Tracing the origin of SARS-CoV-2 omicron-like spike sequences detected in an urban sewershed: a targeted, longitudinal surveillance study of a cryptic wastewater lineage.

BACKGROUND: The origin of novel SARS-CoV-2 spike sequences found in wastewater, without corresponding detection in clinical specimens, remains unclear. We sought to determine the origin of one such cryptic wastewater lineage by tracking and characterising its persistence and genomic evolution over time. METHODS: We first detected a cryptic lineage, WI-CL-001, in municipal wastewater in Wisconsin, USA, in January, 2022. To determine the source of WI-CL-001, we systematically sampled wastewater from targeted sub-sewershed lines and maintenance holes using compositing autosamplers. Viral concentrations in wastewater samples over time were measured by RT digital PCR. In addition to using metagenomic 12s rRNA sequencing to determine the virus's host species, we also sequenced SARS-CoV-2 spike receptor binding domains, and, where possible, whole viral genomes to identify and characterise the evolution of this lineage. FINDINGS: We traced WI-CL-001 to its source at a single commercial building. There we detected the cryptic lineage at concentrations as high as 2·7 × 109 genome copies per L. The majority of 12s rRNA sequences detected in wastewater leaving the identified source building were human. Additionally, we generated over 100 viral receptor binding domain and whole-genome sequences from wastewater samples containing the cryptic lineage collected over the 13 consecutive months this virus was detectable (January, 2022, to January, 2023). These sequences contained a combination of fixed nucleotide substitutions characteristic of Pango lineage B.1.234, which circulated in humans in Wisconsin at low levels from October, 2020, to February, 2021. Despite this, mutations in the spike gene and elsewhere resembled those subsequently found in omicron variants. INTERPRETATION: We propose that prolonged detection of WI-CL-001 in wastewater indicates persistent shedding of SARS-CoV-2 from a single human initially infected by an ancestral B.1.234 virus. The accumulation of convergent omicron-like mutations in WI-CL-001's ancestral B.1.234 genome probably reflects persistent infection and extensive within-host evolution. People who shed cryptic lineages could be an important source of highly divergent viruses that sporadically emerge and spread. FUNDING: The Rockefeller Foundation, Wisconsin Department of Health Services, Centers for Disease Control and Prevention, National Institute on Drug Abuse, and the Center for Research on Influenza Pathogenesis and Transmission.

Wastewater Surveillance Data as a Complement to Emergency Department Visit Data for Tracking Incidence of Influenza A and Respiratory Syncytial Virus - Wisconsin, August 2022-March 2023.

Wastewater surveillance has been used to assist public health authorities in tracking local transmission of SARS-CoV-2. The usefulness of wastewater surveillance to track community spread of other respiratory pathogens, including influenza virus and respiratory syncytial virus (RSV), is less clear. During the 2022-23 respiratory diseases season, concentrations of influenza A virus and RSV in wastewater samples in three major Wisconsin cities were compared with emergency department (ED) visits associated with these pathogens. In all three cities, higher concentrations of influenza A virus and RSV in wastewater were associated with higher numbers of associated ED visits (Kendall's tau range = 0.50-0.63 for influenza-associated illness and 0.30-0.49 for RSV-associated illness). Detections of both influenza A virus and RSV in wastewater often preceded a rise in associated ED visits for each pathogen, and virus material remained detectable in wastewater for up to 3 months after pathogen-specific ED visits declined. These results demonstrate that wastewater surveillance has the potential to complement conventional methods of influenza and RSV surveillance, detecting viral signals earlier and for a longer duration than do clinical data. Continued use of wastewater surveillance as a supplement to established surveillance systems such as ED visits might improve local understanding and response to seasonal respiratory virus outbreaks.

Evaluating the Role of Corrals and Insects in the Transmission of Porcine Cysticercosis: A Cohort Study.

The widespread dispersion of pigs infected with cysticercosis across endemic villages, low cyst burden among infected pigs, and low prevalence of taeniasis all suggest that pig ingestion of human feces is not the only mode of transmission for Taenia solium. Our objective was to evaluate the risk of porcine cysticercosis associated with exposure to human feces, dung beetles, and flies in an endemic community setting. We used a cluster-randomized cohort design to compare the risk of developing antibodies and infection among 120 piglets raised in either free-roaming (FR), standard corral (SC), or netted corral environments (NC). We collected monthly blood samples to detect serum antibodies and necropsied all pigs after 10 months to identify cysts. A total of 66 piglets developed antibodies with the relative risk of seropositivity in FR vs. all corralled pigs increasing significantly after 18 weeks. Of 108 necropsied pigs, 15 had T. solium cysts, all belonging to the FR group. Corrals were protective against infection but less so against seropositivity. NC, which did not completely exclude insects, did not provide added protection against seropositivity as compared to SC. The results of this study suggest that dung beetles and flies do not play an important role in infection.

