High-Resolution Plasma Metabolomics Identifies Alterations in Fatty Acid, Energy, and Micronutrient Metabolism in Adults Across the Leprosy Spectrum.

BACKGROUND: High-resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism. METHODS: From 2018 to 2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil. Plasma metabolites were detected using an established HRM workflow and characterized by accurate mass, mass to charge ratio m/z and retention time. The mummichog informatics package compared metabolic pathways between cases and controls and between multibacillary (MB) and paucibacillary (PB) leprosy. Additionally, select individual metabolites were quantified and compared. RESULTS: Thirty-nine cases (62% MB and 38% PB) and 25 controls were enrolled. We found differences (P < .05) in several metabolic pathways, including fatty acid metabolism, carnitine shuttle, retinol, vitamin D3, and C-21 steroid metabolism, between cases and controls with lower retinol and associated metabolites in cases. Between MB and PB, leukotrienes, prostaglandins, tryptophan, and cortisol were all found to be lower in MB (P < .05). DISCUSSION: Metabolites associated with several nutrient-related metabolic pathways appeared differentially regulated in leprosy, especially MB versus PB. This pilot study demonstrates the metabolic interdependency of these pathways, which may play a role in the pathophysiology of disease.

COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (n = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.

Evaluation of Patients for Zika Virus Infection in a Travel Clinic in the Southeast United States, 2016.

OBJECTIVES: Zika virus is an emerging infection that has posed vexing challenges to the US public health system. Improved characterization of patients with possible and confirmed infection is needed to better understand risks for infection in US travelers and to inform evolving evaluation guidelines. METHODS: We performed a retrospective electronic health record review of patients evaluated for Zika virus infection at an academic travel clinic in Atlanta, Georgia, from January 1 through August 31, 2016. We evaluated 46 patients who presented to the clinic during this period for evaluation of possible Zika virus infection, including patients with Zika virus symptoms, asymptomatic patients with possible exposure to Zika virus, and referral visits for Zika virus testing. RESULTS: Among the 46 patients evaluated, 30 (65.2%) were tested for Zika virus, 8 of whom (17.4%) had laboratory evidence of infection (7 confirmed, 1 probable). Cases, including confirmed and probable infections, most commonly had fever, rash, conjunctivitis, headache, and myalgia, although differences compared with noncases were not statistically significant. Many patients evaluated were not tested because of stringent testing criteria. CONCLUSIONS: Our findings may help inform improvements in timely clinical decision making for Zika virus testing. This may assist clinicians and public health agencies. Wider access to accurate screening modalities will help providers evaluate and advise patients.

Innate, T-, and B-Cell Responses in Acute Human Zika Patients.

Background: There is an urgent need for studies of viral persistence and immunity during human Zika infections to inform planning and conduct of vaccine clinical trials. Methods: In 5 returned US travelers with acute symptomatic Zika infection, clinical features, viral RNA levels, and immune responses were characterized. Results: Two pregnant, flavivirus-experienced patients had viral RNA persist in plasma for >44 and >26 days. Three days after symptom onset, transient increases in proinflammatory monocytes began followed at 5 days by transient decreases in myeloid dendritic cells. Anti-Zika virus immunoglobulin M was detected at day 7 after symptom onset, persisted beyond 103 days, and remained equivocal through day 172. Zika virus-specific plasmablasts and neutralizing antibodies developed quickly; dengue virus-specific plasmablasts and neutralizing antibodies at high titers developed only in flavivirus-experienced patients. Zika virus- and dengue virus-specific memory B cells developed in both flavivirus-naive and -experienced patients. CD4+ T cells were moderately activated and produced antiviral cytokines after stimulation with Zika virus C, prM, E, and NS5 peptides in 4/4 patients. In contrast, CD8+ T cells were massively activated, but virus-specific cells that produced cytokines were present in only 2/4 patients assessed. Conclusions: Acute infections with Zika virus modulated antigen-presenting cell populations early. Flavivirus-experienced patients quickly recalled cross-reactive MBCs to secrete antibodies. Dengue virus-naive patients made little dengue-specific antibody but developed MBCs that cross-reacted against dengue virus. Zika virus-specific functional CD4+ T cells were readily detected, but few CD8+ T cells specific for the tested peptides were found.

