STI self-testing: ensuring representation and outreach to teens and adolescents in expanded approaches.

In our correspondence, we describe the results from a quality improvement survey in a sexual health clinic in North Carolina regarding attitudes and perceptions among adolescents and providers regarding specimen self-collection. We find that adolescents have high levels of acceptability for self-collection and confidence in their ability to self-collection; however, providers expressed hesitation regarding the ability of adolescents to self-collection. Our study shows that while self-collection may provide a way to expand testing access to difficult-to-reach populations, we must ensure that providers are confident in the corresponding results.

Association of social vulnerability index and masking adherence among children enrolled in COVID-19 community research partnership study.

BACKGROUND: Individuals with high social vulnerability index (SVI) have poorer outcomes with COVID-19. Masking reduces transmission of COVID-19 among children, but how SVI plays a role in masking behavior is unknown. We aimed to measure the association of SVI with masking adherence among children during the COVID-19 pandemic. METHODS: We conducted a multi-site, prospective syndromic surveillance study among children aged 2 - 17 years in the Southeastern United States by daily electronic surveys which solicited symptoms of COVID-19-like illness, infection with or exposure to SARS-CoV-2, masking habits, and any receipt of COVID-19 vaccines. Parents/guardians submitted surveys for their children; adolescents 13 years and older could opt to submit their own surveys. Multivariable and univariate linear models were used to measure the associations of different predictors such as SVI with masking adherence. RESULTS: One thousand four hundred sixty-one children from 6 states and 55 counties predominately from North and South Carolina were included in the analysis. Most children in the cohort were 5 - 11 years old, non-Hispanic White, from urban counties, and with low-moderate SVI. Overall masking adherence decreased over time, and older children had higher masking adherence throughout the study period compared with younger children. Children who resided in urban counties had greater masking adherence throughout the study period than those who resided in suburban or rural counties. Masking adherence was higher among children with both low and medium SVI than those with high SVI. CONCLUSIONS: Despite being at risk for more severe outcomes with COVID-19, children with high SVI had lower levels of masking adherence compared to those with low SVI. Our findings highlight opportunities for improved and targeted messaging in these vulnerable communities.

COVID-19 Symptoms by Variant Period in the North Carolina COVID-19 Community Research Partnership, North Carolina, USA.

In North Carolina, USA, the SARS-CoV-2 Omicron variant was associated with changing symptomology in daily surveys, including increasing rates of self-reported cough and sore throat and decreased rates of loss of taste and smell. Compared with the pre-Delta period, Delta and Omicron (pre-BA.4/BA.5) variant periods were associated with shorter symptom duration.

Characterisation of infection-induced SARS-CoV-2 seroprevalence amongst children and adolescents in North Carolina.

Few prospective studies have documented the seropositivity among those children infected with severe acute respiratory syndrome coronavirus 2. From 2 April 2021 to 24 June 2021, we prospectively enrolled children between the ages of 2 and 17 years at three North Carolina healthcare systems. Participants received at least four at-home serological tests detecting the presence of antibodies against, but not differentiating between, the nucleocapsid or spike antigen. A total of 1,058 participants were enrolled in the study, completing 2,709 tests between 1 May 2021 and 31 October 2021. Using multilevel regression with poststratification techniques and considering our assay sensitivity and sensitivity, we estimated that the seroprevalence of infection-induced antibodies among unvaccinated children and adolescents aged 2-17 years in North Carolina increased from 15.2% (95% credible interval, CrI 9.0-22.0) in May 2021 to 54.1% (95% CrI 46.7-61.1) by October 2021, indicating an average infection-to-reported-case ratio of 5. A rapid rise in seropositivity was most pronounced in those unvaccinated children aged 12-17 years, based on our estimates. This study underlines the utility of serial, serological testing to inform a broader understanding of the regional immune landscape and spread of infection.

Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults.

