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Analysis of metapopulation models of the transmission of SARS-CoV-2 in the United States

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MyVan Vo
MyVan Vo
MyVan Vo
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Zhilan Feng at Purdue University
Zhilan Feng
John Glasser at Centers for Disease Control and Prevention
John Glasser
Kristie E. N. Clarke
Kristie E. N. Clarke
Kristie E. N. Clarke
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Abstract and Figures

During the COVID-19 pandemic, renewal equation estimates of time-varying effective reproduction numbers were useful to policymakers in evaluating the need for and impact of mitigation measures. Our objective here is to illustrate the utility of mechanistic expressions for the basic and effective (or intrinsic and realized) reproduction numbers, [Formula: see text] and related quantities derived from a Susceptible-Exposed-Infectious-Removed (SEIR) model including features of COVID-19 that might affect transmission of SARS-CoV-2, including asymptomatic, pre-symptomatic, and symptomatic infections, with which people may be hospitalized. Expressions from homogeneous host population models can be analyzed to determine the effort needed to reduce [Formula: see text] from [Formula: see text] to 1 and contributions of modeled mitigation measures. Our model is stratified by age, 0-4, 5-9, …, 75+ years, and location, the 50 states plus District of Columbia. Expressions from such heterogeneous host population models include subpopulation reproduction numbers, contributions from the above-mentioned infectious states, metapopulation numbers, subpopulation contributions, and equilibrium prevalence. While the population-immunity at which [Formula: see text] has captured the popular imagination, the metapopulation [Formula: see text] could be attained in an infinite number of ways even if only one intervention (e.g., vaccination) were capable of reducing [Formula: see text] However, gradients of expressions derived from heterogeneous host population models,[Formula: see text] can be evaluated to identify optimal allocations of limited resources among subpopulations. We illustrate the utility of such analytical results by simulating two hypothetical vaccination strategies, one uniform and other indicated by [Formula: see text] as well as the actual program estimated from one of the CDC's nationwide seroprevalence surveys conducted from mid-summer 2020 through the end of 2021.
Diagram of a modified SEIR model. This metapopulation model includes asymptomatic and pre-symptomatic stages, disease-induced mortality, vaccination, and the waning and boosting of immunity, features of COVID-19 that affect SARS-CoV-2 transmission. It is cross classified by age and location
Diagram of a modified SEIR model. This metapopulation model includes asymptomatic and pre-symptomatic stages, disease-induced mortality, vaccination, and the waning and boosting of immunity, features of COVID-19 that affect SARS-CoV-2 transmission. It is cross classified by age and location
… 
Proportions immune by virtue of a) infection, vaccination and both and b) vaccination by age and time during 2021 in the United States. These data are from a subset of blood-donors who were queried about their vaccination status (Busch et al. 2022)
Proportions immune by virtue of a) infection, vaccination and both and b) vaccination by age and time during 2021 in the United States. These data are from a subset of blood-donors who were queried about their vaccination status (Busch et al. 2022)
… 
Subpopulation and contributions to the metapopulation R0\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathcal{R}}_{0}$$\end{document}(a and b), which we estimate to have been 5.2 for the ancestral variant circulating during the fall of 2020, and subpopulation and contributions to the metapopulation RE\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathcal{R}}_{E}$$\end{document}(c and d), which we estimate to have been 1.3 on 25 December 2020. The legends for Figs. 3, 4, 5 are the same as Fig. 7, but Figs. 3, 4, 5 are repeated by HHS Region in the Supplement, where jurisdictions are more easily distinguished
Subpopulation and contributions to the metapopulation R0\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathcal{R}}_{0}$$\end{document}(a and b), which we estimate to have been 5.2 for the ancestral variant circulating during the fall of 2020, and subpopulation and contributions to the metapopulation RE\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathcal{R}}_{E}$$\end{document}(c and d), which we estimate to have been 1.3 on 25 December 2020. The legends for Figs. 3, 4, 5 are the same as Fig. 7, but Figs. 3, 4, 5 are repeated by HHS Region in the Supplement, where jurisdictions are more easily distinguished
… 
