Comparison of RT-PCR and antigen test sensitivity across nasopharyngeal, nares, and oropharyngeal swab, and saliva sample types during the SARS-CoV-2 omicron variant.

Limited data highlight the need to understand differences in SARS-CoV-2 omicron (B.1.1.529) variant viral load between the gold standard nasopharyngeal (NP) swab, mid-turbinate (MT)/anterior nasal swabs, oropharyngeal (OP) swabs, and saliva. MT, OP, and saliva samples from symptomatic individuals in Atlanta, GA, in January 2022 and longitudinal samples from a small familial cohort were tested by both RT-PCR and ultrasensitive antigen assays. Higher concentrations in the nares were observed in the familial cohort, but a dominant sample type was not found among 39 cases in the cross-sectional cohort. The composite of positive MT or OP assay for both RT-PCR and antigen assay trended toward higher diagnostic yield but did not achieve significant difference. Our data did not identify a singular preferred sample type for SARS-CoV-2 testing, but higher levels of saliva nucleocapsid, a trend toward higher yield of composite OP/MT result, and association of apparent MT or OP predominance with symptoms warrant further study.

Clinical and epidemiological characteristics of Madariaga and Venezuelan equine encephalitis virus infections.

Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, there are limited clinical and epidemiological reports available, and outbreaks are occurring at an increasing frequency. We addressed this gap by analyzing all the available clinical and epidemiological data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 of human alphavirus encephalitis cases were detected in Panama from 1961 to 2023. Here we describe the clinical signs and symptoms and epidemiological characteristics of these cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection when compared to those of other arbovirus infections occurring in the region. Our results highlight the challenges clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.

Characterization of Dengue Virus 4 Cases in Paraguay, 2019-2020.

In 2019-2020, dengue virus (DENV) type 4 emerged to cause the largest DENV outbreak in Paraguay's history. This study sought to characterize dengue relative to other acute illness cases and use phylogenetic analysis to understand the outbreak's origin. Individuals with an acute illness (≤7 days) were enrolled and tested for DENV nonstructural protein 1 (NS1) and viral RNA by real-time RT-PCR. Near-complete genome sequences were obtained from 62 DENV-4 positive samples. From January 2019 to March 2020, 799 participants were enrolled: 253 dengue (14 severe dengue, 5.5%) and 546 other acute illness cases. DENV-4 was detected in 238 dengue cases (94.1%). NS1 detection by rapid test was 52.5% sensitive (53/101) and 96.5% specific (387/401) for dengue compared to rRT-PCR. DENV-4 sequences were grouped into two clades within genotype II. No clustering was observed based on dengue severity, location, or date. Sequences obtained here were most closely related to 2018 DENV-4 sequences from Paraguay, followed by a 2013 sequence from southern Brazil. DENV-4 can result in large outbreaks, including severe cases, and is poorly detected with available rapid diagnostics. Outbreak strains seem to have been circulating in Paraguay and Brazil prior to 2018, highlighting the importance of sustained DENV genomic surveillance.

An economical in-class sticker microfluidic activity develops student expertise in microscale physics and device manufacturing.

Educating new students in miniaturization science remains challenging due to the non-intuitive behavior of microscale objects and specialized layer-by-layer assembly approaches. In our analysis of the existing literature, we noted that it remains difficult to have low cost activities that elicit deep learning. Furthermore, few activities have stated learning goals and measurements of effectiveness. To that end, we created a new educational activity that enables students to build and test microfluidic mixers, valves, and bubble generators in the classroom setting with inexpensive, widely-available materials. Although undergraduate and graduate engineering students are able to successfully construct the devices, our activity is unique in that the focus is not on successfully building and operating each device. Instead, it is to gain understanding about miniaturization science, device design, and construction so as to be able to do so independently. Our data show that the activity is appropriate for developing the conceptual understanding of graduate and advanced undergraduate students (n = 57), as well as makes a lasting impression on the students. We also report on observations related to student patterns of misunderstanding and how miniaturization science provides a unique opportunity for educational researchers to elicit and study misconceptions. More broadly, since this activity teaches participants a viable approach to creating microsystems and can be implemented in nearly any global setting, our work democratizes the education of miniaturization science. Noting the broad potential of point-of-care technologies in the global setting, such an activity could empower local experts to address their needs.

Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA.

While SARS-CoV-2 vaccines have shown strong efficacy, their suboptimal uptake combined with the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples. We found no difference in disease severity between individuals infected with Delta and Omicron variants among the participants in this study, after controlling for other factors, and we found no specific mutations associated with disease severity. Compared to those who were unvaccinated, vaccinated individuals experienced less severe SARS-CoV-2 disease, and the effect was similar for both variants. Vaccination within 270 days before infection was associated with decreased odds of moderate and severe outcomes, with the strongest association observed at 91-270 days post-vaccination. Older age and underlying health conditions, especially immunosuppression and renal disease, were associated with increased disease severity. Overall, this study provides insights into the impact of vaccination status, variants/mutations, and clinical factors on disease severity in SARS-CoV-2 infection when vaccination rates are low. Understanding these associations will help refine and reinforce messaging around the crucial importance of vaccination in mitigating the severity of SARS-CoV-2 disease.

Real-time RT-PCR for Venezuelan equine encephalitis complex, Madariaga, and Eastern equine encephalitis viruses: application in human and mosquito public health surveillance in Panama.

Eastern equine encephalitis virus (EEEV), Madariaga virus (MADV), and Venezuelan equine encephalitis virus complex (VEEV) are New World alphaviruses transmitted by mosquitoes. They cause febrile and sometimes severe neurological diseases in human and equine hosts. Detecting them during the acute phase is hindered by non-specific symptoms and limited diagnostic tools. We designed and clinically assessed real-time reverse transcription polymerase chain reaction assays (rRT-PCRs) for VEEV complex, MADV, and EEEV using whole-genome sequences. Validation involved 15 retrospective serum samples from 2015 to 2017 outbreaks, 150 mosquito pools from 2015, and 118 prospective samples from 2021 to 2022 surveillance in Panama. The rRT-PCRs detected VEEV complex RNA in 10 samples (66.7%) from outbreaks, with one having both VEEV complex and MADV RNAs. VEEV complex RNA was found in five suspected dengue cases from disease surveillance. The rRT-PCR assays identified VEEV complex RNA in three Culex (Melanoconion) vomerifer pools, leading to VEEV isolates in two. Phylogenetic analysis revealed the VEEV ID subtype in positive samples. Notably, 11.9% of dengue-like disease patients showed VEEV infections. Together, our rRT-PCR validation in human and mosquito samples suggests that this method can be incorporated into mosquito and human encephalitic alphavirus surveillance programs in endemic regions.

Cumulative Febrile, Respiratory, and Gastrointestinal Illness Among Infants in Rural Guatemala and Association With Neurodevelopmental and Growth Outcomes.

BACKGROUND: Infectious disease exposures in early life are increasingly recognized as a risk factor for poor subsequent growth and neurodevelopment. We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. METHODS: From June 2017 to July 2018, infants 0-3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and underwent weekly at-home surveillance for caregiver-reported cough, fever, and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, 6 months, and 1 year. RESULTS: Of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12-15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score < -2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] < -2 SD). In multivariable analysis, greater cumulative instances of reported cough illness (beta = -0.08/illness-week, P = 0.06) and febrile illness (beta = -0.36/illness-week, P < 0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12-15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; P = 0.27) or with cumulative instances of diarrheal/vomiting illness alone ( P = 0.66). No association was shown between cumulative instances of illness and stunting or microcephaly at 12-15 months. CONCLUSIONS: These findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore pathogen-specific illnesses, host response associated with these syndromic illnesses, and their association with neurodevelopment.

Investigation of Blood Plasma Viral Nucleocapsid Antigen as a Marker of Active Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Infection.

