SARS-CoV-2 infection between 1 January and 16 March 2022. [ABSTRACT FROM AUTHOR]

Background Prospective cohort studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence complement case-based surveillance and cross-sectional seroprevalence surveys. Methods We estimated the incidence of SARS-CoV-2 infection in a national cohort of 6738 US adults, enrolled in March–August 2020. Using Poisson models, we examined the association of social distancing and a composite epidemiologic risk score with seroconversion. The risk score was created using least absolute shrinkage selection operator (LASSO) regression to identify factors predictive of seroconversion. The selected factors were household crowding, confirmed case in household, indoor dining, gathering with groups of ≥10, and no masking in gyms or salons. Results Among 4510 individuals with ≥1 serologic test, 323 (7.3% [95% confidence interval (CI), 6.5%–8.1%]) seroconverted by January 2021. Among 3422 participants seronegative in May–September 2020 and retested from November 2020 to January 2021, 161 seroconverted over 1646 person-years of follow-up (9.8 per 100 person-years [95% CI, 8.3–11.5]). The seroincidence rate was lower among women compared with men (incidence rate ratio [IRR], 0.69 [95% CI,.50–.94]) and higher among Hispanic (2.09 [1.41–3.05]) than white non-Hispanic participants. In adjusted models, participants who reported social distancing with people they did not know (IRR for always vs never social distancing, 0.42 [95% CI,.20–1.0]) and with people they knew (IRR for always vs never, 0.64 [.39–1.06]; IRR for sometimes vs never, 0.60 [.38–.96]) had lower seroconversion risk. Seroconversion risk increased with epidemiologic risk score (IRR for medium vs low score, 1.68 [95% CI, 1.03–2.81]; IRR for high vs low score, 3.49 [2.26–5.58]). Only 29% of those who seroconverted reported isolating, and only 19% were asked about contacts. Conclusions Modifiable risk factors and poor reach of public health strategies drove SARS-CoV-2 transmission across the United States. [ABSTRACT FROM AUTHOR]

We examined racial/ethnic disparities for COVID-19 seroconversion and hospitalization within a prospective cohort (n = 6,740) in the United States enrolled in March 2020 and followed-up through October 2021. Potential SARS-CoV-2 exposure, susceptibility to COVID-19 complications, and access to healthcare varied by race/ethnicity. Hispanic and Black non-Hispanic participants had more exposure risk and difficulty with healthcare access than white participants. Participants with more exposure had greater odds of seroconversion. Participants with more susceptibility and more barriers to healthcare had greater odds of hospitalization. Race/ethnicity positively modified the association between susceptibility and hospitalization. Findings might help to explain the disproportionate burden of SARS-CoV-2 infections and complications among Hispanic/Latino/a and Black non-Hispanic persons. Primary and secondary prevention efforts should address disparities in exposure, vaccination, and treatment for COVID-19. [ABSTRACT FROM AUTHOR]

We estimated the trends and correlates of vaccine hesitancy and its association with subsequent vaccine uptake among 5,458 adults in the United States. Participants belonged to the Communities, Households, and SARS-CoV-2 Epidemiology COVID (CHASING COVID) Cohort, a national longitudinal study. Trends and correlates of vaccine hesitancy were examined longitudinally in 8 interview rounds from October 2020 to July 2021. We also estimated the association between willingness to vaccinate and subsequent vaccine uptake through July 2021. Vaccine delay and refusal decreased from 51% and 8% in October 2020 to 8% and 6% in July 2021, respectively. Compared with non-Hispanic (NH) White participants, NH Black and Hispanic participants had higher adjusted odds ratios (aOR) for both vaccine delay (for NH Black, aOR = 2.0 (95% confidence interval (CI): 1.5, 2.7), and for Hispanic, 1.3 (95% CI: 1.0, 1.7)) and vaccine refusal (for NH Black, aOR = 2.5 (95% CI: 1.8, 3.6), and for Hispanic, 1.4 (95% CI: 1.0, 2.0)) in June 2021. COVID-19 vaccine hesitancy, compared with vaccine-willingness, was associated with lower odds of subsequent vaccine uptake (for vaccine delayers, aOR = 0.15, 95% CI: 0.13, 0.18; for vaccine refusers, aOR = 0.02; 95% CI: 0.01, 0.03), adjusted for sociodemographic factors and COVID-19 history. Vaccination awareness and distribution efforts should focus on vaccine delayers. [ABSTRACT FROM AUTHOR]

