Modeling serological testing to inform relaxation of social distancing for COVID-19 control

Kraay, Alicia N M; Nelson, Kristin N.; Zhao, Changxuan; Demory, David; Weitz, Joshua S.; Lopman, Benjamin A.

doi:10.1101/2020.04.24.20078576

Cited by 18 publications

(19 citation statements)

References 38 publications

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“…Patterns of IgM and IgG detection align with immunological expectations, as IgM antibodies are typically present during the early phase of the immune response, while IgG antibodies remain detectable for much longer periods ( Xiao et al, 2020 ). We detected IgG and IgM antibodies in nearly all (98–100%) individuals by days 22–23 post-symptom onset, consistent with recent findings ( Kraay et al, 2020 ). While IgG detection remains at this level for at least the range of times in the dataset (60 days for ELISA-Spike), the proportion of IgM-positive samples decreases after roughly 28 days post symptom onset, reaching around 65% by day 60.…”

Section: Discussionsupporting

confidence: 92%

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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Section: Discussionsupporting

confidence: 92%

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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“…antibodies are typically present during the early phase of the immune response while IgG antibodies remain detectable for much longer periods (Xiao et al 2020). We detected IgG and IgM antibodies in nearly all (98-100%) individuals by day 22-23 after symptom onset, consistent with recent findings (Kraay et al 2020). While IgG detection remains at this level for at least the remainder of available times in the dataset (60 days), the proportion of IgM-positive samples decreases again, reaching 60-70% by 60 dpo.…”

Section: Patterns Of Igm and Igg Detection Align With Immunological Esupporting

confidence: 92%

Quantifying antibody kinetics and RNA shedding during early-phase SARS-CoV-2 infection

Borremans

Gamble

Prager

et al. 2020

Preprint

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Our ability to understand and mitigate the spread of SARS-CoV-2 depends largely on antibody and viral RNA data that provide information about past exposure and shedding. Five months into the outbreak there is an impressive number of studies reporting antibody kinetics and RNA shedding dynamics, but extensive variation in detection assays, study group demographics, and laboratory protocols has presented a challenge for inferring the true biological patterns. Here, we combine existing data on SARS-CoV-2 IgG, IgM and RNA kinetics using a formal quantitative approach that enables integration of 3,214 data points from 516 individuals, published in 22 studies. This allows us to determine the mean values and distributions of IgG and IgM seroconversion times and titer kinetics, and to characterize how antibody and RNA detection probabilities change during the early phase of infection. We observe extensive variation in antibody response patterns and RNA detection patterns, explained by both individual heterogeneity and protocol differences such as targeted antigen and sample type. These results provide a robust reference for clinical management of individual patients, and a foundation for the mathematical models and serological surveys that underpin public health policies.

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“…Assuming such individuals are immune to reinfection, they can be deployed to provide "shield immunity" to preferentially interact with susceptible or infected individuals, thus reducing transmission. 11,28 A model showed that such an immune shielding approach could potentially lead to a reduction in outbreak size. 11 While conceptually sound, it is unclear if such a serological testing-based strategy is viable for college campuses.…”

Section: Serological Testing For Antibodies and "Immune Shield" Strategymentioning

confidence: 99%

“…31,33 If an individual is placed into an "immune shield" position despite not actually being immune, this could lead to an increase in transmission. 28 Fourth, preliminary results of seroprevalence studies suggest that immune individuals will be in short supply. A meta-analysis of multiple seroprevalence studies using Bayesian hierarchical models, 34 found that seroprevalence is low among the populations investigated, with 2-6% in Los Angeles County, California, 35 0-2% in Santa Clara County, California, 36 1.6-2.6% in San Miguel County, Colorado, and 15-41% in Chelsea, Massachusetts.…”

Section: Serological Testing For Antibodies and "Immune Shield" Strategymentioning

confidence: 99%

SARS-CoV-2 Viral and Serological Testing When College Campuses Reopen: Some Practical Considerations

Fung

Cheung

Handel

2020

Disaster med. public health prep.

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The coronavirus disease 2019 (COVID-19) pandemic prompted universities across the United States to close campuses in Spring 2020. Universities are deliberating whether, when, and how they should resume in-person instruction in Fall 2020. In this essay, we discuss some practical considerations for the use of two potentially useful control strategies based on testing: 1) SARS-CoV-2 RT-PCR testing followed by case-patient isolation and quarantine of close contacts, and 2) serological testing followed by an “immune shield” approach; i.e., low social distancing requirements for seropositive persons. The isolation of case-patients and quarantine of close contacts may be especially challenging, and perhaps prohibitively difficult, on many university campuses. The “immune shield” strategy might be hobbled by a low positive predictive value of the tests used in populations with low seroprevalence. Both strategies carry logistical, ethical and financial implications. The main non-pharmaceutical interventions will remain methods based on social distancing (e.g., capping class size) and personal protective behaviors (e.g., universal facemask wearing in public space) until vaccines become available, or unless the issues discussed herein can be resolved in such a way that using mass testing as main control strategies becomes viable.

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Modeling serological testing to inform relaxation of social distancing for COVID-19 control

Abstract: 15

Cited by 18 publications

References 38 publications

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

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

Quantifying antibody kinetics and RNA shedding during early-phase SARS-CoV-2 infection

SARS-CoV-2 Viral and Serological Testing When College Campuses Reopen: Some Practical Considerations

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