Background: Nasopharyngeal qualitative reverse-transcription polymerase chain reaction (RT-PCR) is the gold standard for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is not practical or sufficient in every clinical scenario due to its inability to distinguish active from resolved infection. Alternative or adjunct testing may be needed to guide isolation precautions and treatment in patients admitted to the hospital. Methods: We performed a single-center, retrospective analysis of residual clinical specimens and medical record data to examine blood plasma nucleocapsid antigen as a candidate biomarker of active SARS-CoV-2. Adult patients admitted to the hospital or presenting to the emergency department with SARS-CoV-2 ribonucleic acid (RNA) detected by RT-PCR from a nasopharyngeal swab specimen were included. Both nasopharyngeal swab and a paired whole blood sample were required to be available for analysis. Results: Fifty-four patients were included. Eight patients had positive nasopharyngeal swab virus cultures, 7 of whom (87.5%) had concurrent antigenemia. Nineteen (79.2%) of 24 patients with detectable subgenomic RNA and 20 (80.0%) of 25 patients with N2 RT-PCR cycle threshold ≤ 33 had antigenemia. Conclusions: Most individuals with active SARS-CoV-2 infection are likely to have concurrent antigenemia, but there may be some individuals with active infection in whom antigenemia is not detectable. The potential for high sensitivity and convenience of a blood test prompts interest in further investigation as a screening tool to reduce reliance on nasopharyngeal swab sampling and as an adjunct diagnostic test to aid in clinical decision making during the period after acute coronavirus disease 2019.

SARS-CoV-2 molecular testing and whole genome sequencing following RNA recovery from used BinaxNOW COVID-19 antigen self tests.

Widespread use of over-the-counter rapid diagnostic tests for SARS-CoV-2 has led to a decrease in availability of clinical samples for viral genomic surveillance. As an alternative sample source, we evaluated RNA isolated from BinaxNOW swabs stored at ambient temperature for SARS-CoV-2 rRT-PCR and full viral genome sequencing. 81 of 103 samples (78.6%) yielded detectable RNA, and 46 of 57 samples (80.7 %) yielded complete genome sequences. Our results illustrate that SARS-CoV-2 RNA extracted from used Binax test swabs provides an important opportunity for improving SARS-CoV-2 genomic surveillance, evaluating transmission clusters, and monitoring within-patient evolution.

Severe Acute Respiratory Syndrome Coronavirus 2 Evolution and Escape From Combination Monoclonal Antibody Treatment in a Person With HIV.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape from combination monoclonal antibody treatment is rarely reported. We describe an immunocompromised individual with human immunodeficiency virus and persistent SARS-CoV-2 infection in whom substantial SARS-CoV-2 evolution occurred, including the emergence of 2 mutations associated with escape from the monoclonal antibody cocktail received.

Serum biomarkers and anti-flavivirus antibodies at presentation as indicators of severe dengue.

BACKGROUND: Dengue is the most common vector-borne viral disease worldwide. Most cases are mild, but some evolve into severe dengue (SD), with high lethality. Therefore, it is important to identify biomarkers of severe disease to improve outcomes and judiciously utilize resources. METHODS/PRINCIPAL FINDINGS: One hundred forty-five confirmed dengue cases (median age, 42; range <1-91 years), enrolled from February 2018 to March 2020, were selected from an ongoing study of suspected arboviral infections in metropolitan Asunción, Paraguay. Cases included dengue virus types 1, 2, and 4, and severity was categorized according to the 2009 World Health Organization guidelines. Testing for anti-dengue virus IgM and IgG and serum biomarkers (lipopolysaccharide binding protein and chymase) was performed on acute-phase sera in plate-based ELISAs; in addition, a multiplex ELISA platform was used to measure anti-dengue virus and anti-Zika virus IgM and IgG. Complete blood counts and chemistries were performed at the discretion of the care team. Age, gender, and pre-existing comorbidities were associated with SD vs. dengue with/without warning signs in logistic regression with odds ratios (ORs) of 1.07 (per year; 95% confidence interval, 1.03, 1.11), 0.20 (female; 0.05,0.77), and 2.09 (presence; 1.26, 3.48) respectively. In binary logistic regression, for every unit increase in anti-DENV IgG in the multiplex platform, odds of SD increased by 2.54 (1.19-5.42). Platelet count, lymphocyte percent, and elevated chymase were associated with SD in a combined logistic regression model with ORs of 0.99 (1,000/µL; 0.98,0.999), 0.92 (%; 0.86,0.98), and 1.17 (mg/mL; 1.03,1.33) respectively. CONCLUSIONS: Multiple, readily available factors were associated with SD in this population. These findings will aid in the early detection of potentially severe dengue cases and inform the development of new prognostics for use in acute-phase and serial samples from dengue cases.

