Immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination among nursing home residents-Georgia, October 2020-July 2022.

BACKGROUND: Understanding the immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination is important in nursing home (NH) residents, a high-risk population. METHODS: An observational longitudinal evaluation of 37 consenting vaccinated NH residents with/without SARS-CoV-2 infection from October 2020 to July 2022 was conducted to characterize the immune response to spike protein due to infection and/or mRNA COVID-19 vaccine. Antibodies (IgG) to SARS-CoV-2 full-length spike, nucleocapsid, and receptor binding domain protein antigens were measured, and surrogate virus neutralization capacity was assessed using Meso Scale Discovery immunoassays. The participant's spike exposure status varied depending on the acquisition of infection or receipt of a vaccine dose. Longitudinal linear mixed effects modeling was used to describe trajectories based on the participant's last infection or vaccination; the primary series mRNA COVID-19 vaccine was considered two spike exposures. Mean antibody titer values from participants who developed an infection post receipt of mRNA COVID-19 vaccine were compared with those who did not. In a subset of participants (n = 15), memory B cell (MBC) S-specific IgG (%S IgG) responses were assessed using an ELISPOT assay. RESULTS: The median age of the 37 participants at enrollment was 70.5 years; 30 (81%) had prior SARS-CoV-2 infection, and 76% received Pfizer-BioNTech and 24% Moderna homologous vaccines. After an observed augmented effect with each spike exposure, a decline in the immune response, including %S IgG MBCs, was observed over time; the percent decline decreased with increasing spike exposures. Participants who developed an infection at least two weeks post-receipt of a vaccine were observed to have lower humoral antibody levels than those who did not develop an infection post-receipt. CONCLUSIONS: These findings suggest that understanding the durability of immune responses in this vulnerable NH population can help inform public health policy regarding the timing of booster vaccinations as new variants display immune escape.

Providing Lesbian, Gay, Bisexual, Transgender, Nonbinary, and Queer Adolescents With Nurturance, Trustworthiness, and Safety: Protocol for Pilot Cluster Randomized Controlled Trial Design.

BACKGROUND: Sexual and gender minority youths (lesbian, gay, bisexual, transgender, nonbinary, and queer individuals) face elevated risks of substance use (eg, alcohol and tobacco) and mental health issues (eg, depressive symptoms and suicidality) compared to their cisgender heterosexual peers. These inequities are hypothesized to be reduced by building supportive high school environments via the training of school staff. An intervention that trains school staff to better understand and support sexual and gender minority youths and engage in positive bystander behaviors that protect them from bullying exposure may reduce disparities in drug and alcohol use among them. Experts, school staff, and sexual and gender minority youths developed Providing LGBTQ+ Adolescents with Nurturance, Trustworthiness, and Safety (PLANTS), a web-based intervention to train school staff on how to support, affirm, and protect sexual and gender minority youths. OBJECTIVE: This paper describes the design of the PLANTS pilot trial primarily aimed at assessing its acceptability, usability, appropriateness, and feasibility. We hypothesize PLANTS will have high acceptability, usability, appropriateness, and feasibility as rated by the school staff. Secondary objectives focus on implementation, safety, and pre-post changes in high school staff outcomes, including self-efficacy and skills (eg, active-empathic listening and bullying intervention). Exploratory objectives focus on the impact of PLANTS on student health outcomes. METHODS: In a 2-arm cluster randomized controlled trial, high schools in Massachusetts are allocated to PLANTS or an active comparator group (publicly available sexual and gender minority youths resources or training). High school staff complete pretest and posttest surveys containing validated scales. Primary outcomes are validated measures of acceptability, usability, appropriateness, and feasibility of the intervention completed by staff during posttest surveys. To test our primary hypotheses for each outcome, we will calculate means and 95% CIs and P values using 1-sample 2-sided t tests against a priori thresholds or benchmarks of success. Secondary outcomes include staff's active-empathetic listening skills, self-efficacy for working with sexual and gender minority youths, bystander intervention behaviors for bullying and cyberbullying, and self-efficacy for PLANTS' change objectives completed during pretest and posttest staff surveys. Staff can also complete a posttest interview guided by the Information-Motivation-Behavior model and Consolidated Framework for Implementation Research. Exploratory outcomes include student-level data collected via the 2021 and 2023 MetroWest Adolescent Health Surveys, a health behavior surveillance system in 30 Massachusetts schools. RESULTS: School enrollment began in May 2023 and participant enrollment began in June 2023. Data collection is expected to be completed by February 2024. CONCLUSIONS: This pilot trial will yield important information about the PLANTS intervention and provide necessary information to conduct a fully powered trial of the efficacy of PLANTS for reducing the deleterious health inequities experienced by sexual and gender minority youths. TRIAL REGISTRATION: ClinicalTrials.gov NCT05897827; https://clinicaltrials.gov/study/NCT05897827. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55210.

