Research, scholarship and creative work is the foundation upon which faculty passion is built, the vehicle that engages deep student-faculty mentorships that inspire the next generation of thought leaders, and a central part of how DU contributes to our vision for the public good. Throughout the pandemic, research, scholarship and creative work remained a priority in the campus plan for these reasons. Some research facilities remained open during Phase I, in alignment with the Stay At Home orders, as essential to support lifeforms, maintain specialized equipment, and conduct COVID-19 research. During Phase II, in alignment with Safer At Home orders, we allowed for the resumption of all research on campus for any DU employee (faculty, staff or student employee). To comply with Safer At Home, staggered scheduling was utilized to de-densify buildings and common workspaces. Through this, we established methods for gathering feedback from the research community regularly and refined protocols that were effective in supporting the research community, streamlining efforts and supporting the culture of caring necessary to keep the campus community safe.
Phase III opens research, scholarship and creative work activities to student researchers who are not employees, driving the DU research community back to full strength on campus in a de-densified work environment. The Office of Research and Sponsored Programs (ORSP) established a comprehensive Research, Scholarship and Creative Work Protocol for faculty, staff and students to follow in order to mitigate and protect against the spread of the virus. All individuals requesting access to the campus during any phase of campus access and support plan should refer to this protocol for detailed information.
Because research, scholarship and creative work was prioritized for return to campus, laboratory safety protocols were some of the first established during Phase I and II. Procedures continue to be refined over time to streamline the efforts and support faculty and student success. Shared equipment and workspaces have been the largest challenge to overcome in determining how to safely allow individuals to continue working. Allowing faculty to establish protocols that meet requirements for safety was already a central tenet for success in research for decades, and we transferred those same guiding principles to the current operation to recognize that the discipline, infrastructure and size of the research group must drive outcomes. All employees follow all applicable University protocols including symptom monitoring, wearing face coverings and maintaining social distancing while in laboratories. While working in shared workspaces, individuals should be mindful to comply with scheduling requirements and minimize time around other people. Appropriate precautions beyond those defined by the protocols should be followed including but not limited to not sharing objects and regular disinfection of shared surfaces between users.
Key attributes of all laboratory protocols include developing a schedule that minimizes the number of people in each room or workspace and communication of that schedule to division leads and COVID-19 Access Managers to coordinate the total number of individuals in a building. Augmenting the schedules by using a sign-in procedure also supports contact tracing should it become necessary. Researchers must create and submit their plan to maintain social distancing. Based on guidance from the CDC, 100 square feet is recommended for a single-person workspace. Thus, assigning workspaces and defining traffic flow in tight spaces is critical to the development of a suitable plan. Plans that support cleaning and reduce or eliminate equipment sharing have proven most effective. Finally, contact-less transfer between labs or lab members of items is preferred.
During Phase I and Phase II of the campus access and support plan, human subject research is limited to DU’s campus facilities, other higher education institutions, and other community-based organizations with developed safety protocols. The collection of bodily fluids was permitted once basic protocols for laboratory safety matured enough to provide confidence in the campus’ ability to establish and implement effective safety protocols and monitor compliance. In Phase III, in-home visits will resume as long as new cases of COVID-19 per day remain below 10 per 100,000 residents. At all times, human subjects research limits the amount of time interacting with participants in order to minimize risk.
Human subjects that need to come to campus will follow the established visitor protocols and must coordinate scheduling with COVID-19 Access Managers in order to maintain social distancing and the de-densification requirements for the facility. Research staff are responsible for contacting participants and determining interest, sharing precautions and procedures, providing the visitor survey link and describing participants’ responsibilities for personal hygiene, face coverings and social distancing during the visit to campus. Participants will be required to complete the visitor symptom survey within two hours of arrival. Waiting rooms are closed during Phase I through IV, and participants will be escorted into DU buildings directly to laboratories to minimize exposure.
All Human Subject Protocols that require in person interactions or intervention with human subjects during Phases I through IV must submit an addendum to the currently approved IRB submission to document safety procedures. A template is available to support researchers and streamline the process. If conducting research at another site, investigators must submit an amendment through IRBNet along with the other universities’ safety protocol. Researchers must review additional requirements mandated by the affiliated faculty or community-based organization.
All on-campus Human Subject research for external participants is regularly evaluated and allowed/disallowed depending on the relative conditions in Denver versus on campus. Exceptions will be reviewed by ORSP.
In Phase I and II of the campus access and support plan, in-home field research was prohibited. When cases are below 10 new cases per day per 100,000 residents, in-home field research may return during Phase III.
In Phase I and II of the Campus Access and Support Plan, travel was prohibited for non-essential domestic and international locations which limited field research to that which satisfied the definition of essential and met three of the following criteria. Academic deans are responsible for determining what travel for research in their division met criteria for essential.
