Comparative analysis of temporal variation of heavy metal accumulation by two sea urchin species from a harbour region, including pre and post COVID 19 lock down period.

Sea urchins are marine invertebrates belonging to phylum Echinodermata, recognized as relevant biological tool for assessing environmental pollution. In the present study, we assessed the bioaccumulation potential of different heavy metals by two sea urchin species, Stomopneustes variolaris Lamarck, 1816 and Echinothrix diadema Linnaeus, 1758, collected from a harbour region, along the south west coast of India, during four different sampling periods for 2 years, from the same sea urchin bed. Heavy metals like Pb, Cr, As, Cd, Co, Se, Cu, Zn, Mn and Ni were analysed from water, sediment and different body parts of sea urchins, such as shell, spine, tooth, gut and gonad. The sampling periods also included the pre and post COVID 19 lockdown period during which the harbour activities were closed. The bio-water accumulation factor (BWAF), bio-sediment accumulation factor (BSAF) and the metal content/test weight index (MTWI) were calculated, in order to compare the bioaccumulation of metals by both the species. The results showed that S. variolaris had higher bioaccumulation potential than E. diadema, for metals like Pb, As, Cr, Co and Cd especially in the soft body parts like gut and gonad. The hard parts of S. variolaris like shell, spine, and tooth also accumulated more Pb, Cu, Ni and Mn than E. diadema. Following the lockdown period, there was a decline in the concentration of all heavy metals in water, whereas in sediment, Pb, Cr, and Cu levels were reduced. The gut and gonad tissues of both the urchins showed a decrease in the concentration of most of the heavy metals following the lockdown phase and no significant reduction was observed in the hard parts. This study reveals the use of S. variolaris as an excellent bioindicator of heavy metal contamination in the marine environment which can be employed for coastal monitoring programs.

The concentrations of essential/toxic elements in serum of COVID-19 patients are not directly related to the severity of the disease.

BACKGROUND: In recent months, the current COVID-19 pandemic has generated thousands of studies directly or indirectly related with this disease and/or the coronavirus SARS-CoV-2 causing the infection. On August 22, 2022, the database PUBMED included 287,639 publications containing the term COVID-19. However, in spite of the importance of trace elements in human health, including the immune system, data on the levels of metals/metalloids in COVID-19 patients is very limited. METHODS: The concentrations of As, Cd, Cr, Cu, Hg, Fe, Mg, Mn, Pb, Se, V and Zn were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in 126 serum samples of individuals infected with SARS-CoV-2, as well as in 88 samples of non-infected individuals. Participants were divided into four groups: i) individuals COVID-19 positive (COVID-19 +) with an asymptomatic infection course; ii) individuals suffering mild COVID-19; iii) individuals suffering severe COVID-19, and iv) individuals COVID-19 negative (COVID-19-) (control group). The occurrence of the analyzed metals/metalloids was evaluated along with the biochemical profile, including blood cell counts, lipids, proteins and crucial enzymes. RESULTS: Serum levels of Mg, V, Cr, Cu, Cd, and Pb were higher in COVID-19 positive patients than those in the control group. Although no significant differences were observed between the different groups of patients, the concentrations of Cd, Pb, V and Zn showed a tendency to be higher in individuals with severe COVID-19 than in those showing mild symptoms or being asymptomatic. Arsenic and Hg were rarely detected, regardless if the subjects were infected by SARS-CoV-2, or not. The current results did not show significant differences in the levels of the rest of analyzed elements according to the severity of the disease (asymptomatic, mild and severe). CONCLUSIONS: In spite of the results here obtained, we highlight the need to reduce the exposure to Cd, Pb and V to minimize the potential adverse health outcomes after COVID-19 infection. On the other hand, although a protective role of essential elements was not found, Mg and Cu concentrations were higher in severe COVID-19 patients than in non-infected individuals.

Potentially toxic elements (PTEs) in Gomti-Ganga Alluvial Plain, associated human health risks assessment and potential remediation using novel-nanomaterials.

