Genomic epidemiology of the Los Angeles COVID-19 outbreak

Los Angeles (LA) County has sustained a large outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To learn about the transmission history of SARS-CoV-2 in LA County, we sequenced 142 viral genomes from unique patients seeking care at UCLA Health System. 86 of these genomes are from samples collected before April 19, 2020. We found that the early outbreak in LA, as in other international air travel hubs, was seeded by multiple introductions of strains from Asia and Europe. We identified a US-specific strain, B.1.43, which has been found predominantly in California and Washington State. While samples from LA County carry the ancestral B.1.43 genome, viral genomes from neighbouring counties in California and from counties in Washington State carry additional mutations, suggesting a potential origin of B.1.43 in Southern California. We quantified the transmission rate of SARS-CoV-2 over time, and found evidence that the public health measures put in place in LA County to control the virus were effective at preventing transmission, but may have been undermined by the many introductions of SARS-CoV-2 into the region. Our work demonstrates that genome sequencing can be a powerful tool for investigating outbreaks and informing the public health response. Our results reinforce the critical need for the U.S. to have coordinated inter-state responses to the pandemic.

Expanding COVID-19 symptom screening to retail, restaurants, and schools by preserving privacy using relaxed digital signatures

Symptom screening is a widely deployed strategy to mitigate the COVID-19 pandemic and many public health authorities are mandating its use by employers for all employees in the workplace. While symptom screening has the benefit of reducing the number of infected individuals in the workplace, it raises some inherently difficult privacy issues as a traditional approach requires the employer to collect symptom data from each employee which is essentially medical information. In this paper, we describe a system to implement Cryptographic Anonymous Symptom Screening (CASS) which allows for individuals to perform COVID symptom screening anonymously while avoiding the privacy issues of traditional approaches. In the system, individuals report their symptoms without any identifying information and are issued a completion certificate. This certificate contains a cryptographic code which certifies that the certificate was obtained from the screener after reporting no symptoms. The codes can be verified using a cryptographic algorithm which is publicly available. A standard cryptography approach to implement such a system would be to use digital signatures. Unfortunately, standard digital signatures have some limitations for this application in that the signatures are often hundreds of characters long and if the signature contains the name of the individual, then there is also a risk of compromising privacy. In our approach, we develop and utilize a relaxed digital signature scheme to provide 16 character long codes and handle names using equivalence classes which helps preserve privacy. Both of these extensions technically compromise the security but in a way that is negligible for this application. Our system can either serve the function of standard symptom screening system approaches for employees, but can also extend symptom screening to non-employees such as visitors or customers. In this case, the system can be utilized in retail, restaurants and schools to ensure that everyone in the physical space, including employees, customers, visitors and students have performed symptom screening.

Swab-Seq: A high-throughput platform for massively scaled up SARS-CoV-2 testing

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is due to the high rates of transmission by individuals who are asymptomatic at the time of transmission1, 2. Frequent, widespread testing of the asymptomatic population for SARS-CoV-2 is essential to suppress viral transmission. Despite increases in testing capacity, multiple challenges remain in deploying traditional reverse transcription and quantitative PCR (RT-qPCR) tests at the scale required for population screening of asymptomatic individuals. We have developed SwabSeq, a high-throughput testing platform for SARS-CoV-2 that uses next-generation sequencing as a readout. SwabSeq employs sample-specific molecular barcodes to enable thousands of samples to be combined and simultaneously analyzed for the presence or absence of SARS-CoV-2 in a single run. Importantly, SwabSeq incorporates an in vitro RNA standard that mimics the viral amplicon, but can be distinguished by sequencing. This standard allows for end-point rather than quantitative PCR, improves quantitation, reduces requirements for automation and sample-to-sample normalization, enables purification-free detection, and gives better ability to call true negatives. After setting up SwabSeq in a high-complexity CLIA laboratory, we performed more than 80,000 tests for COVID-19 in less than two months, confirming in a real world setting that SwabSeq inexpensively delivers highly sensitive and specific results at scale, with a turn-around of less than 24 hours. Our clinical laboratory uses SwabSeq to test both nasal and saliva samples without RNA extraction, while maintaining analytical sensitivity comparable to or better than traditional RT-qPCR tests. Moving forward, SwabSeq can rapidly scale up testing to mitigate devastating spread of novel pathogens.

Projecting hospital resource utilization during a surge using parametric bootstrapping

During the initial wave of the COVID-19 pandemic in the United States, hospitals took drastic action to ensure sufficient capacity, including canceling or postponing elective procedures, expanding the number of available intensive care beds and ventilators, and creating regional overflow hospital capacity. However, in most locations the actual number of patients did not reach the projected surge leaving available, unused hospital capacity. As a result, patients may have delayed needed care and hospitals lost substantial revenue. These initial recommendations were made based on observations and worst-case epidemiological projections, which generally assume a fixed proportion of COVID-19 patients will require hospitalization and advanced resources. This assumption has led to an overestimate of resource demand as clinical protocols improve and testing becomes more widely available throughout the course of the pandemic. Here, we present a parametric bootstrap model for forecasting the resource demands of incoming patients in the near term, and apply it to the current pandemic. We validate our approach using observed cases at UCLA Health and simulate the effect of elective procedure cancellation against worst-case pandemic scenarios. Using our approach, we show that it is unnecessary to cancel elective procedures unless the actual capacity of COVID-19 patients approaches the hospital maximum capacity. Instead, we propose a strategy of balancing the resource demands of elective procedures against projected patients by revisiting the projections regularly to maintain operating efficiency. This strategy has been in place at UCLA Health since mid-April.