Travel may be deemed “essential and not possible to postpone” if THREE of following from the list below is likely to occur should the travel be cancelled or significantly delayed:
- Loss of grant funding or failure to meet required completion deadlines
- Failure to meet contract deliverable requirements
- Significant damage to relationship with institutional partner
- Significant delay in academic progress, degree completion or graduation
Supports for Research
Since March 2020, the University research, scholarship and creative work community has suffered along with the rest of campus as a result of the pandemic. The movement of the campus to remote work and distance learning required limiting personnel to only those with essential research projects or those dedicated to supporting lifeforms and specialized equipment. Moreover, the prohibition of international and domestic travel limited field work, conference attendance, collaborative exchanges and other activities that fuel the creativity and passions of faculty and enhance the experiences of our students. The lift of 2,000 classes in two weeks from a face-to-face to online modality required that faculty shift their time away from research, scholarship and creative work. This redistribution of faculty effort created a pause in our progress, or, if our work was aligned with the current needs of the region, nation or world, we were called to dramatically increase our efforts. We did not get to celebrate our accomplishments as we traditionally would and suffered pay cuts that applied to our grant funded positions. At times, it felt like there was no room for our research, scholarship and creative work in the middle of so many other demands.
However, in the midst of financial distress, the University has remained steadfast in its commitment to supporting faculty in research, scholarship and creative work. External research expenditure hit an all-time high of over $41.4 million. Although there was some decline in spending, awards and renewals hint at how exceptional FY21 might be. The continued growth of research, scholarship and creative work remains a priority because it will help us surpass our competitors, draw in and launch DU faculty careers and provide an even richer educational experience for our students. To support research, the University prioritized research for faculty and students in our return to campus, expanded resources for copy/editing of grant applications and journal manuscripts, created assistance for grant prospecting, committed to continued seed funding at or above historical levels, invested in new faculty learning communities, streamlined administrative processes and enhanced stipends for GRAs.
Research, scholarship and creative work was of highest priority to relaunch once the governor moved away from the Stay at Home orders. As a result, among the first personnel authorized to return to campus were the research community. In those early weeks, the research community helped define how the University would reopen campus activities. We learned quickly that, in order to fuel our passions, we needed to resume our research, scholarship and creative work, and we needed to resume it together. As we have moved to later phases in the Campus Access and Support Plan, we have streamlined the return to campus approval process to make it easier and less burdensome to get back on campus and to allow more students back to join us in our scholarly passions.
The free copy/edit service available for faculty on journal articles and grant applications has restarted and expanded to meet demand. To access this service, please email Corinne.Lengsfeld@du.edu with completed documents for review. ORSP grant and contract administrators have added services related to grant prospecting and are available to support faculty and staff looking to identify and apply for grants. Contact your grants administrator for help. The University is seeking ways to streamline administrative processes to reduce the burden on faculty. One example was the development of the template IRB amendment for IRB protocols to document lab safety procedures. This made updating existing approve IRB protocols as simple as possible.
Seed funding to support faculty remained in place through spring 2020. With 80% of all the allocated seed funding for PROF, FRF, and Knowledge Bridges and others moved forward. One-year no-cost extensions were granted rapidly for any faculty member who could not travel or conduct the proposed work from a prior PROF award, enabling the faculty member to continue the work after a pause as a result of conditions world-wide. Additional funds were allocated to respond to and support high-need, emergent projects related to COVID-19. These seed funding programs remain in the FY2021 base budget and will be allocated with the usual timelines and funding rates as in previous years. We know that these financial supports for faculty around research, scholarship and creative work remain essential to the University’s progression to elevated research activity as measured by faculty retention, paper publication and citation rate, and growth in research expenditures. More importantly, these funds are pivotal to faculty career progression, institutional visibility, and faculty/student recruitment.
The new faculty learning community launched for the second year this fall. This program is more important than ever and is designed to keep first- and second-year faculty members focused on career path progression. This is especially important to maintain a scholarly focus even when the teaching load maybe unusually high.
The FY21 budget included a salary increase for GTA/GRA stipends to enhance student recruitment and retention. The raise was similar to the merit raise awarded in January 2020 of 2.5%.
Finally, town halls have been an essential element to keep the research community informed, because they provide an effective method to listen to and understand the struggles and provide an another opportunity to meet the needs of our faculty. These will continue as part of a greater effort to support faculty research during a year of difficult teaching responsibilities. We will explore funding for infrastructure needs and grant mechanism for specific learning communities.
