Single-cell analysis of lung epithelial cells reveals age and cell population-specific responses to SARS-CoV-2 infection in ciliated cells (preprint)

The ability of SARS-CoV-2 to evade antiviral immune signaling in the airway contributes to the severity of COVID-19 disease. Additionally, COVID-19 is influenced by age and has more severe presentations in older individuals. This raises questions about innate immune signaling as a function of lung development and age. Therefore, we investigated the transcriptome of different cell populations of the airway epithelium using pediatric and adult lung tissue samples from the LungMAP Human Tissue Core Biorepository. Specifically, lung lobes were digested and cultured into a biomimetic model of the airway epithelium on an air-liquid interface. Cells were then infected with SARS-CoV-2 and subjected to single-cell RNA sequencing. Transcriptional profiling and differential expression analysis were carried out using Seurat. The clustering analysis identified several cell populations: club cells, proliferating epithelial cells, multiciliated precursor cells, ionocytes, and two biologically distinct clusters of ciliated cells (FOXJ1high and FOXJ1low). Interestingly, the two ciliated cell clusters showed different infection rates and enrichment of processes involved in ciliary biogenesis and function; we observed a cell-type-specific suppression of innate immunity in infected cells from the FOXJ1low subset. We also identified a significant number of genes that were differentially expressed in lung cells derived from children as compared to adults, suggesting the differential pathogenesis of SARS-CoV-2 infection in children versus adults. We discuss how this work can be used to identify drug targets to modulate molecular signaling cascades that mediate an innate immune response and begin to understand differences in COVID-19 outcomes for pediatric vs. adult populations.

Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine (preprint)

As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains the same mRNA backbone as the original BNT162b2 vaccine, modified by the incorporation of XBB.1.5-specific sequence changes in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation that adopts a flexible and predominantly open one-RBD-up state, with high affinity binding to the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and the phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose primary series in naive mice. Strong S-specific Th1 CD4+ and IFN{gamma}+ CD8+ T cell responses were also observed. These findings, together with prior experience with variant-adapted vaccine responses in preclinical and clinical studies, suggest that the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine is anticipated to confer protective immunity against dominant SARS-CoV-2 strains. ONE-SENTENCE SUMMARYThe monovalent Omicron XBB.1.5-adapted BNT162b2 mRNA vaccine encodes a prefusion-stabilized spike immunogen that elicits more potent neutralizing antibody responses against homologous XBB.1.5 and other circulating sublineage pseudoviruses compared to the bivalent Wild Type + Omicron BA.4/5 BNT162b2 vaccine, thus demonstrating the importance of annual strain changes to the COVID-19 vaccine.

mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting (preprint)

To address the limitations of whole-spike COVID vaccines, we explored mRNA vaccines encoding membrane-anchored receptor-binding domain (RBD-TMs), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail (CT) fragments of the SARS-CoV-2 spike protein. In naive mice, RBD-TM mRNA vaccines against ancestral SARS-CoV-2, Beta, Delta, Delta-plus, Kappa, Omicron BA.1 or BA.5, all induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays indicated broad neutralizing activity against a range of variant RBDs. In the setting of a heterologous boost, against the background of exposure to ancestral whole spike vaccines, sVNT studies suggested that RBD-TM vaccines were able to overcome the detrimental effects of immune imprinting. Omicron BA.1 and BA.5 RBD-TM booster vaccines induced serum antibodies with 12 and 22-fold higher neutralizing activity against the target RBD than their equivalent whole spike variants. Boosting with BA.1 or BA.5 RBD-TM provided good protection against more recent variants including XBB and XBB.1.5. Each RBD-TM mRNA is 28% of the length of its whole-spike equivalent. This advantage will enable tetravalent mRNA vaccines to be developed at well-tolerated doses of formulated mRNA.

KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution (preprint)

Testing was paramount in the management of the COVID-19 pandemic. Rapid deployment of new laboratories became widespread worldwide. Our university established KCL TEST: a SARS-CoV-2 asymptomatic testing programme that enabled sensitive and accessible PCR testing of SARS-CoV-2 RNA in saliva at 20 to 50% the price of commercial kits. We performed 158,277 PCRs in saliva for staff, students and their household contacts of Kings College London, free of charge and with an average turnaround time of 8 hours. Our pipeline is mainly made of open-source automation and non-commercial reagents and has been recently recommended for ISO15189 accreditation. Here we provide our blueprint and results to enable the rapid launch of diagnostic laboratories where and when needed. Our data span over 18 months and parallels that of the UK Office for National Statistics, with a lower positive rate and virtually no delta wave. Our observations strongly support regular asymptomatic community testing to decrease outbreaks and provide safe working spaces. KCL TEST demonstrates that universities can provide agile, resilient and accurate testing that reflects the infection rate and trend of the general population. We call for the integration of academic institutions in pandemic preparedness, with capabilities to rapidly deploy highly skilled staff, as well as develop, test and accommodate efficient low-cost pipelines.

Household conditions, COVID-19, and equity: Insight from two nationally representative surveys (preprint)

Background: With people across the United States spending increased time at home since the emergence of COVID-19, housing characteristics may have an even greater impact on health. Therefore, we assessed associations between household conditions and COVID-19 experiences. Methods: We used data from two nationally representative surveys: the Tufts Equity Study (TES; n = 1449 in 2021; n = 1831 in 2022) and the Household Pulse Survey (HPS; n = 147,380 in 2021; n = 62,826 in 2022). In the TES, housing conditions were characterized by heating/cooling methods; smoking inside the home; visible water damage/mold; age of housing unit; and self-reported concern about various environmental factors. In TES and HPS, household size was assessed. Accounting for sampling weights, we examined associations between each housing exposure and COVID-19 outcomes (diagnosis, vaccination) using separate logistic regression models with covariates selected based on an evidence-based directed acyclic graph. Results: Having had COVID-19 was more likely among people who reported poor physical housing condition (odds ratio [OR] = 2.32; 95% confidence interval [CI] = 1.17-4.59; 2021), visible water damage or mold/musty smells (OR = 1.50; 95% CI = 1.10-2.03; 2022), and larger household size (5+ versus 1-2 people; OR = 1.53, 95% CI = 1.34-1.75, HPS 2022). COVID-19 vaccination was less likely among participants who reported smoke exposure inside the home (OR = 0.53; 95% CI = 0.31-0.90; 2022), poor water quality (OR = 0.42; 95% CI = 0.21-0.85; 2021), noise from industrial activity/construction (OR = 0.44; 95% CI = 0.19-0.99; 2022), and larger household size (OR = 0.57; 95% CI = 0.46-0.71; HPS 2022). Vaccination was also positively associated with poor indoor air quality (OR = 1.96; 95% CI = 1.02-3.72; 2022) and poor physical housing condition (OR = 2.27; 95% CI = 1.01-5.13; 2022). Certain heating/cooling sources were associated with COVID-19 outcomes. Conclusions: Our study found poor housing conditions associated with increased COVID-19 burden, which may be driven by systemic disparities in housing, healthcare, and financial access to resources during the COVID-19 pandemic.

Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential (preprint)

Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.

A human primary airway microphysiological system infected with SARS-CoV-2 distinguishes the treatment efficacy between nirmatrelvir and repurposed compounds fluvoxamine and amodiaquine (preprint)

The COVID-19 pandemic necessitated a rapid mobilization of resources toward the development of safe and efficacious vaccines and therapeutics. Finding effective treatments to stem the wave of infected individuals needing hospitalization and reduce the risk of adverse events was paramount. For scientists and healthcare professionals addressing this challenge, the need to rapidly identify medical countermeasures became urgent, and many compounds in clinical use for other indications were repurposed for COVID-19 clinical trials after preliminary preclinical data demonstrated antiviral activity against SARS-CoV-2. Two repurposed compounds, fluvoxamine and amodiaquine, showed efficacy in reducing SARS-CoV-2 viral loads in preclinical experiments, but ultimately failed in clinical trials, highlighting the need for improved predictive preclinical tools that can be rapidly deployed for events such as pandemic emerging infectious diseases. The PREDICT96-ALI platform is a high-throughput, high-fidelity microphysiological system (MPS) that recapitulates primary human tracheobronchial tissue and supports highly robust and reproducible viral titers of SARS-CoV-2 variants Delta and Omicron. When amodiaquine and fluvoxamine were tested in PREDICT96-ALI, neither compound demonstrated an antiviral response, consistent with clinical outcomes and in contrast with prior reports assessing the efficacy of these compounds in other human cell-based in vitro platforms. These results highlight the unique prognostic capability of the PREDICT96-ALI proximal airway MPS to assess the potential antiviral response of lead compounds.