Background: Medical care re-engagement is critical to suppressing viral load and preventing HIV transmission, morbidity and mortality, yet few rigorous intervention studies address this outcome. We assessed the effectiveness of a Ryan White Part A-funded HIV Care Coordination Program relative to 'usual care,' for short-term care re-engagement and viral suppression among people without recent HIV medical care. Methods: The Care Coordination Program was launched in 2009 at 28 hospitals, health centers, and community-based organizations in New York City. Designed for people with HIV (PWH) experiencing or at risk for poor HIV outcomes, the Care Coordination Program provides long-term, comprehensive medical case management utilizing interdisciplinary teams, structured health education and patient navigation. The intervention was implemented as a safety-net services program, without a designated comparison group. To evaluate it retrospectively, we created an observational, matched cohort of clients and controls. Using the HIV surveillance registry, we identified individuals meeting program eligibility criteria from December 1, 2009 to March 31, 2013 and excluded those dying prior to 12 months of follow-up. We then matched clients to controls on baseline status (lacking evidence of viral suppression, consistently suppressed, inconsistently suppressed, or newly diagnosed in the past 12 months), start of follow-up and propensity score. For this analysis, we limited to those out of care at baseline (defined as having no viral load test in the 12 months pre-enrollment) and still residing within jurisdiction (defined as having a viral load or CD4 test reported to local surveillance and dated within the 12-month follow-up period). Using a GEE model with binary error distribution and logit link, we compared odds of care re-engagement (defined as having ≥ 2 laboratory events ≥ 90 days apart) and viral suppression (defined as having HIV RNA ≤ 200 copies/mL on the most recent viral load test) at 12-month follow-up. Results: Among 326 individuals out of care at baseline, 87.2% of clients and 48.2% of controls achieved care re-engagement (Odds Ratio: 4.53; 95%CI 2.66, 7.71); 58.3% of clients and 49.3% of controls achieved viral suppression (Odds Ratio: 2.05; 95%CI 1.30, 3.23). Conclusions: HIV Care Coordination shows evidence of effectiveness for care and treatment re-engagement. [ABSTRACT FROM AUTHOR]

Background We estimated the time from human immunodeficiency virus (HIV) seroconversion to antiretroviral therapy (ART) initiation during an era of expanding HIV testing and treatment efforts. Methods Applying CD4 depletion parameters from seroconverter cohort data to our population-based sample, we related the square root of the first pretreatment CD4 count to time of seroconversion through a linear mixed model and estimated the time from seroconversion. Results Among 28 162 people diagnosed with HIV during 2006–2015, 89% initiated ART by June 2017. The median CD4 count at diagnosis increased from 326 (interquartile range [IQR], 132–504) cells/µL to 390 (IQR, 216–571) cells/µL from 2006 to 2015. The median time from estimated seroconversion to ART initiation decreased by 42% from 6.4 (IQR, 3.3–11.4) years in 2006 to 3.7 (IQR, 0.5–8.3) years in 2015. The time from estimated seroconversion to diagnosis decreased by 28%, from a median of 4.6 (IQR, 0.5–10.5) years to 3.3 (IQR, 0–8.1) years from 2006 to 2015, and the time from diagnosis to ART initiation reduced by 60%, from a median of 0.5 (IQR, 0.2–2.1) years to 0.2 (IQR, 0.1–0.3) years from 2006 to 2015. Conclusions The estimated time from seroconversion to ART initiation was reduced in tandem with expanded HIV testing and treatment efforts. While the time from diagnosis to ART initiation decreased to 0.2 years, the time from seroconversion to diagnosis was 3.3 years among people diagnosed in 2015, highlighting the need for more effective strategies for earlier HIV diagnosis. [ABSTRACT FROM AUTHOR]