A survey on outcomes of accidental atovaquone-proguanil exposure in pregnancy.

BACKGROUND: Malaria chemoprophylaxis options in pregnancy are limited, and atovaquone-proguanil (AP) is not recommended because of insufficient safety evidence. An anonymous, internet-based survey was disseminated to describe outcomes of pregnancies accidentally exposed to AP. Outcomes of interest included miscarriage (defined as pregnancy loss before 20 weeks), stillbirth (defined as pregnancy loss at or after 20 weeks), preterm birth or live birth prior to 37 weeks, and the presence of congenital anomalies. RESULTS: A total of 487 women responded and reported on 822 pregnancies. Of the 807 pregnancies with information available on exposure and outcomes, 10 (1.2%) had atovaquone-proguanil exposure, all in the first trimester, and all resulted in term births with no birth defects. CONCLUSIONS: Use of an anti-malarial not recommended in pregnancy is likely to occur before the woman knows of her pregnancy. This study adds to the limited evidence of the safety of AP in pregnancy. Further study on use of AP in pregnancy should be a high priority, as an alternative option for the prevention of malaria in pregnancy in non-immune travellers is urgently needed.

A tale of two neglected tropical infections: using GIS to assess the spatial and temporal overlap of schistosomiasis and leprosy in a region of Minas Gerais, Brazil.

BACKGROUND: Despite public health efforts to reduce the global burden of leprosy, gaps remain in the knowledge surrounding transmission of infection. Helminth co-infections have been associated with a shift towards the lepromatous end of the disease spectrum, potentially increasing transmission in co-endemic areas. OBJECTIVES: Using this biologically plausible association, we conducted a geographic information systems (GIS) study to investigate the spatial associations of schistosomiasis and leprosy in an endemic area of Minas Gerais (MG), Brazil. METHODS: Data on new cases of Mycobacterium leprae and Schistosoma mansoni infections from 2007-2014 were retrieved from the Brazilian national notifiable diseases information system for seven municipalities in and surrounding Vespasiano, MG. A total of 139 cases of leprosy and 200 cases of schistosomiasis were mapped to a municipality level. For one municipality, cases were mapped to a neighborhood level and a stratified analysis was conducted to identify spatial associations. FINDINGS: A relative risk of 6.80 [95% confidence interval (CI) 1.46 - 31.64] of leprosy was found in neighborhoods with schistosomiasis. Incidence rates of leprosy increased with corresponding incidence rates of schistosomiasis, and the temporal trends of both infections were similar. CONCLUSIONS: The associations found in this project support the hypothesis that helminth infections may influence the transmission of leprosy in co-endemic areas.

Intersections of climate change, migration, and health: experiences of first-generation migrants from Latin America to the Atlanta-metropolitan area.

Climate change is an important driver of migration, but little research exists on whether migrant communities in the U.S. identify climate change-related factors as reasons for migrating. In 2021, we conducted a multidisciplinary, collaborative project to better understand the nexus of climate change and immigrant health in the Atlanta area. This paper presents one arm of this collaboration that explored both the role of climate change in decisions to immigrate to Georgia and the ways that climate change intersects with other possible drivers of migration. First generation migrants from Latin America were recruited primarily through CPACS Cosmo Health Center and were invited to participate in an intake survey and an in-depth interview. Results were analyzed using descriptive statistics and thematic analysis. Findings suggest that while participants may not have explicitly identified climate change as a primary reason for migration, in both surveys and in-depth interviews, participants reported multiple and intersecting social, economic, political, and environmental factors that are directly or indirectly influenced by climate change and that are involved in their decisions to migrate. The narratives that emerged from in-depth interviews further contextualised survey data and elucidated the complex nexus of climate change, migration, and health.

Genomic Epidemiology of a Severe Acute Respiratory Syndrome Coronavirus 2 Outbreak in a US Major League Soccer Club: Was It Travel Related?