Infectious state contributions to the m × n age- and location-specific effective reproduction numbers RE(i)=RA(i)+RP(i)+RS(i)+RH(i),\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathcal{R}}_{E(i)} = {\mathcal{R}}_{A(i)} + {\mathcal{R}}_{P(i)} + {\mathcal{R}}_{S(i)} + {\mathcal{R}}_{H(i)} ,$$\end{document} where i = 1, …, 816, a) asymptomatic, b) pre-symptomatic, c) symptomatic, and d) hospitalized (for legend, see Fig. 7b). On 25 December 2020, Florida, New Jersey, and Washington, DC, dominated
Infectious state contributions to the m × n age- and location-specific effective reproduction numbers RE(i)=RA(i)+RP(i)+RS(i)+RH(i),\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathcal{R}}_{E(i)} = {\mathcal{R}}_{A(i)} + {\mathcal{R}}_{P(i)} + {\mathcal{R}}_{S(i)} + {\mathcal{R}}_{H(i)} ,$$\end{document} where i = 1, …, 816, a) asymptomatic, b) pre-symptomatic, c) symptomatic, and d) hospitalized (for legend, see Fig. 7b). On 25 December 2020, Florida, New Jersey, and Washington, DC, dominated
… 
Prevalence of infection implied by the metapopulation a) basic and b) effective reproduction numbers. Had interventions remained at their levels on 25 December 2020, the prevalence of infection would have been greater in Florida and New Jersey than the District of Columbia
+9
Prevalence of infection implied by the metapopulation a) basic and b) effective reproduction numbers. Had interventions remained at their levels on 25 December 2020, the prevalence of infection would have been greater in Florida and New Jersey than the District of Columbia
… 
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Journal of Mathematical Biology (2023) 87:24
https://doi.org/10.1007/s00285-023-01948-y
Mathematical Biology
Analysis of metapopulation models of the transmission
of SARS-CoV-2 in the United States
MyVan Vo1·Zhilan Feng1,2 ·John W. Glasser3·Kristie E. N. Clarke4·
Jefferson N. Jones3
Received: 5 October 2022 / Revised: 18 April 2023 / Accepted: 8 June 2023 /
Published online: 8 July 2023
This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may
apply 2023
Abstract
During the COVID-19 pandemic, renewal equation estimates of time-varying effec-
tive reproduction numbers were useful to policymakers in evaluating the need for
and impact of mitigation measures. Our objective here is to illustrate the utility
of mechanistic expressions for the basic and effective (or intrinsic and realized)
reproduction numbers, R0,RE, and related quantities derived from a Susceptible-
Exposed-Infectious-Removed (SEIR) model including features of COVID-19 that
might affect transmission of SARS-CoV-2, including asymptomatic, pre-symptomatic,
and symptomatic infections, with which people may be hospitalized. Expressions from
homogeneous host population models can be analyzed to determine the effort needed
to reduce REfrom R0to 1 and contributions of modeled mitigation measures. Our
model is stratified by age, 0–4, 5–9, …, 75+ years, and location, the 50 states plus
District of Columbia. Expressions from such heterogeneous host population models
include subpopulation reproduction numbers, contributions from the above-mentioned
infectious states, metapopulation numbers, subpopulation contributions, and equilib-
rium prevalence. While the population-immunity at which RE1 has captured the
popular imagination, the metapopulation RE≤1 could be attained in an infinite num-
ber of ways even if only one intervention (e.g., vaccination) were capable of reducing
RE.However, gradients of expressions derived from heterogeneous host population
models,∇RE, can be evaluated to identify optimal allocations of limited resources
among subpopulations. We illustrate the utility of such analytical results by simulating
BJohn W. Glasser
jglasser@cdc.gov
1Department of Mathematics, Purdue University, West Lafayette, USA
2Division of Mathematical Sciences, NSF, Alexandria, USA
3Coronavirus and Other Respiratory Viruses Division, National Center for Immunization and
Respiratory Diseases, CDC, 1600 Clifton Road NE, Atlanta, GA 30333, USA
4Center for Surveillance, Epidemiology, and Laboratory Services, CDC, Atlanta, USA
123
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Analysis of Serological Surveys of Antibodies to SARS-CoV-2 in the United States to Estimate Parameters Needed for Transmission Modeling and to Evaluate and Improve the Accuracy of Predictions
Article
  • Oct 2022
  • J THEOR BIOL
Seroprevalence studies can estimate proportions of the population that have been infected or vaccinated, including infections that were not reported because of the lack of symptoms or testing. Based on information from studies in the United States from mid-summer 2020 through the end of 2021, we describe proportions of the population with antibodies to SARS-CoV-2 as functions of age and time. Slices through these surfaces at arbitrary times provide initial and target conditions for simulation modeling. They also provide the information needed to calculate age-specific forces of infection, attack rates, and – together with contact rates – age-specific probabilities of infection on contact between susceptible and infectious people. We modified the familiar