Introduction Growing evidence supports combining social, behavioural and biomedical strategies to strengthen the HIV care continuum. However, combination interventions can be resource-intensive and challenging to scale up. Research is needed to identify intervention components and delivery models that maximise uptake, engagement and effectiveness. In New York City (NYC), a multicomponent Ryan White Part A-funded medical case management intervention called the Care Coordination Programme (CCP) was launched at 28 agencies in 2009 in order to address barriers to care and treatment. Effectiveness estimates based on >7000 clients enrolled by April 2013 and their controls indicated modest CCP benefits over ‘usual care’ for short-term and long-term viral suppression, with substantial room for improvement. Methods and analysis Integrating evaluation findings and CCP service-provider and community-stakeholder input on modifications, the NYC Health Department packaged a Care Coordination Redesign (CCR) in a 2017 request for proposals. Following competitive re-solicitation, 17 of the original CCP implementing agencies secured contracts. These agencies were randomised within matched pairs to immediate or delayed CCR implementation. Data from three 9-month periods (pre-implementation, partial implementation and full implementation) will be examined to compare CCR versus CCP effects on timely viral suppression (TVS, within 4months of enrolment) among individuals with unsuppressed HIV viral load newly enrolling in the CCR/CCP. Based on current enrolment (n=933) and the pre-implementation outcome probability (TVS=0.54), the detectable effect size with 80% power is an OR of 2.75 (relative risk: 1.41). Ethics and dissemination This study was approved by the NYC Department of Health and Mental Hygiene Institutional Review Board (IRB, Protocol 18–009) and the City University of New York Integrated IRB (Protocol 018– 0057) with a waiver of informed consent. Findings will be disseminated via publications, conferences, stakeholder meetings, and Advisory Board meetings with implementing agency representatives. [ABSTRACT FROM AUTHOR]

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: We describe the timing of human immunodeficiency virus (HIV) diagnosis and antiretroviral treatment (ART) initiation after implementation of universal testing and treatment policies in New York City (NYC).Methods: Using NYC population-based HIV registry data for persons with HIV diagnosed from 2012 through 2015 and followed up through June 2017, we examined trends in the proportion with diagnosis soon after HIV infection (ie, with CD4 cell count ≥500/μL or with acute HIV infection) and used Kaplan-Meier plots and proportional hazards regression to examine the timing of ART initiation after diagnosis.Results: Among 9987 NYC residents with HIV diagnosed from 2012 to 2015, diagnosis was early in 35%, and 87% started ART by June 2017. The annual proportion of persons with early diagnosis did not increase appreciably (35% in 2012 vs 37% in 2015; P = .08). By 6 months after diagnosis, 62%, 67%, 72% and 77% of persons with HIV diagnosed in 2012, 2013, 2014, or 2015, respectively, had started ART, with median (interquartile range) times to ART initiation of 3.34 (1.34-12.75), 2.62 (1.28-10.13), 2.16 (1.15-7.11), and 2.03 (1.11-5.61) months, respectively.Conclusions: Although recommendations for ART initiation on diagnosis are increasingly being implemented, the findings of the current study suggest that immediate treatment initiation is not universal. Continued efforts are needed to expand and better target HIV testing to promote earlier diagnosis. [ABSTRACT FROM AUTHOR]

The New York City HIV Care Coordination Program (CCP) combines multiple evidence-based strategies to support persons living with HIV (PLWH) at risk for, or with a recent history of, poor HIV outcomes. We assessed the comparative effectiveness of the CCP by merging programmatic data on CCP clients with population-based surveillance data on all New York City PLWH. A non-CCP comparison group of similar PLWH who met CCP eligibility criteria was identified using surveillance data. The CCP and non-CCP groups were matched on propensity for CCP enrollment within four baseline treatment status groups (newly diagnosed or previously diagnosed and either consistently unsuppressed, inconsistently suppressed or consistently suppressed). We compared CCP to non-CCP proportions with viral load suppression at 12-month follow-up. Among the 13,624 persons included, 15∙3% were newly diagnosed; among the 84∙7% previously diagnosed, 14∙2% were consistently suppressed, 28∙9% were inconsistently suppressed, and 41∙6% were consistently unsuppressed in the year prior to baseline. At 12-month follow-up, 59∙9% of CCP and 53∙9% of non-CCP participants had viral load suppression (Relative Risk = 1.11, 95%CI:1.08–1.14). Among those newly diagnosed and those consistently unsuppressed at baseline, the relative risk of viral load suppression in the CCP versus non-CCP participants was 1.15 (95%CI:1.09–1.23) and 1.32 (95%CI:1.23–1.42), respectively. CCP exposure shows benefits over no CCP exposure for persons newly diagnosed or consistently unsuppressed, but not for persons suppressed in the year prior to baseline. We recommend more targeted case finding for CCP enrollment and increased attention to viral load suppression maintenance. [ABSTRACT FROM AUTHOR]