Effects of changing ions on the crystal design, non-covalent interactions, antimicrobial activity, and molecular docking of Cu(II) complexes with a pyridoxal-hydrazone ligand.

The present work reports the influence of the presence of different ions (Cl-, Br-, NO3 -, or SO4 2-) on the formation and proprieties of Cu(II) complexes with pyridoxal-benzoylhydrazone (PLBHZ). Four new complexes were successfully synthesized, [CuCl2(PLBHZ)] (1), [CuBr2(PLBHZ)] (2), [CuCl(PLBHZ)H2O]⋅NO3⋅H2O (3), and [CuSO4(PLBHZ)H2O]⋅3H2O (4), and characterized by spectroscopic and physicochemical methods. A single-crystal X-ray study reveals the Schiff base coordinated to the metal center tridentate by the ONS-donor system, resulting in distorted square pyramidal coordination geometries. Noncovalent interactions were investigated by 3D Hirshfeld surface analysis by the d norm function, 2D fingerprint plots, and full interaction maps. The ion exchange is important in forming three-dimensional networks with π⋅⋅⋅π stacking interactions and intermolecular hydrogen bonds. The in vitro biological activity of the free ligand and metal complexes was evaluated against Gram-positive and Gram-negative bacterial strains and the free pyridoxal-hydrazone ligand showed higher activity than their Cu(II) complexes. Molecular docking was used to predict the inhibitory activity of the ligand and complexes against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria.

Introduction and acceptability of the Surveillance Outbreak Response Management and Analysis System (SORMAS) during the COVID-19 pandemic in Côte d'Ivoire.

BACKGROUND: The Surveillance Outbreak Response Management and Analysis System (SORMAS) has been implemented for various infectious diseases since 2015. 2020, at the beginning of the COVID-19 pandemic, SORMAS was adapted to SARS-CoV2. METHODS: We assessed the acceptability and usability of SORMAS and accompanied its implementation in two pilot regions of Côte d'Ivoire (Abidjan 2 and Gbêkê) from July/August 2021 to March 2022. We conducted 136 semi-structured interviews to cover knowledge on COVID-19, information on conventional surveillance systems for disease monitoring including COVID-19, acceptability of SORMAS, and impact of SORMAS on epidemic preparedness and surveillance. Scores before and 6-8 months after implementation were compared. RESULTS: SORMAS was implemented in two pilot regions in Côte d'Ivoire. The conventional software for the surveillance of the COVID-19 pandemic by the company MAGPI was maintained in parallel; the additional time needs to enter and manage the data in SORMAS were the main concern. SORMAS acceptance and satisfaction scores were high after the user training, which was prior to implementation, and after 6-8 months of use. The ability of SORMAS to improve COVID-19 preparedness and early detection of cases and contacts was widely acknowledged. To keep the understanding and skills of users up-to-date, regular refresher trainings were requested. The expectation to be able to make decisions based on data produced by SORMAS was high at baseline and the perceived experience after several months of use of the software was very positive. Unfortunately, the link with the laboratories could not be established in the pilot regions, but it is an existing feature of SORMAS that many users were asking for. Following the positive experience using SORMAS for COVID-19, the pilot regions expanded its use for monitoring and management of measles, yellow fever, meningitis, and cholera. CONCLUSION: SORMAS was very well accepted by users and decision makers in the two pilot regions of Côte d'Ivoire and its ability to improve epidemic preparedness and surveillance was acknowledged. If the hurdles of maintenance (tablets, server, and maintaining user skills) are handled sustainably, it can serve as a valid tool to identify, surveil and manage future outbreaks of various infectious diseases in Côte d'Ivoire.

