Leveraging genomic sequencing data to evaluate disease surveillance strategies.

In the face of scarce public health resources, it is critical to understand which disease surveillance strategies are effective, yet such validation has historically been difficult. From May 1 to December 31, 2021, a cohort study was carried out in Santa Clara County, California, in which 10,131 high-quality genomic sequences from COVID-19 polymerase chain reaction tests were merged with disease surveillance data. We measured the informational value, the fraction of sequenced links surfaced that are biologically plausible according to genomic sequence data, of different disease surveillance strategies. Contact tracing appeared more effective than spatiotemporal methods at uncovering nonresidential spread settings, school reporting appeared more fruitful than workplace reporting, and passively retrieved links through survey information presented some promise. Given the rapidly dwindling cost of sequencing, the informational value metric may enable near real-time, readily available evaluation of strategies by public health authorities to fight viral diseases beyond COVID-19.

Integrating social services with disease investigation: A randomized trial of COVID-19 high-touch contact tracing.

COVID-19 exposed and exacerbated health disparities, and a core challenge has been how to adapt pandemic response and public health in light of these disproportionate health burdens. Responding to this challenge, the County of Santa Clara Public Health Department designed a model of "high-touch" contact tracing that integrated social services with disease investigation, providing continued support and resource linkage for clients from structurally vulnerable communities. We report results from a cluster randomized trial of 5,430 cases from February to May 2021 to assess the ability of high-touch contact tracing to aid with isolation and quarantine. Using individual-level data on resource referral and uptake outcomes, we find that the intervention, randomized assignment to the high-touch program, increased the referral rate to social services by 8.4% (95% confidence interval, 0.8%-15.9%) and the uptake rate by 4.9% (-0.2%-10.0%), with the most pronounced increases in referrals and uptake of food assistance. These findings demonstrate that social services can be effectively combined with contact tracing to better promote health equity, demonstrating a novel path for the future of public health.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) outbreak investigation in a hospital emergency department-California, December 2020-January 2021.

We describe a large outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) involving an acute-care hospital emergency department during December 2020 and January 2021, in which 27 healthcare personnel worked while infectious, resulting in multiple opportunities for SARS-CoV-2 transmission to patients and other healthcare personnel. We provide recommendations for improving infection prevention and control.

Automated vs. manual case investigation and contact tracing for pandemic surveillance: Evidence from a stepped wedge cluster randomized trial.

Background: Case investigation and contact tracing (CICT) is an important tool for communicable disease control, both to proactively interrupt chains of transmission and to collect information for situational awareness. We run the first randomized trial of COVID-19 CICT to investigate the utility of manual (i.e., call-based) vs. automated (i.e., survey-based) CICT for pandemic surveillance. Methods: Between December 15, 2021 and February 5, 2022, a stepped wedge cluster randomized trial was run in which Santa Clara County ZIP Codes progressively transitioned from manual to automated CICT. Eleven individual-level data fields on demographics and disease dynamics were observed for non-response. The data contains 106,522 positive cases across 29 ZIP Codes. Findings: Automated CICT reduced overall collected information by 29 percentage points (SE = 0.08, p < 0.01), as well as the response rate for individual fields. However, we find no evidence of differences in information loss by race or ethnicity. Interpretations: Automated CICT can serve as a useful alternative to manual CICT, with no substantial evidence of skewing data along racial or ethnic lines, but manual CICT improves completeness of key data for monitoring epidemiologic patterns. Funding: This research was supported in part by the Stanford Office of Community Engagement and the Stanford Institute for Human-Centered Artificial Intelligence.

Genomic Epidemiology and Transmission Dynamics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Congregate Healthcare Facilities in Santa Clara County, California.

BACKGROUND: Outbreaks of SARS-CoV-2 in long-term care facilities (LTCFs) cause significant morbidity and mortality. Mapping viral transmission within and between facilities by combining genomic sequencing with epidemiologic investigations enables targeting infection-control interventions. METHODS: We conducted weekly surveillance of residents and staff in LTCFs in Santa Clara County, California, with ≥1 confirmed COVID-19 case between March and July 2020. Positive samples were referred for whole-genome sequencing. Epidemiological investigations and phylogenetic analyses of the largest outbreaks (>30 cases) were carried out in 6 LTCFs (Facilities A through F). RESULTS: Among the 61 LTCFs in the county, 41 had ≥1 confirmed case during the study period, triggering weekly SARS-CoV-2 testing. The 6 largest outbreaks accounted for 60% of cases and 90% of deaths in LTCFs, although the bed capacity of these facilities represents only 11% of the LTCF beds in the county. Phylogenetic analysis of 196 whole-genome sequences recovered from those facilities showed that each outbreak was monophyletic, with staff and residents sharing a common viral lineage. Outbreak investigations revealed that infected staff members often worked at multiple facilities, and in 1 instance, a staff member infected while working in 1 facility was the likely index case in another. CONCLUSIONS: We detected a pattern of rapid and sustained transmission after a single introduction of SARS-CoV-2 in 6 large LTCF outbreaks, with staff playing a key role in transmission within and between facilities. Infection control, testing, and occupational policies to reduce exposure and transmission risk for staff are essential components to keeping facility residents safe.

A language-matching model to improve equity and efficiency of COVID-19 contact tracing.