COVID-19 on the Nile: a cross-sectional investigation of COVID-19 among Nile River cruise travellers returning to the United States, February-March 2020.

BACKGROUND: Early in the pandemic, cruise travel exacerbated the global spread of SARS-CoV-2. We report epidemiologic and molecular findings from an investigation of a cluster of travellers with confirmed COVID-19 returning to the USA from Nile River cruises in Egypt. METHODS: State health departments reported data on real-time reverse transcription-polymerase chain reaction-confirmed COVID-19 cases with a history of Nile River cruise travel during February-March 2020 to the Centers for Disease Control and Prevention (CDC). Demographic and epidemiologic data were collected through routine surveillance channels. Sequences were obtained either from state health departments or from the Global Initiative on Sharing Avian Flu Data (GISAID). We conducted descriptive analyses of epidemiologic data and explored phylogenetic relationships between sequences. RESULTS: We identified 149 Nile River cruise travellers with confirmed COVID-19 who returned to 67 different US counties in 27 states: among those with complete data, 4.7% (6/128) died and 28.1% (38/135) were hospitalized. These individuals travelled on 20 different Nile River cruise voyages (12 unique vessels). Fifteen community transmission events were identified in four states, with 73.3% (11/15) of these occurring in Wisconsin (as the result of a more detailed contact investigation in that state). Phylogenetic analyses supported the hypothesis that travellers were most likely infected in Egypt, with most sequences in Nextstrain clade 20A 93% (87/94). We observed genetic clustering by Nile River cruise voyage and vessel. CONCLUSIONS: Nile River cruise travellers with COVID-19 introduced SARS-CoV-2 over a very large geographic range, facilitating transmission across the USA early in the pandemic. Travellers who participate in cruises, even on small river vessels as investigated in this study, are at increased risk of SARS-CoV-2 exposure. Therefore, history of river cruise travel should be considered in contact tracing and outbreak investigations.

Measuring Work-related Risk of Coronavirus Disease 2019 (COVID-19): Comparison of COVID-19 Incidence by Occupation and Industry-Wisconsin, September 2020 to May 2021.

BACKGROUND: Work-related exposures play an important role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, yet few studies have compared SARS-CoV-2 expsoure risk across occupations and industries. METHODS: During September 2020 to May 2021, the Wisconsin Department of Health Services collected occupation and industry data as part of routine coronavirus disease 2019 (COVID-19) case investigations. Adults aged 18-64 years with confirmed or probable COVID-19 in Wisconsin were assigned standardized occupation and industry codes. Cumulative incidence rates were weighted for non-response and calculated using full-time equivalent (FTE) workforce denominators from the 2020 American Community Survey. RESULTS: An estimated 11.6% of workers (347 013 of 2.98 million) in Wisconsin, ages 18-64 years, had COVID-19 from September 2020 to May 2021. The highest incidence by occupation (per 100 FTE) occurred among personal care and services workers (22.1), healthcare practitioners and support staff (20.7), and protective services workers (20.7). High-risk sub-groups included nursing assistants and personal care aides (28.8), childcare workers (25.8), food and beverage service workers (25.3), personal appearance workers (24.4), and law enforcement workers (24.1). By industry, incidence was highest in healthcare (18.6); the highest risk sub-sectors were nursing care facilities (30.5) and warehousing (28.5). CONCLUSIONS: This analysis represents one of the most complete examinations to date of COVID-19 incidence by occupation and industry. Our approach demonstrates the value of standardized occupational data collection by public health and may be a model for improved occupational surveillance elsewhere. Workers at higher risk of SARS-CoV-2 exposure may benefit from targeted workplace COVID-19 vaccination and mitigation efforts.

School District Prevention Policies and Risk of COVID-19 Among In-Person K-12 Educators, Wisconsin, 2021.