Factors Associated With Receiving Longer Than Recommended Therapy Among Culture-Negative Pulmonary Tuberculosis Patients.

Background: US tuberculosis (TB) guidelines recommend treatment ≥6 months with a regimen composed of multiple effective anti-TB drugs. Since 2003, a 4-month regimen for a specific subset of TB patients has also been recommended. Methods: We used 2011-2018 US National Tuberculosis Surveillance System data to characterize factors associated with 4-month (111-140 days) therapy among adult patients who had completed treatment and were potentially eligible at that time for 4-month therapy (culture-negative pulmonary-only TB, absence of certain risk factors, and initial treatment that included pyrazinamide). We used modified Poisson regression with backward elimination of main effect variables to calculate adjusted relative risks (aRRs). Results: During 2011-2018, 63 393 adults completed TB treatment: 5560 (8.8%) were potentially eligible for 4-month therapy; of these, 5560 patients (79%) received >4-month therapy (median, 193 days or ∼6 months). Patients with cavitary disease were more likely to receive >4-month therapy (aRR, 1.10; 95% CI, 1.07-1.14) vs patients without cavitary disease. Patients more likely to receive 4-month therapy included patients treated by health departments vs private providers only (aRR, 0.94; 95% CI, 0.91-0.98), those in the South and West vs the Midwest, non-US-born persons (aRR, 0.95; 95% CI, 0.91-0.99) vs US-born persons, and aged 25-64 years vs 15-24 years. Conclusions: Most patients potentially eligible for 4-month therapy were treated with standard 6-month courses. Beyond clinical eligibility criteria, other patient- and program-related factors might be more critical determinants of treatment duration.

Pharmacological TRPC6 inhibition improves survival and muscle function in mice with Duchenne muscular dystrophy.

Gene mutations causing loss of dystrophin result in the severe muscle disease known as Duchenne muscular dystrophy (DMD). Despite efforts at genetic repair, DMD therapy remains largely palliative. Loss of dystrophin destabilizes the sarcolemmal membrane, inducing mechanosensitive cation channels to increase calcium entry and promote cell damage and, eventually, muscle dysfunction. One putative channel is transient receptor potential canonical 6 (TRPC6); we have shown that TRPC6 contributed to abnormal force and calcium stress-responses in cardiomyocytes from mice lacking dystrophin that were haplodeficient for utrophin (mdx/utrn+/- [HET] mice). Here, we show in both the HET mouse and the far more severe homozygous mdx/utrn-/- mouse that TRPC6 gene deletion or its selective pharmacologic inhibition (by BI 749327) prolonged survival 2- to 3-fold, improving skeletal and cardiac muscle and bone defects. Gene pathways reduced by BI 749327 treatment most prominently regulated fat metabolism and TGF-ß1 signaling. These results support the testing of TRPC6 inhibitors in human trials for other diseases as a novel DMD therapy.

Effects of rumen-native microbial feed supplementation on milk yield, composition, and feed efficiency in lactating dairy cows.