Susceptible-Exposed-Infectious-Removed (SEIR) model to include features of the biology of COVID-19 that might affect transmission of SARS-CoV-2 and stratified by age and location. We consulted the primary literature or subject matter experts for contact rates and other parameter values. Using time-varying Oxford COVID-19 Government Response Tracker assessments of US state and DC efforts to mitigate the pandemic and compliance with non-pharmaceutical interventions (NPIs) from a YouGov survey fielded in the US during 2020, we estimate that the efficacy of social-distancing when possible and mask-wearing otherwise at reducing susceptibility or infectiousness was 31% during the fall of 2020. Initialized from seroprevalence among people having commercial laboratory tests for purposes other than SARS-CoV-2 infection assessments on 7 September 2020, our age- and location-stratified SEIR population model reproduces seroprevalence among members of the same population on 25 December 2020 quite well. Introducing vaccination mid-December 2020, first of healthcare and other essential workers, followed by older adults, people who were otherwise immunocompromised, and then progressively younger people, our metapopulation model reproduces seroprevalence among blood donors on 4 April 2021 less well, but we believe that the discrepancy is due to vaccinations being under-reported or blood donors being disproportionately vaccinated, if not both. As experimenting with reliable transmission models is the best way to assess the indirect effects of mitigation measures, we determined the impact of vaccination, conditional on NPIs. Results indicate that, during this period, vaccination substantially reduced infections, hospitalizations and deaths. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics.”
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Protection and Waning of Natural and Hybrid Immunity to SARS-CoV-2
Article
Full-text available
  • May 2022
Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown. Methods: Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event. Results: The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously. Conclusions: Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.
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Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants - United States, June 2021-January 2022
Article
Full-text available
  • Feb 2022
Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action.† The SARS-CoV-2 Delta (B.1.617.2 and AY sublineages) variant rose from 1% to >50% of viral lineages circulating nationally during 8 weeks, from May 1-June 26, 2021. Delta-associated infections remained predominant until being rapidly overtaken by infections associated with the Omicron (B.1.1.529 and BA sublineages) variant in December 2021, when Omicron increased from 1% to >50% of circulating viral lineages during a 2-week period. As of the week ending January 22, 2022, Omicron was estimated to account for 99.2% (95% CI = 99.0%-99.5%) of SARS-CoV-2 infections nationwide, and Delta for 0.7% (95% CI = 0.5%-1.0%). The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice.
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The Impact of Age Difference on the Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis
Article
Full-text available
  • Dec 2021
Objective This meta-analysis compared the efficacy and safety of five kinds of COVID-19 vaccines in different age groups (young adults and older adults), aiming to analyze the difference of adverse events (AEs) rate and virus geometric mean titer (GMT) values between young and older people, in order to find a specific trend, and explore the causes of this trend through meta-analysis. Method Meta-analysis was used to analyze the five eligible articles. The modified Jadad scoring scale was used to evaluate the quality of eligible literature with a scoring system of 1 to 7. The primary endpoint of the effectiveness index was GMT. The primary endpoints of the safety index were the incidence of local AEs and systemic AEs. Stata 12.0 software was used for meta-analysis. Revman 5.0 software was used to map the risk of publication bias, and Egger’s test was used to analyze publication bias. Results The GMT values of young adults were higher than older adults (SMD = 1.40, 95% CI (0.79, 2.02), P<0.01). There was a higher incidence of local and systemic AEs in young people than in the elderly (OR = 1.10, 95% CI (1.08, 1.12), P<0.01; OR = 1.18, 95% CI (1.14, 1.22), P<0.01). Conclusion The immune effect of young people after being vaccinated with COVID-19 vaccines was better than that of the elderly, but the safety was worse than that of old people, the most common AEs were fever, rash, and local muscle pain, which were tolerable for young people. As the AEs of the elderly were lower, they can also be vaccinated safely; the reason for the low level of GMT in the elderly was related to Immunosenescence. The vaccine tolerance of people of different ages needs to be studied continuously.
