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Background The coronavirus disease 2019 pandemic spread to >200 countries in Methods Given high residence hall student density, the University of Colorado Boulder established a mandatory weekly screening test program. We analyzed longitudinal data from 6408 students and identified 116 likely transmission events in which a second roommate tested positive within 14 days of the index roommate. Results Although the infection rate was lower in single-occupancy rooms (10%) than in multiple-occupancy rooms (19%), interroommate transmission occurred only about 20% of the time. Cases were usually asymptomatic at the time of detection. Notably, individuals who likely transmitted had an average viral load approximately 6.5-fold higher than individuals who did not (mean quantification cycle [Cq], 26.2 vs 28.9). Although students with diagnosed SARS-CoV-2 infection moved to isolation rooms, there was no difference in time to isolation between cases with or without interroommate transmission. Conclusions This analysis argues that interroommate transmission occurs infrequently in residence halls and provides strong correlative evidence that viral load is proportional to transmission probability.

To assist in the COVID-19 public health guidance on a college campus, daily composite wastewater samples were withdrawn at 20 manhole locations across the University of Colorado Boulder campus. Low-cost autosamplers were fabricated in-house to enable an economical approach to this distributed study. These sample stations operated from August 25th until November 23rd during the fall 2020 semester, with 1,512 samples collected. The concentration of SARS-CoV-2 in each sample was quantified through two comparative reverse transcription quantitative polymerase chain reactions (RT-qPCRs). These methods were distinct in the utilization of technical replicates and normalization to an endogenous control. (1) Higher temporal resolution compensates for supply chain or other constraints that prevent technical or biological replicates. (2) The data normalized by an endogenous control agreed with the raw concentration data, minimizing the utility of normalization. The raw wastewater concentration values reflected SARS-CoV-2 prevalence on campus as detected by clinical services. Overall, combining the low-cost composite sampler with a method that quantifies the SARS-CoV-2 signal within six hours enabled actionable and time-responsive data delivered to key stakeholders. With daily reporting of the findings, wastewater surveillance assisted in decision making during critical phases of the pandemic on campus, from detecting individual cases within populations ranging from 109 to 2,048 individuals to monitoring the success of on-campus interventions., Graphical abstract Tracking SARS-CoV-2 in on-campus wastewater informs and monitors public health decisions and actions. Image, graphical abstract

Significance We analyzed data from saliva-based COVID-19 screening deployed on the University of Colorado Boulder campus. Our dataset is unique in that all SARS-CoV-2−positive individuals reported no symptoms at the time of saliva collection, and therefore were infected but asymptomatic or presymptomatic. We found that 1) the distribution of viral loads observed in our asymptomatic college population was indistinguishable from what has been reported in hospitalized populations; 2) regardless of symptomatic status, approximately 50% of individuals who test positive for SARS-CoV-2 seem to be in noninfectious phases of the infection; and 3) just 2% of infected individuals carry 90% of the virions circulating within communities, serving as viral “supercarriers” and likely also superspreaders., We analyze data from the fall 2020 pandemic response efforts at the University of Colorado Boulder, where more than 72,500 saliva samples were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using qRT-PCR. All samples were collected from individuals who reported no symptoms associated with COVID-19 on the day of collection. From these, 1,405 positive cases were identified. The distribution of viral loads within these asymptomatic individuals was indistinguishable from what has been previously observed in symptomatic individuals. Regardless of symptomatic status, ∼50% of individuals who test positive for SARS-CoV-2 seem to be in noninfectious phases of the disease, based on having low viral loads in a range from which live virus has rarely been isolated. We find that, at any given time, just 2% of individuals carry 90% of the virions circulating within communities, serving as viral “supercarriers” and possibly also superspreaders.

In 2019-2020, the COVID-19 pandemic spread to over 200 countries in less than six months. To understand the basis of this aggressive spread, it is essential to determine the transmission rate and define the factors that increase the risk of transmission. One complication is the large fraction of asymptomatic cases, particularly in young populations: these individuals have viral loads indistinguishable from symptomatic people and do transmit the SARS-CoV-2 virus, but they often go undetected. As university students living in residence halls commonly share a small living space with roommates, some schools established regular, high density testing programs to mitigate on-campus spread. In this study, we analyzed longitudinal testing data of residence hall students at the University of Colorado Boulder. We observed that students in single rooms were infected at a lower rate than students in multiple occupancy rooms. However, this was not due to high rates of transmission between roommates, which only occurred approximately 20% of the time. Since these cases were usually asymptomatic at the time of diagnosis, this provides further evidence for asymptomatic transmission. Notably, individuals who likely transmitted to their roommates had an average viral load ∼6.5 times higher than individuals who did not. Although students were moved to separate isolation rooms after diagnosis, there was no difference in time to isolation between these cases with or without transmission. This analysis argues that inter-roommate transmission occurs in a minority of cases in university residence halls and provides strong correlative evidence that viral load can be proportional to the probability of transmission.