The health risks associated with consumption of water from river Gomti polluted with potentially toxic elements (PTEs), including As, Fe, Pb, Cd, Mn, Cr, Ni, and Hg were investigated at the initiation of unlocking of COVID-19 lockdown and compared with pre-COVID-19 lockdown status. In the current investigation, the total hazard index (THI) values exceeded the acceptable limit of "unity" at all sampling stations. The use of river water for drinking and domestic purposes by millions of people with high THI values has emerged as a matter of huge concern. The individual hazard quotients associated with Cd and Pb were found to be most severe (> 1). A vivid difference between the THI values during the two study phases indicated the positive impact of COVID-19 lockdown signifying the prominent impact of anthropogenic activities on the PTE concentrations. The closure of local manufacturing units (textile, battery, etc.) emerged as a potential reason for decreased health risks associated with PTE levels. The higher susceptibility of children to health risks in comparison with adults through the values of THI and HQs was interpreted across the study area. Potential remedial measures for PTE contamination have also been suggested in the study.

The Potential Utility of Lead Compound, E18, in Inhibiting Docking of SARS-CoV-2 by inhibiting ACE2-B0AT1 Complex.

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Effect of the COVID-19 Global Pandemic on Illinois Children Tested for Blood Lead Level and Exposure.

Objectives. To determine whether the number of children tested for lead exposure and the number of case rates increased (rate ratio [RR] > 1), decreased (RR < 1), or remained stable (RR = 1) during COVID-19 pandemic year 2020 compared with prepandemic year 2019. Methods. We analyzed more than 415 000 children's records reported to the Illinois Department of Public Health in 2019 and 2020 by demographic characteristics. The testing rate was the number of children tested yearly per population. The case rate was the proportion of children whose yearly tests showed a blood lead level of 5 or more micrograms per deciliter. RR was the 2020 case rate divided by the 2019 case rate. Results. In 2020, 19.6% of children were tested for lead compared with 25.5% in 2019. Testing decreased in 97% of counties. The 24% decreased testing in 2020 was notably in African Americans (36.4% decrease), high-risk zip codes (29.8% decrease), and rural counties (26.9% decrease). Case rates increased in rural counties, high-risk zip codes, Whites, and Hispanics. Conclusions. During pandemic year 2020, the number of children tested for lead decreased by 24%, and case rates increased in 51% of counties. Public Health Implications. Redesignation of high-risk zip codes is recommended to increase the testing of at-risk populations. (Am J Public Health. 2023;113(1):89-95. https://doi.org/10.2105/AJPH.2022.307109).

Immune Responses to COVID-19 Vaccines in Patients with Chronic Kidney Disease and Lead Exposure.

Literature data regarding the response rate to COVID-19 vaccination in chronic kidney disease (CKD) patients remain inconclusive. Furthermore, studies have reported a relationship between lead exposure and susceptibility to viral infections. This study examined immune responses to COVID-19 vaccines in patients with CKD and lead exposure. Between October and December 2021, 50 lead-exposed CKD patients received two doses of vaccination against COVID-19 at Chang Gung Memorial Hospital. Patients were stratified into two groups based on the median blood lead level (BLL): upper (≥1.30 µg/dL, n = 24) and lower (<1.30 µg/dL, n = 26) 50th percentile. The patients were aged 65.9 ± 11.8 years. CKD stages 1, 2, 3, 4 and 5 accounted for 26.0%, 20.0%, 22.0%, 8.0% and 24.0% of the patients, respectively. Patients in the lower 50th percentile of BLL had a lower proportion of CKD stage 5 than patients in the upper 50th percentile BLL group (p = 0.047). The patients in the lower 50th percentile BLL group also received a higher proportion of messenger RNA vaccines and a lower proportion of adenovirus-vectored vaccines than the patients in the upper 50th percentile BLL group (p = 0.031). Notably, the neutralizing antibody titers were higher in the lower 50th percentile than in the upper 50th percentile BLL group. Furthermore, the circulating levels of granulocyte-colony stimulating factor, interleukin-8, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α were higher in the upper 50th percentile than in the lower 50th percentile BLL group. Therefore, it was concluded that lead-exposed CKD patients are characterized by an impaired immune response to COVID-19 vaccination with diminished neutralizing antibodies and augmented inflammatory reactions.

Theorizing on neo public assistance: How do race and class impact resource uptake and behavior following disaster?