Objectives. To assess the rate of COVID-19 among in-person K-12 educators and the rate's association with various COVID-19 prevention policies in school districts. Methods. We linked actively working, in-person K-12 educators in Wisconsin to COVID-19 cases with onset from September 2 to November 24, 2021. A mixed-effects Cox proportional hazards model, adjusted for pertinent person- and community-level confounders, compared the hazard rate of COVID-19 among educators working in districts with and without specific COVID-19 prevention policies. Results. In-person educators working in school districts that required masking for students and staff experienced 19% lower hazards of COVID-19 than did those in districts without any masking policy (hazard ratio = 0.81; 95% confidence interval = 0.72, 0.92). Reduced COVID-19 hazards were consistent and remained statistically significant when educators were stratified by elementary, middle, and high school environments. Conclusions. In Wisconsin's K-12 school districts, during the fall 2021 academic semester, a policy that required both students and staff to mask was associated with significantly reduced risk of COVID-19 among in-person educators across all grade levels. (Am J Public Health. 2022;112(12):1791-1799. https://doi.org/10.2105/AJPH.2022.307095).

Lost time: COVID-19 indemnity claim reporting and results in the Wisconsin workers' compensation system from March 12 to December 31, 2020.

BACKGROUND: The COVID-19 pandemic introduced a new compensable infectious disease to workplaces. METHODS: This was a descriptive analysis of Wisconsin COVID workers' compensation (WC) claims between March 12 and December 31, 2020. The impact of the presumption law (March 12 to June 10, 2020) was also evaluated. RESULTS: Less than 1% of working-age residents with COVID-19 filed a claim. COVID-19 WC claim rates (per 100,000 FTE) were notably low for frontline industry sectors such as Retail Trade (n = 115), Manufacturing (n = 88), and Wholesale Trade (n = 31). Healthcare workers (764 claims per 100,000 FTE) comprised 73.2% of COVID-19 claims. Most claims (52.8%) were denied and the proportion of denied claims increased significantly after the presumption period for both first responders and other occupations. CONCLUSION: The presumption law made benefits accessible primarily to first responders. Further changes to WC systems are needed to offset the individual and collective costs of infectious diseases.

Non-local validated parametrization of an agent-based model of local-scale Taenia solium transmission in North-West Peru.

The pork tapeworm, Taenia solium, is the cause of a preventable zoonotic disease, cysticercosis, affecting both pigs and humans. Continued endemic transmission of T. solium is a major contributor of epilepsy and other neurologic morbidity, and the source of important economic losses, in many rural areas of developing countries. Simulation modelling can play an important role in aiding the design and evaluation of strategies to control or even eliminate transmission of the parasite. In this paper, we present a new agent based model of local-scale T. solium transmission and a new, non-local, approach to the model calibration to fit model outputs to observed human taeniasis and pig cysticercosis prevalence simultaneously for several endemic villages. The model fully describes all relevant aspects of T. solium transmission, including the processes of pig and human infection, the spatial distribution of human and pig populations, the production of pork for human consumption, and the movement of humans and pigs in and out in several endemic villages of the northwest of Peru. Despite the high level of uncertainty associated with the empirical measurements of epidemiological data associated with T. solium, the non-local calibrated model parametrization reproduces the observed prevalences with an acceptable precision. It does so not only for the villages used to calibrate the model, but also for villages not included in the calibration process. This important finding demonstrates that the model, including its calibrated parametrization, can be successfully transferred within an endemic region. This will enable future studies to inform the design and optimization of T. solium control interventions in villages where the calibration may be prevented by the limited amount of empirical data, expanding the possible applications to a wider range of settings compared to previous models.

Movements of free-range pigs in rural communities in Zambia: an explorative study towards future ring interventions for the control of Taenia solium.

