Discovery of novel dihydronaphthalene-imidazole ligands as potential inhibitors of Staphylococcus aureus multidrug resistant NorA efflux pump: A combination of experimental and in silico molecular docking studies.

Overexpression of the efflux pump is a predominant mechanism by which bacteria show antimicrobial resistance (AMR) and leads to the global emergence of multidrug resistance (MDR). In this work, the inhibitory potential of library of dihydronapthyl scaffold-based imidazole derivatives having structural resemblances with some known efflux pump inhibitors (EPI) were designed, synthesized and evaluated against efflux pump inhibitor against overexpressing bacterial strains to study the synergistic effect of compounds and antibiotics. Out of 15 compounds, four compounds (Dz-1, Dz-3, Dz-7, and Dz-8) were found to be highly active. DZ-3 modulated the MIC of ciprofloxacin, erythromycin, and tetracycline by 128-fold each against 1199B, XU212 and RN4220 strains of S. aureus respectively. DZ-3 also potentiated tetracycline by 64-fold in E. coli AG100 strain. DZ-7 modulated the MIC of both tetracycline and erythromycin 128-fold each in S. aureus XU212 and S. aureus RN4220 strains. DZ-1 and DZ-8 showed the moderate reduction in MIC of tetracycline in E. coli AG100 only by 16-fold and 8-fold, respectively. DZ-3 was found to be the potential inhibitor of NorA as determined by ethidium bromide efflux inhibition and accumulation studies employing NorA overexpressing strain SA-1199B. DZ-3 displayed EPI activity at non-cytotoxic concentration to human cells and did not possess any antibacterial activity. Furthermore, molecular docking studies of DZ-3 was carried out in order to understand the possible binding sites of DZ-3 with the active site of the protein. These studies indicate that dihydronaphthalene scaffolds could serve as valuable cores for the development of promising EPIs.

Temporal Vascular Endothelial Growth Factor Sub-type gene Switching in SARS-CoV Pathogenesis. Interpretation through in vivo Murine C57BL Models

IntroductionIncreased Vascular Endothelial Growth Factor A (VEGF-A) levels are associated with Severe Acute Respiratory (SARS) infection. The aim was to investigate in vivo VEGF-A and VEGF-B (VEGF-A/B) gene expression (GE) in severe pulmonary disease pathogenesis. MethodTwelve temporal Mus musculus Wildtype (WT) C57BL/6 SARS-CoV MA15 lung studies were selected from the NCBI GEO database for GE profiling. ResultsIn murine dataset (GSE68820) Day 2 was compared to Day 7 demonstrating a downregulation trend in VEGF-A GE, with an opposite effect on VEGF-B GE (p=4.147e-03, p=7.580e-07, respectively). A v-shaped VEGF-B gene expression trajectory was noteworthy across certain datasets and after dORF6 stimulation. In addition, MA15 dose stimulation studies showed that a higher antigenic load caused more profound effects on VEGF-A resulting in a steeper fall in GE compared to other antigens. ConclusionsDistinct temporal trajectory patterns of VEGF-A and VEGF-B gene expression were associated with SARS-CoV MA15 stimulation. Unraveling the importance of VEG-A/B dynamics offers exciting prospects for improved bio-marking and therapeutic precision.

A Huge Chondrosarcoma of the Nasal Septum.

Chondrosarcoma of the nasal septum is a rare malignancy. Its early diagnosis is difficult because of its non-specific sinonasal complaints. We report a case report of a 72-year-old woman who presented with progressive nasal obstruction and anosmia. Nasal endoscopy showed a nasal mass obstructing both nasal cavities, which was not separable from the nasal septum. Endoscopic biopsy confirmed chondrosarcoma. The tumour was operated on with complete margins by an endoscopic approach. The clinical presentation of the disease, diagnosis and treatment of this case, and a review of the literature are discussed.

Distinguishing features of Long COVID identified through immune profiling

SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID1-3. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions1-3; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.

Prevalence and burden of COPD misclassification in the Canadian Longitudinal Study on Aging (CLSA).