The consequences of environmental disasters and other ecologic and communal crises are frequently worst in racially/ethnically minoritized and low-income populations relative to other groups. This disproportionality may create or deepen patterns of governmental distrust and stoke health promotion disengagement in these groups. To date, there has been limited contextualization of how historically disenfranchised populations utilize government-administered or facilitated resources following such disasters. Focusing on the water crisis in Flint, Michigan, we examine and theorize on the usage of neo public assistance, free risk reduction resources that are provided to disaster survivors as a liminal means of redressing ills created and/or insufficiently mitigated by the state. We surveyed 331 Flint residents, evaluating their usage of four neo public assistance resources following the FWC, finding low to moderate uptake: 131 residents (39.6%) indicated that they obtained blood lead level (BLL) screenings, 216 (65.3%) had their tap water tested for lead (Pb) and other contaminants, 137 (41.4%) had their home water infrastructure replaced, and 293 (88.5%) had acquired bottled water at community distribution sites. Unemployment, receiving public benefits, and lacking reliable transportation and stable housing were associated with lower uptake of some resources. Compared to White and "Other" race individuals, Black residents were generally more likely to acquire/utilize these resources, suggesting heightened concerns and health promotion proclivities even in the face of observed macro and individual-level challenges. Potential reasons and implications are discussed.

An Innovative Approach to Increase Lead Testing by Pediatricians in Children, United States, 2019-2021.

Opportunities for lead exposure are common in the United States. The American Academy of Pediatrics, in collaboration with the Centers for Disease Control and Prevention, launched the Increasing Capacity for Blood Lead Testing Extension for Community Healthcare Outcomes (ECHO) project to educate pediatricians on the importance of testing children for lead exposure and to assess practice behavior change. We found that two weeks to one month after receiving training, more than 80% of participants reported increased lead testing and practice changes. Our results support use of the ECHO model as a mechanism for practice change. (Am J Public Health. 2022;112(S7):S647-S650. https://doi.org/10.2105/AJPH.2022.307084).

Incorporating field-based research into remote learning: An assessment of soil lead pollution in different land-use types in Los Angeles.

A research-based course was developed to investigate the legacy of soil lead (Pb) pollution in Los Angeles, California. During the course, undergraduate and graduate students collected a total of 270 soil samples for analyses of metal (loid) concentrations in different land-use types (residential, park, and school). Residential soils had significantly higher Pb concentrations than other land uses (p < 0.01) exceeding the California recommended safety level for soil Pb (80 mg/kg) at the highest frequency (64% of samples), followed by schools (42%) and parks (6.0%). Soil Pb from all 87 census block groups was correlated with battery recycling plant and railroad proximity as geospatial indicators of childhood Pb exposure risk. Meanwhile, census block groups with higher Pb levels were correlated with higher percentages of the following population: those without health insurance, without college degrees, with a lower median household income and income below the poverty line, and ethnic and racial minorities (r = -0.46 to 0.59, p < 0.05). Principal component regression models significantly improved soil Pb estimation over correlation analysis by incorporating sociodemographic, economic, and geospatial risk factors for Pb exposure (R2 = 0.58, p < 0.05). This work provides new insights into how topsoil Pb prevails in various land-use types and their co-occurring sociodemographic, economic, and geospatial risk factors, indicating the need for multi-scalar assessment across urban land uses.

Comparison of concentrations of chemical species and emission sources PM2.5 before pandemic and during pandemic in Krakow, Poland.

Observations of air pollution in Krakow have shown that air quality has been improved during the last decade. In the presented study two factors affecting the physicochemical characteristic of PM2.5 fraction at AGH station in Krakow were observed. One is the ban of using solid fuels for heating purposes and the second is COVID-19 pandemic in Krakow. The PM2.5 fraction was collected during the whole year every 3rd day between 2nd March 2020 and 28th February 2021 at AGH station in Krakow. In total 110 PM2.5 fraction samples were collected. The chemical composition was determined for these samples. The elemental analysis was performed by energy dispersive X-ray fluorescence (EDXRF) technique, ions analysis was performed by ion chromatography (IC) and black carbon by optical method. In order to identify the emission sources the positive matrix factorization (PMF) was used. The results of such study were compared to similar analysis performed for PM2.5 for the period from June 2018 to May 2019 at AGH station in Krakow. The PM2.5 concentration dropped by 25% in 2020/2021 in comparison to 2018/2019 at this station. The concentrations of Si, K, Fe, Zn and Pb were lowering by 43-64% in the year 2020/2021 in comparison to 2018/2019. Cu, Mn, Zn and Pb come from mechanical abrasion of brakes and tires while Ti, Fe, Mn and Si are crustal species. They are the indicators of road dust (non-exhaust traffic source). Moreover, the annual average contribution of traffic/industrial/soil/construction work source was reduced in 2020/2021 in comparison to 2018/2019. As well the annual average contribution of fuels combustion was declining by 22% in 2020/2021 in comparison to 2018/2019. This study shows that the ban and lockdown, during COVID-19 pandemic, had significant impact on the characteristic of air pollution in Krakow.

