Reopening Society and the Need for Real-Time Assessment of COVID-19 at the Community Level

Angulo, Frederick J.; Finelli, Lyn; Swerdlow, David L.

doi:10.1001/jama.2020.7872

Cited by 47 publications

(43 citation statements)

References 8 publications

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“…The objectives of this study were: (1) to develop and validate a multiplex bead-based immunoassay for detection of SARS-CoV-2-specific IgG, IgA, and IgM responses; (2) to evaluate the assay performance using saliva compared to using serum specimens and identify SARS-CoV-2 antigens that could result in high sensitivity and specificity to identify antibody responses to prior SARS-CoV-2 infection; and (3) to describe the antibody kinetics in saliva to those in serum by time since onset of COVID-19 symptoms.…”

Section: Downloaded Frommentioning

confidence: 99%

“…(1) There is a critical need to perform broad-scale population-based testing to improve COVID-19 prevention and control efforts, understand transmission dynamics and track herd immunity. (2,3) Saliva offers several advantages as a diagnostic medium in that it is a non-invasive, painless, safe, and convenient specimen. Whereas some consider phlebotomy specimens to be too invasive and uncomfortable, saliva sampling is widely accepted, particularly among vulnerable or difficult-to-reach populations, and could facilitate home-based self-collection.…”

Section: Introductionmentioning

confidence: 99%

“…(10)(11)(12)(13)(14) Development of high performing antibody assays to detect prior infection with SARS-CoV-2 was identified as a critical priority from early in the COVID-19 pandemic response. (2,3) We hypothesize that saliva-based antibody testing can fill this critical gap and provide a pivotal capacity for combating the COVID-19 pandemic.…”

Section: Introductionmentioning

confidence: 99%

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COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva

et al. 2020

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SARS-CoV-2 is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a non-invasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed COVID-19 cases and from the pre-COVID-19 era were tested for IgG, IgA and IgM to the antigen panel. Matched saliva and serum IgG responses (n=28) were significantly correlated. The salivary anti-N IgG response resulted in highest sensitivity (100%), exhibiting a positive response in 24/24 RT-PCR-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert around 10 DPSO. Algorithms employing a combination of the IgG response to N and S antigens result in high diagnostic accuracy (100%) as early as 10 DPSO. These results support the use of saliva-based antibody testing as a non-invasive and scalable alternative to blood-based antibody testing.

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confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva

et al. 2020

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“…At the level of populations, serologic data can provide insights into virus spread by enabling estimation of the overall attack rate, and seroprevalence estimates can elucidate the potential for herd immunity ( Stringhini et al, 2020 ; Bryant et al, 2020 ). In addition, these estimates are essential for developing accurate mathematical models of virus transmission dynamics, which provide the foundation for policies to reopen societies ( Krsak et al, 2020 ; Angulo et al, 2020 ; Kissler et al, 2020 ). At the level of individuals, the presence and concentration of antibodies against SARS-CoV-2 are indicators of past exposure, providing insights over a much wider temporal window than other metrics.…”

Section: Introductionmentioning

confidence: 99%

Quantifying antibody kinetics and RNA detection during early-phase SARS-CoV-2 infection by time since symptom onset

Borremans

Gamble

Prager

et al. 2020

eLife

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Understanding and mitigating SARS-CoV-2 transmission hinges on antibody and viral RNA data that inform exposure and shedding, but extensive variation in assays, study group demographics and laboratory protocols across published studies confounds inference of true biological patterns. Our meta-analysis leverages 3,214 datapoints from 516 individuals in 21 studies to reveal that seroconversion of both IgG and IgM occurs around 12 days post symptom onset (range 1-40), with extensive individual variation that is not significantly associated with disease severity. IgG and IgM detection probabilities increase from roughly 10% at symptom onset to 98-100% by day 22, after which IgM wanes while IgG remains reliably detectable. RNA detection probability decreases from roughly 90% to zero by day 30, and is highest in faeces and lower respiratory tract samples. Our findings provide a coherent evidence base for interpreting clinical diagnostics, and for the mathematical models and serological surveys that underpin public health policies.

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“…Areas of the world such as South Korea and Northeastern Italy that have quickly tested their population en masse for SARS-CoV-2 have significantly reduced the spread of the disease. The relatively low incidence and mortality from these examples in comparison with adjacent countries and regions suggests that extensive population testing will be important for the foreseeable future, as cities and countries re-open their businesses and borders, to assess the COVID-19 status in real-time, at the community level(14).…”

mentioning

confidence: 99%

REMBRANDT: A high-throughput barcoded sequencing approach for COVID-19 screening

Palmieri

Siddiqui

Gardner

et al. 2020

Preprint

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The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV), is a highly infectious RNA virus. A still-debated percentage of patients develop coronavirus disease 2019 (COVID-19) after infection, whose symptoms include fever, cough, shortness of breath and fatigue. Acute and life-threatening respiratory symptoms are experienced by 10-20% of symptomatic patients, particularly those with underlying medical conditions that includes diabetes, COPD and pregnancy. One of the main challenges in the containment of COVID-19 is the identification and isolation of asymptomatic/presymptomatic individuals. As communities re-open, large numbers of people will need to be tested and contact-tracing of positive patients will be required to prevent additional waves of infections and enable the continuous monitoring of the viral loads COVID-19 positive patients. A number of molecular assays are currently in clinical use to detect SARS-CoV-2. Many of them can accurately test hundreds or even thousands of patients every day. However, there are presently no testing platforms that enable more than 10,000 tests per day. Here, we describe the foundation for the REcombinase Mediated BaRcoding and AmplificatioN Diagnostic Tool (REMBRANDT), a high-throughput Next Generation Sequencing-based approach for the simultaneous screening of over 100,000 samples per day. The REMBRANDT protocol includes direct two-barcoded amplification of SARS-CoV-2 and control amplicons using an isothermal reaction, and the downstream library preparation for Illumina sequencing and bioinformatics analysis. This protocol represents a potentially powerful approach for community screening, a major bottleneck for testing samples from a large patient population for COVID-19.

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Reopening Society and the Need for Real-Time Assessment of COVID-19 at the Community Level

Cited by 47 publications

References 8 publications

COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva

COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva

Quantifying antibody kinetics and RNA detection during early-phase SARS-CoV-2 infection by time since symptom onset

REMBRANDT: A high-throughput barcoded sequencing approach for COVID-19 screening

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