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A global panel database of pandemic policies (Oxford COVID-19 Government Response Tracker)
Article
Full-text available
  • Apr 2021
  • Nat. Hum. Behav.
COVID-19 has prompted unprecedented government action around the world. We introduce the Oxford COVID-19 Government Response Tracker (OxCGRT), a dataset that addresses the need for continuously updated, readily usable and comparable information on policy measures. From 1 January 2020, the data capture government policies related to closure and containment, health and economic policy for more than 180 countries, plus several countries’ subnational jurisdictions. Policy responses are recorded on ordinal or continuous scales for 19 policy areas, capturing variation in degree of response. We present two motivating applications of the data, highlighting patterns in the timing of policy adoption and subsequent policy easing and reimposition, and illustrating how the data can be combined with behavioural and epidemiological indicators. This database enables researchers and policymakers to explore the empirical effects of policy responses on the spread of COVID-19 cases and deaths, as well as on economic and social welfare. The Oxford COVID-19 Government Response Tracker (OxCGRT) records data on 19 different government COVID-19 policy indicators for over 190 countries. Covering closure and containment, health and economics measures, it creates an evidence base for effective responses.
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Estimated SARS-CoV-2 Seroprevalence in the US as of September 2020
Article
Full-text available
  • Nov 2020
Importance Case-based surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimates the true prevalence of infections. Large-scale seroprevalence surveys can better estimate infection across many geographic regions. Objective To estimate the prevalence of persons with SARS-CoV-2 antibodies using residual sera from commercial laboratories across the US and assess changes over time. Design, Setting, and Participants This repeated, cross-sectional study conducted across all 50 states, the District of Columbia, and Puerto Rico used a convenience sample of residual serum specimens provided by persons of all ages that were originally submitted for routine screening or clinical management from 2 private clinical commercial laboratories. Samples were obtained during 4 collection periods: July 27 to August 13, August 10 to August 27, August 24 to September 10, and September 7 to September 24, 2020. Exposures Infection with SARS-CoV-2. Main Outcomes and Measures The proportion of persons previously infected with SARS-CoV-2 as measured by the presence of antibodies to SARS-CoV-2 by 1 of 3 chemiluminescent immunoassays. Iterative poststratification was used to adjust seroprevalence estimates to the demographic profile and urbanicity of each jurisdiction. Seroprevalence was estimated by jurisdiction, sex, age group (0-17, 18-49, 50-64, and ≥65 years), and metropolitan/nonmetropolitan status. Results Of 177 919 serum samples tested, 103 771 (58.3%) were from women, 26 716 (15.0%) from persons 17 years or younger, 47 513 (26.7%) from persons 65 years or older, and 26 290 (14.8%) from individuals living in nonmetropolitan areas. Jurisdiction-level seroprevalence over 4 collection periods ranged from less than 1% to 23%. In 42 of 49 jurisdictions with sufficient samples to estimate seroprevalence across all periods, fewer than 10% of people had detectable SARS-CoV-2 antibodies. Seroprevalence estimates varied between sexes, across age groups, and between metropolitan/nonmetropolitan areas. Changes from period 1 to 4 were less than 7 percentage points in all jurisdictions and varied across sites. Conclusions and Relevance This cross-sectional study found that as of September 2020, most persons in the US did not have serologic evidence of previous SARS-CoV-2 infection, although prevalence varied widely by jurisdiction. Biweekly nationwide testing of commercial clinical laboratory sera can play an important role in helping track the spread of SARS-CoV-2 in the US.
