Transmission Dynamics and Rare Clustered Transmission Within an Urban University Population Before Widespread Vaccination.

BACKGROUND: Universities returned to in-person learning in 2021 while SARS-CoV-2 spread remained high. At the time, it was not clear whether in-person learning would be a source of disease spread. METHODS: We combined surveillance testing, universal contact tracing, and viral genome sequencing to quantify introductions and identify likely on-campus spread. RESULTS: Ninety-one percent of viral genotypes occurred once, indicating no follow-on transmission. Less than 5% of introductions resulted in >3 cases, with 2 notable exceptions of 40 and 47 cases. Both partially overlapped with outbreaks defined by contact tracing. In both cases, viral genomics eliminated over half the epidemiologically linked cases but added an equivalent or greater number of individuals to the transmission cluster. CONCLUSIONS: Public health interventions prevented within-university transmission for most SARS-CoV-2 introductions, with only 2 major outbreaks being identified January to May 2021. The genetically linked cases overlap with outbreaks identified by contact tracing; however, they persisted in the university population for fewer days and rounds of transmission than estimated via contact tracing. This underscores the effectiveness of test-trace-isolate strategies in controlling undetected spread of emerging respiratory infectious diseases. These approaches limit follow-on transmission in both outside-in and internal transmission conditions.

Early Introduction and Rise of the Omicron Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant in Highly Vaccinated University Populations.

BACKGROUND: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible in vaccinated and unvaccinated populations. The dynamics that govern its establishment and propensity toward fixation (reaching 100% frequency in the SARS-CoV-2 population) in communities remain unknown. Here, we describe the dynamics of Omicron at 3 institutions of higher education (IHEs) in the greater Boston area. METHODS: We use diagnostic and variant-specifying molecular assays and epidemiological analytical approaches to describe the rapid dominance of Omicron following its introduction into 3 IHEs with asymptomatic surveillance programs. RESULTS: We show that the establishment of Omicron at IHEs precedes that of the state and region and that the time to fixation is shorter at IHEs (9.5-12.5 days) than in the state (14.8 days) or region. We show that the trajectory of Omicron fixation among university employees resembles that of students, with a 2- to 3-day delay. Finally, we compare cycle threshold values in Omicron vs Delta variant cases on college campuses and identify lower viral loads among college affiliates who harbor Omicron infections. CONCLUSIONS: We document the rapid takeover of the Omicron variant at IHEs, reaching near-fixation within the span of 9.5-12.5 days despite lower viral loads, on average, than the previously dominant Delta variant. These findings highlight the transmissibility of Omicron, its propensity to rapidly dominate small populations, and the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.

Viral Dynamics of Omicron and Delta Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants With Implications for Timing of Release from Isolation: A Longitudinal Cohort Study.

BACKGROUND: In January 2022, US guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask-wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown. METHODS: We conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for reverse-transcription polymerase chain reaction (RT-PCR) testing and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared with culture. RESULTS: Among 92 SARS-CoV-2 RT-PCR-positive participants, all completed the initial vaccine series; 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset, with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For 14 substudy participants, sensitivity and specificity of day 4-6 RDT were 100% and 86%, respectively. CONCLUSIONS: The majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though guidance to mask for days 6-10 is supported by our finding that 17% of participants remained culture-positive after isolation.

Linking contact tracing with genomic surveillance to deconvolute SARS-CoV-2 transmission on a university campus.

Contact tracing and genomic data, approaches often used separately, have both been important tools in understanding the nature of SARS-CoV-2 transmission. Linked analysis of contact tracing and sequence relatedness of SARS-CoV-2 genomes from a regularly sampled university environment were used to build a multilevel transmission tracing and confirmation system to monitor and understand transmission on campus. Our investigation of an 18-person cluster stemming from an athletic team highlighted the importance of linking contact tracing and genomic analysis. Through these findings, it is suggestive that certain safety protocols in the athletic practice setting reduced transmission. The linking of traditional contact tracing with rapid-return genomic information is an effective approach for differentiating between multiple plausible transmission scenarios and informing subsequent public health protocols to limit disease spread in a university environment.

Comparison of BinaxNOW and SARS-CoV-2 qRT-PCR Detection of the Omicron Variant from Matched Anterior Nares Swabs.