INTRODUCTION: To examine the prevalence of chronic obstructive pulmonary disease (COPD) misclassification and the associated burden of symptoms, healthcare utilisation and physical performance status in the Canadian general population. This information is presently lacking from large population-based studies with high-quality spirometry data that can be generalised to the general population. METHODS: The prevalence of self-reported physician-diagnosed COPD and the concordance with spirometry airflow obstruction (AO) were assessed in a cross-sectional cohort of Canadian older adults. The associations between confirmed COPD, under-diagnosis and over-diagnosis with self-reported respiratory symptoms, healthcare utilisation and physical performance (timed up and go, handgrip strength and 4 metres walk test) were assessed, adjusting for baseline characteristics using multivariable linear and logistic models. RESULTS: A total of 21 242 participants (mean age 64 (SD 10) years; 42% men) with high quality spirometry were included. Physician-diagnosed COPD was reported in (n=973) 5% of the participants. Only (n=217) 1% of the entire cohort had confirmed COPD supported by spirometry AO. Discordance between self-reported COPD and spirometry findings was observed in (n=1565) 8%: with 4% representing under-diagnosis cases (no self-reported COPD but AO) and 4% representing over-diagnosis cases (self-reported COPD but no AO). Compared with normals (no self-reported COPD and normal spirometry), those with confirmed, under-diagnosed or over-diagnosed COPD showed higher risks for respiratory symptoms (adjusted OR (aOR) 2.1 (95% CI: 1.6 to 2.7); aOR 1.8 (95% CI: 1.6 to 2.1]; aOR 1.6 (95% CI: 1.4 to 1.9)); healthcare utilisation in the prior 12 months (ß coefficient 0.8 (95% CI: 0.2 to 2.6); ß 0.9 (95% CI: 0.5 to 1.5); ß 1.6 (95% CI: 0.7 to 4.0)). Mood disorders were higher in confirmed and over-diagnosed COPD (aOR 1.7 (95% CI: 1.3 to 2.4); 1.7 (95% CI: 1.4 to 2.0), respectively). Physical performance was lower for COPD groups. CONCLUSIONS: The prevalence of COPD misclassification is high in the general population of older adults. These were associated with significantly high burden of respiratory symptoms, healthcare utilisation and low physical performance compared with the general population with normal spirometry and no self-reported COPD. These findings highlight the high burden of COPD misclassification, which may be substantially reduced with greater accessibility to spirometry measurements in the community.

Presence of Mediastinal Lymphadenopathy in Hospitalized Covid-19 Patients in a Tertiary Care Hospital in Pakistan - A cross-sectional study

BackgroundThe aim of this study was to investigate the presence of mediastinal lymphadenopathy in hospitalized Covid-19 patients in a tertiary care hospital in the metropolitan city of Lahore, Pakistan from September 2020 till July 2021. MethodsWe retrospectively collected data of Covid-19 patients hospitalized from September 2020 till July 2021. Only those patients who tested PCR positive through a nasopharyngeal swab, were enrolled in the study. Patients whose data were missing were excluded from this study. Our exclusion criteria included patients who tested negative on Covid-19 PCR, patients with comorbidities that may cause enlarged mediastinal lymphadenopathies such as haemophagocytic lymphohistiocytosis, neoplasia, tuberculosis, sarcoidosis or a systemic disease. The extent of lung involvement in Covid-19 patients was quantified by using a 25-point visual quantitative assessment called the Chest Computed Tomography Score. This score was then correlated with the presence of mediastinal lymphadenopathy. FindingsOf the 210 hospitalized patients included in the study, 131 (62.4%) had mediastinal lymphadenopathy. The mean and median Severity Score of Covid-19 patients with mediastinal lymphadenopathy (mean: 17.1, SD:5.7; median: 17, IQR: 13-23) were higher as compared to those without mediastinal lymphadenopathy (mean: 12.3, SD:5.4; median: 12, IQR:9-16) InterpretationOur study documents a high prevalence of mediastinal lymphadenopathy in hospitalized patients with Covid-19 with the severity score being higher in its presence representing a more severe course of disease.

Prevalence of Chronic Diseases, Depression, and Stress among U.S. Child Care Professionals during the COVID-19 Pandemic