COVID-19 Research at DU
DU faculty member Julia Dmitrieva developed a model to predict the impact of various public health measures and epidemiologic conditions on the rates of infection throughout the academic year. Key variables were social distancing, positivity rates of the Denver community, contact tracing, testing and surveillance programs, as well as the number of people returning to campus. This tool helped to devise the return to campus protocols the University employed with success in the fall. The model is being modified to take weekly data from the DU campus and use it to forecast future resurgences so that the COVID Coordinator team can develop effective mitigation strategies.
Aerosol Modeling of DU Classrooms
Using a mathematical model and small CO2 sensors to estimate the probability of airborne infection within individual classrooms, DU faculty member Alex Huffman found ways to improve prevention efforts. These models incorporated classroom dimensions, HVAC specifications and mask effectiveness to adjust classroom occupancy, course duration and break length for courses with higher aerosol generation, such as theater, to match the same possible transmission rates in a typical classroom. A database was made available to the community on selected COVID-19 resources. The models were validated using carbon dioxide detectors as a surrogate for viral loaded aerosols. These same models are now being utilized to identify the best spaces to move previous outdoor event spaces inside.
Wastewater Surveillence Program
Wastewater testing allows for hundreds of residents to be monitored with a single test which reduces cost while providing estimates of the prevalence of SARS-CoV-2 in our community. Wastewater surveillance for infectious diseases worldwide is not new and began in the 1990’s with poliovirus, therefore the adaptation of wastewater testing to SARS-CoV-2 has been well accepted worldwide as one of several surveillance options. SARS-CoV-2 is rapidly rendered inactive from gastrointestinal-tract fluid, thus what is detected in wastewater is largely a non-infectious state. The concentration from viral RNA can vary from person to person as well as over the course of the disease. No definitive correlation to a measurement of the RNA copies/L measured from wastewater and the number of infected individuals has emerged but this continues to be an area of development. DU is contributing to this empirical question.
The University of Denver established a wastewater monitoring program in conjunction with GT Molecular and Insitu. The first samples were taken on September 10, 2020 using grab samples from two dormitories housing primarily first year students. The program expanded rapidly over a three-week period. Samples are now taken at six sites, Johnson–McFarlan Hall, Dimond Family Residential Village, Centennial Towers, Centennial Halls, Nelson Hall and Nagel Hall, on Monday, Wednesday and Friday of every week. Reliance on grab samples or single point in time sampling methods has been largely replaced by composite samples. Composite samples are collected by taking 100mL every 15 minutes for 15 hours from early afternoon through to the next morning. Composite samples provide a more representative analysis of all the residents in the building than grab samples—but both techniques have been demonstrated to be effective. Samples are taken by courier to GT Molecular in Fort Collins immediately after collection. Results regarding the number of SARS-CoV-2 RNA copies/L found in the sample are reported back to the University in approximately 28 hours after collection. We have successfully used the test results to identify emerging cases and align them with RT-PCR Nasal Swab test results to determine if additional symptom monitoring, testing or quarantine measures are needed to control a potential outbreak. As our experience with the program grows so does our ability to estimate the number of infected residents base on reported results.
Current program expansion plans include collaboration with the state, city and regional Wastewater districts to pool results to help larger public health initiatives. DU is the only institution in Colorado measuring a single building; thus, we have the ability to correlate positive cases to wastewater results directly. Most programs are using micro sewer sheds downstream to understand prevalence. The potential contribution of DU to observing the impact of previous positives returning to congregate living on detected levels and to establish correlations for infected individuals is unique and valuable to the region.
Below is an example of wastewater and nasal PCR results for a residence hall. The increased positive test in orange is the result of required tests based on the wastewater elevation.
Saliva-Based SARS-CoV-2 on-Campus Screening
The University of Denver research enterprise is dedicated to being responsive to the needs of our community, state, region and nation in support of our vision for public good. The best way the state and the University remain open and face-to-face during the resurgence of the virus is by minimizing the number of positive cases on campus at the start of every term, and rapidly identifying and isolating infected individuals, thus reducing the number of days any single person spreads the disease. One mechanism for enhanced success, prior to broad vaccination, is testing. Frequent testing, reduced testing times, reduced testing cost and testing large populations of individuals enhances early detection, including the detection of asymptomatic people.
DU has built a saliva-based testing program, to provide low cost, high through-put, and reliable salivary PCR testing. Salivary testing not only provides a less invasive testing route than the current best practice mid-turbinate or nasopharyngeal swab, thus enhancing compliance, but it also targets bodily fluids associated with the known mode of transmission (e.g., orally generated aerosols). Understanding viral shedding in this bodily fluid also lends insight into viral transmission.