Background: Professional soccer athletes are at risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). United States Major League Soccer (MLS) uses protocol-based SARS-CoV-2 testing for identification of individuals with coronavirus disease 2019. Methods: Per MLS protocol, fully vaccinated players underwent SARS-CoV-2 real-time polymerase chain reaction testing weekly; unvaccinated players were tested every other day. Demographic and epidemiologic data were collected from individuals who tested positive, and contact tracing was performed. Whole genome sequencing (WGS) was performed on positive specimens, and phylogenetic analyses were used to identify potential transmission patterns. Results: In the fall of 2021, all 30 players from 1 MLS team underwent SARS-CoV-2 testing per protocol; 27 (90%) were vaccinated. One player who had recently traveled to Africa tested positive for SARS-CoV-2; within the following 2 weeks, 10 additional players and 1 staff member tested positive. WGS yielded full genome sequences for 10 samples, including 1 from the traveler. The traveler's sample was Delta sublineage AY.36 and was closely related to a sequence from Africa. Nine samples yielded other Delta sublineages including AY.4 (n = 7), AY.39 (n = 1), and B.1.617.2 (n = 1). The 7 AY.4 sequences clustered together; suggesting a common source of infection. Transmission from a family member visiting from England to an MLS player was identified as the potential index case. The other 2 AY.4 sequences differed from this group by 1-3 nucleotides, as did a partial genome sequence from an additional team member. Conclusions: WGS is a useful tool for understanding SARS-CoV-2 transmission dynamics in professional sports teams.

Associations between occupation, leprosy disability and other sociodemographic factors in an endemic area of Brazil.

BACKGROUND: In Brazil, new leprosy cases with grade-2 disability (G2D) have been increasing. Physical disability has been associated with experienced stigmatization, psychological distress, and social restriction. OBJECTIVES: To identify factors associated with leprosy disability in an endemic area of Brazil focusing on occupational and other sociodemographic factors. METHODS: Between July and December 2015, adult patients with multibacillary leprosy who attended a clinic in Belo Horizonte, Brazil were enrolled. Social, clinical, and demographic factors were collected from an administered questionnaire and medical charts. Occupations were categorized as manual vs non-manual. Descriptive statistics and multivariable logistic regression were performed to study associated factors with disability (Grade 1 disability (G1D) and G2D combined). FINDINGS: Seventy-three patients were enrolled with 48 (65.8%) presenting with either G1D or G2D at the time of enrollment. Twenty-nine (39.7%) had G2D. About half of the patients (n = 36, 49%) reported a manual labor occupation and reactions were common (n = 53, 73%). On univariate analyses, older age (p = 0.048) and low education (p = 0.007) were associated with disability. On multivariable analyses, only low education (primary or less) was associated with disability (OR = 6.34, 95% CI 1.37, 29.26). Greater distance from clinic, income, smoking, marital status, and occupation were not associated. MAIN CONCLUSIONS: Low education was associated with leprosy disability, consistent with prior studies, and therefore should be a focus for disability reduction programs. While the sample size of this study may have limited detection of associations between disability and social determinants tested, half of the patients reported a manual job, highlighting the need for more extensive studies on associations between occupation, disability, and related injuries.

Safety of integrated preventive chemotherapy for neglected tropical diseases.