BACKGROUND: Taenia solium typically affects resource-poor communities where pigs are allowed to roam freely, and sanitation and hygiene levels are suboptimal. Sustainable, long-term strategies are urgently needed to control the disease. Geographically targeted interventions, i.e. screening or treatment of taeniosis among people living near infected pigs (defined as ring screening and ring treatment, respectively), have been shown to be effective control options in Peru. However, these results might not be directly generalizable to sub-Saharan African settings. Pig movements play a vital role in the transmission and, consequently, the success of ring interventions against T. solium. The aim of the present study was to explore roaming patterns of pigs in T. solium endemic communities in Zambia as a first step toward evaluating whether ring interventions should be considered as a treatment option in Zambia. METHODS: In total, 48 free-roaming pigs in two rural neighborhoods in the Eastern Province of Zambia were tracked using a Global Positioning System (GPS) receiver. Tracking took place in April (end of the rainy season) 2019 and October (end of the dry season) 2019. The number of revisitations and the time spent within rings of different radii (50, 100 and 250 m) around the coordinates of each pig owner's household were calculated for each pig. RESULTS: The total tracking time for 43 pigs in the final analysis set ranged between 43 and 94 h. Pigs spent a median of 31% and 13% of the tracked time outside the 50- and 100-m radius, respectively, although large variations were observed between pigs. Overall, 25 pigs (58%) went outside the 250-m ring at least once, and individual excursions lasting up to 16 h were observed. In the dry season, 17 out of 23 pigs went outside the 250-m radius compared to only eight out of 20 pigs in the rainy season (P = 0.014). CONCLUSIONS: In our study sites in Zambia, the majority of pigs spent most of their time within 50 or 100 m of their owner's home, and these results are comparable with those on Peruvian pigs. Both radii could therefore be considered reasonable options in future ring interventions.

Public Health Actions to Control Measles Among Afghan Evacuees During Operation Allies Welcome - United States, September-November 2021.

On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases,† with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.§ On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2).

Investigation of SARS-CoV-2 Transmission Associated With a Large Indoor Convention - New York City, November-December 2021.

During November 19-21, 2021, an indoor convention (event) in New York City (NYC), was attended by approximately 53,000 persons from 52 U.S. jurisdictions and 30 foreign countries. In-person registration for the event began on November 18, 2021. The venue was equipped with high efficiency particulate air (HEPA) filtration, and attendees were required to wear a mask indoors and have documented receipt of at least 1 dose of a COVID-19 vaccine.* On December 2, 2021, the Minnesota Department of Health reported the first case of community-acquired COVID-19 in the United States caused by the SARS-CoV-2 B.1.1.529 (Omicron) variant in a person who had attended the event (1). CDC collaborated with state and local health departments to assess event-associated COVID-19 cases and potential exposures among U.S.-based attendees using data from COVID-19 surveillance systems and an anonymous online attendee survey. Among 34,541 attendees with available contact information, surveillance data identified test results for 4,560, including 119 (2.6%) persons from 16 jurisdictions with positive SARS-CoV-2 test results. Most (4,041 [95.2%]), survey respondents reported always wearing a mask while indoors at the event. Compared with test-negative respondents, test-positive respondents were more likely to report attending bars, karaoke, or nightclubs, and eating or drinking indoors near others for at least 15 minutes. Among 4,560 attendees who received testing, evidence of widespread transmission during the event was not identified. Genomic sequencing of 20 specimens identified the SARS-CoV-2 B.1.617.2 (Delta) variant (AY.25 and AY.103 sublineages) in 15 (75%) cases, and the Omicron variant (BA.1 sublineage) in five (25%) cases. These findings reinforce the importance of implementing multiple, simultaneous prevention measures, such as ensuring up-to-date vaccination, mask use, physical distancing, and improved ventilation in limiting SARS-CoV-2 transmission, during large, indoor events.†.

Application of a Serial Antigen-Based Testing Strategy for Severe Acute Respiratory Syndrome Coronavirus 2 and Student Adherence in a University Setting: Wisconsin, October-November 2020.

BACKGROUND: Serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing has been implemented at institutions of higher education (IHEs) and other settings. Testing strategies can include algorithms specifying confirmatory reverse-transcription polymerase chain reaction (RT-PCR) testing after an antigen test. It is unknown how testing strategies perform detecting SARS-CoV-2, including individual adherence to serial testing requirements. METHODS: Student serial testing adherence was defined as completing ≥80% of weekly tests from October 5, 2020 to November 14, 2020 and evaluated using logistic regression. Medical records were reviewed for all positive antigen test encounters and 10% of daily negative antigen test encounters during October 19-November 30, 2020. Results were used to estimate the proportion of individuals requiring only antigen tests, requiring and completing RT-PCR testing, and associated costs of tests. RESULTS: Two thirds (66.5%; 1166 of 1754) of eligible on-campus students adhered to weekly testing; female students were more adherent (adjusted odds ratio [aOR], 2.07; 95% confidence interval, 1.66-2.59) than male students. Of all antigen test encounters, 11.5% (1409 of 12 305) reported >1 COVID-19 symptoms. Of non-COVID-19-exposed antigen test encounters, 88% (10 386 of 11 769) did not require confirmatory RT-PCR testing. Only 28% (390 of 1387) of testing encounters had an associated recommended confirmatory RT-PCR test performed. We estimated the testing strategy captured 61% (235 of 389) of predicted RT-PCR-positive specimens. CONCLUSIONS: At this IHE, most students voluntarily adhered to serial testing. The majority of antigen test results did not require confirmatory RT-PCR testing, but when required, most students did not obtain it. Including strategies to increase the proportion of individuals obtaining indicated confirmatory testing might improve the testing program's performance.