BACKGROUND: Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses. METHODS: We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used linear regression with clustered error for antibody titers over multiple timepoints with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used linear regression models with clinical predictors and cellular memory phenotype variables. RESULTS: Participants (n = 15) had median age of 90 years and mild, moderate, or severe frailty scores (n = 3, 7, or 5 respectively). Over the study time course, anti-spike antibody titers were 10-fold higher in individuals with lower frailty status (p = 0.001 and p = 0.005, unadjusted and adjusted for prior COVID-19 infection). Following the booster, titers to spike protein improved regardless of COVID-19 infection or degree of frailty (p = 0.82 and p = 0.29, respectively). Antibody avidity significantly declined over 6 months in all participants following 2 vaccine doses (p < 0.001), which was further impaired with higher frailty (p = 0.001). Notably, avidity increased to peak levels after the booster (p < 0.001). Overall antibody response was inversely correlated with a phenotype of immune-senescent T cells, CD8 + CD28- TEMRA cells (p = 0.036, adjusted for COVID-19 infection). Furthermore, there was increased detection of CD8 + CD28- TEMRA cells in individuals with greater frailty (p = 0.056, adjusted for COVID-19). CONCLUSIONS: We evaluated the immune responses to the Moderna COVID-19 mRNA vaccine in frail older adults in a retirement community. A higher degree of frailty was associated with diminished antibody quantity and quality. However, a booster vaccine dose at 6 months overcame these effects. Frailty was associated with an increased immune-senescence phenotype that may contribute to the observed changes in the vaccine response. While the strength of our conclusions was limited by a small cohort, these results are important for guiding further investigation of vaccine responses in frail older adults.

Automatic case cluster detection using hospital electronic health record data.

Case detection through contact tracing is a key intervention during an infectious disease outbreak. However, contact tracing is an intensive process where a given contact tracer must locate not only confirmed cases but also identify and interview known contacts. Often these data are manually recorded. During emerging outbreaks, the number of contacts could expand rapidly and beyond this, when focused on individual transmission chains, larger patterns may not be identified. Understanding if particular cases can be clustered and linked to a common source can help to prioritize contact tracing effects and understand underlying risk factors for large spreading events. Electronic health records systems are used by the vast majority of private healthcare systems across the USA, providing a potential way to automatically detect outbreaks and connect cases through already collected data. In this analysis, we propose an algorithm to identify case clusters within a community during an infectious disease outbreak using Bayesian probabilistic case linking and explore how this approach could supplement outbreak responses; especially when human contact tracing resources are limited.

Venous or arterial thrombosis in COVID-19 cases in the North Carolina COVID-19 Community Research Partnership (NC-CCRP).

Background: Although the incidence of venous and arterial thrombosis after a COVID-19 diagnosis and hospitalization has been well described using data available from electronic health records (EHR), little is known about their incidence after mild infections. Objectives: To characterize the cumulative incidence and risk factors for thrombosis after a COVID-19 diagnosis among those identified through the EHR and those with a self-reported case. Methods: We calculated the cumulative incidence of thromboembolism diagnoses after EHR-identified and self-reported cases in the North Carolina COVID-19 Community Partnership, a prospective, multisite, longitudinal surveillance cohort using a Kaplan-Meier approach. We performed Cox regression to estimate the hazard of a thromboembolism diagnosis after COVID-19 by comorbidities, vaccination status, and dominant SARS-CoV-2 variant. Results: Of a cohort of comprising more than 39,500 participants from 6 North Carolina sites, there were 6271 self-reported or EHR-diagnosed cases of COVID-19 reported between July 1, 2020, and April 30, 2022, of which 46 participants were diagnosed with a new-onset thromboembolism in the 365 days after their reported case. Self-reported cases had a lower estimated cumulative incidence of 0.15% (95% CI, 0.03-0.28) by day 90 and 0.64% (95% CI, 0.30-0.97) by day 365 compared with EHR-based diagnoses that had cumulative incidences of 0.73% (95% CI, 0.36-1.09) and 1.78 (95% CI, 1.14-2.46) by days 90 and 365 (log-rank test P value <.001). Those hospitalized and with pre-existing pulmonary and cardiovascular diseases were associated with the highest risk of a thromboembolism. Conclusion: We observed a higher cumulative incidence of thromboembolism after EHR-identified COVID-19 than self-reported cases.

Assessing Barriers to Human Papillomavirus (HPV) Vaccination in At-Risk Rural Communities of Western North Carolina, United States.

