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

BackgroundIn 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. MethodsWe 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. ResultsAmong 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. ConclusionsThe 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 PointBeyond 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.

Adherence to and enforcement of non-pharmaceutical interventions (NPIs) for COVID-19 prevention in Nigeria, Rwanda, and Zambia: A mixed-methods analysis

IntroductionIn the early parts of the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) were implemented worldwide, including in sub-Saharan Africa, to prevent and control SARS-CoV-2 transmission. This mixed-methods study examines adherence to and enforcement of NPIs implemented to curb COVID-19 in Nigeria, Rwanda, and Zambia, leading up to the 10,000th case of laboratory-confirmed COVID-19 in each country. Additionally, we aim to evaluate the relationship between levels and changes of NPIs over time and changes in COVID-19 cases and deaths. MethodsThis mixed-methods analysis utilized semi-structured interviews and a quantitative dataset constructed using multiple open data sources, including the Oxford COVID-19 Government Response Tracker. To understand potential barriers and facilitators in implementing and enforcing NPIs qualitative data were collected from those involved in the COVID-19 response and analyzed using NVivo. Quantitative results were analyzed using descriptive statistics, plots, ANOVA, and post hoc Tukey. ResultsIndividual indicator scores varied with the COVID-19 response in all three countries. Nigeria had sustained levels of strict measures for containment and closure NPIs, while in Rwanda there was substantial variation in NPI score as it transitioned through the different case windows for the same measures. Zambia implemented moderate stringency throughout the pandemic using gathering restrictions and business/school closure measures but maintained low levels of strictness for other containment and closure measures. Rwanda had far more consistent and stringent measures compared to Nigeria and Zambia. Rwandas success in implementing COVID-related measures was partly due to strong enforcement and having a population that generally obeys its government. ConclusionVarious forces either facilitated or hindered adherence and compliance to COVID-19 control measures. This research highlights important lessons, including the need to engage communities early and create buy-in, as well as the need for preparation to ensure that response efforts are proactive rather than reactive when faced with an emergency.

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.

Early introduction and rise of the Omicron SARS-CoV-2 variant in highly vaccinated university populations

The Omicron variant of SARS-CoV-2 is transmissible in vaccinated and unvaccinated populations. Here, we describe the rapid dominance of Omicron following its introduction to three Massachusetts universities with asymptomatic surveillance programs. We find that Omicron was established and reached fixation earlier on these campuses than in Massachusetts or New England as a whole, rapidly outcompeting Delta despite its association with lower viral loads. These findings highlight the transmissibility of Omicron and its propensity to fixate in small populations, as well as the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.

Comparison of Anterior Nares Viral Loads in Asymptomatic and Symptomatic Individuals Diagnosed with SARS-CoV-2 in a University Screening Program

RT-qPCR has been used as the gold standard method for detecting SARS-CoV-2 since early in the pandemic. At our university based high throughput screening program, we test all members of our community weekly. RT-qPCR cycle threshold (CT) values are inversely proportional to the amount of viral RNA in a sample, and thus 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 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.

Detailed Overview of the 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 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, created an on-campus Covid-19 screening protocol as part of planning for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we stood up an automated high-throughput clinical testing lab with the capacity to run 45,000 individual tests weekly by fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed RT-PCR test, robotic instrumentation, and trained CLIA certified staff. There were challenges to overcome, including the supply chain issues for PPE testing materials, and equipment that were in high demand. The Boston University Clinical Testing Laboratory was operational at the start of the fall 2020 academic year. The lab performed over 1 million SARS-CoV-2 RT-PCR tests during the 2020-2021 academic year.