The objective of this study was to evaluate the effects of two rumen-native microbial feed supplements (MFS) on milk production, milk composition, and feed efficiency. A total of 90 multiparous cows between 40 and 60 d in milk were enrolled in a randomized block design study. Within each block (baseline milk yield), cows were randomly assigned to: control (no microbial feed supplementation), MFS1 (0.33 g/kg total mixed ration [TMR] of an MFS containing a minimum of Clostridium beijerinckii at 2 × 106 CFU/g and Pichia kudriavzevii at 2 × 107 CFU/g), or MFS2 (0.33 g/kg TMR of a MFS containing a minimum of C. beijerinckii at 2 × 106 CFU/g, P. kudriavzevii at 2 × 107 CFU/g, Ruminococcus bovis at 2 × 107 CFU/g, and Butyrivibrio fibrisolvens at 2 × 107 CFU/g). Cows were housed in a single group and fed the study diets ad libitum for 270 d. Individual milk yield was recorded using electronic milk meters, and milk fat and protein were measured using optical in-line analyzers at each of two daily milkings. Treatment and treatment by time effects were assessed through multiple linear regression analyses. Treatment effects were observed for milk and energy-corrected milk (ECM) yields, milk fat and protein yields and concentrations, dry matter intake (DMI), and feed efficiency; those effects were conditional to time for milk yield, DMI, and feed efficiency. Overall, milk, ECM, fat, and protein yields were higher for MFS2 compared with control cows (+3.0, 3.7, 0.12, and 0.12 kg/d, respectively). Compared with MFS1, milk yield was higher and protein yield tended to be higher for MFS2 cows (+2.9 and 0.09 kg/d, respectively). In contrast, MFS1 cows produced 0.17 and 0.08 units of percentage per day more fat and protein than MFS2 cows, and 0.07 units of percentage per day more protein than control cows. Dry matter intake and feed efficiency were higher for MFS2 cows compared with MFS1 cows (+1.3 kg/d and 0.06, respectively), and feed efficiency was higher for MFS2 cows compared with control cows (+0.04). Where observed, treatment by time effects suggest that the effects of MFS2 were more evident as time progressed after supplementation was initiated. No effects of microbial supplementation were observed on body weight, body condition score, somatic cell count, or clinical mastitis case incidence. In conclusion, the supplementation of MFS2 effectively improved economically important outcomes such as milk yield, solids, and feed efficiency.

This study evaluates the effects of two rumen-native microbial feed supplements (MFS) on milk yield, composition, and feed efficiency in lactating dairy cows. Ninety multiparous Holstein cows between 40 and 60 d in milk were assigned to control (no microbial feed supplementation), MFS1 (Clostridium beijerinckii and Pichia kudriavzevii), or MFS2 (C. beijerinckii, P. kudriavzevii, Ruminococcus bovis, and Butyrivibrio fibrisolvens) total mixed ration supplementation. Overall, MFS2 cows had higher milk and milk component yields than control and MFS1, while MFS1 cows had higher milk component concentrations than control and MFS2. Feed efficiency was higher for MFS2 compared with control and MFS1 cows. Microbial feed supplementation improved economically important outcomes such as milk yield, solids, and feed efficiency.

Tuberculosis Among Native Hawaiian and Other Pacific Islander Persons: United States and U.S.-Affiliated Pacific Islands, 2010-2019.

Background: In recent years, tuberculosis (TB) incidence in the United States has declined overall but remained high among Native Hawaiian and Other Pacific Islander (NH/PI) persons. Few studies have examined the epidemiology of TB among NH/PI persons, particularly in the U.S.-Affiliated Pacific Islands (USAPI). We describe TB incidence and characteristics of NH/PI patients during 2010-2019. Methods: We used data from the National Tuberculosis Surveillance System to characterize TB cases reported among NH/PI persons born in the 50 U.S. states (defined to include District of Columbia) and the USAPI. We calculated annual TB incidence among NH/PI patients, stratified by place of birth (U.S. states or USAPI). Using Asian persons born outside the United States-persons historically grouped with NH/PI persons as one racial category-as the reference, we compared demographic, clinical, and socio-behavioral characteristics of NH/PI TB patients. Results: During 2010-2019, 4359 TB cases were reported among NH/PI patients born in the U.S. states (n=205) or the USAPI (n=4154). Median annual incidence per 100,000 persons was 6.5 cases (persons born in the U.S. states) and 150.7 cases (persons born in the USAPI). The proportion of TB patients aged <15 years was higher among NH/PI persons (U.S. states: 54%, USAPI: 24%) than among Asian persons born outside the United States (1%). Conclusions: TB incidence among NH/PI persons is high, particularly among persons born in the USAPI, emphasizing the need to enhance TB prevention strategies in these communities. Interventions should be tailored toward those who experience the highest risk, including NH/PI children and adolescents.

Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing and/or sequencing capacity, which can also introduce biases1-3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing4,5. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We developed and deployed improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detected emerging variants of concern up to 14 days earlier in wastewater samples, and identified multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission.