Human papillomavirus (HPV) vaccination among adolescents in rural, western North Carolina (NC) remains suboptimal. Data are needed to understand the barriers to HPV vaccination in these communities. We conducted a cross-sectional pilot study of parental attitudes and provider practices regarding HPV vaccination in rural western NC counties with lower HPV vaccination rates. Eight health department clinics were enrolled in the study. Further, 29 provider and 32 parent surveys were analyzed along with environmental scans. Median provider comfort regarding knowledge of HPV-associated diseases was 85% (IQR = 75-95), on a scale of 0-100% (100% representing complete comfort). Median parental comfort level regarding knowledge of HPV-associated diseases and the HPV vaccine was 75% (IQR = 50-89) and 75% (IQR = 49-96), respectively. Less than 25% of parents rated the HPV vaccine as 'extremely effective' against genital (16.7%) and anal cancers (17.9%). Parents were more likely to rate the vaccine as 'extremely effective' to 'very effective' if their child was female. There was no significant difference between parental- and provider-reported comfort with knowledge about HPV-associated diseases (p = 0.0725) and the HPV vaccine (p = 0.167). This study identified multiple opportunities to increase HPV vaccine coverage among unvaccinated adolescents at parental, provider, and clinic levels. Health education of rural NC residents and providers in public health settings may identify future interventions to increase HPV vaccine uptake.

Evaluation of a health system's implementation of a monkeypox care model under the RE-AIM framework.

Objective: Emerging infectious diseases challenge healthcare systems to implement new models of care. We aim to evaluate the rapid implementation of a new care model for monkeypox in our health system. Design: This is a retrospective case series evaluation under the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework of implementation of a testing and care model for monkeypox in a large, integrated health system. Methods: Atrium Health implemented education of providers, testing protocols, and management of potential monkeypox cases using electronic health record (EHR) data capabilities, telehealth, and collaboration between multiple disciplines. The first 4 weeks of care model implementation were evaluated under the RE-AIM framework. Results: One hundred fifty-three patients were tested for monkeypox by 117 unique providers at urgent care, emergency departments, and infectious disease clinics in our healthcare system between 18 July 2022 and 14 August 2022. Fifty-eight monkeypox cases were identified, compared with 198 cases in the state during the time period, a disproportionate number compared with the health system service area, and 52 patients were assessed for need for tecovirimat treatment. The number of tests performed and providers sending tests increased during the study period. Conclusion: Implementation of a dedicated care model leveraging EHR data support, telehealth, and cross-disciplinary collaboration led to more effective identification and management of emerging infectious diseases and is important for public health. Plain Language Summary: Impact of care model implementation on monkeypox New infectious diseases challenge health systems to implement new care practices. Our health system responded to this challenge by implementing a care model for education, testing, and clinical care of monkeypox patients. We analyzed results from implementing the model. We were able to identify a disproportionate number of monkeypox cases compared with the rest of our state by using our model to educate medical providers, encourage testing, and ensure patients had access to best disease care. Implementation of care models for testing and management of new diseases will improve patient care and public health.

Frailty and Age Impact Immune Responses to Moderna COVID-19 mRNA Vaccine.

BACKGROUND: Immune responses to COVID-19 mRNA vaccines have not been well characterized in frail older adults. We postulated that frailty is associated with impaired antibody and cellular mRNA vaccine responses. METHODS: We followed older adults in a retirement facility with longitudinal clinical and serological samples from the first Moderna mRNA-1273 vaccine dose starting in February 2021 through their 3rd (booster) vaccine dose. Outcomes were antibody titers, antibody avidity, and AIM+ T cell function and phenotype. Statistical analysis used antibody titers in linear mixed-effects linear regression with clinical predictors including, age, sex, prior infection status, and clinical frailty scale (CFS) score. T cell function analysis used clinical predictors and cellular phenotype variables in linear regression models. RESULTS: Participants (n=15) had median age of 90 years and mild, moderate, or severe frailty scores (n=3, 7, or 5 respectively). After 2 vaccine doses, anti-spike antibody titers were higher in 5-fold higher in individuals with mild frailty compared to severe frailty and 9-fold higher in individuals with prior COVID-19 infection compared to uninfected (p=0.02 and p<0.001). Following the booster, titers improved regardless of COVID-19 infection or frailty. Antibody avidity significantly declined following 2 vaccine doses regardless of frailty status, but reached maximal avidity after the booster. Spike-specific CD4+ T cell responses were modulated by frailty and terminally differentiated effector memory TEMRA cells, and spike-specific TFH cell responses were inversely correlated with age. Additionally, an immune-senescent memory T cell phenotype was correlated with frailty and functional decline. CONCLUSIONS: We described the separate influences of frailty and age on adaptive immune responses to the Moderna COVID-19 mRNA vaccine. Though overall antibody responses were robust, higher frailty diminished initial antibody quantity, and all older adults had impaired antibody avidity. Following the booster, antibody responses improved, overcoming the effects of age and frailty. CD4+ T cell responses were independently impacted by age, frailty, and burden of immune-senescence. Frailty was correlated with increased burden of immune-senescence, suggesting an immune-mediated mechanism for physiological decline.