Impact of COVID-19 Pandemic on Beach Tourism in India

COVID-19 Pandemic has a profound Impact on the Indian tourism sector, especially on beach tourism. Research shows significant changes in the pattern of the ecological terrain of coastal areas and on the community dependent on tourism business and marine life, due to the imposition of lockdown for several months. The paper discusses the change in behavioral patterns of people during Pre and Post COVID-19 for visiting any beach destination in near future in terms of preferences in accommodation, selection of beaches based on crowd and other factors that will be considered in post pandemic days. This study brings out various key indicators shaping the pattern of beach holidays in the future based on the survey conducted among tourists belonging to youth population. The survey considered the tourists preferences of visits and factors they would look upon to choose beach holidaying in the Post COVID-19 years. The influence of the pandemic on quality of beaches, visitors'willingness to visit beaches in future, Post Pandemic opportunities and strategies of destinations for shaping tourism further have also been examined. ©Copyright IJHTS.

Impact of the COVID-19 Pandemic Hiatus From Sports Activities on Injuries Observed Among Division I NCAA Athletes.

Background: The coronavirus disease 2019 (COVID-19) pandemic significantly disrupted athletic activities, including those in the Pacific 12 (Pac-12) Conference of the National Collegiate Athletic Association. It is currently unknown how the disruption in training and competition impacted athletes' risk of injury upon resumption of activities. Purpose: To describe and compare the rate, timing, mechanism, and severity of injuries among collegiate athletes across multiple sports in the Pac-12 Conference before and after the COVID-19 pandemic-associated hiatus of intercollegiate athletic activities. Study Design: Descriptive epidemiology study. Methods: Descriptive and injury data among intercollegiate athletes from both the season before the hiatus and the season after the hiatus were acquired from the Pac-12 Health Analytics Program database. Injury elements (timing of injury onset, injury severity, mechanism, recurrence, outcome, need for procedural intervention, and event segment during which the injury took place) were compared by time using the chi-square test and a multivariate logistic regression model. Subgroup analyses were performed on knee and shoulder injuries among athletes participating in sports with traditionally high rates of knee and shoulder injuries. Results: A total of 12,319 sports-related injuries across 23 sports were identified, with 7869 pre-hiatus injuries and 4450 post-hiatus injuries. There was no difference in the overall incidence of injury between the pre-hiatus and post-hiatus seasons. However, the proportion of noncontact injuries was higher in the post-hiatus season for football, baseball, and softball players, and the proportion of nonacute injuries in the post-hiatus season was higher among football, basketball, and rowing athletes. Finally, the overall proportion of injuries sustained by football players in the final 25% of competition or practice was higher in the post-hiatus season. Conclusion: Athletes competing in the post-hiatus season were observed to have higher rates of noncontact injuries and injuries sustained in the final 25% of competition. This study demonstrates that the COVID-19 pandemic has had varied effects on athletes from different sports, suggesting that many factors must be considered when designing return-to-sports programs for athletes after an extended absence from organized training.

Agent-based modeling of the COVID-19 pandemic in Florida (preprint)

The onset of the COVID-19 pandemic drove a widespread, often uncoordinated effort by research groups to develop mathematical models of SARS-CoV-2 to study its spread and inform control efforts. The urgent demand for insight at the outset of the pandemic meant early models were typically either simple or repurposed from existing research agendas. Our group predominantly uses agent-based models (ABMs) to study fine-scale intervention scenarios. These high-resolution models are large, complex, require extensive empirical data, and are often more detailed than strictly necessary for answering qualitative questions like "Should we lockdown?" During the early stages of an extraordinary infectious disease crisis, particularly before clear empirical evidence is available, simpler models are more appropriate. As more detailed empirical evidence becomes available, however, and policy decisions become more nuanced and complex, fine-scale approaches like ours become more useful. In this manuscript, we discuss how our group navigated this transition as we modeled the pandemic. The role of modelers often included nearly real-time analysis, and the massive undertaking of adapting our tools quickly. We were often playing catch up with a firehose of evidence, while simultaneously struggling to do both academic research and real-time decision support, under conditions conducive to neither. By reflecting on our experiences of responding to the pandemic and what we learned from these challenges, we can better prepare for future demands.