The COVID-19 pandemic has increased use of rapid diagnostic tests (RDTs). In winter 2021 to 2022, the Omicron variant surge made it apparent that although RDTs are less sensitive than quantitative reverse transcription-PCR (qRT-PCR), the accessibility, ease of use, and rapid readouts made them a sought after and often sold-out item at local suppliers. Here, we sought to qualify the Abbott BinaxNOW RDT for use in our university testing program as a method to rule in positive or rule out negative individuals quickly at our priority qRT-PCR testing site. To perform this qualification study, we collected additional swabs from individuals attending this site. All swabs were tested using BinaxNOW. Initially as part of a feasibility study, test period 1 (n = 110) samples were stored cold before testing. In test period 2 (n = 209), samples were tested immediately. Combined, 102/319 samples tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive via qRT-PCR. All sequenced samples were Omicron (n = 92). We calculated 53.9% sensitivity, 100% specificity, a 100% positive predictive value, and an 82.2% negative predictive value for BinaxNOW (n = 319). Sensitivity would be improved (75.3%) by changing the qRT-PCR positivity threshold from a threshold cycle (CT) value of 40 to a CT value of 30. The receiver operating characteristic (ROC) curve shows that for qRT-PCR-positive CT values of between 24 and 40, the BinaxNOW test is of limited value diagnostically. Results suggest BinaxNOW could be used in our setting to confirm SARS-CoV-2 infection in individuals with substantial viral load, but a significant fraction of infected individuals would be missed if we used RDTs exclusively to rule out infection. IMPORTANCE Our results suggest BinaxNOW can rule in SARS-CoV-2 infection but would miss infections if RDTs were exclusively used.

Examination of SARS-CoV-2 In-Class Transmission at a Large Urban University With Public Health Mandates Using Epidemiological and Genomic Methodology.

Importance: SARS-CoV-2, the causative agent of COVID-19, has displayed person-to-person transmission in a variety of indoor situations. This potential for robust transmission has posed significant challenges and concerns for day-to-day activities of colleges and universities where indoor learning is a focus for students, faculty, and staff. Objective: To assess whether in-class instruction without any physical distancing, but with other public health mitigation strategies, is a risk for driving SARS-CoV-2 transmission. Design, Setting, and Participants: This cohort study examined the evidence for SARS-CoV-2 transmission on a large urban US university campus using contact tracing, class attendance, and whole genome sequencing during the 2021 fall semester. Eligible participants were on-campus and off-campus individuals involved in campus activities. Data were analyzed between September and December 2021. Exposures: Participation in class and work activities on a campus with mandated vaccination and indoor masking but that was otherwise fully open without physical distancing during a time of ongoing transmission of SARS-CoV-2, both at the university and in the surrounding counties. Main Outcomes and Measures: Likelihood of in-class infection was assessed by measuring the genetic distance between all potential in-class transmission pairings using polymerase chain reaction testing. Results: More than 600 000 polymerase chain reaction tests were conducted throughout the semester, with 896 tests (0.1%) showing detectable SARS-CoV-2; there were over 850 cases of SARS-CoV-2 infection identified through weekly surveillance testing of all students and faculty on campus during the fall 2021 semester. The rolling mean average of positive tests ranged between 4 and 27 daily cases. Of more than 140 000 in-person class events and a total student population of 33 000 between graduate and undergraduate students, only 9 instances of potential in-class transmission were identified, accounting for 0.0045% of all classroom meetings. Conclusions and Relevance: In this cohort study, the data suggested that under robust transmission abatement strategies, in-class instruction was not an appreciable source of disease transmission.

Comparison of anterior nares CT values in asymptomatic and symptomatic individuals diagnosed with SARS-CoV-2 in a university screening program.

At our university based high throughput screening program, we test all members of our community weekly using RT-qPCR. RT-qPCR cycle threshold (CT) values are inversely proportional to the amount of viral RNA in a sample and are a proxy for viral load. We hypothesized that CT values would be higher, and thus the viral loads at the time of diagnosis would be lower, in individuals who were infected with the virus but remained asymptomatic throughout the course of the infection. We collected the N1 and N2 target gene CT values from 1633 SARS-CoV-2 positive RT-qPCR tests of individuals sampled between August 7, 2020, and March 18, 2021, at the BU Clinical Testing Laboratory. We matched this data with symptom reporting data from our clinical team. We found that asymptomatic patients had CT values significantly higher than symptomatic individuals on the day of diagnosis. Symptoms were followed by the clinical team for 10 days post the first positive test. Within the entire population, 78.1% experienced at least one symptom during surveillance by the clinical team (n = 1276/1633). Of those experiencing symptoms, the most common symptoms were nasal congestion (73%, n = 932/1276), cough (60.0%, n = 761/1276), fatigue (59.0%, n = 753/1276), and sore throat (53.1%, n = 678/1276). The least common symptoms were diarrhea (12.5%, n = 160/1276), dyspnea on exertion (DOE) (6.9%, n = 88/1276), foot or skin changes (including rash) (4.2%, n = 53/1276), and vomiting (2.1%, n = 27/1276). Presymptomatic individuals, those who were not symptomatic on the day of diagnosis but became symptomatic over the following 10 days, had CT values higher for both N1 (median = 27.1, IQR 20.2-32.9) and N2 (median = 26.6, IQR 20.1-32.8) than the symptomatic group N1 (median = 21.8, IQR 17.2-29.4) and N2 (median = 21.4, IQR 17.3-28.9) but lower than the asymptomatic group N1 (median = 29.9, IQR 23.6-35.5) and N2 (median = 30.0, IQR 23.1-35.7). This study supports the hypothesis that viral load in the anterior nares on the day of diagnosis is a measure of disease intensity at that time.