Validation of a spatial agent-based model for Taenia solium transmission ("CystiAgent") against a large prospective trial of control strategies in northern Peru.

BACKGROUND: The pork tapeworm (Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. CystiAgent is a spatially-explicit agent based model for T. solium that is unique among T. solium models in its ability to represent key spatial and environmental features of transmission and simulate spatially targeted interventions, such as ring strategy. METHODS/PRINCIPAL FINDINGS: We validated CystiAgent against results from the Ring Strategy Trial (RST)-a large cluster-randomized trial conducted in northern Peru that evaluated six unique interventions for T. solium control in 23 villages. For the validation, each intervention strategy was replicated in CystiAgent, and the simulated prevalences of human taeniasis, porcine cysticercosis, and porcine seroincidence were compared against prevalence estimates from the trial. Results showed that CystiAgent produced declines in transmission in response to each of the six intervention strategies, but overestimated the effect of interventions in the majority of villages; simulated prevalences for human taenasis and porcine cysticercosis at the end of the trial were a median of 0.53 and 5.0 percentages points less than prevalence observed at the end of the trial, respectively. CONCLUSIONS/SIGNIFICANCE: The validation of CystiAgent represented an important step towards developing an accurate and reliable T. solium transmission model that can be deployed to fill critical gaps in our understanding of T. solium transmission and control. To improve model accuracy, future versions would benefit from improved data on pig immunity and resistance, field effectiveness of anti-helminthic treatment, and factors driving spatial clustering of T. solium infections including dispersion and contact with T. solium eggs in the environment.

Interventions to Disrupt Coronavirus Disease Transmission at a University, Wisconsin, USA, August-October 2020.

University settings have demonstrated potential for coronavirus disease (COVID-19) outbreaks; they combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin-Madison, Madison, Wisconsin, USA. During August-October 2020, a total of 3,485 students, including 856/6,162 students living in dormitories, tested positive. Case counts began rising during move-in week, August 25-31, 2020, then rose rapidly during September 1-11, 2020. The university initiated multiple prevention efforts, including quarantining 2 dormitories; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, in which the university is located, did not find evidence of transmission from a large cluster of cases in the 2 quarantined dorms during the outbreak. Coordinated implementation of prevention measures can reduce COVID-19 spread in university settings and may limit spillover to the surrounding community.

Geographically Targeted Interventions versus Mass Drug Administration to Control Taenia solium Cysticercosis, Peru.

Optimal control strategies for Taenia solium taeniasis and cysticercosis have not been determined. We conducted a 2-year cluster randomized trial in Peru by assigning 23 villages to 1 of 3 geographically targeted intervention approaches. For ring screening (RS), participants living near pigs with cysticercosis were screened for taeniasis; identified cases were treated with niclosamide. In ring treatment (RT), participants living near pigs with cysticercosis received presumptive treatment with niclosamide. In mass treatment (MT), participants received niclosamide treatment every 6 months regardless of location. In each approach, half the villages received targeted or mass oxfendazole for pigs (6 total study arms). We noted significant reductions in seroincidence among pigs in all approaches (67.1% decrease in RS, 69.3% in RT, 64.7% in MT; p<0.001), despite a smaller proportion of population treated by targeted approaches (RS 1.4%, RT 19.3%, MT 88.5%). Our findings suggest multiple approaches can achieve rapid control of T. solium transmission.

Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Intercollegiate Athletics Not Fully Mitigated With Daily Antigen Testing.