Frailty and COVID-19 mRNA Vaccine Antibody Response in the COVID-19 Community Research Partnership.

BACKGROUND: COVID-19 has disproportionately affected older adults. Frailty has been associated with impaired vaccine response in other vaccine types, but the impact of frailty on mRNA vaccine response is undefined. METHODS: Observational study of adults aged 55 and older from 1 U.S. health care system between January 22, 2021 and September 16, 2021 with self-reported Moderna or Pfizer COVID-19 mRNA vaccine and an electronic frailty index (eFI) score from their medical record (n = 1 677). Participants' frailty status was compared with positive antibody detection (seroconversion) following full vaccination and subsequent loss of positive antibody detection (seroreversion) using logistic regression models. RESULTS: Of 1 677 older adults with median (interquartile range) age, 67 (62 and 72) years, and frailty status (nonfrail: 879 [52%], prefrail: 678 [40%], and frail: 120 [7.2%]), seroconversion was not detected in 23 (1.4%) over 60 days following full vaccination. Frail individuals were less likely to seroconvert than nonfrail individuals, adjusted odds ratio (OR) 3.75, 95% confidence interval (CI; 1.04, 13.5). Seroreversion was detected in 50/1 631 individuals (3.1%) over 6 months of median follow-up antibody testing. Frail individuals were more likely to serorevert than nonfrail individuals, adjusted OR 3.02, 95% CI (1.17, 7.33). CONCLUSION: Overall antibody response to COVID-19 mRNA vaccination was high across age and frailty categories. While antibody detection is an incomplete descriptor of vaccine response, the high sensitivity of this antibody combined with health-system data reinforce our conclusions that frailty is an independent predictor of impaired antibody response to the COVID-19 mRNA vaccines. Frailty should be considered in vaccine studies and prevention strategies.

Global monkeypox case hospitalisation rates: A rapid systematic review and meta-analysis.

Background: Estimates of the case hospitalization rate and case fatality rate when hospital care is available for monkeypox (MPX) infections have not been well defined. This rapid systematic review and meta-analysis aimed to estimate the case hospitalisation rate and case fatality rate where hospital care is available. Methods: We systematically searched PubMed, Embase, the Lancet Preprints, and MedRxiv for studies published between Jan 1, 1950 and Aug 2, 2022. We included documents which contained both the number of cases and associated hospitalisations of MPX infections. From eligible studies we extracted the country, the year of the study, the study design type, the clade of MPX, the participant characteristics, transmission type, any treatments used, number of cases (including suspected, probable, or laboratory confirmed diagnosis), number of hospitalizations, hospitalized patient outcomes, and case definition. Case hospitalization rate (CHR) was defined as the proportion of cases that were admitted to hospital care while case fatality rate (CFR) was defined as the proportion of cases that died. CHR and CFR were analysed in a fully Bayesian meta-analytic framework using random effects models, including sub-group analysis with heterogeneity assessed using I2. Findings: Of the 259 unique documents identified, 19 studies were eligible for inclusion. Included studies represented 7553 reported cases among which there were 555 hospitalizations. Of the 7540 cases for which outcomes were available, there were 15 recorded deaths. The median age of cases was 35 years (interquartile range 28-38, n = 2010) and primarily male (7339/7489, 98%) in studies where age or sex were available. Combined CHR was estimated to be 14.1% (95% credible interval, 7.5-25.0, I2 97.4%), with a high degree of heterogeneity. Further analysis by outbreak period indicates CHRs of 49.8% (28.2-74.0, I2 81.4%), 21.7% (7.2-52.1, I2 57.7%), and 5.8% (3.2-9.4, I2 92.4%) during the pre-2017, 2017-2021, and 2022 outbreaks, respectively, again with high levels of heterogeneity. CFR was estimated to be 0.03% (0.0-0.44, I2 99.9%), with evidence of large heterogeneity between the studies. Interpretation: There is limited data for MPX hospitalization rates in countries where MPX has been traditionally non-endemic until the current outbreak. Due to substantial heterogeneity, caution is needed when interpreting these findings. Health care organizations should be cognizant of the potential increase in healthcare utilization. Rapid identification of infection and use of appropriate therapies such as antivirals play a role reducing the CHR and associated CFR. Funding: None.