Buildout and integration of an automated high-throughput CLIA laboratory for SARS-CoV-2 testing on a large urban campus.

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the first cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for COVID-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University (BU), created an on-campus COVID-19 screening protocol as part of a plan for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we put together an automated high-throughput clinical testing laboratory with the capacity to run 45,000 individual tests weekly by Fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed reverse transcription PCR (RT-qPCR) test, robotic instrumentation, and trained staff. There were many challenges including supply chain issues for personal protective equipment and testing materials in addition to equipment that were in high demand. The BU Clinical Testing Laboratory (CTL) was operational at the start of Fall 2020 and performed over 1 million SARS-CoV-2 PCR tests during the 2020-2021 academic year.

Viral dynamics of Omicron and Delta SARS-CoV-2 variants with implications for timing of release from isolation: a longitudinal cohort study.

Background: In January 2022, United States guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown. Methods: We conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for RT-PCR and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by SARS-CoV-2 variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared to culture. Results: Among 92 SARS-CoV-2 RT-PCR positive participants, all completed the initial vaccine series, 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For the 14 sub-study participants, sensitivity and specificity of RDT were 100% and 86% respectively. Conclusions: The majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though masking for a full 10 days is necessary to prevent transmission from the 17% of individuals who remain culture positive after isolation. Main Point: Beyond day 5, 17% of our Delta and Omicron-infected cohort were culture positive. We saw no significant impact of booster vaccination on within-host Omicron viral dynamics. Additionally, we found that rapid antigen testing may provide reassurance of lack of infectiousness.

Minimal SARS-CoV-2 classroom transmission at a large urban university experiencing repeated into campus introduction.

SARS-CoV-2, the causative agent of COVID-19, has displayed person to person transmission in a variety of indoor situations. This potential for robust transmission has posed significant challenges to day-to-day activities of colleges and universities where indoor learning is a focus. Concerns about transmission in the classroom setting have been of concern for students, faculty and staff. With the simultaneous implementation of both non-pharmaceutical and pharmaceutical control measures meant to curb the spread of the disease, defining whether in-class instruction without any physical distancing is a risk for driving transmission is important. We examined the evidence for SARS-CoV-2 transmission on a large urban university campus that mandated vaccination and masking but was otherwise fully open without physical distancing during a time of ongoing transmission of SARS-CoV-2 both at the university and in the surrounding counties. Using weekly surveillance testing of all on-campus individuals and rapid contact tracing of individuals testing positive for the virus we found little evidence of in-class transmission. Of more than 140,000 in-person class events, only nine instances of potential in-class transmission were identified. When each of these events were further interrogated by whole-genome sequencing of all positive cases significant genetic distance was identified between all potential in-class transmission pairings, providing evidence that all individuals were infected outside of the classroom. These data suggest that under robust transmission abatement strategies, in-class instruction is not an appreciable source of disease transmission.

Association of COVID-19 Quarantine Duration and Postquarantine Transmission Risk in 4 University Cohorts.

Importance: Optimal quarantine length for COVID-19 infection is unclear, in part owing to limited empirical data. Objective: To assess postquarantine transmission risk for various quarantine lengths and potential associations between quarantine strictness and transmission risk. Design, Setting, and Participants: Retrospective cohort study in 4 US universities from September 2020 to February 2021, including 3641 university students and staff who were identified as close contacts to individuals who tested positive for SARS-CoV-2 infection. Individuals were tested throughout the 10 to 14-day quarantine, and follow-up testing continued at least weekly throughout the 2020-2021 academic year. Exposures: Strict quarantine, including designated housing with a private room, private bathroom, and meal delivery, vs nonstrict, which potentially included interactions with household members. Main Outcomes and Measures: Dates of last known exposure, last negative test result, and first positive test result during quarantine. Results: This study included 301 quarantined university students and staff who tested SARS-CoV-2-positive (of 3641 quarantined total). These 301 individuals had a median (IQR) age of 22.0 (20.0-25.0) years; 131 (43.5%) identified as female; and 20 (6.6%) were staff. Of the 287 self-reporting race and ethnicity according to university-defined classifications, 21 (7.3%) were African American or Black, 60 (20.9%) Asian, 17 (5.9%) Hispanic or Latinx, 174 (60.6%) White, and 15 (5.2%) other (including multiracial and/or multiethnic). Of the 301 participants, 40 (13.3%; 95% CI, 9.9%-17.6%) had negative test results and were asymptomatic on day 7 compared with 15 (4.9%; 95% CI, 3.0%-8.1%) and 4 (1.4%; 95% CI, 0.4%-3.5%) on days 10 and 14, respectively. Individuals in strict quarantine tested positive less frequently than those in nonstrict quarantine (10% vs 12%; P = .04). Conclusions and Relevance: To maintain the 5% transmission risk used as the basis for US Centers for Disease Control and Prevention's 7-day test-based quarantine guidance, our data suggest that quarantine with quantitative polymerase chain reaction testing 1 day before intended release should be 10 days for nonstrict quarantine and 8 days for strict quarantine, as ongoing exposure during quarantine may be associated with the higher rate of positive test results following nonstrict quarantine.