SARS-CoV-2 genotyping and sequencing following a simple and economical RNA extraction and storage protocol.

Since the beginning of the SARS-CoV-2 pandemic, supply chain shortages have caused major disruptions in sourcing the materials needed for laboratory-based molecular assays. With increasing demand for molecular testing, these disruptions have limited testing capacity and hindered efforts to mitigate spread of the virus and new variants. Here we evaluate an economical and reliable protocol for the extraction and short-term ambient temperature storage of SARS-CoV-2 RNA. Additional objectives of the study were to evaluate RNA from this protocol for 1) detection of single nucleotide polymorphisms (SNPs) in the spike gene and 2) whole genome sequencing of SARS-CoV-2. The RNAES protocol was evaluated with residual nasopharyngeal (NP) samples collected from Emory Healthcare and Emory Student Health services. All RNAES extractions were performed in duplicate and once with a commercial extraction robot for comparison. Following extraction, eluates were immediately tested by rRT-PCR. SARS-CoV-2 RNA was successfully detected in 56/60 (93.3%) RNAES replicates, and Ct values corresponded with comparator results. Upon testing in spike SNP assays, three genotypes were identified, and all variant calls were consistent with those previously obtained after commercial extraction. Additionally, the SARS-RNAES protocol yield eluate pure enough for downstream whole genome sequencing, and results were consistent with SARS-CoV-2 whole genome sequencing of eluates matched for Ct value. With reproducible results across a range of virus concentrations, the SARS-RNAES protocol could help increase SARS-CoV-2 diagnostic testing and monitoring for emerging variants in resource-constrained communities.

SARS-CoV-2 molecular testing and whole genome sequencing following RNA recovery from used BinaxNOW COVID-19 Antigen Self Tests.

Widespread use of over-the-counter rapid diagnostic tests for SARS-CoV-2 has led to a decrease in availability of clinical samples for viral genomic surveillance. As an alternative sample source, we evaluated RNA isolated from BinaxNOW swabs stored at ambient temperature for SARS-CoV-2 rRT-PCR and full viral genome sequencing. 81 of 103 samples (78.6%) yielded detectable RNA, and 46 of 57 samples (80.7 %) yielded complete genome sequences. Our results illustrate that SARS-CoV-2 RNA extracted from used Binax test swabs provides an important opportunity for improving SARS-CoV-2 genomic surveillance, evaluating transmission clusters, and monitoring within-patient evolution.

Outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in hospitalized hemodialysis patients: An epidemiologic and genomic investigation.

We performed an epidemiological investigation and genome sequencing of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to define the source and scope of an outbreak in a cluster of hospitalized patients. Lack of appropriate respiratory hygiene led to SARS-CoV-2 transmission to patients and healthcare workers during a single hemodialysis session, highlighting the importance of infection prevention precautions.

Subgenomic RNA Abundance Relative to Total Viral RNA Among Severe Acute Respiratory Syndrome Coronavirus 2 Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subgenomic RNA (sgRNA) may indicate actively replicating virus, but sgRNA abundance has not been systematically compared between SARS-CoV-2 variants. sgRNA was quantified in 169 clinical samples by real-time reverse-transcription polymerase chain reaction, demonstrating similar relative abundance among known variants. Thus, sgRNA detection can identify individuals with active viral replication regardless of variant.

Severe acute respiratory syndrome coronavirus 2 vaccine breakthrough infections: A single metro-based testing network experience.