BACKGROUND: Preventive chemotherapy (PC) is a central strategy for control and elimination of neglected tropical diseases (NTDs). Increased emphasis has been given to "integration" of NTD programs within health systems and coadministration of NTD drugs offers significant programmatic benefits. Guidance from the World Health Organization (WHO) reflects current evidence for safe drug coadministration and highlights measures to prevent choking of young children during PC. METHODOLOGY: To understand how coadministration of NTD drugs might affect PC safety, we reviewed literature on choking risk in young children and safety of coadministered NTD drugs. To understand current practices of drug coadministration, we surveyed 15 NTD program managers and implementing partners. PRINCIPAL FINDINGS: In high-income countries, choking on medication is an infrequent cause of death in young children. In low-resource settings, data are limited, but age-appropriate drug formulations are less available. During PC, fatal choking, although infrequent, occurs primarily in young children; forcing them to swallow tablets appears to be the major risk factor. The WHO currently recommends 6 drugs and 5 possible drug combinations for use in PC. Of 105 nations endemic for the 5 PC-NTDs, 72 (68.6%) are co-endemic for 2 or more diseases and could benefit from drug coadministration during PC. All 15 survey respondents reported coadministering medications during PC. Reported responses to a child refusing to take medicine included: not forcing the child to do so (60.0%), encouraging the child (46.7%), bringing the child back later (26.7%), offering powder for oral suspension (POS) for azithromycin (13.3%), and having parents or community members intervene to calm the child (6.7%). CONCLUSIONS: Coadministration of NTD drugs during PC appears to be increasingly common. Safety of coadministered PC drugs requires attention to choking prevention, use of approved drug combinations, and increased access to age-appropriate drug formulations.

Algorithm Design for a Cytokine Release Assay of Antigen-Specific In Vitro Stimuli of Circulating Leukocytes to Classify Leprosy Patients and Household Contacts.

BACKGROUND: Immunological biomarkers have often been used as a complementary approach to support clinical diagnosis in several infectious diseases. The lack of commercially available laboratory tests for conclusive early diagnosis of leprosy has motivated the search for novel methods for accurate diagnosis. In the present study, we describe an integrated analysis of a cytokine release assay using a machine learning approach to create a decision tree algorithm. This algorithm was used to classify leprosy clinical forms and monitor household contacts. METHODS: A model of Mycobacterium leprae antigen-specific in vitro assay with subsequent cytokine measurements by enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor (TNF), interferon-γ, interleukin 4, and interleukin 10 (IL-10) in culture supernatants of peripheral blood mononuclear cells from patients with leprosy, healthy controls, and household contacts. Receiver operating characteristic curve analysis was carried out to define each cytokine's global accuracy and performance indices to identify clinical subgroups. RESULTS: Data demonstrated that TNF (control culture [CC]: AUC = 0.72; antigen-stimulated culture [Ml]: AUC = 0.80) and IL-10 (CC: AUC = 0.77; Ml: AUC = 0.71) were the most accurate biomarkers to classify subgroups of household contacts and patients with leprosy, respectively. Decision tree classifier algorithms for TNF analysis categorized subgroups of household contacts according to the operational classification with moderate accuracy (CC: 79% [48/61]; Ml: 84% [51/61]). Additionally, IL-10 analysis categorized leprosy patients' subgroups with moderate accuracy (CC: 73% [22/30] and Ml: 70% [21/30]). CONCLUSIONS: Together, our findings demonstrated that a cytokine release assay is a promising method to complement clinical diagnosis, ultimately contributing to effective control of the disease.

Undernutrition, food insecurity, and leprosy in North Gondar Zone, Ethiopia: A case-control study to identify infection risk factors associated with poverty.

BACKGROUND: Ethiopia has over 3,200 new cases of leprosy diagnosed every year. Prevention remains a challenge as transmission pathways are poorly understood. Susceptibility and disease manifestations are highly dependent on individual host-immune response. Nutritional deficiencies, such as protein-energy malnutrition, have been linked to reduced cell-mediated immunity, which in the case of leprosy, could lead to a higher chance of active leprosy and thus an increased reservoir of transmissible infection. METHODOLOGY/PRINCIPAL FINDINGS: Between June and August 2018, recently diagnosed patients with leprosy and individuals without known contact with cases were enrolled as controls in North Gondar regional health centers. Participants answered survey questions on biometric data, demographics, socioeconomic situation, and dietary habits. Descriptive statistics, univariate, and multivariate logisitic regression examined associations between undernutrition, specifically body mass index (BMI), middle upper arm circumference (MUAC), and leprosy. Eighty-one participants (40 cases of leprosy, 41 controls) were enrolled (75% male) with an average age of 38.6 years (SD 18.3). The majority of cases were multibacillary (MB) (90%). There was a high prevalence of undernutrition with 24 (29.6%) participants underweight (BMI <18.5) and 17 (21%) having a low MUAC. On multivariate analysis, underweight was significantly associated with leprosy (aOR = 9.25, 95% CI 2.77, 30.81). Also found to be associated with leprosy was cutting the size of meals/skipping meals (OR = 2.9, 95% CI 1.0, 8.32) or not having enough money for food (OR = 10, 95% CI 3.44 29.06). CONCLUSIONS/SIGNIFICANCE: The results suggest a strong association between leprosy and undernutrition, while also supporting the framework that food insecurity may lead to undernutrition that then could increase susceptibility to leprosy. In conclusion, this study highlights the need to study the interplay of undernutrition, food insecurity, and the manifestations of leprosy.