In July of 2020, the chancellor authorized a research project evaluating salivary PCR as a method to support nasal swab PCR testing at the University of Denver following the successful protocol developed by the University of Illinois (and with whom we have a letter of understanding). Beginning with a broad call to all PIs using PCR methodologies, a voluntary scientific team was assembled to build the SPIT lab, with integrated funds from the VPR budget used to stimulate research as well an authorized contribution from the COVID fund together totaling $300k. Across fall term, under the direction of Dr. Phil Danielson, the SPIT lab became operational, using standardized kits, machinery and protocols similar to those being employed at other universities (i.e. University of Illinois, Yale).
On November 17, 2020, the University of Denver began inviting individuals seeking SARS-CoV-2 testing at the Carepod to voluntarily participate in a research study collecting salivary samples at the same time as the nasal samples. The objective of the study was to validate a non-invasive high-throughput PCR based surveillance tool that could scale to 1000 tests/per day with reduced supply chain and medical staffing needs (and therefore with resultant lower costs). Since inception more than 2500 samples have been collected and analyzed. Over the few weeks of operation, the SPIT lab has refined techniques and with the help National Jewish Health adjusted thresholds to increase specificity (NPA) and sensitivity (PPA).
To assess the degree of concordance and characterize the temporal characteristics of SARS-CoV-2 detection in saliva versus mid-turbinate nasal swabs, over 1440 paired samples (saliva and mid-turbinate nasal swabs collected at the same time from the same individuals) have been analyzed. Approximately 24% of these samples were tested using the saliva direct (i.e., extraction free) method together with the commercial TaqPath™ COVID-19 Combo Kit (this assay targets three separate genetic markers in the SARS-CoV-2 genome and is the standard approach used in all PCR testing, including from nasal swabs). The remaining 76% of these samples were tested using extracted RNA and the same TaqPath™ COVID-19 Combo Kit. Although direct saliva has the advantage of not requiring extraction (additional time and extraction beads), the failure rate is elevated (due to sample quality). Therefore, after initially switching to saliva direct to provide a method that can be used even when extraction supplies are compromised, we are now returning to the optimized extraction approach. Concordance has been found to be between 98 and 99%.
A standard laboratory validation of the saliva assay was also completed using appropriate specimens for validation in accordance with FDA and CLIA validation guidelines and recommendations. Specifically, this consisted of 30 known SARS-CoV-2 positive and 30 SARS-CoV-2 negative saliva samples or contrived laboratory equivalents (e.g., saliva spiked with SARS-CoV-2 virus). Using these samples, the following validation studies were performed using the optimized saliva assay SOPs and interpretation guidelines:
Limit of Detection (LoD) - Analytical Sensitivity: The limit of detection (LoD) of the salivary SARS-CoV-2 assay spikes a known quantity of inactivated virus (e.g., heat treated) into saliva) or using an inactivated SARS-CoV-2 positive specimen quantitated against a standard curve for the SARS-CoV-2 amplicon(s). The FDA recommends that a preliminary LoD be determined by testing a 2-3-fold dilution series of three extraction replicates per concentration. The lowest concentration that gives positive results 100% of the time is defined as the preliminary LoD. The final LoD concentration should then be confirmed by testing 20 individual extraction replicates at the preliminary LoD. The FDA defines the LoD as the lowest concentration at which 95% of replicates are positive. The SPIT lab used a positive specimen per the requirements to perform an analytical sensitivity. The final LoD concentration from 20 individual extraction replicates for the DU salivary PCR was determined to be 10 copies/ul which matches exactly the limit of detection recorded by the manufacture specifications.
Clinical specimen recommendations made by the FDA for SARS-VoV-2 are for respiratory samples. To validate the use of saliva as an alternative specimen type, paired specimens from 30 positive and 30 negative individuals were collected and analyzed . The alternative specimen validation study found that using the SPIT lab saliva extraction PCR technique, the sensitivity or the ability of the technique to find patients with COVID was 96.7% and the specificity or the ability of the technique to find patients without the disease was 100%.
Starting in January, the lab will have three locations on campus: Nagel Hall, Centennial Halls and Driscoll Bridge. We will also continue to collect validation samples at the carepod that are collected concurrently with nasal swabs (this is voluntary). Collection will be contactless where individuals pick up a vial, swipe their DU ID, scan the vail, provide a small salivary sample directly into the vial and deposit the vial in a cooler. Sample collection currently is anticipating operating seven days a week, collecting and analyzing 1000 test per day for 62,000 saliva tests in winter term. Saliva testing is fully optional; individuals may choose to complete all required testing via nasal swab PCR. However, the saliva-based testing is designed to be faster and easier, supporting increased required testing. Following your individual testing scheduled, you will be able to use saliva sampling in place of nasal sampling to meet the testing requirement much of the time should you so choose.