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Effectiveness and cost of an incentive-based intervention on food safety and income in "dibiteries" in Dakar, Senegal.

BACKGROUND: Rapid urbanisation in Sub-Saharan African cities such as Dakar, Senegal, leads to proliferation of informal braised meat restaurants known as "dibiteries". Dibiteries do not often comply with minimal hygiene and food safety standards. The primary objective of this study was to assess the effectiveness and cost of a good hygiene practice intervention, identify factors that incentivize hygiene improvement and how that impacts on dibiteries' income. METHODS: A randomized controlled trial was carried out in Dakar dibiteries. The 120 random samples of braised meat were collected in three phases: (i) one-month pre-intervention, (ii) 2 months post-intervention, (iii) 10 months post-intervention. The trial comprised four groups of 10 dibiteries each: (a) (control) received no intervention, (b) a standardized training module, (c) a hygiene kit, (d) a training module and hygiene kit. Laboratory analysis of samples determined the total aerobic mesophilic flora (TAMF), thermotolerant coliforms (TC) and Staphylococcus aureus (SA). A questionnaire-based survey and focus group discussion were used to identify pre-intervention hygiene practices, and socioeconomic determinants of hygiene management in dibiteries post-intervention, respectively. RESULTS: Samples were found to be contaminated with TAMF, TC and SA. In phase 1, 27 and 13% of the samples contained TC and SA, respectively. In phase 2, no significant improvement of contamination rates was seen. In phase 3, microbiological quality of samples was significantly improved, with only 11.5% showing contamination with any of the bacterial species analysed (p < 0.1). Compared to the control group, only samples from dibiteries in group (b) had significantly reduced bacterial load in phase 3. The cost of intervention and hygiene improvement was estimated at 67 FCFA ($ 0.12) and 41 FCFA ($ 0.07) / day respectively and did not significantly impact on dibiterie profitability. Incentives to sustainably implement good hygiene practices were mainly linked to access to secure long-term workspaces. CONCLUSION: This intervention may have worked, but globally the results are mixed and not quite significant. However, continuous training in good hygiene practice and access to secure and sustainable infrastructure for dibiterie restaurants are the incentives necessary to achieve sustainable investments and behavioural change. We recommend further intervention refinement and testing other factors for promoting the adoption of good hygiene practices in the dibiteries in relation to consumers health risk.

Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Analysis of SARS-CoV-2 RNA Persistence across Indoor Surface Materials Reveals Best Practices for Environmental Monitoring Programs.

Environmental monitoring in public spaces can be used to identify surfaces contaminated by persons with coronavirus disease 2019 (COVID-19) and inform appropriate infection mitigation responses. Research groups have reported detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on surfaces days or weeks after the virus has been deposited, making it difficult to estimate when an infected individual may have shed virus onto a SARS-CoV-2-positive surface, which in turn complicates the process of establishing effective quarantine measures. In this study, we determined that reverse transcription-quantitative PCR (RT-qPCR) detection of viral RNA from heat-inactivated particles experiences minimal decay over 7 days of monitoring on eight out of nine surfaces tested. The properties of the studied surfaces result in RT-qPCR signatures that can be segregated into two material categories, rough and smooth, where smooth surfaces have a lower limit of detection. RT-qPCR signal intensity (average quantification cycle [Cq]) can be correlated with surface viral load using only one linear regression model per material category. The same experiment was performed with untreated viral particles on one surface from each category, with essentially identical results. The stability of RT-qPCR viral signal demonstrates the need to clean monitored surfaces after sampling to establish temporal resolution. Additionally, these findings can be used to minimize the number of materials and time points tested and allow for the use of heat-inactivated viral particles when optimizing environmental monitoring methods. IMPORTANCE Environmental monitoring is an important tool for public health surveillance, particularly in settings with low rates of diagnostic testing. Time between sampling public environments, such as hospitals or schools, and notifying stakeholders of the results should be minimal, allowing decisions to be made toward containing outbreaks of coronavirus disease 2019 (COVID-19). The Safer At School Early Alert program (SASEA) (https://saseasystem.org/), a large-scale environmental monitoring effort in elementary school and child care settings, has processed >13,000 surface samples for SARS-CoV-2, detecting viral signals from 574 samples. However, consecutive detection events necessitated the present study to establish appropriate response practices around persistent viral signals on classroom surfaces. Other research groups and clinical labs developing environmental monitoring methods may need to establish their own correlation between RT-qPCR results and viral load, but this work provides evidence justifying simplified experimental designs, like reduced testing materials and the use of heat-inactivated viral particles.