Objectives: Understanding the incidence and characteristics that influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections (VBIs) is imperative for developing public health policies to mitigate the coronavirus disease of 2019 (COVID-19) pandemic. We examined these factors and post-vaccination mitigation practices in individuals partially and fully vaccinated against SARS-CoV-2. Materials and methods: Adults >18 years old were voluntarily enrolled from a single metro-based SARS-CoV-2 testing network from January to July 2021. Participants were categorized as asymptomatic or symptomatic, and as unvaccinated, partially vaccinated, or fully vaccinated. All participants had confirmed SARS-CoV-2 infection based on standard of care (SOC) testing with nasopharyngeal swabs. Variant analysis by rRT-PCR was performed in a subset of time-matched vaccinated and unvaccinated individuals. A subgroup of partially and fully vaccinated individuals with a positive SARS-CoV-2 rRT-PCR was contacted to assess disease severity and post-vaccination mitigation practices. Results: Participants (n = 1,317) voluntarily underwent testing for SARS-CoV-2 during the enrollment period. A total of 29.5% of the population received at least one SARS-CoV-2 vaccine (n = 389), 12.8% partially vaccinated (n = 169); 16.1% fully vaccinated (n = 213). A total of 21.3% of partially vaccinated individuals tested positive (n = 36) and 9.4% of fully vaccinated individuals tested positive (n = 20) for SARS-CoV-2. Pfizer/BioNTech mRNA-1273 was the predominant vaccine received (1st dose = 66.8%, 2nd dose = 67.9%). Chronic liver disease and immunosuppression were more prevalent in the vaccinated (partially/fully) group compared to the unvaccinated group (p = 0.003, p = 0.021, respectively). There were more asymptomatic individuals in the vaccinated group compared to the unvaccinated group [n = 6 (10.7%), n = 16 (4.1%), p = 0.045]. CT values were lower for the unvaccinated group (median 24.3, IQR 19.1-30.5) compared to the vaccinated group (29.4, 22.0-33.7, p = 0.004). In the vaccinated group (n = 56), 18 participants were successfully contacted, 7 were lost to follow-up, and 2 were deceased. A total of 50% (n = 9) required hospitalization due to COVID-19 illness. Adherence to nationally endorsed mitigation strategies varied post-vaccination. Conclusion: The incidence of SARS-CoV-2 infection at this center was 21.3% in the partially vaccinated group and 9.4% in the fully vaccinated group. Chronic liver disease and immunosuppression were more prevalent in the vaccinated SARS-CoV-2 positive group, suggesting that these may be risk factors for VBIs. Partially and fully vaccinated individuals had a higher incidence of asymptomatic SARS-CoV-2 and higher CT values compared to unvaccinated SARS-CoV-2 positive individuals.

Arboviruses as an unappreciated cause of non-malarial acute febrile illness in the Dschang Health District of western Cameroon.

Acute febrile illness is a common problem managed by clinicians and health systems globally, particularly in the Tropics. In many regions, malaria is a leading and potentially deadly cause of fever; however, myriad alternative etiologies exist. Identifying the cause of fever allows optimal management, but this depends on many factors including thorough knowledge of circulating infections. Arboviruses such as dengue (DENV) cause fever and may be underdiagnosed in sub-Saharan Africa where malaria is a major focus. We examined cases of fever in western Cameroon that tested negative for malaria and found 13.5% (13/96) were due to DENV, with 75% (9/12) of these being DENV serotype 2 infections. Two complete DENV2 genomes were obtained and clustered closely to recent isolates from Senegal and Burkina Faso. The seroprevalence of DENV in this region was 24.8% (96/387). Neutralizing antibodies to DENV2 were detected in all (15/15) seropositive samples tested. Chikungunya (CHIKV) is an arthritogenic alphavirus that is transmitted by Aedes mosquitoes, the same principal vector as DENV. The seroprevalence for CHIKV was 15.7% (67/427); however, CHIKV did not cause a single case of fever in the 96 subjects tested. Of note, being seropositive for one arbovirus was associated with being seropositive for the other (Χ2 = 16.8, p<0.001). Taken together, these data indicate that Aedes-transmitted arboviruses are endemic in western Cameroon and are likely a common but underappreciated cause of febrile illness. This work supports the need for additional study of arboviruses in sub-Saharan Africa and efforts to improve diagnostic capacity, surveillance systems, and arbovirus prevention strategies.