Many nonrandomized interventions rely upon a pre-post design to evaluate effectiveness. Such designs cannot account for events external to the intervention that may produce the outcome. We describe a method to construct a surveillance registry–based comparison group, which allows for estimating the effectiveness of the intervention while controlling for secular trends in the outcome of interest. Using data from the population-based, human immunodeficiency virus Surveillance Registry in New York City, we created a contemporaneous comparison group for persons enrolled in the New York City human immunodeficiency virus Care Coordination Program (CCP) from December 2009 to March 2013. Inclusion in the Registry-based (non-CCP) comparison group required meeting CCP eligibility criteria. To control for secular trends in the outcome, we randomly assigned persons in the non-CCP, Registry-based comparison group a pseudoenrollment date such that the distribution of pseudoenrollment dates matched the distribution of enrollment dates among CCP enrollees. We then matched CCP to non-CCP persons on propensity for enrollment in the CCP, enrollment dates, and baseline viral load. Registry-based comparison group estimates were attenuated relative to pre-post estimates of program effectiveness. These methods have broad applicability for observational intervention effectiveness studies and programmatic evaluations for conditions with surveillance registries. [ABSTRACT FROM AUTHOR]

Background:  Trends in CD4+ T-cell count at human immunodeficiency virus (HIV) infection diagnosis and antiretroviral therapy (ART) initiation can be characterized using laboratory tests from surveillance.Methods:  We used CD4+ T-cell counts and viral loads from New York City for persons who received a diagnosis of HIV infection during 2006-2012.Results:  From 2006 to 2012, the median CD4+ T-cell count increased from 325 to 379 cells/µL at diagnosis and from 178 to 360 cells/μL at ART initiation. CD4+ T-cell counts were consistently lower in women, blacks, Hispanics, persons who inject drugs, and heterosexuals.Discussion:  Increases in CD4+ T-cell count at diagnosis and ART initiation suggest that the time from HIV infection to ART initiation has been reduced substantially in New York City. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Proliferative defects in dyskeratosis congenita skin keratinocytes are corrected by expression of the telomerase reverse transcriptase, TERT, or by activation of endogenous telomerase through expression of papillomavirus E6/E7 or the telomerase RNA component, TERC. Experimental Dermatology 2010; 19: 279–288. Dyskeratosis congenita (DC) is characterized by the triad of reticulate skin pigmentation, nail dystrophy and leukoplakia. Epidermal atrophy, hair growth defects, bone marrow failure and increased risk of cancer are also common in DC patients. DC is caused by mutations in genes encoding for telomerase complex factors. Although there is an association of epidermal abnormalities with DC, epidermal cells from DC donors have not been previously characterized. We have isolated skin keratinocytes from affected members of a family with an autosomal dominant form of DC that is caused by a mutation in the RNA component of telomerase, TERC. Here, we demonstrate that, similar to DC fibroblasts from these donors, DC keratinocytes have short telomeres and a short lifespan. DC keratinocytes also exhibited impaired colony forming efficiency (CFE) and migration capacity. Exogenous expression of the reverse transcriptase (RT) component of telomerase, TERT, activated telomerase levels to half that of TERT expressing normal cells and maintained telomeres at a short length with concomitant extension of lifespan. Unlike fibroblasts, transduction of human papillomavirus type 16 E6/E7 genes into DC keratinocytes activated telomerase to half that of E6/E7 expressing normal cells, and robust proliferation was observed. While expression of TERC has no measurable effect on telomerase in fibroblasts, expression of TERC in keratinocytes upregulated telomerase activity and, rarely, allowed rescue of proliferative defects. Our results point to important differences between DC fibroblasts and keratinocytes and show, for the first time, that expression of TERC can increase the lifespan of primary human epithelial cells. [ABSTRACT FROM AUTHOR]