Comparison of heat-inactivated and infectious SARS-CoV-2 across indoor surface materials shows comparable RT-qPCR viral signal intensity and persistence.

Environmental monitoring in public spaces can be used to identify surfaces contaminated by persons with COVID-19 and inform appropriate infection mitigation responses. Research groups have reported detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on surfaces days or weeks after the virus has been deposited, making it difficult to estimate when an infected individual may have shed virus onto a SARS-CoV-2 positive surface, which in turn complicates the process of establishing effective quarantine measures. In this study, we determined that reverse transcription-quantitative polymerase chain reaction (RT-qPCR) detection of viral RNA from heat-inactivated particles experiences minimal decay over seven days of monitoring on eight out of nine surfaces tested. The properties of the studied surfaces result in RT-qPCR signatures that can be segregated into two material categories, rough and smooth, where smooth surfaces have a lower limit of detection. RT-qPCR signal intensity (average quantification cycle (Cq)) can be correlated to surface viral load using only one linear regression model per material category. The same experiment was performed with infectious viral particles on one surface from each category, with essentially identical results. The stability of RT-qPCR viral signal demonstrates the need to clean monitored surfaces after sampling to establish temporal resolution. Additionally, these findings can be used to minimize the number of materials and time points tested and allow for the use of heat-inactivated viral particles when optimizing environmental monitoring methods.

Automated, miniaturized, and scalable screening of healthcare workers, first responders, and students for SARS-CoV-2 in San Diego County

BackgroundSuccessful containment strategies for SARS-CoV-2, the causative virus of the COVID-19 pandemic, have involved widespread population testing that identifies infections early and enables rapid contact tracing. In this study, we developed a rapid and inexpensive RT- qPCR testing pipeline for population-level SARS-CoV-2 detection, and used this pipeline to establish a clinical laboratory dedicated to COVID-19 testing at the University of California San Diego (UCSD) with a processing capacity of 6,000 samples per day and next-day result turnaround times. Methods and findingsUsing this pipeline, we screened 6,786 healthcare workers and first responders, and 21,220 students, faculty, and staff from UCSD. Additionally, we screened 6,031 preschool-grade 12 students and staff from public and private schools across San Diego County that remained fully or partially open for in-person teaching during the pandemic. Between April 17, 2020 and February 5, 2021, participants provided 161,582 nasal swabs that were tested for the presence of SARS-CoV-2. Overall, 752 positive tests were obtained, yielding a test positivity rate of 0.47%. While the presence of symptoms was significantly correlated with higher viral load, most of the COVID-19 positive participants who participated in symptom surveys were asymptomatic at the time of testing. The positivity rate among preschool-grade 12 schools that remained open for in-person teaching was similar to the positivity rate at UCSD and lower than that of San Diego County, with the children in private schools being less likely to test positive than the adults at these schools. ConclusionsMost schools across the United States have been closed for in-person learning for much of the 2020-2021 school year, and their safe reopening is a national priority. However, as there are no vaccines against SARS-CoV-2 currently available to the majority of school-aged children, the traditional strategies of mandatory masking, physical distancing, and repeated viral testing of students and staff remain key components of risk mitigation in these settings. The data presented here suggest that the safety measures and repeated testing actions taken by participating healthcare and educational facilities were effective in preventing outbreaks, and that a similar combination of risk-mitigation strategies and repeated testing may be successfully adopted by other healthcare and educational systems.

Knowledge, Attitudes, and Practices (KAP) Regarding the COVID-19 Outbreak in Côte d'Ivoire: Understanding the Non-Compliance of Populations with Non-Pharmaceutical Interventions.