Repeated Rapid Active Sampling Surveys Demonstrated a Rapidly Changing Zika Seroprevalence among Children in a Rural Dengue-endemic Region in Southwest Guatemala during the Zika Epidemic (2015-2016).

Although Central America is largely dengue virus (DENV)-endemic, the 2015-2016 Zika virus (ZIKV) pandemic brought new urgency to develop surveillance approaches capable of characterizing the rapidly changing disease burden in resource-limited settings. We conducted a pediatric DENV surveillance study in rural Guatemala, including serial cross-sectional surveys from April through September 2015 (Survey 1), in October-November 2015 (Survey 2), and January-February 2016 (Survey 3). Serum underwent DENV IgM MAC ELISA and polymerase chain reaction testing. Using banked specimens from Surveys 2 and 3, we expanded testing to include DENV 1-4 and ZIKV microneutralization (MN50), DENV NS1 IgG ELISA, and ZIKV anti-NS1 antibody Blockage of Binding (BoB) ELISA testing. Demographic risk factors for ZIKV BoB positivity were explored using multivariable generalized linear regression models. Of Survey 2 and 3 samples available (N = 382), DENV seroprevalence slightly increased (+1%-10% depending on the assay) during the surveillance period and increased with age. In contrast, ZIKV seroprevalence consistently increased over the 3-month period, including from 6% to 34% (P < 0.0001) and 10%-37% (P < 0.0001) using the MN50 ≥100 and BoB ELISA assays, respectively. Independent risk factors for ZIKV seropositivity included older age (prevalence ratio (PR)/year = 1.12, 95% confidence interval (CI) = 1.07-1.17) and primary caregiver literacy (PR = 2.80, CI = 1.30-6.06). Rapid active surveillance (RAS) surveys demonstrated a nearly 30% increase in ZIKV prevalence and a slight (≤ 10%) increase in DENV seroprevalence from October to November 2015 to January to February 2016 in rural southwest Guatemala, regardless of serologic assay used. RAS surveys may be a useful "off-the-shelf" tool to characterize arboviruses and other emerging pathogens rapidly in resource-limited settings.

Concordance of SARS-CoV-2 Results in Self-collected Nasal Swabs vs Swabs Collected by Health Care Workers in Children and Adolescents.

Importance: Despite the expansion of SARS-CoV-2 testing, available tests have not received Emergency Use Authorization for performance with self-collected anterior nares (nasal) swabs from children younger than 14 years because the effect of pediatric self-swabbing on SARS-CoV-2 test sensitivity is unknown. Objective: To characterize the ability of school-aged children to self-collect nasal swabs for SARS-CoV-2 testing compared with collection by health care workers. Design, Setting, and Participants: Cross-sectional study of 197 symptomatic children and adolescents aged 4 to 14 years old. Individuals were recruited based on results of testing in the Children's Healthcare of Atlanta system from July to August 2021. Exposures: Children and adolescents were given instructional material consisting of a short instructional video and a handout with written and visual steps for self-swab collection. Participants first provided a self-collected nasal swab. Health care workers then collected a second specimen. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 detection and relative quantitation by cycle threshold (Ct) in self- vs health care worker-collected nasal swabs when tested with a real-time reverse transcriptase-polymerase chain reaction test with Emergency Use Authorization. Results: Among the study participants, 108 of 194 (55.7%) were male and the median age was 9 years (IQR, 6-11). Of the 196 participants, 87 (44.4%) tested positive for SARS-CoV-2 and 105 (53.6%) tested negative by both self- and health care worker-collected swabs. Two children tested positive by self- or health care worker-collected swab alone; 1 child had an invalid health care worker swab. Compared with health care worker-collected swabs, self-collected swabs had 97.8% (95% CI, 94.7%-100.0%) and 98.1% (95% CI, 95.6%-100.0%) positive and negative percent agreement, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups (mean [SD] Ct, self-swab: 26.7 [5.4] vs health care worker swab: 26.3 [6.0]; P = .65). Conclusions and Relevance: After hearing and seeing simple instructional materials, children and adolescents aged 4 to 14 years self-collected nasal swabs that closely agreed on SARS-CoV-2 detection with swabs collected by health care workers.