ImportanceThere is no published national research reporting child care professionals physical health, depression, or stress during the COVID-19 pandemic. Given their central role in supporting childrens development, child care professionals overall physical and mental health is important. ObjectivesTo evaluate the prevalence of chronic diseases, depression, and stress levels during the COVID-19 pandemic among U.S. child care professionals. DesignIn this large-scale national survey, data were collected through an online survey from May 22, 2020 to June 8, 2020. We analyzed the association of sociodemographic characteristics with four physical health conditions (asthma, heart disease, diabetes, and obesity), depression, and stress weighted to national representativeness. Sociodemographic characteristics included race, ethnicity, age, gender, medical insurance status, and child care type. SettingCenter- and home-based child care. ParticipantsChild care professionals (n = 81,682) from all U.S. states and the District of Columbia. ResultsMean age was 42.1 years (standard deviation = 14.1); 96.0% (n = 78,725) were female, 2.5% (n = 2,033) were male, and 0.3% (n = 225) were non-binary. For physical health conditions, 14.3% (n = 11,717) reported moderate to severe asthma, 6.5% (n = 5,317) diabetes, 4.9% (n = 3,971) heart disease, and 19.8% (n = 16,207) being obese. Regarding mental health, 45.7% (n = 37,376) screened positive for depression and 66.5% (n = 54,381) reported moderate to high stress levels. Race, ethnicity, and gender disparities were evidenced for physical health conditions of child care professionals, but not for mental health during the pandemic. Conclusions and RelevanceOur findings highlight that child care professionals depression rates during the pandemic were much higher than before the pandemic, and depression, stress and asthma rates were higher than U.S. adult depression rates during the pandemic. Given the essential work child care professionals provide during the pandemic, policy makers and public health officials should consider what can be done to support the physical and mental health of child care professionals. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the prevalence of chronic diseases, depression, and stress among U.S. child care professionals during the COVID-19 pandemic? FindingsIn this survey of 81,682 U.S. child care professionals, 14.3% reported moderate to severe asthma, 6.5% diabetes, 4.9% heart disease, 19.8% being obese, 45.7% screening positive for depression, and 66.5% moderate to high stress levels. MeaningDuring the pandemic, child care professionals reported depression rates much higher than before the pandemic, and asthma, stress, and depression much greater than U.S. adult estimates, highlighting a need for effective supports for the wellbeing of this essential workforce.

COVID-19 Vaccine Uptake among U.S. Child Care Providers

STRUCUTRED ABSTRACTO_ST_ABSObjectivesC_ST_ABSEnsuring a high COVID-19 vaccine uptake among U.S. child care providers is crucial to mitigating the public health implications of child-to-staff and staff-to-child transmission of SARS-CoV-2; however, the vaccination rate among this group is unknown. MethodsTo characterize the vaccine uptake among U.S. child care providers, we conducted a cross-sectional survey of the child care workforce. Providers were identified through various national databases and state registries. A link to the survey was sent via email between May 26 and June 23, 2021. Out of 44,771 potential respondents, 21,663 responded (48.4%). ResultsOverall COVID-19 vaccine uptake among U.S. child care providers (78.1%, 95% CI [77.3% to 78.9%]) was higher than that of the U.S. adult population (65%). Vaccination rates varied from 53.5% to 89.4% between states. Vaccine uptake differed significantly (p < .01) based on respondent age (70.0% for ages 25-34, 91.5% for ages 75-84), race (70.0% for Black or African Americans, 92.5% for Asian-Americans), annual household income (70.7% for <$35,000, 85.0% for>$75,000), and childcare setting (72.9% for home-based, 79.7% for center-based). ConclusionsCOVID-19 vaccine uptake among U.S. child care providers was higher than that of the general U.S. adult population. Those who were younger, lower income, Black or African American, resided in states either in the Mountain West or the South, and/or worked in home-based childcare programs reported the lowest rates of vaccination; state public health leaders and lawmakers should prioritize these subgroups for placement on the policy agenda to realize the largest gains in vaccine uptake among providers. Tables of Contents SummaryThis article describes the results of a national survey of childcare providers to determine the overall COVID-19 vaccine uptake and the gaps in vaccine coverage. Whats Known on This SubjectEnsuring a high COVID-19 vaccine uptake among U.S. child care providers is crucial to mitigating the public health implications of child-to-staff and staff-to-child transmission of SARS-CoV-2; however, the vaccination rate among this group is unknown. What This Study AddsWhile the vaccine uptake among U.S. child care providers was higher than that of U.S. adults, certain subgroups continue to warrant focused attention for outreach and/or placement on the policy agenda.

Prevalence and prognostic impact of physical frailty in interstitial lung disease: A prospective cohort study.