Does normalization of SARS-CoV-2 concentrations by Pepper Mild Mottle Virus improve correlations and lead time between wastewater surveillance and clinical data in Alberta (Canada): comparing twelve SARS-CoV-2 normalization approaches.

Wastewater-based surveillance (WBS) data normalization is an analyte measurement correction that addresses variations resulting from dilution of fecal discharge by non-sanitary sewage, stormwater or groundwater infiltration. No consensus exists on what WBS normalization parameters result in the strongest correlations and lead time between SARS-CoV-2 WBS data and COVID-19 cases. This study compared flow, population size and biomarker normalization impacts on the correlations and lead times for ten communities in twelve sewersheds in Alberta (Canada) between September 2020 and October 2021 (n = 1024) to determine if normalization by Pepper Mild Mottle Virus (PMMoV) provides any advantages compared to other normalization parameters (e.g., flow, reported and dynamic population sizes, BOD, TSS, NH3, TP). PMMoV concentrations (GC/mL) corresponded with plant influent flows and were highest in the urban centres. SARS-CoV-2 target genes E, N1 and N2 were all negatively associated with wastewater influent pH, while PMMoV was positively associated with temperature. Pooled data analysis showed that normalization increased ρ-values by almost 0.1 and was highest for ammonia, TKN and TP followed by PMMoV. Normalization by other parameters weakened associations. None of the differences were statistically significant. Site-specific correlations showed that normalization of SARS-CoV-2 data by PMMoV only improved correlations significantly in two of the twelve systems; neither were large sewersheds or combined sewer systems. In five systems, normalization by traditional wastewater strength parameters and dynamic population estimates improved correlations. Lead time ranged between 1 and 4 days in both pooled and site-specific comparisons. We recommend that WBS researchers and health departments: a) Investigate WWTP influent properties (e.g., pH) in the WBS planning phase and use at least two parallel approaches for normalization only if shown to provide value; b) Explore normalization by wastewater strength parameters and dynamic population size estimates further; and c) Evaluate purchasing an influent flow meter in small communities to support long-term WBS efforts and WWTP management.

Kinetic Characterization of Cerium and Gallium Ions as Inhibitors of Cysteine Cathepsins L, K, and S.

Heavy metal ions can disrupt biological functions via multiple molecular mechanisms, including inhibition of enzymes. We investigate the interactions of human papain-like cysteine endopeptidases cathepsins L, K, and S with gallium and cerium ions, which are associated with medical applications. We compare these results with zinc and lead, which are known to inhibit thiol enzymes. We show that Ga3+, Ce3+, and Ce4+ ions inhibit all tested peptidases with inhibition constants in the low micromolar range (between 0.5 µM and 10 µM) which is comparable to Zn2+ ions, whereas inhibition constants of Pb2+ ions are one order of magnitude higher (30 µM to 150 µM). All tested ions are linear specific inhibitors of cathepsin L, but cathepsins K and S are inhibited by Ga3+, Ce3+, and Ce4+ ions via hyperbolic inhibition mechanisms. This indicates a mode of interaction different from that of Zn2+ and Pb2+ ions, which act as linear specific inhibitors of all peptidases. All ions also inhibit the degradation of insoluble elastin, which is a common target of these peptidases in various inflammatory diseases. Our results suggest that these ions and their compounds have the potential to be used as cysteine cathepsin inhibitors in vitro and possibly in vivo.

How long-term metal and lead exposure among foundry workers affect COVID-19 infection outcomes in Jordan.

Foundry workers face a number of occupational health hazards, which may lead to an increased risk of respiratory disease, cancer, and anxiety level and are associated with endocrine, hematologic, renal, and neurological problems in humans. This study aims to evaluated thyroid functions, glutathione level, and the risk of infection with SARS-CoV-2 after vaccinated (two doses of the BNT162b2 mRNA COVID-19 vaccine) foundry workers in Jordan. We examined the efficacy BNT162b2 vaccine by calculating the rate of mortality and the degree of severity from mild to severe respiratory infections in 105 adult males foundry workers occupationally exposed to metals and Pb who had been received two doses, 21 days apart, of the BNT162b2 vaccine. Seventy-five male subjects not exposed to the Pb and who received two shots of the BNT162b2 vaccine (Pfizer-BioNTech) served as the control group. In foundry workers who were infected with COVID-19, the mortality rate (0%) was similar as in the control group (0%), and increased transmission of infection with SARS-CoV-2; the non-hospitalized infections increased nearly 3.4-times and hospitalized infections increased 4.29-times among people exposed to lead and metal contamination compared to the healthy persons control group. Also, among the foundry workers, the blood lead, FT3, and FT4 levels were significantly higher (p < 0.0001) and the levels of glutathione and TSH were significantly decreased (p < 0.0001) compared with the control group. In conclusion, long-term exposure to Pb is associated with a risk of infection with COVID-19 despite the 2 doses of the BNT162b2 vaccine (Pfizer-BioNTech). Also, exposure to Pb is associated with hyperthyroidism and a reduction in glutathione.