At the beginning of the COVID-19 outbreak, preventive measures seemed the most appropriate method to control its spread. We assessed the knowledge, attitudes, and practices of the Ivorian public regarding preventive measures, conducting a hybrid survey across the country. Participants were invited to complete a questionnaire online, by phone, or face-to-face. Chi-squared, Fisher's exact, and Kruskal-Wallis tests were used to compare the frequency of responses regarding compliance with preventive measures. Data were validated for 564 individuals. Over one-third of respondents believed that COVID-19 was related to non-natural causes. Though the disease was perceived as severe, respondents did not consider it to be highly infectious. Overall, 35.6% of respondents fully trust health officials in the management of the pandemic, and 34.6% trusted them moderately. Individuals who believed COVID-19 was a disease caused by a pathogen and the well-educated were likely to comply with preventive measures. About 70% of respondents stated that their daily expenses had increased due to preventive measures. The study concludes that beyond unfavorable socioeconomic conditions, the level of knowledge regarding COVID-19 and trust in the government/health system are more likely to influence compliance with preventive measures such as self-reporting, physical distancing, the use of face masks, and eventually the acceptability of vaccines.

Multisystem Inflammatory Syndrome in Infants <12 months of Age, United States, May 2020-January 2021.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified in infants <12 months old. Clinical characteristics and follow-up data of MIS-C in infants have not been well described. We sought to describe the clinical course, laboratory findings, therapeutics and outcomes among infants diagnosed with MIS-C. METHODS: Infants of age <12 months with MIS-C were identified by reports to the CDC's MIS-C national surveillance system. Data were obtained on clinical signs and symptoms, complications, treatment, laboratory and imaging findings, and diagnostic SARS-CoV-2 testing. Jurisdictions that reported 2 or more infants were approached to participate in evaluation of outcomes of MIS-C. RESULTS: Eighty-five infants with MIS-C were identified and 83 (97.6%) tested positive for SARS-CoV-2 infection; median age was 7.7 months. Rash (62.4%), diarrhea (55.3%) and vomiting (55.3%) were the most common signs and symptoms reported. Other clinical findings included hypotension (21.2%), pneumonia (21.2%) and coronary artery dilatation or aneurysm (13.9%). Laboratory abnormalities included elevated C-reactive protein, ferritin, d-dimer and fibrinogen. Twenty-three infants had follow-up data; 3 of the 14 patients who received a follow-up echocardiogram had cardiac abnormalities during or after hospitalization. Nine infants had elevated inflammatory markers up to 98 days postdischarge. One infant (1.2%) died after experiencing multisystem organ failure secondary to MIS-C. CONCLUSIONS: Infants appear to have a milder course of MIS-C than older children with resolution of their illness after hospital discharge. The full clinical picture of MIS-C across the pediatric age spectrum is evolving.

Tuberculosis - United States, 2020.

Tuberculosis (TB) disease incidence has decreased steadily since 1993 (1), a result of decades of work by local TB programs to detect, treat, and prevent TB disease and transmission. During 2020, a total of 7,163 TB cases were provisionally reported to CDC's National Tuberculosis Surveillance System (NTSS) by the 50 U.S. states and the District of Columbia (DC), a relative reduction of 20%, compared with the number of cases reported during 2019.* TB incidence per 100,000 persons was 2.2 during 2020, compared with 2.7 during 2019. Since 2010, TB incidence has decreased by an average of 2%-3% annually (1). Pandemic mitigation efforts and reduced travel might have contributed to the reported decrease. The magnitude and breadth of the decrease suggest potentially missed or delayed TB diagnoses. Health care providers should consider TB disease when evaluating patients with signs and symptoms consistent with TB (e.g., cough of >2 weeks in duration, unintentional weight loss, and hemoptysis), especially when diagnostic tests are negative for SARS-CoV-2, the virus that causes COVID-19. In addition, members of the public should be encouraged to follow up with their health care providers for any respiratory illness that persists or returns after initial treatment. The steep, unexpected decline in TB cases raises concerns of missed cases, and further work is in progress to better understand factors associated with the decline.

Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes. METHODS: In this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities. FINDINGS: 1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]). INTERPRETATION: Identification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C. FUNDING: None.