Leprosy Screening Based on Artificial Intelligence: Development of a Cross-Platform App.

BACKGROUND: According to the World Health Organization, achieving targets for control of leprosy by 2030 will require disease elimination and interruption of transmission at the national or regional level. India and Brazil have reported the highest leprosy burden in the last few decades, revealing the need for strategies and tools to help health professionals correctly manage and control the disease. OBJECTIVE: The main objective of this study was to develop a cross-platform app for leprosy screening based on artificial intelligence (AI) with the goal of increasing accessibility of an accurate method of classifying leprosy treatment for health professionals, especially for communities further away from major diagnostic centers. Toward this end, we analyzed the quality of leprosy data in Brazil on the National Notifiable Diseases Information System (SINAN). METHODS: Leprosy data were extracted from the SINAN database, carefully cleaned, and used to build AI decision models based on the random forest algorithm to predict operational classification in paucibacillary or multibacillary leprosy. We used Python programming language to extract and clean the data, and R programming language to train and test the AI model via cross-validation. To allow broad access, we deployed the final random forest classification model in a web app via shinyApp using data available from the Brazilian Institute of Geography and Statistics and the Department of Informatics of the Unified Health System. RESULTS: We mapped the dispersion of leprosy incidence in Brazil from 2014 to 2018, and found a particularly high number of cases in central Brazil in 2014 that further increased in 2018 in the state of Mato Grosso. For some municipalities, up to 80% of cases showed some data discrepancy. Of a total of 21,047 discrepancies detected, the most common was "operational classification does not match the clinical form." After data processing, we identified a total of 77,628 cases with missing data. The sensitivity and specificity of the AI model applied for the operational classification of leprosy was 93.97% and 87.09%, respectively. CONCLUSIONS: The proposed app was able to recognize patterns in leprosy cases registered in the SINAN database and to classify new patients with paucibacillary or multibacillary leprosy, thereby reducing the probability of incorrect assignment by health centers. The collection and notification of data on leprosy in Brazil seem to lack specific validation to increase the quality of the data for implementations via AI. The AI models implemented in this work had satisfactory accuracy across Brazilian states and could be a complementary diagnosis tool, especially in remote areas with few specialist physicians.

Postacute Sequelae of SARS-CoV-2 Infection and Impact on Quality of Life 1-6 Months After Illness and Association With Initial Symptom Severity.

BACKGROUND: Individuals with coronavirus disease 2019 (COVID-19) may have persistent symptoms following their acute illness. The prevalence and predictors of these symptoms, termed postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; PASC), have not been fully described. METHODS: Participants discharged from an outpatient telemedicine program for COVID-19 were emailed a survey (1-6 months after discharge) about ongoing symptoms, acute illness severity, and quality of life. Standardized telemedicine notes from acute illness were used for covariates (comorbidities and provider-assessed symptom severity). Bivariate and multivariable analyses were performed to assess predictors of persistent symptoms. RESULTS: Two hundred ninety patients completed the survey, of whom 115 (39.7%) reported persistent symptoms including fatigue (n = 59, 20.3%), dyspnea on exertion (n = 41, 14.1%), and mental fog (n = 39, 13.5%), among others. The proportion of persistent symptoms did not differ based on duration since illness (<90 days: n = 32, 37.2%; vs >90 days: n = 80, 40.4%; P = .61). Predictors of persistent symptoms included provider-assessed moderate-severe illness (adjusted odds ratio [aOR], 3.24; 95% CI, 1.75-6.02), female sex (aOR, 1.99; 95% CI, 0.98-4.04; >90 days out: aOR, 2.24; 95% CI, 1.01-4.95), and middle age (aOR, 2.08; 95% CI, 1.07-4.03). Common symptoms associated with reports of worse physical health included weakness, fatigue, myalgias, and mental fog. CONCLUSIONS: Symptoms following acute COVID-19 are common and may be predicted by factors during the acute phase of illness. Fatigue and neuropsychiatric symptoms figured prominently. Select symptoms seem to be particularly associated with perceptions of physical health following COVID-19 and warrant specific attention on future studies of PASC.