Implementation of Uniform Processes of Care Across an Academic Health System During the Initial COVID-19 Pandemic Surge and Their Association with Outcomes. (preprint)

IntroductionDisparities in care delivery and outcomes are common in healthcare in the United States. The SARS-CoV-2 pandemic in the spring of 2020 in the United States and around the world resulted in a surge in the need for acute and critical care services for patient with acute respiratory disease. Many individual hospitals and health systems were unprepared for this surge of patients with a novel and acute respiratory disease which may have exacerbated pre-existing disparities. To prepare for this challenge the Yale New Haven Health System developed a response to the SARS-CoV-2 pandemic in 2020 which was multifactorial including: 1) Implementation of a uniform COVID management protocol across the care continuum, 2) Precise criteria for hospital and Intensive Care Unit (ICU) and Stepdown Unit (SDU) admission, 3) Augmented ICU and SDU bed availability, 4) Implemented load balancing across the entire health system. To understand the impact of these interventions we reviewed and compared mortality across the Yale-New Haven Health System both between hospitals and to national data. We also analyzed administration of medications to understand local adherence to the COVID-19 management protocol implemented during the initial wave of the pandemic. MethodsThis investigation is an observational, retrospective study of 3,112 patients infected with SARS-CoV-2 during the first wave of the pandemic in southern Connecticut and Rhode Island. All COVID-19 admissions to the Yale New Have Health System from March through June of 2020 were included. Patients all received care at a hospital within the Yale New Haven Health System which has 2693 beds across 7 campuses in southern Connecticut and Rhode Island. The primary outcome was in-hospital mortality for patients with COVID-19. Demographics were extracted as well as specific data associated with process of care including timing of administration of Tocilizumab, aspirin, and corticosteroids. Transfers between hospitals within the health system were identified. Mortality rates were compared between the central tertiary care hospital and the smaller community and community teaching hospitals using logistic regression to adjust for patient factors. ResultsAnalysis of process of care metrics including time to Tocilizumab, aspirin, and corticosteroids shows adherence of recommended processes of care across Yale New Haven Health System. The overall mortality rate of 15.9% was lower than published national comparators. Hospital mortality rates compared between the central tertiary care center and smaller hospitals within the system were similar when adjusted for multiple patient factors including race and ethnicity. ConclusionsIn this investigation of COVID-19 outcomes in an academic health system with geographic and social diversity, we find that the observed low mortality rate was consistent across the health system. We propose that this is in part related to consistency of care and structural factors such as load balancing. We believe that these findings highlight the potential value of implementing uniform processes designed to reduce noise and bias in clinical judgment.

Increased Levels of Inflammatory and Endothelial Biomarkers in Blood of Long COVID Patients Point to Thrombotic Endothelialitis.

The prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of von Willebrand factor (VWF), platelet factor 4 (PF4), serum amyloid A (SAA), α-2 antiplasmin (α-2AP), endothelial-leukocyte adhesion molecule 1 (E-selectin), and platelet endothelial cell adhesion molecule (PECAM-1) in the soluble part of the blood. It was noteworthy that the mean level of α-2 antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We conclude that presence of microclotting, together with relatively high levels of six biomarkers known to be key drivers of endothelial and clotting pathology, points to thrombotic endothelialitis as a key pathological process in Long COVID.

High-Performance Graphene-Modified Sensing Chip for SARS-CoV-2 Detection.