A Comprehensive Review of Andrographis paniculata (Burm. f.) Nees and Its Constituents as Potential Lead Compounds for COVID-19 Drug Discovery.

The COVID-19 pandemic has intensively disrupted global health, economics, and well-being. Andrographis paniculata (Burm. f.) Nees has been used as a complementary treatment for COVID-19 in several Asian countries. This review aimed to summarize the information available regarding A. paniculata and its constituents, to provide critical points relating to its pharmacological properties, safety, and efficacy, revealing its potential to serve as a source of lead compounds for COVID-19 drug discovery. A. paniculata and its active compounds possess favorable antiviral, anti-inflammatory, immunomodulatory, and antipyretic activities that could be beneficial for COVID-19 treatment. Interestingly, recent in silico and in vitro studies have revealed that the active ingredients in A. paniculata showed promising activities against 3CLpro and its virus-specific target protein, human hACE2 protein; they also inhibit infectious virion production. Moreover, existing publications regarding randomized controlled trials demonstrated that the use of A. paniculata alone or in combination was superior to the placebo in reducing the severity of upper respiratory tract infection (URTI) manifestations, especially as part of early treatment, without serious side effects. Taken together, its chemical and biological properties, especially its antiviral activities against SARS-CoV-2, clinical trials on URTI, and the safety of A. paniculata, as discussed in this review, support the argument that A. paniculata is a promising natural source for drug discovery regarding COVID-19 post-infectious treatment, rather than prophylaxis.

Lead-start isothermal polymerase amplification controlled by DNAzymatic switches.

As DNA polymerases are even active at ambient temperature, there is inevitable non-specific amplification; to avoid the undesired amplification of analytes, a heat activation-based polymerase chain reaction (PCR), called hot-start PCR, is widely used to be highly precise and quantitative in detection. Unlike thermocycling amplification, isothermal amplification, compatible for point-of-care (PoC) tests, cannot be benefited by the heat-activation technique, making the method qualitative rather than quantitative. In this work, we newly developed a lead ion (Pb2+) activation technique, called lead-start isothermal amplification, allowing on-demand activation or deactivation of DNA polymerases at room temperature. We systematically correlated the DNA polymerase inhibition by the TQ30 aptamer with Pb2+-responsive strand cleavage by the GR5 DNAzyme, and relying on the type of interconnectors, Pb2+ successfully served as an initiator or a terminator of isothermal DNA amplification. Our lead-start isothermal amplification was exceptionally Pb2+-specific, dramatically increasing the enzymatic activity of DNA polymerase (>25 times) only by Pb2+ introduction. Despite one-by-one sample preparation, a number of reactions can begin and end at the same time, sharing the identical amplification conditions, and thereby allowing their quantitative analysis and comparison. Using a portable UV lamp and a smartphone camera, we also succeeded in quantifying the amounts of clinically important and human papillomavirus type 16 genes in human serum and SARS-CoV-2's nucleocapsid genes in human serum and saliva, and the limit of detection was as low as 0.1 nM, highly applicable for actual PoC tests in the field with no purification process.

Health Risk Assessment of Heavy Metals (Pb, Cd, Hg) in Hydroalcoholic Gels of Abidjan, Côte d'Ivoire.