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Analysis of Serological Surveys of Antibodies to SARS-CoV-2 in the United States to Estimate Parameters Needed for Transmission Modeling and to Evaluate and Improve the Accuracy of Predictions
Article
  • Oct 2022
  • J THEOR BIOL
Seroprevalence studies can estimate proportions of the population that have been infected or vaccinated, including infections that were not reported because of the lack of symptoms or testing. Based on information from studies in the United States from mid-summer 2020 through the end of 2021, we describe proportions of the population with antibodies to SARS-CoV-2 as functions of age and time. Slices through these surfaces at arbitrary times provide initial and target conditions for simulation modeling. They also provide the information needed to calculate age-specific forces of infection, attack rates, and – together with contact rates – age-specific probabilities of infection on contact between susceptible and infectious people. We modified the familiar Susceptible-Exposed-Infectious-Removed (SEIR) model to include features of the biology of COVID-19 that might affect transmission of SARS-CoV-2 and stratified by age and location. We consulted the primary literature or subject matter experts for contact rates and other parameter values. Using time-varying Oxford COVID-19 Government Response Tracker assessments of US state and DC efforts to mitigate the pandemic and compliance with non-pharmaceutical interventions (NPIs) from a YouGov survey fielded in the US during 2020, we estimate that the efficacy of social-distancing when possible and mask-wearing otherwise at reducing susceptibility or infectiousness was 31% during the fall of 2020. Initialized from seroprevalence among people having commercial laboratory tests for purposes other than SARS-CoV-2 infection assessments on 7 September 2020, our age- and location-stratified SEIR population model reproduces seroprevalence among members of the same population on 25 December 2020 quite well. Introducing vaccination mid-December 2020, first of healthcare and other essential workers, followed by older adults, people who were otherwise immunocompromised, and then progressively younger people, our metapopulation model reproduces seroprevalence among blood donors on 4 April 2021 less well, but we believe that the discrepancy is due to vaccinations being under-reported or blood donors being disproportionately vaccinated, if not both. As experimenting with reliable transmission models is the best way to assess the indirect effects of mitigation measures, we determined the impact of vaccination, conditional on NPIs. Results indicate that, during this period, vaccination substantially reduced infections, hospitalizations and deaths. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics.”
View
Population-weighted seroprevalence from SARS-CoV-2 infection, vaccination, and hybrid immunity among U.S. blood donations from January-December 2021
Article
  • Jun 2022
Background Previous SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) vaccination, independently and combined (“hybrid immunity”), result in partial protection from subsequent infection and strong protection from severe disease. Proportions of the U.S. population that have been infected, vaccinated, or with hybrid immunity remain unclear, posing a challenge for assessing effective pandemic mitigation strategies. Methods In this serial cross-sectional study, nationwide blood donor specimens collected during January–December 2021 were tested for spike and nucleocapsid antibodies, and donor COVID-19 vaccination history of ≥1 dose was collected. Monthly seroprevalence induced from SARS-CoV-2 infection, COVID-19 vaccination, or both, were estimated. Estimates were weighted to account for demographic differences from the general population, and were compared temporally and by demographic factors. Results Overall, 1,123,855 blood samples were assayed. From January to December 2021, the weighted percentage of donations with seropositivity due to: vaccination without previous infection increased from 3.5% (95% CI, 3.4%-3.7%) to 64.0%, (95% CI, 63.5%-64.5%); previous infection without vaccination decreased from 15.6% (95% CI, 15.2%-16.0%) to 11.7% (95% CI, 11.4%-12.0%); hybrid immunity increased from 0.7% (95% CI, 0.6%-0.7%) to 18.9% (95% CI, 18.5%-19.3%); and from infection, vaccination, or both increased from 19.8% (95% CI (19.3-20.2) to 94.5% (95% CI, 93.5%-94.0% 0.1%). Infection- and vaccination-induced antibody responses varied significantly by age, race-ethnicity, and region, but not by gender. Conclusions Our results indicate substantial increases in population humoral immunity from SARS-CoV-2 infection, COVID-19 vaccination, and hybrid immunity during 2021. These findings are important to consider in future COVID-19 studies and long-term pandemic mitigation efforts.