Here, we develop a simple molecular test for SARS-CoV-2 in saliva based on reverse transcription loop-mediated isothermal amplification (RT-LAMP). The test has two steps: 1) heat saliva with a stabilization solution, and 2) detect virus by incubating with a primer/enzyme mix. After incubation, saliva samples containing the SARS-CoV-2 genome turn bright yellow. Because this test is pH dependent, it can react falsely to some naturally acidic saliva samples. We report unique saliva stabilization protocols that rendered 295 healthy saliva samples compatible with the test, producing zero false positives. We also evaluated the test on 278 saliva samples from individuals who were infected with SARS-CoV-2 but had no symptoms at the time of saliva collection, and from 54 matched pairs of saliva and anterior nasal samples from infected individuals. The Saliva TwoStep test described herein identified infections with 94% sensitivity and >99% specificity in individuals with sub-clinical (asymptomatic or pre-symptomatic) infections.

he Calgary Health Region (the Region) is one of the largest completely integrated health regions in Canada, covering an area of 39,260 square kilometres. With four urban hospitals and eight rural hospitals (total of 2,104 acute care beds), the Region provides population health, preventive health, acute care, long-term care and home care services for 1.14 million residents, as well as tertiary care services for residents of southern Alberta, southwestern British Columbia and south-eastern Saskatchewan. In 2004, a batch of citrated renal dialysis solution was mistakenly prepared by the Region’s central pharmacy with potassium chloride rather than sodium chloride. Two patients in our critical care units undergoing continuous renal replacement therapy who were dialyzed with this solution developed severe hyperkalemia and subsequently died. The Region immediately recalled the remaining dialysate solutions and also informed other acute care sites in Canada that produced this type of dialysate about the adverse event. A subsequent internal review led to changes in the storage and labelling of potassium chloride in the central pharmacy and also to the dialysate solution production process. The Region disclosed the details of the adverse events to the families of the involved patients and shortly thereafter, with their permission, the Region informed the public. The Region commissioned a comprehensive external review of its pharmacy services and its organizational approach to patient safety. From this, and through its own internal processes, the Region has developed a comprehensive organizational patient safety strategy. In the last several years, many excellent reports have recommended approaches for improving healthcare safety (Institute of Medicine 2001; National Steering Committee on Patient Safety 2002; Institute of Medicine 2004). However, we were unable to find a report or guide written specifically for large integrated health regions that provided a comprehensive “how to” roadmap to address the complex area of patient safety. The internal and external reviews suggested opportunities that would assist the Region in creating a safer environment for patients. An important outcome of these efforts was the production of a framework that highlighted the key areas that needed to be addressed (Figure 1), and which has also served as the basis for the creation of the Region’s patient safety strategy. We acknowledged that in its broadest context patient safety encompasses occupational safety, environmental safety, physical plant and equipment safety, and business risk management, as well as clinical safety (i.e., the day-to-day practices that directly impact patients). Our patient safety strategy, however, deals only with the narrower context of “clinical safety.” Designing an Agenda for Change

Neonatal polycythemia is a well-established perinatal complication in infants of diabetic mothers (IDM). To investigate the regulation of erythropoiesis in these infants, we measured cord blood erythropoietin (EP) levels by a sensitive radioimmune assay and examined the growth of erythroid progenitor colonies in a series of IDM and control infants. Fifteen of 18 diabetic mothers were managed on a protocol emphasizing careful glycemic control throughout pregnancy; 10 had glycosolated hemoglobin values within the normal, nondiabetic range during the third trimester. Cord blood EP was elevated in one of 18 IDM and in two of 13 controls (p=NS). In IDM, cord blood EP values were higher in infants delivered following maternal labor and were inversely correlated with umbilical artery pH (r=-0.72; p=0.006). Growth of burst forming units-erythroid was similar in IDM and controls in the presence of 0.1 to 2.0 U of exogenous EP per ml of methylcellulose medium. Individual infants tended to respond consistently over the entire range of EP doses tested. The number of burst forming units-erythroid observed did not correlate with cord blood EP, birth weight, or neonatal hematocrits. We conclude that: (a) umbilical cord blood EP levels are generally normal in IDM delivered by mothers in whom good glycemic control is maintained throughout gestation, (b) cord blood EP values are strongly influenced by perinatal events, and (c) the response of erythroid progenitors to EP is intrinsically normal in IDM. These data suggest that polycythemia is an adaptive response in IDM and is not associated with a primary abnormality in erythropoiesis. In addition, because perinatal stress appears to acutely increase cord blood EP, elevated levels in cord blood may not accurately reflect baseline EP release in utero.

The relative requirements of colonies derived from erythroid (BFU-E) and myeloid (CFU-c) progenitors for transferrin were examined using monoclonal antibodies directed against the transferrin molecule (TF-6) or its cell surface receptor (TFR-A12, TFR1–2B). Growth of erythroid bursts was profoundly reduced at concentrations of all three antibodies that had no effect on CFU-c-derived colonies. When TFR1–2B was layered over cultures established one to seven days previously, further burst development was inhibited, and degeneration of early erythroid colonies was observed. Addition of erythropoietin augmented transferrin receptor expression on cells harvested after 1 to 2 weeks in culture and analyzed by flow cytometry. Recombinant human erythropoietin gave results comparable to those obtained in experiments using human urinary erythropoietin. Analysis of erythroblasts plucked directly from culture plates confirmed the presence of transferrin receptors on BFU-E-derived colonies. Thymidine incorporation was maximal early in the second week of culture and coincided with high transferrin receptor expression. These data demonstrate that transferrin must be available into the second week of culture to support the growth and differentiation of BFU- E-derived erythroid bursts, that the generation of erythroid colonies from BFU-E is more dependent on transferrin than myeloid colony formation from CFU-c, and that erythropoietin modulates the expression of transferrin receptors on growing bursts.