BACKGROUND AND OBJECTIVE: Physical frailty is associated with increased mortality and hospitalizations in older adults. We describe the prevalence of physical frailty and its prognostic impact in patients with a spectrum of fibrotic interstitial lung disease (ILD). METHODS: Patients with fibrotic ILD at the McMaster University ILD programme were prospectively followed up from November 2015 to March 2020. Baseline data were used to classify patients as non-frail (score = 0), pre-frail (score = 1-2) or frail (score = 3-5) based on modified Fried physical frailty criteria. The association between physical frailty and mortality was assessed using time-to-event models, adjusted for age, sex, lung function and diagnosis using the ILD Gender-Age-Physiology (ILD-GAP) score. RESULTS: We included 463 patients (55% male, mean [SD] age 68 [11] years); 82 (18%) were non-frail, 258 (56%) pre-frail and 123 (26%) frail. The most common ILD diagnoses were idiopathic pulmonary fibrosis (n = 183, 40%) and connective tissue disease-associated-ILD (n = 79, 17%). Mean time since diagnosis was 2.7 ± 4.6 years. There were 56 deaths within the median follow-up of 1.71 (interquartile range [IQR] 1.24, 2.31) years. Both frail and pre-frail individuals had a higher risk of death compared to those categorized as non-frail at baseline (adjusted hazard ratio [aHR] 4.14, 95% CI 1.27-13.5 for pre-frail and aHR 4.41, 95% CI 1.29-15.1 for frail). CONCLUSION: Physical frailty is prevalent in patients with ILD and is independently associated with an increased risk of death. Assessment of physical frailty provides additional prognostic value to recognized risk scores such as the ILD-GAP score, and may present a modifiable target for intervention.

COVID-19 Vaccine Acceptance and Hesitancy in Low and Middle Income Countries, and Implications for Messaging

We analyze COVID-19 vaccine acceptance across 15 survey samples covering ten low- and middle-income countries (LMICs) in Asia, Africa, and South America, Russia (an upper-middle-income country), and the United States, using survey responses from 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in LMIC samples (80% on average) compared to the United States (65%) and Russia (30%). Vaccine acceptance was primarily explained by an interest in personal protection against COVID-19, while concern about side effects was the most commonly expressed reason for reluctance. Health workers were the most trusted sources of information about COVID-19 vaccines. Our findings suggest that prioritizing vaccine distribution to LMICs should yield high returns in promoting global immunization coverage, and that vaccination campaigns in these countries should focus on translating acceptance into uptake. Messaging highlighting vaccine efficacy and safety, delivered by healthcare workers, may be most effective in addressing remaining hesitancy.

Beliefs about Mask Efficacy and the Effect of Social Norms on Mask Wearing Intentions for COVID-19 Risk Reduction

In the absence of widespread vaccination for COVID-19, governments and public health officials have advocated for the public to wear masks during the pandemic. The decision to wear a mask in public is likely affected by both beliefs about its efficacy and the prevalence of the behavior. Greater mask use in the community may encourage others to follow this norm, but it also creates an incentive for individuals to free ride on the protection afforded to them by others. We report the results of two vignette-based experiments conducted in the United States and Italy to examine the causal relationship between beliefs, social norms, and reported intentions to engage in mask promoting behavior. We find that providing factual information about how masks protect others increases the likelihood that someone would wear a mask or encourage others to do so in the United States, but not in Italy. There is no effect of providing information about how masks protect the wearer in either country. Additionally, greater mask use increases intentions to wear a mask and encourage someone else to wear theirs properly in both the United States and Italy. Thus, community mask use may be self-reinforcing.

Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus.

Coeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-sectional pilot study was to identify whether there are distinct gut microbiota alterations in children with CD (n = 19), T1DM (n = 18) and both CD and T1DM (n = 9) compared to healthy controls (n = 12). Our second goal was to explore the relationship between neuropathy (corneal nerve fiber damage) and the gut microbiome composition. Microbiota composition was determined by 16S rRNA gene sequencing. Corneal confocal microscopy was used to determine nerve fiber damage. There was a significant difference in the overall microbial diversity between the four groups with healthy controls having a greater microbial diversity as compared to the patients. The abundance of pathogenic proteobacteria Shigella and E. coli were significantly higher in CD patients. Differential abundance analysis showed that several bacterial amplicon sequence variants (ASVs) distinguished CD from T1DM. The tissue transglutaminase antibody correlated significantly with a decrease in gut microbial diversity. Furthermore, the Bacteroidetes phylum, specifically the genus Parabacteroides was significantly correlated with corneal nerve fiber loss in the subjects with neuropathic damage belonging to the diseased groups. We conclude that disease-specific gut microbial features traceable down to the ASV level distinguish children with CD from T1DM and specific gut microbial signatures may be associated with small fiber neuropathy. Further research on the mechanisms linking altered microbial diversity with neuropathy are warranted.