Mycobacterium leprae-helminth co-infections and vitamin D deficiency as potential risk factors for leprosy: A case-control study in south-eastern Brazil.

BACKGROUND: Evidence suggests that biological mechanisms involved in helminth infections and vitamin deficiencies increase susceptibility to other infections. The aim of this study was to investigate the associations of helminth co-infection and select micronutrient deficiencies with leprosy using a case-control design. METHODS: From 2016 to 2018, individuals aged ≥3 years were recruited at clinics in and around Governador Valadares, Minas Gerais, Brazil in three groups: cases of leprosy, household contacts and community-matched (non-contact) controls. Helminths were diagnosed through stool Kato Katz examination and serum reactivity to anti-soluble adult worm antigen preparation IgG4. Serum ferritin, 25-OH vitamin D and retinol concentrations were measured. Multi-variate logistic regression was conducted to identify associations with active leprosy. RESULTS: Seventy-nine cases of leprosy, 96 household contacts and 81 non-contact controls were recruited; 48.1% of participants were male with a median age of 40 years. Helminths were found in 7.1% of participants on Kato Katz test, all but one of which were Schistosoma mansoni, and 32.3% of participants were positive for S. mansoni serology. On multi-variate analysis, cases were more likely to be infected with helminths (diagnosed by stool) than household contacts [adjusted odds ratio (aOR) 8.69, 95% confidence interval (CI) 1.50-50.51]. Vitamin D deficiency was common, and was more likely in cases compared with non-contact controls (aOR 4.66, 95% CI 1.42,-15.33). Iron deficiency was not associated with leprosy, and vitamin A deficiency was not detected. CONCLUSION: These associations suggest that the immune consequences of schistosomiasis and vitamin D deficiency may increase the risk of active leprosy. Comorbid conditions of poverty deserve further study as addressing co-infections and nutritional deficiencies could be incorporated into programmes to improve leprosy control.

Application of SARS-CoV-2 Serology to Address Public Health Priorities.

Background: Antibodies against SARS-CoV-2 can be detected by various testing platforms, but a detailed understanding of assay performance is critical. Methods: We developed and validated a simple enzyme-linked immunosorbent assay (ELISA) to detect IgG binding to the receptor-binding domain (RBD) of SARS-CoV-2, which was then applied for surveillance. ELISA results were compared to a set of complimentary serologic assays using a large panel of clinical research samples. Results: The RBD ELISA exhibited robust performance in ROC curve analysis (AUC> 0.99; Se = 89%, Sp = 99.3%). Antibodies were detected in 23/353 (6.5%) healthcare workers, 6/9 RT-PCR-confirmed mild COVID-19 cases, and 0/30 non-COVID-19 cases from an ambulatory site. RBD ELISA showed a positive correlation with neutralizing activity (p = <0.0001, R2 = 0.26). Conclusions: We applied a validated SARS-CoV-2-specific IgG ELISA in multiple contexts and performed orthogonal testing on samples. This study demonstrates the utility of a simple serologic assay for detecting prior SARS-CoV-2 infection, particularly as a tool for efficiently testing large numbers of samples as in population surveillance. Our work also highlights that precise understanding of SARS-CoV-2 infection and immunity at the individual level, particularly with wide availability of vaccination, may be improved by orthogonal testing and/or more complex assays such as multiplex bead assays.