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SARS-CoV-2 Seroprevalence and Reported COVID-19 Cases in U.S. Children, August 2020—May 2021
Article
  • Jan 2022
Background Case-based surveillance of pediatric COVID-19 cases underestimates the prevalence of SARS-CoV-2 infections among children and adolescents. Our objectives were to estimate monthly SARS-CoV-2 antibody seroprevalence and calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 8 U.S. states. Methods Using data from the Nationwide Commercial Laboratory Seroprevalence Survey, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years from August 2020 through May 2021. We calculated and compared cumulative incidence of SARS-CoV-2 infection extrapolated from population-standardized seroprevalence of antibodies to SARS-CoV-2, cumulative COVID-19 case reports since March 2020, and infection: case ratios among persons of all ages and children aged 0-17 years for each state. Results Of 41,583 residual serum specimens tested, children aged 0-4, 5-11 and 12-17 years accounted for 1,619 (3.9%), 10,507 (25.3%) and 29,457 (70.8%), respectively. Median SARS-CoV-2 antibody seroprevalence among children increased from 8% (range, 6% to 20%) in August 2020 to 37% (range, 26% to 44%) in May 2021. Estimated ratios of SARS-CoV-2 infections to reported COVID-19 cases in May 2021 ranged by state from 4.7-8.9 among children and adolescents to 2.2-3.9 for all ages combined. Conclusions Through May 2021 in selected states, the majority of children with serum specimens included in serosurveys did not have evidence of prior SARS-CoV-2 infection. Case-based surveillance underestimated the number of children infected with SARS-CoV-2 more than among all ages. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies.
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Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021
Article
  • Sep 2021
Importance People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. Objective To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. Design, Setting, and Participants In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. Exposure Calendar time. Main Outcomes and Measures Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. Results Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. Conclusions and Relevance Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population.
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Assessing the burden of congenital rubella syndrome in China and evaluating mitigation strategies: a metapopulation modelling study
Article
  • Jan 2021
  • LANCET INFECT DIS
Background A rubella vaccine was licensed in China in 1993 and added to the Expanded Programme on Immunization in 2008, but a national cross-sectional serological survey during 2014 indicates that many adolescents remain susceptible. Maternal infections during the first trimester often cause miscarriages, stillbirths, and, among livebirths, congenital rubella syndrome. We aimed to evaluate possible supplemental immunisation activities (SIAs) to accelerate elimination of rubella and congenital rubella syndrome. Methods We analysed residual samples from the national serological survey done in 2014, data from monthly rubella surveillance reports from 2005 and 2016, and additional publications through a systematic review. Using an age-structured population model with provincial strata, we calculated the reproduction numbers and evaluated the gradient of the metapopulation effective reproduction number with respect to potential supplemental immunisation rates. We corroborated these analytical results and estimated times-to-elimination by simulating SIAs among adolescents (ages 10–19 years) and young adults (ages 20–29 years) using a model with regional strata. We estimated the incidence of rubella and burden of congenital rubella syndrome by simulating transmission in a relatively small population lacking only spatial structure. Findings By 2014, childhood immunisation had reduced rubella's reproduction number from 7·6 to 1·2 and SIAs among adolescents were the optimal elimination strategy. We found that less than 10% of rubella infections were reported; that although some women with symptomatic first-trimester infections might have elected to terminate their pregnancies, 700 children could have been born with congenital rubella syndrome during 2014; and that timely SIAs would avert outbreaks that, as susceptible adolescents reached reproductive age, could greatly increase the burden of this syndrome. Interpretation Our findings suggest that SIAs among adolescents would most effectively reduce congenital rubella syndrome as well as eliminate rubella, owing both to fewer infections in the immunised population and absence of infections that those immunised would otherwise have caused. Metapopulation models with realistic mixing are uniquely capable of assessing such indirect effects. Funding WHO and National Science Foundation.
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