Assessment of a Multifaceted Approach, Including Frequent PCR Testing, to Mitigation of COVID-19 Transmission at a Residential Historically Black University.

Importance: COVID-19 posed an unprecedented threat to residential colleges in the fall of 2020. While there were mathematical models of COVID-19 transmission, there were no established or tested protocols of COVID-19 testing or mitigation for school administrators to follow. Objective: To investigate the association of a multifaceted COVID-19 mitigation strategy using social, behavioral, and educational interventions and a program of frequent testing with prevalence of disease spread. Design, Setting, and Participants: This cohort study was conducted as a retrospective review of COVID-19 positivity from August 16, 2020, to April 30, 2021, at Delaware State University, a publicly funded historically Black university. Participants included all students, faculty, and staff members with a campus presence. Positivity rates after use of mitigation strategies and testing on campus were compared with those of the surrounding community. Data were analyzed from July through September 2021. Exposures: Mitigation strategies included education and outreach about social distancing, masking, and handwashing, and a COVID-19 testing plan consisted of twice-weekly polymerase chain reaction (PCR) screening using anterior nasal samples (fall and early spring semester) and then saliva-based samples (middle to late spring semester). Main Outcomes and Measures: Cumulative tests, infections, daily quarantine, and isolation residence hall occupancy were measured, and comparisons were made with statewide COVID-19 positivity rates. Results: The campus cohort included 2320 individuals (1575 resident students, 415 nonresident students, and 330 faculty or staff members). There were 1488 (64.1%) women and 832 (35.9%) men; mean (SD) age was 27.5 (12.9) years. During the fall semester, 36 500 COVID-19 PCR tests were performed. Weekly positivity rates ranged from 0 of 372 tests to 16 of 869 tests (1.8%) (mean [SD] positivity rate, 0.5% [0.5%]; 168 positive results and 36 312 negative results). During the same period, statewide positivity ranged from 589 of 25 120 tests (2.3%) to 5405 of 54 596 tests (9.9%) (mean [SD] positivity rate, 4.8% [2.6%]). In the spring semester, 39 045 PCR tests were performed. Weekly positivity rates ranged from 4 of 2028 tests (0.2%) to 36 of 900 tests (4.0%) (mean [SD] positivity rate, 0.8% [0.9%]; 267 positive results and 38 767 negative results). During the same period, statewide positivity ranged from 1336 of 37 254 tests (3.6%) to 3630 of 42 458 tests (8.5%) (mean [SD] positivity rate, 5.1% [1.3%]). Compared with statewide rates, campus positivity rates were mean (SD) 4.4 (2.6) percentage points lower during the fall semester (P < .001) and mean (SD) 5.6 (1.6) percentage points lower during the spring semester (P < .001). Total daily quarantine and isolation residence hall occupancy ranged from 0 to 43 students in the fall and 1 to 47 students during the spring. Conclusions and Relevance: This study found that the combination of campuswide mitigation policies and twice-weekly COVID-19 PCR screening was associated with a significant decrease in COVID-19 positivity at a residential historically Black university campus compared with the surrounding community. Given the socioeconomic demographics of many students at historically Black colleges and universities, keeping these resident campuses open is critical not only to ensure access to educational resources, but also to provide housing and food security.

Loss of DNA polymerase beta stacking interactions with templating purines, but not pyrimidines, alters catalytic efficiency and fidelity.

Structures of DNA polymerases bound with DNA reveal that the 5'-trajectory of the template strand is dramatically altered as it exits the polymerase active site. This distortion provides the polymerase access to the nascent base pair to interrogate proper Watson-Crick geometry. Upon binding a correct deoxynucleoside triphosphate, alpha-helix N of DNA polymerase beta is observed to form one face of the binding pocket for the new base pair. Asp-276 and Lys-280 stack with the bases of the incoming nucleotide and template, respectively. To determine the role of Lys-280, site-directed mutants were constructed at this position, and the proteins were expressed and purified, and their catalytic efficiency and fidelity were assessed. The catalytic efficiency for single-nucleotide gap filling with the glycine mutant (K280G) was strongly diminished relative to wild type for templating purines (>15-fold) due to a decreased binding affinity for the incoming nucleotide. In contrast, catalytic efficiency was hardly affected by glycine substitution for templating pyrimidines (<4-fold). The fidelity of the glycine mutant was identical to the wild type enzyme for misinsertion opposite a template thymidine, whereas the fidelity of misinsertion opposite a template guanine was modestly altered. The nature of the Lys-280 side-chain substitution for thymidine triphosphate insertion (templating adenine) indicates that Lys-280 "stabilizes" templating purines through van der Waals interactions.