This sensing prototype model involves the development of a reusable, twofold graphene oxide (GrO)-glazed double inter-digitated capacitive (DIDC) detecting chip for detecting severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) specifically and rapidly. The fabricated DIDC comprises a Ti/Pt-containing glass substrate glazed with graphene oxide (GrO), which is further chemically modified with EDC-NHS to immobilize antibodies (Abs) hostile to SARS-CoV-2 based on the spike (S1) protein of the virus. The results of insightful investigations showed that GrO gave an ideal engineered surface for Ab immobilization and enhanced the capacitance to allow higher sensitivity and low sensing limits. These tunable elements helped accomplish a wide sensing range (1.0 mg/mL to 1.0 fg/mL), a minimum sensing limit of 1 fg/mL, high responsiveness and good linearity of 18.56 nF/g, and a fast reaction time of 3 s. Besides, in terms of developing financially viable point-of-care (POC) testing frameworks, the reusability of the GrO-DIDC biochip in this study is good. Significantly, the biochip is specific against blood-borne antigens and is stable for up to 10 days at 5 °C. Due to its compactness, this scaled-down biosensor has the potential for POC diagnostics of COVID-19 infection. This system can also detect other severe viral diseases, although an approval step utilizing other virus examples is under development.

COVID-19 and the Indian economy: The debate about a wage-led recovery

The COVID-19 pandemic has triggered multiple crises-of health, economy, and livelihoods-in India. The restoration of at least a part of the incomes lost by the overwhelmingly informal workforce in the country during the lockdown period should have been a priority for the government. However, the stimulus packages announced by the government have been inadequate, especially given the magnitude of the employment and livelihood crisis. Some of the policies taken in the wake of the crisis, such as the approval to increase daily working hours to twelve, have led to a weakening of labour's position vis-a-vis capital. Rather than boosting economic growth, such measures will only worsen the deficiency in aggregate demand and prolong the recession. India's policy-makers should reconsider the faith they have put in neoclassical economic ideas, which have slowed down employment growth and left millions of people with little access to basic health or education facilities. The pandemic should be an opportunity to build in India an effective and publicly provided social security system as well as rural infrastructure and research institutions. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

When preemptive risk mitigation is insufficient: The effectiveness of continuity and resilience techniques during COVID‐19

The extreme demand volatility caused by corona virus 2019 (COVID‐19) overwhelmed most preemptive measures enacted by firms to mitigate disruptions in their supply chains. This led to the rapid implementation of reactive measures to provide business continuity. The operations and supply chain management literature has grouped these reactive techniques into those that involve the reconfiguration of firm resources and those that involve changes to its decision‐making processes. Unfortunately, little of this work has empirically assessed the efficacy of individual reactive techniques on business continuity after the onset of a disruption such as COVID‐19. The research reported in this paper addresses this gap through an experimental design and discrete‐event simulation to empirically test the impact on firm outcomes of resource reconfiguration techniques versus those related to adaptive decision‐making processes. Data from a canned foods manufacturer is used to populate the simulation and isolate the impact of these reactive changes implemented in March 2020 at the beginning of the COVID‐19 disruption on the attainment of business continuity in the 3 months following the COVID‐19 disruption. The results show that for this company, decision‐making changes—specifically changes to planning process cadence and time horizon—had more impact on business continuity than those focused on resource reconfiguration (increasing capacity through stock keeping unit (SKU) prioritization and increasing the number of shifts). These results, in addition to qualitative data collected from company executives to provide context for the modeling results, are used to provide insights that are generalizable to many firms.

Disparities in Access to Unemployment Insurance During the COVID-19 Pandemic: Lessons from U.S. and California Claims Data

To what extent did jobless Americans benefit from unemployment insurance (UI) during the COVID-19 pandemic? This article documents geographic disparities in access to UI during 2020. We leverage aggregated and individual-level claims data to perform an integrated analysis across four measures of access to UI. In addition to the traditional UI recipiency rate, we construct rates of application among the unemployed, rates of first payment among applicants, and exhaustion rates among paid claimants. Through correlations across California counties and across states, we show that areas with more disadvantaged residents had less access to UI during the pandemic. Although these disparities are large in magnitude, cross-state analysis suggests that policy can play a salient role in mitigating them.

Design of effective outpatient sentinel surveillance for COVID-19 decision-making: a modeling study.

