SARS-CoV-2 Innate Effector Associations and Viral Load in Early Nasopharyngeal Infection (preprint)

To examine innate immune responses in early SARS-CoV-2 infection that may change clinical outcomes, we compared nasopharyngeal swab data from 20 virus-positive and 20 virus-negative individuals. Multiple innate immune-related and ACE-2 transcripts increased with infection and were strongly associated with increasing viral load. We found widespread discrepancies between transcription and translation. Interferon proteins were unchanged or decreased in infected samples suggesting virally-induced shut-off of host anti-viral protein responses. However, IP-10 and several interferon-stimulated gene proteins increased with viral load. Older age was associated with modifications of some effects. Our findings may characterize the disrupted immune landscape of early disease.

Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis (preprint)

Background: A rapidly increasing number of serological surveys for anti-SARS-CoV-2 antibodies have been reported worldwide. A synthesis of this large corpus of data is needed. Purpose: To evaluate the quality of serological studies and provide a global picture of seroprevalence across demographic and occupational groups, and to provide guidance for conducting better serosurveys. Data sources: PubMed, Embase, Web of Science, medRxiv, bioRxiv, SSRN and Wellcome were searched for English-language papers published from December 1, 2019 to August 28, 2020. Study selection: Serological studies that evaluated seroprevalence of SARS-CoV-2 infections in humans. Data extraction: Two investigators independently extracted data from included studies. Data Synthesis: Most of 178 serological studies, representing tests in >800,000 individuals, identified were of low quality. Close contacts and high-risk healthcare workers had higher seroprevalence of 22.9% (95% CI: 11.1-34.7%) and 14.9% (4.8-25.0%), compared to low-risk healthcare workers and general population of 5.5% (4.6-6.4%) and 6.3% (5.5-7.1%). Generally, young people (0-20 yrs) were less likely to be seropositive compared to the middle-aged (21-55 yrs) populations (RR, 0.8, 95% CI: 0.7-0.8). Seroprevalence correlated with clinical COVID-19 reports with 10 (range: 2 to 34) infections per confirmed COVID-19 case. Limitations: Some heterogeneity cannot be well explained quantitatively. Conclusions: The overall quality of seroprevalence studies examined was low. The relatively low seroprevalence among general populations suggest that in most settings, antibody-mediated herd immunity is far from being reached. Given that ratio of infections to confirmed cases is on the same order of magnitude across different locales, reported case numbers may help provide insights into the proportion of the population infected. Primary Funding source: National Science Fund for Distinguished Young Scholars (PROSPERO: CRD42020198253).

Modeling reductions in SARS-CoV-2 transmission and hospital burden achieved by prioritizing testing using a clinical prediction rule (preprint)

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.

Comprehensive Testing Highlights Racial, Ethnic, and Age Disparities in the COVID-19 Outbreak (preprint)

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 0-19), 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.