National interest may require distributing COVID-19 vaccines to other countries

As the clinical trials for COVID-19 vaccine progress, understanding how to distribute the initially scarce doses is of paramount importance and a quantitative analysis of the trade-offs involved in domestic-only versus cooperative distribution is still missing. In this study we use a network Susceptible-Infected-Removed (SIR) model to show under which circumstances it is in a countrys self-interest to ensure other countries can also obtain a COVID-19 vaccine rather than focusing only on vaccination of their own residents. In particular, we focus our analysis on the USs decision and estimate the internal burden of COVID-19 disease under different scenarios about vaccine cooperation. We show that in scenarios in which the US has reached the threshold for domestic herd immunity, the US may find it optimal to donate doses to other countries with lower vaccination coverage, as this would allow for a sharp reduction in the inflow of infected individuals from abroad.

Modeling Dynamic Network Strategies for SARS-CoV-2 Control on a Cruise Ship

SARS-CoV-2 outbreaks have occurred on several nautical vessels, driven by the high-density contact networks on these ships. Optimal strategies for prevention and control that account for realistic contact networks are needed. We developed a network-based transmission model for SARS-CoV-2 on the Diamond Princess outbreak to characterize transmission dynamics and to estimate the epidemiological impact of outbreak control and prevention measures. This model represented the dynamic multi-layer network structure of passenger-passenger, passengercrew, and crew-crew contacts, both before and after the large-scale network lockdown imposed on the ship in response to the disease outbreak. Model scenarios evaluated variations in the timing of the network lockdown, reduction in contact intensity within the sub-networks, and diagnosis-based case isolation on outbreak prevention. We found that only extreme restrictions in contact patterns during network lockdown and idealistic clinical response scenarios could avert a major COVID-19 outbreak. Contact network changes associated with adequate outbreak prevention were the restriction of passengers to their cabins, with limited passenger-crew contacts. Clinical response strategies required for outbreak prevention included early mass screening with an ideal PCR test (100% sensitivity) and immediate case isolation upon diagnosis. Public health restrictions on optional leisure activities like these should be considered until longer-term effective solutions such as a COVID-19 vaccine become widely available.

COVID-19 Risk Perception Among U.S. Adults: Changes from February to May 2020

The COVID-19 pandemic continues to detrimentally impact the United States. Using a survey, we collected demographic and COVID-19 risk perception, behavior, knowledge, and attitude data from 672 adults across the U.S. in May 2020. These variables were compared with the results from a survey in February 2020. Participants who were older (55+ years; M = 6.3, SD = 2.0), identified as Native American/Alaska Native (M = 6.8, SD = 1.0) or Asian (M = 6.0, SD = 2.0), and those who had contracted (M = 6.8, SD = 2.0) or knew someone who had contracted COVID-19 (M = 6.2, SD = 1.7) reported higher perceived risk. Health behaviors, such as physical distancing, have shown to impact infectious disease trajectories. As the U.S. reopens its economy, public health officials and politicians must formulate culturally appropriate and evidence-based messaging and policies, based on the publics COVID-19 risk perceptions, to encourage preventive behaviors.

Aligning SARS-CoV-2 Indicators via an Epidemic Model: Application to Hospital Admissions and RNA Detection in Sewage Sludge

Ascertaining the state of coronavirus outbreaks is crucial for public health decision-making. Absent repeated representative viral test samples in the population, public health officials and researchers alike have relied on lagging indicators of infection to make inferences about the direction of the outbreak and attendant policy decisions. Recently researchers have shown that SARS-CoV-2 RNA can be detected in municipal sewage sludge with measured RNA concentrations rising and falling suggestively in the shape of an epidemic curve while providing an earlier signal of infection than hospital admissions data. The present paper presents a SARS-CoV-2 epidemic model to serve as a basis for estimating the incidence of infection, and shows mathematically how modeled transmission dynamics translate into infection indicators by incorporating probability distributions for indicator-specific time lags from infection. Hospital admissions and SARS-CoV-2 RNA in municipal sewage sludge are simultaneously modeled via maximum likelihood scaling to the underlying transmission model. The results demonstrate that both data series plausibly follow from the transmission model specified, provide a direct estimate of the reproductive number R0 = 2.38, and suggest that the detection of viral RNA in sewage sludge leads hospital admissions by 4.6 days on average.

Determinants of COVID-19 Vaccine Acceptance in the U.S.