BACKGROUND: High-frequency, rapid-turnaround severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, 2 SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester, despite mandatory directly observed daily antigen testing. METHODS: During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel's Sofia SARS Antigen Fluorescent Immunoassay, with positive antigen results requiring confirmatory testing with real-time reverse-transcription polymerase chain reaction. We used genomic sequencing to investigate transmission dynamics in these 2 outbreaks. RESULTS: In the first outbreak, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious, despite a negative antigen test on the day of the meeting. Among isolates sequenced from that outbreak, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In the second outbreak, 12 confirmed cases occurred among athletes from 2 university programs that faced each other in an athletic competition, despite receipt of negative antigen test results on the day of the competition. Sequences from both teams were closely related and distinct from viruses circulating in the community for team 1, suggesting transmission during intercollegiate competition in the community for team 2. CONCLUSIONS: These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and they highlight the importance of vaccination to prevent SARS-CoV-2 outbreak in congregate settings.

Epidemiologic Characteristics Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antigen-Based Test Results, Real-Time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) Cycle Threshold Values, Subgenomic RNA, and Viral Culture Results From University Testing.

BACKGROUND: Real-time reverse transcription polymerase chain reaction (rRT-PCR) and antigen tests are important diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sensitivity of antigen tests has been shown to be lower than that of rRT-PCR; however, data to evaluate epidemiologic characteristics that affect test performance are limited. METHODS: Paired mid-turbinate nasal swabs were collected from university students and staff and tested for SARS-CoV-2 using both Quidel Sofia SARS Antigen Fluorescent Immunoassay (FIA) and rRT-PCR assay. Specimens positive by either rRT-PCR or antigen FIA were placed in viral culture and tested for subgenomic RNA (sgRNA). Logistic regression models were used to evaluate characteristics associated with antigen results, rRT-PCR cycle threshold (Ct) values, sgRNA, and viral culture. RESULTS: Antigen FIA sensitivity was 78.9% and 43.8% among symptomatic and asymptomatic participants, respectively. Among rRT-PCR positive participants, negative antigen results were more likely among asymptomatic participants (odds ratio [OR] 4.6, 95% confidence interval [CI]: 1.3-15.4) and less likely among participants reporting nasal congestion (OR 0.1, 95% CI: .03-.8). rRT-PCR-positive specimens with higher Ct values (OR 0.5, 95% CI: .4-.8) were less likely, and specimens positive for sgRNA (OR 10.2, 95% CI: 1.6-65.0) more likely, to yield positive virus isolation. Antigen testing was >90% positive in specimens with Ct values < 29. Positive predictive value of antigen test for positive viral culture (57.7%) was similar to that of rRT-PCR (59.3%). CONCLUSIONS: SARS-CoV-2 antigen test advantages include low cost, wide availability and rapid turnaround time, making them important screening tests. The performance of antigen tests may vary with patient characteristics, so performance characteristics should be accounted for when designing testing strategies and interpreting results.

SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing.

BACKGROUND: High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing. METHODS: During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel's Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks. RESULTS: In Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition. CONCLUSIONS: These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings. SUMMARY: High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, here we describe two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester.

Persistent SARS-CoV-2 RNA Shedding Without Evidence of Infectiousness: A Cohort Study of Individuals With COVID-19.

BACKGROUND: To better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding and infectivity, we estimated SARS-CoV-2 RNA shedding duration, described participant characteristics associated with the first negative rRT-PCR test (resolution), and determined if replication-competent viruses was recoverable ≥10 days after symptom onset. METHODS: We collected serial nasopharyngeal specimens from 109 individuals with rRT-PCR-confirmed COVID-19 in Utah and Wisconsin. We calculated viral RNA shedding resolution probability using the Kaplan-Meier estimator and evaluated characteristics associated with shedding resolution using Cox proportional hazards regression. We attempted viral culture for 35 rRT-PCR-positive nasopharyngeal specimens collected ≥10 days after symptom onset. RESULTS: The likelihood of viral RNA shedding resolution at 10 days after symptom onset was approximately 3%. Time to shedding resolution was shorter among participants aged <18 years (adjusted hazards ratio [aHR], 3.01; 95% confidence interval [CI], 1.6-5.6) and longer among those aged ≥50 years (aHR, 0.50; 95% CI, .3-.9) compared to participants aged 18-49 years. No replication-competent viruses were recovered. CONCLUSIONS: Although most patients were positive for SARS-CoV-2 for ≥10 days after symptom onset, our findings suggest that individuals with mild to moderate COVID-19 are unlikely to be infectious ≥10 days after symptom onset.