Despite the high consumption of hydroalcoholic gels worldwide and particularly in Côte d'Ivoire since the outbreak of the COVID-19 pandemic, very few studies have measured the heavy metal content and human exposure in this product. Thus, 30 samples from supermarkets in Abidjan, Côte d'Ivoire, were collected for the study of risk assessment of exposure to heavy metals contained in hydroalcoholic gels. This study consists of the characterization of the danger by calculating the carcinogenic and non-carcinogenic risk by skin contact. Almost all samples analysed contain trace of lead, cadmium and mercury but at concentrations below the Canadian limit in cosmetic products applied to the skin and below the US FDA limit as an impurity in colour additives used in cosmetic products. The mean values of chronic daily intake via dermal absorption (CDIdermal) for adults were found in the order of mercury > lead > cadmium. The health risk estimation indicated that the mean total hazard quotient for dermal adsorption (HIdermal) obtained is 7.10 × 10-5 ± 5.52 × 10-5. This value was below 1, the acceptable limit, representing a non-carcinogenic risk for Abidjan residents through dermal adsorption. Moreover, the incremental lifetime cancer risk (ILCR) evaluation for lead and cadmium was insignificant, and the cancer risk can be neglected, but in case of their overusing, they can cause long-term health problems for consumers.

Reaction Times among Batik Workers: The Influence of Gender and Occupational Lead Exposure.

(1) Background: Neglected occupational health and safety aspects in batik industries cause their workers to have an increased risk of lead exposure. The effect of occupational lead exposure on neurocognitive performance is inconclusive. Therefore, we conducted an observational study to examine the difference in simple reaction time between lead-exposed batik workers and non-exposed referents. (2) Methods: This cross-sectional study was conducted in seven batik enterprises in Lendah District, Indonesia, excluding workers with medical conditions impairing reaction time. Simple reaction time tests were conducted using an online tool. Two-way model ANCOVAs examined interactions between gender and job types on the mean differences in reaction time. (3) Results: After controlling for age and body mass index, we observed longer reaction times among lead-exposed batik workers than non-exposed referents with an adjusted mean difference of 0.19 (95% CI: 0.016-0.368) seconds. A more prominent detrimental effect of lead exposure on reaction time among female workers than among male workers was observed. (4) Conclusions: Our results suggest that occupational lead exposure could contribute to longer reaction time, notably among female workers. Thus, occupational health and safety precautions are vital to protect batik workers and preserve their important contributions to cultural heritage.

Development and optimization of heavy metal lead biosensors in biomedical and environmental applications.

The detrimental impact of the heavy metal lead (Pb) on human health has been studied for years. The fact that Pb impairs human body has been established from countless painful and sad historical events. Nowadays, World Health Organization and many developmental countries have established regulations concerning the use of Pb. Measuring the blood lead level (BLL) is so far the only way to officially evaluate the degree of Pb exposure, but the so-called safety value (10 µg/dL in adults and 5 µg/dL in children) seems unreliable to represent the security checkpoint for children through daily intake of drinking water or physical contact with a lower contaminated level of Pb contents. In general, unsolved mysteries about the Pb toxicological mechanisms still remain. In this review article, we report on the methods to prevent Pb poison for further Pb toxicological research. We establish high-sensitivity Pb monitoring, and also report on the use of fluorescent biosensors such as genetically-encoded fluorescence resonance energy transfer-based biosensors built for various large demands such as the detection of severe acute respiratory syndrome coronavirus 2. We also contribute to the development and optimization of the FRET-based Pb biosensors. Our well-performed version of Met-lead 1.44 M1 has achieved a limit of detection of 10 nM (2 ppb; 0.2 µg/dL) and almost 5-fold in dynamic range (DR) supported for the real practical applications-that is, the in-cell Pb sensing device for blood and blood-related samples, and the Pb environmental detections in vitro. The perspective of our powerful Pb biosensor incorporated with a highly sensitive bio-chip of the portable device for quick Pb measurements will be addressed for further manipulation.

Making waves: Defining the lead time of wastewater-based epidemiology for COVID-19.

Individuals infected with SARS-CoV-2, the virus that causes COVID-19, may shed the virus in stool before developing symptoms, suggesting that measurements of SARS-CoV-2 concentrations in wastewater could be a "leading indicator" of COVID-19 prevalence. Multiple studies have corroborated the leading indicator concept by showing that the correlation between wastewater measurements and COVID-19 case counts is maximized when case counts are lagged. However, the meaning of "leading indicator" will depend on the specific application of wastewater-based epidemiology, and the correlation analysis is not relevant for all applications. In fact, the quantification of a leading indicator will depend on epidemiological, biological, and health systems factors. Thus, there is no single "lead time" for wastewater-based COVID-19 monitoring. To illustrate this complexity, we enumerate three different applications of wastewater-based epidemiology for COVID-19: a qualitative "early warning" system; an independent, quantitative estimate of disease prevalence; and a quantitative alert of bursts of disease incidence. The leading indicator concept has different definitions and utility in each application.