BackgroundThe COVID-19 pandemic continues to adversely affect the U.S., which leads globally in total cases and deaths. As COVID-19 vaccines are under development, public health officials and policymakers need to create strategic vaccine-acceptance messaging to effectively control the pandemic and prevent thousands of additional deaths. MethodsUsing an online platform, we surveyed the U.S. adult population in May 2020 to understand risk perceptions about the COVID-19 pandemic, acceptance of a COVID-19 vaccine, and trust in sources of information. These factors were compared across basic demographics. FindingsOf the 672 participants surveyed, 450 (67%) said they would accept a COVID-19 vaccine if it is recommended for them. Males (72%), older adults ([≥]55 years; 78%), Asians (81%), and college and/or graduate degree holders (75%) were more likely to accept the vaccine. When comparing reported influenza vaccine uptake to reported acceptance of the COVID-19 vaccine: 1) participants who did not complete high school had a very low influenza vaccine uptake (10%), while 60% of the same group said they would accept the COVID-19 vaccine; 2) unemployed participants reported lower influenza uptake and lower COVID-19 vaccine acceptance when compared to those employed or retired; and, 3) black Americans reported lower influenza vaccine uptake and lower COVID-19 vaccine acceptance than nearly all other racial groups. Lastly, we identified geographic differences with Department of Health and Human Services regions 2 (New York) and 5 (Chicago) reporting less than 50 percent COVID-19 vaccine acceptance. InterpretationAlthough our study found a 67% acceptance of a COVID-19 vaccine, there were noticeable demographic and geographical disparities in vaccine acceptance. Before a COVID-19 vaccine is introduced to the U.S., public health officials and policymakers must prioritize effective COVID-19 vaccine-acceptance messaging for all Americans, especially those who are most vulnerable. FundingThe study was funded by the Yale Institute for Global Health.

SARS-CoV-2 RNA concentrations in primary municipal sewage sludge as a leading indicator of COVID-19 outbreak dynamics

We report a time course of SARS-CoV-2 RNA concentrations in primary sewage sludge during the Spring COVID-19 outbreak in a northeastern U.S. metropolitan area. SARS-CoV-2 RNA was detected in all environmental samples, and when adjusted for the time lag, the virus RNA concentrations tracked the COVID-19 epidemiological curve. SARS-CoV-2 RNA concentrations were a leading indicator of community infection ahead of compiled COVID-19 testing data and local hospital admissions. Decisions to implement or relax public health measures and restrictions require timely information on outbreak dynamics in a community.

Measuring voluntary social distancing behavior during the COVID-19 pandemic

Staying home and avoiding unnecessary contact is an important part of the effort to contain COVID-19 and limit deaths. Every state in the United States enacted policies to encourage distancing, and some mandated staying home. Understanding how these policies interact with individuals voluntary responses to the COVID-19 epidemic is critical for estimating the transmission dynamics of the pathogen and assessing the impact of policies. We use the variation in policy responses along with smart device data, which measures the amount of time Americans stayed home, to show that there was substantial voluntary avoidance behavior. We disentangle the extent to which observed shifts in behavior are induced by policy and find evidence of a non-trivial voluntary response to local reported COVID-19 cases and deaths, such that around 45 cases in a home county is associated with the same amount of time at home as a stay-at-home order. People responded to the risk of contracting COVID-19 and to policy orders, though the response to policy orders crowds out or displaces a large share of the voluntary response, suggesting that, during early stages of the U.S. outbreak, better compliance with social distancing recommendations could have been achieved with policy crafted to complement voluntary behavior. Significance StatementAmericans are spending substantially more time at home to reduce the spread of COVID-19. This behavioral shift is a mix of voluntary disease avoidance and policy-induced behavioral changes. Both need to be accounted for. Disentangling voluntary from policy-induced behavioral changes is critical for governments relaxing or renewing restrictions. A substantial share of the behavioral response appears to be voluntary, but this behavior was offset by strong stay-at-home orders. Local testing and rapid reporting is a first step to making better use of voluntary behavioral changes.

Influenza-Negative Influenza-Like Illness (fnILI) Z-Score as a Proxy for Incidence and Mortality of COVID-19

Though ideal for determining the burden of disease, SARS-CoV2 test shortages preclude its implementation as a robust surveillance system in the US. We correlated the use of the derivative influenza-negative influenza-like illness (fnILI) z-score from the CDC as a proxy for incident cases and disease-specific deaths. For every unit increase of fnILI z-score, the number of cases increased by 70.2 (95%CI[5.1,135.3]) and number of deaths increased by 2.1 (95%CI[1.0,3.2]). FnILI data may serve as an accurate outcome measurement to track the spread of the and allow for informed and timely decision-making on public health interventions.