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SARS-CoV-2 spreads quickly in dense populations, with serious implications for universities, workplaces, and other settings where exposure reduction practices are difficult to implement. Rapid screening has been proposed as a tool to slow the spread of the virus; however, many commonly used diagnostic tests (e.g., RT-qPCR) are expensive, difficult to deploy (e.g., require a nasopharyngeal specimen), and have extended turn-around times. We evaluated testing regimes that combined diagnostic testing using qPCR with high-frequency screening using a novel reverse-transcription loop-mediated isothermal amplification (RT-LAMP, herein LAMP) assay. We used a compartmental susceptible-exposed-infectious-recovered (SEIR) model to simulate screening of a university population. We also developed a Shiny application to allow administrators and public health professionals to develop optimal testing strategies given site-specific assumptions about testing investment, target population, and cost. The frequency of screening, especially when pooling samples, was more important for minimizing epidemic size than test sensitivity, behavioral compliance, contact tracing capacity, and time between testing and results. Our results suggest that when testing budgets are limited, it is safer and more cost-effective to allocate the majority of funds to screening. Rapid, cost-effective, and scalable screening tests, like LAMP, should be viewed as critical components of SARS-CoV-2 testing in high-density populations.
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BackgroundReturning university students represent large-scale, transient demographic shifts and a potential source of transmission to adjacent communities during the COVID-19 pandemic. MethodsIn this prospective longitudinal cohort study, we tested for IgG antibodies against SARS-CoV-2 in a non-random cohort of residents living in Centre County prior to the Fall 2020 term at the Pennsylvania State University and following the conclusion of the Fall 2020 term. We also report the seroprevalence in a non-random cohort of students collected at the end of the Fall 2020 term. ResultsOf 1313 community participants, 42 (3.2%) were positive for SARS-CoV-2 IgG antibodies at their first visit between 07 August and 02 October 2020. Of 684 student participants who returned to campus for fall instruction, 208 (30.4%) were positive for SARS-CoV-2 antibodies between 26 October and 21 December. 96 (7.3%) community participants returned a positive IgG antibody result by 19 February. Only contact with known SARS-CoV-2-positive individuals and attendance at small gatherings (20-50 individuals) were significant predictors of detecting IgG antibodies among returning students (aOR, 95% CI: 3.1, 2.07-4.64; 1.52, 1.03-2.24; respectively). ConclusionsDespite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents was low and stable from before student arrival for the Fall 2020 term to after student departure. The study implies that heterogeneity in SARS-CoV-2 transmission can occur in geographically coincident populations. Authors summaryDespite high seroprevalence observed within the student population, seroprevalence in a longitudinal cohort of community residents remained low and stable from before student arrival for the Fall term to after their departure, implying limited transmission between these subpopulations.
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The optimal timeframe for donating convalescent plasma to be used for COVID-19 immunotherapy is unknown. To address this important knowledge deficit, we determined in vitro live-virus neutralizing capacity and persistence of IgM and IgG antibody responses against the receptor-binding domain and S1 ectodomain of the SARS-CoV-2 spike glycoprotein in 540 convalescent plasma samples obtained from 175 COVID-19 plasma donors for up to 142 days post-symptom onset. Robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 persist, in the aggregate, for at least 100 days post-symptom onset. However, a notable acceleration in decline in virus neutralization titers [≥]160, a value suitable for convalescent plasma therapy, was observed starting 60 days after first symptom onset. Together, these findings better define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor, including age and COVID-19 disease severity score. One Sentence SummaryEvaluation of SARS-CoV-2 anti-spike protein IgM, IgG, and live-virus neutralizing titer profiles reveals that the optimal window for donating convalescent plasma for use in immunotherapy is within the first 60 days of symptom onset.
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Prompt identification of cases is critical for slowing the spread of COVID-19. However, many areas have faced diagnostic testing shortages, requiring difficult decisions to be made regarding who receives a test, without knowing the implications of those decisions on population-level transmission dynamics. Clinical prediction rules (CPRs) are commonly used tools to guide clinical decisions. We used data from electronic health records to develop a parsimonious 5-variable CPR to identify those who are most likely to test positive, and found that its application to prioritize testing increases the proportion of those testing positive in settings of limited testing capacity. To consider the implications of these gains in daily case detection on the population level, we incorporated testing using the CPR into a compartmentalized disease transmission model. We found that prioritized testing led to a delayed and lowered infection peak (i.e. "flattens the curve"), with the greatest impact at lower values of the effective reproductive number (such as with concurrent social distancing measures), and when higher proportions of infectious persons seek testing. Additionally, prioritized testing resulted in reductions in overall infections as well as hospital and intensive care unit (ICU) burden. In conclusion, we present a novel approach to evidence-based allocation of limited diagnostic capacity, to achieve public health goals for COVID-19. One Sentence SummaryA clinical prediction rule to prioritize SARS-CoV-2 testing improves daily case detection, flattens and delays the curve, and reduces hospital burden.
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The United States (US), which is currently the epicenter for the COVID-19 pandemic, is a country whose demographic composition differs from that of other highly-impacted countries. US-based descriptions of SARS-CoV-2 infections have, for the most part, focused on patient populations with severe disease, captured in areas with limited testing capacity. The objective of this study is to compare characteristics of positive and negative SARS-CoV-2 patients, in a population primarily comprised of mild and moderate infections, identified from comprehensive population-level testing. Here, we extracted demographics, comorbidities, and vital signs from 20,088 patients who were tested for SARS-CoV-2 at University of Utah Health clinics, in Salt Lake County, Utah; and for a subset of tested patients, we performed manual chart review to examine symptoms and exposure risks. To determine risk factors for testing positive, we used logistic regression to calculate the odds of testing positive, adjusting for symptoms and prior exposure. Of the 20,088 individuals, 1,229 (6.1%) tested positive for SARS-CoV-2. We found that Non-White persons were more likely to test positive compared to non-Hispanic Whites (adjOR=1.1, 95% CI: 0.8, 1.6), and that this increased risk is more pronounced among Hispanic or Latino persons (adjOR=2.0, 95%CI: 1.3, 3.1). However, we did not find differences in the duration of symptoms nor type of symptom presentation between non-Hispanic White and non-White individuals. We found that risk of hospitalization increases with age (adjOR=6.9 95% CI: 2.1, 22.5 for age 60+ compared to 0-19), and additionally show that younger individuals (aged 019), were underrepresented both in overall rates of testing as well as rates of testing positive. We did not find major race/ethnic differences in hospitalization rates. In this analysis of predominantly non-hospitalized individuals tested for SARS-CoV-2, enabled by expansive testing capacity, we found disparities in both testing and SARS-CoV-2 infection status by race/ethnicity and by age. Further work on addressing racial and ethnic disparities, particularly among Hispanic/Latino communities (where SARS-CoV-2 may be spreading more rapidly due to increased exposure and comparatively reduced testing), will be needed to effectively combat COVID-19 in the US.