Contact tracing is a pillar of COVID-19 response, but language access and equity have posed major obstacles. COVID-19 has disproportionately affected minority communities with many non-English-speaking members. Language discordance can increase processing times and hamper the trust building necessary for effective contact tracing. We demonstrate how matching predicted patient language with contact tracer language can enhance contact tracing. First, we show how to use machine learning to combine information from sparse laboratory reports with richer census data to predict the language of an incoming case. Second, we embed this method in the highly demanding environment of actual contact tracing with high volumes of cases in Santa Clara County, CA. Third, we evaluate this language-matching intervention in a randomized controlled trial. We show that this low-touch intervention results in 1) significant time savings, shortening the time from opening of cases to completion of the initial interview by nearly 14 h and increasing same-day completion by 12%, and 2) improved engagement, reducing the refusal to interview by 4%. These findings have important implications for reducing social disparities in COVID-19; improving equity in healthcare access; and, more broadly, leveling language differences in public services.

Introduction, Transmission Dynamics, and Fate of Early Severe Acute Respiratory Syndrome Coronavirus 2 Lineages in Santa Clara County, California.

We combined viral genome sequencing with contact tracing to investigate introduction and evolution of severe acute respiratory syndrome coronavirus 2 lineages in Santa Clara County, California, from 27 January to 21 March 2020. From 558 persons with coronavirus disease 2019, 101 genomes from 143 available clinical samples comprised 17 lineages, including SCC1 (n = 41), WA1 (n = 9; including the first 2 reported deaths in the United States, with postmortem diagnosis), D614G (n = 4), ancestral Wuhan Hu-1 (n = 21), and 13 others (n = 26). Public health intervention may have curtailed the persistence of lineages that appeared transiently during February and March. By August, only D614G lineages introduced after 21 March were circulating in Santa Clara County.

Evaluation of Allocation Schemes of COVID-19 Testing Resources in a Community-Based Door-to-Door Testing Program.

Importance: Overcoming social barriers to COVID-19 testing is an important issue, especially given the demographic disparities in case incidence rates and testing. Delivering culturally appropriate testing resources using data-driven approaches in partnership with community-based health workers is promising, but little data are available on the design and effect of such interventions. Objectives: To assess and evaluate a door-to-door COVID-19 testing initiative that allocates visits by community health workers by selecting households in areas with a high number of index cases, by using uncertainty sampling for areas where the positivity rate may be highest, and by relying on local knowledge of the health workers. Design Setting and Participants: This cohort study was performed from December 18, 2020, to February 18, 2021. Community health workers visited households in neighborhoods in East San Jose, California, based on index cases or uncertainty sampling while retaining discretion to use local knowledge to administer tests. The health workers, also known as promotores de salud (hereinafter referred to as promotores) spent a mean of 4 days a week conducting door-to-door COVID-19 testing during the 2-month study period. All residents of East San Jose were eligible for COVID-19 testing. The promotores were selected from the META cooperative (Mujeres Empresarias Tomando Acción [Entrepreneurial Women Taking Action]). Interventions: The promotores observed self-collection of anterior nasal swab samples for SARS-CoV-2 reverse transcriptase-polymerase chain reaction tests. Main Outcomes and Measures: A determination of whether door-to-door COVID-19 testing was associated with an increase in the overall number of tests conducted, the demographic distribution of the door-to-door tests vs local testing sites, and the difference in positivity rates among the 3 door-to-door allocation strategies. Results: A total of 785 residents underwent door-to-door testing, and 756 were included in the analysis. Among the 756 individuals undergoing testing (61.1% female; 28.2% aged 45-64 years), door-to-door COVID-19 testing reached different populations than standard public health surveillance, with 87.6% (95% CI, 85.0%-89.8%) being Latinx individuals. The closest available testing site only reached 49.0% (95% CI, 48.3%-49.8%) Latinx individuals. Uncertainty sampling provided the most effective allocation, with a 10.8% (95% CI, 6.8%-16.0%) positivity rate, followed by 6.4% (95% CI, 4.1%-9.4%) for local knowledge, and 2.6% (95% CI, 0.7%-6.6%) for index area selection. The intervention was also associated with increased overall testing capacity by 60% to 90%, depending on the testing protocol. Conclusions and Relevance: In this cohort study of 785 participants, uncertainty sampling, which has not been used conventionally in public health, showed promising results for allocating testing resources. Community-based door-to-door interventions and leveraging of community knowledge were associated with reduced demographic disparities in testing.

Evidence for Limited Early Spread of COVID-19 Within the United States, January-February 2020.

From January 21 through February 23, 2020, public health agencies detected 14 U.S. cases of coronavirus disease 2019 (COVID-19), all related to travel from China (1,2). The first nontravel-related U.S. case was confirmed on February 26 in a California resident who had become ill on February 13 (3). Two days later, on February 28, a second nontravel-related case was confirmed in the state of Washington (4,5). Examination of four lines of evidence provides insight into the timing of introduction and early transmission of SARS-CoV-2, the virus that causes COVID-19, into the United States before the detection of these two cases. First, syndromic surveillance based on emergency department records from counties affected early by the pandemic did not show an increase in visits for COVID-19-like illness before February 28. Second, retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20. Third, analysis of viral RNA sequences from early cases suggested that a single lineage of virus imported directly or indirectly from China began circulating in the United States between January 18 and February 9, followed by several SARS-CoV-2 importations from Europe. Finally, the occurrence of three cases, one in a California resident who died on February 6, a second in another resident of the same county who died February 17, and a third in an unidentified passenger or crew member aboard a Pacific cruise ship that left San Francisco on February 11, confirms cryptic circulation of the virus by early February. These data indicate that sustained, community transmission had begun before detection of the first two nontravel-related U.S. cases, likely resulting from the importation of a single lineage of virus from China in late January or early February, followed by several importations from Europe. The widespread emergence of COVID-19 throughout the United States after February highlights the importance of robust public health systems to respond rapidly to emerging infectious threats.