Seven-day COVID-19 quarantine may be too short: assessing post-quarantine transmission risk in four university cohorts

BackgroundDespite rising rates of vaccination, quarantine remains critical to control SARS-CoV-2 transmission. COVID-19 quarantine length around the world varies in part due to the limited amount of empirical data. ObjectiveTo assess post-quarantine transmission risk for various quarantine lengths. DesignCohort study. SettingFour US universities, September 2020 to February 2021. Participants3,641 students and staff were identified as close contacts to SARS-CoV-2-positive individuals. They entered strict or non-strict quarantine and were tested on average twice per week for SARS-CoV-2. Strict quarantine included designated housing with a private room, private bathroom and meal delivery. Non-strict quarantine potentially included interactions with household members. MeasurementsDates of exposure and last negative and first positive tests during quarantine. ResultsOf the 418 quarantined individuals who eventually converted to positive, 11%, 4.2%, and 1.2% were negative and asymptomatic on days 7, 10 and 14, respectively. The US CDC recently shortened its quarantine guidance from 14 to 7 days based on estimates of 2.3-8.6% post-quarantine transmission risk at day 7, significantly below the 11% risk we report here. Notably, 6% of individuals tested positive after day 7 in strict quarantine, versus 14% in non-strict quarantine. Ongoing exposure during quarantine likely explains the higher rate of COVID-19 in non-strict quarantine. LimitationsQuarantine should be longer for individuals using antigen testing, given antigen testings lower sensitivity than qPCR. Results apply in settings in which SAR-CoV-2 variants do not affect latent period. ConclusionsTo maintain the 5% transmission risk that the CDC used in its guidance, our data suggest that quarantine with qPCR testing 1 day before intended release should extend to 10 days for non-strict quarantine. Funding SourceNone.

Control of COVID-19 transmission on an urban university campus during a second wave of the pandemic

ImportanceThe COVID-19 pandemic had a wide-ranging impact on educational institutions across the United States. Given potential financial challenges and adverse psychosocial effects of campus closure, as done in the spring of 2020 in response to the first wave, many institutions of higher education developed strategies to allow campuses to reopen and operate in the fall despite the ongoing threat of COVID-19. Many however opted to have limited campus re-opening in order to minimize potential risk of spread of SARS-CoV-2. ObjectiveTo analyze how Boston University (BU) fully reopened its campus in the fall of 2020 and controlled COVID-19 transmission despite worsening transmission in the city of Boston. DesignMulti-faceted intervention case study. SettingLarge urban university campus. InterventionsThe BU response included a high-throughput SARS-CoV-2 PCR testing facility with capacity to delivery results in less than 24 hours; routine asymptomatic screening for COVID-19; daily health attestations; compliance monitoring and feedback; robust contact tracing, quarantine and isolation in on campus facilities; face mask use; enhanced hand hygiene; social distancing recommendations; de-densification of classrooms and public places; and enhancement of all building air systems. Main Outcomes and MeasuresBetween August and December 2020, BU conducted >500,000 COVID-19 tests and identified 719 individuals with COVID-19: 627 (87.2%) students, 11 (1.5%) faculty, and 212 (25.5%) staff. Overall, about 1.8% of the BU community tested positive. Infections among faculty and staff were mostly acquired off campus, while undergraduate infections were more likely acquired in non-classroom campus settings. Of 837 close contacts traced, 86 (10.3%) tested positive for COVID-19. BU contact tracers identified a source of transmission for 51.5% of cases with 55.7% identifying a source outside of BU. Among infected faculty and staff with a known source of infection, the majority reported a transmission source outside of BU (100% for faculty and 79.8% for staff). Conclusions and RelevanceBU was successful in containing COVID-19 transmission on campus while minimizing off campus acquisition of COVID-19 from the greater Boston area. A coordinated strategy of testing, contact tracing, isolation and quarantine, with robust management and oversight, can control COVID-19 transmission, even in an urban university setting.

Amplicon contamination in labs masquerades as COVID19 in surveillance tests

A cohort of laboratorians with positive SARS-CoV2 test results were uncovered during asymptomatic COVID-19 screening programs at six universities. Follow-up PCR and antibody tests showed that most of these cases were not true COVID-19 infection but instead arose from reverse-transcribed and amplified viral sequences (amplicons) that are generated during research. Environmental testing showed widespread contamination of amplicons in lab spaces including notebooks, keyboards, glasses, and doorknobs. Minimizing instances of amplicon contamination and developing protocols for handling suspected cases are critical to propel research efforts and to avoid diverting university and healthcare resources from patients with COVID-19. Removal of these individuals from the standard testing protocol, per CDC guidelines for positive cases, risks the spread of true infection. We discuss potential prevention and mitigation strategies.