Efficacy of Pfizer-BioNTech in SARS-CoV-2 Delta cluster.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) sublineage B.1.617.2 or Delta, a variant that began circulating in India and is becoming dominant in the USA, has been responsible for significant morbidity and mortality. In May 2021, the Delta variant was upgraded to a variant of concern by international authorities. This article reports a cluster of SARS-CoV-2 Delta cases detected in Boston, Massachusetts, in May 2021 involving a recent traveller from India and subsequent transmission to two of three close contacts. All three close contacts experienced the same primary exposure events but differed in vaccination status. The two close contacts that eventually tested positive were unvaccinated. The other close contact had received one dose of the BNT162b (Pfizer-BioNTech) vaccine prior to exposure, and received their second dose 2 days after exposure. This case series illustrates the effectiveness of partial vaccination in blocking transmission of the Delta variant to vaccinated individuals under circumstances where the probability of transmission for unvaccinated individuals is high.

Amplicon residues in research laboratories masquerade as COVID-19 in surveillance tests.

Asymptomatic surveillance testing together with COVID-19-related research can lead to positive SARS-CoV-2 tests resulting not from true infections, but non-infectious, non-hazardous by-products of research (amplicons). Amplicons can be widespread and persistent in lab environments and can be difficult to distinguish for true infections. We discuss prevention and mitigation strategies.

Assessment of a COVID-19 Control Plan on an Urban University Campus During a Second Wave of the Pandemic.

Importance: The COVID-19 pandemic has severely disrupted US educational institutions. Given potential adverse financial and psychosocial effects of campus closures, many institutions developed strategies to reopen campuses in the fall 2020 semester despite the ongoing threat of COVID-19. However, many institutions opted to have limited campus reopening to minimize potential risk of spread of SARS-CoV-2. Objective: To analyze how Boston University (BU) fully reopened its campus in the fall of 2020 and controlled COVID-19 transmission despite worsening transmission in Boston, Massachusetts. Design, Setting, and Participants: This multifaceted intervention case series was conducted at a large urban university campus in Boston, Massachusetts, during the fall 2020 semester. The BU response included a high-throughput SARS-CoV-2 polymerase chain reaction testing facility with capacity to deliver results in less than 24 hours; routine asymptomatic screening for COVID-19; daily health attestations; adherence monitoring and feedback; robust contact tracing, quarantine, and isolation in on-campus facilities; face mask use; enhanced hand hygiene; social distancing recommendations; dedensification of classrooms and public places; and enhancement of all building air systems. Data were analyzed from December 20, 2020, to January 31, 2021. Main Outcomes and Measures: SARS-CoV-2 diagnosis confirmed by reverse transcription-polymerase chain reaction of anterior nares specimens and sources of transmission, as determined through contact tracing. Results: Between August and December 2020, BU conducted more than 500 000 COVID-19 tests and identified 719 individuals with COVID-19, including 496 students (69.0%), 11 faculty (1.5%), and 212 staff (29.5%). Overall, 718 individuals, or 1.8% of the BU community, had test results positive for SARS-CoV-2. Of 837 close contacts traced, 86 individuals (10.3%) had test results positive for COVID-19. BU contact tracers identified a source of transmission for 370 individuals (51.5%), with 206 individuals (55.7%) identifying a non-BU source. Among 5 faculty and 84 staff with SARS-CoV-2 with a known source of infection, most reported a transmission source outside of BU (all 5 faculty members [100%] and 67 staff members [79.8%]). A BU source was identified by 108 of 183 undergraduate students with SARS-CoV-2 (59.0%) and 39 of 98 graduate students with SARS-CoV-2 (39.8%); notably, no transmission was traced to a classroom setting. Conclusions and Relevance: In this case series of COVID-19 transmission, BU used a coordinated strategy of testing, contact tracing, isolation, and quarantine, with robust management and oversight, to control COVID-19 transmission in an urban university setting.