BACKGROUND: Decision-makers impose COVID-19 mitigations based on public health indicators such as reported cases, which are sensitive to fluctuations in supply and demand for diagnostic testing, and hospital admissions, which lag infections by up to two weeks. Imposing mitigations too early has unnecessary economic costs while imposing too late leads to uncontrolled epidemics with unnecessary cases and deaths. Sentinel surveillance of recently-symptomatic individuals in outpatient testing sites may overcome biases and lags in conventional indicators, but the minimal outpatient sentinel surveillance system needed for reliable trend estimation remains unknown. METHODS: We used a stochastic, compartmental transmission model to evaluate the performance of various surveillance indicators at reliably triggering an alarm in response to, but not before, a step increase in transmission of SARS-CoV-2. The surveillance indicators included hospital admissions, hospital occupancy, and sentinel cases with varying levels of sampling effort capturing 5, 10, 20, 50, or 100% of incident mild cases. We tested 3 levels of transmission increase, 3 population sizes, and conditions of either simultaneous transmission increase or lagged increase in the older population. We compared the indicators' performance at triggering alarm soon after, but not prior, to the transmission increase. RESULTS: Compared to surveillance based on hospital admissions, outpatient sentinel surveillance that captured at least 20% of incident mild cases could trigger an alarm 2 to 5 days earlier for a mild increase in transmission and 6 days earlier for a moderate or strong increase. Sentinel surveillance triggered fewer false alarms and averted more deaths per day spent in mitigation. When transmission increase in older populations lagged the increase in younger populations by 14 days, sentinel surveillance extended its lead time over hospital admissions by an additional 2 days. CONCLUSIONS: Sentinel surveillance of mild symptomatic cases can provide more timely and reliable information on changes in transmission to inform decision-makers in an epidemic like COVID-19.

SARS-CoV-2 infection and recovery in children: Distinct T cell responses in MIS-C compared to COVID-19.

SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.

Effects of the COVID-19 Pandemic on the Trauma Population in a Level 1 Trauma Center.

In this study, we evaluated the effects of the pandemic on our trauma population. We performed a retrospective review of the trauma registry in the 2 years prior, and then 2 years during the pandemic. We evaluated age, race, gender, injury severity score (ISS), mechanism of trauma, rate of self-inflicted injury, rate of gunshot wounds (GSW), presence of EtOH, drug screen results, mortality, rate of burn traumas, and zip code of residence. Our query captured 5 054 patients before, and 5 731 during the pandemic. We found no statistical difference in age, gender, mechanism of trauma, rate of self-inflicted injuries, and mortality during the pandemic when compared to before. There were statistically significant differences in race, ISS, rate of GSWs, EtOH use, drug screen results, and burn traumas. Geospatial mapping found a rise in GSWs for zip code 36606. Gun violence and substance use rose in our trauma population during COVID-19.

Environmental equity and COVID-19 experiences in the United States: Results from three survey waves of a nationally representative study conducted between 2020-2022 (preprint)

Certain environmental exposures, such as air pollution, are associated with COVID-19 incidence and mortality. To determine whether environmental context is associated with other COVID-19 experiences, we used data from the nationally representative Tufts Equity in Health, Wealth, and Civic Engagement Study data (n=1785; three survey waves 2020-2022). Environmental context was assessed using self-reported climate stress and county-level air pollution, greenness, toxic release inventory site, and heatwave data. Self-reported COVID-19 experiences included willingness to vaccinate against COVID-19, health impacts from COVID-19, receiving assistance for COVID-19, and provisioning assistance for COVID-19. Self-reported climate stress in 2020 or 2021 was associated with increased COVID-19 vaccination willingness by 2022 (odds ratio [OR] = 2.35; 95% confidence interval [CI] = 1.47, 3.76), even after adjusting for political affiliation (OR = 1.79; 95% CI = 1.09, 2.93). Self-reported climate stress in 2020 was also associated with increased likelihood of receiving COVID-19 assistance by 2021 (OR = 1.89; 95% CI = 1.29, 2.78). County-level exposures (i.e., less greenness, more toxic release inventory sites, more heatwaves) were associated with increased vaccination willingness. Air pollution exposure in 2020 was positively associated with likelihood of provisioning COVID-19 assistance in 2020 (OR = 1.16 per ug/m3; 95% CI = 1.02, 1.32). Associations between certain environmental exposures and certain COVID-19 outcomes were stronger among those who identify as a race/ethnicity other than non-Hispanic White and among those who reported experiencing discrimination; however, these trends were not consistent. A latent variable representing a summary construct for environmental context was associated with COVID-19 vaccination willingness. Our results add to the growing body of literature suggesting that intersectional equity issues affecting likelihood of exposure to adverse environmental conditions are also associated with health-related outcomes.