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2.
Science ; 371(6532): 916-921, 2021 02 26.
Article in English | MEDLINE | ID: covidwho-1532943

ABSTRACT

Limited initial supply of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine raises the question of how to prioritize available doses. We used a mathematical model to compare five age-stratified prioritization strategies. A highly effective transmission-blocking vaccine prioritized to adults ages 20 to 49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults greater than 60 years old. Use of individual-level serological tests to redirect doses to seronegative individuals improved the marginal impact of each dose while potentially reducing existing inequities in COVID-19 impact. Although maximum impact prioritization strategies were broadly consistent across countries, transmission rates, vaccination rollout speeds, and estimates of naturally acquired immunity, this framework can be used to compare impacts of prioritization strategies across contexts.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Health Priorities , Mass Vaccination , Adolescent , Adult , Age Factors , Aged , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/mortality , COVID-19/transmission , COVID-19 Vaccines/immunology , Child , Humans , Immunogenicity, Vaccine , Middle Aged , Models, Theoretical , SARS-CoV-2/immunology , Seroepidemiologic Studies , Young Adult
3.
Clin Infect Dis ; 72(9): e412-e414, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1387750

ABSTRACT

Various forms of "immune passports" or "antibody certificates" are being considered in conversations around reopening economies after periods of social distancing. A critique of such programs focuses on the uncertainty around whether seropositivity means immunity from repeat infection. However, an additional important consideration is that the low positive predictive value of serological tests in the setting of low population seroprevalence and imperfect test specificity will lead to many false-positive passport holders. Here, we pose a simple question: how many false-positive passports could be issued while maintaining herd immunity in the workforce? Answering this question leads to a simple mathematical formula for the minimum requirements of serological tests for a passport program, which depend on the population prevalence and the value of the basic reproductive number, R0. Our work replaces speculation in the press with rigorous analysis, and will need to be considered in policy decisions that are based on individual and population serology results.


Subject(s)
COVID-19 , Antibodies, Viral , Humans , Predictive Value of Tests , SARS-CoV-2 , Seroepidemiologic Studies , Serologic Tests
4.
medRxiv ; 2020 May 06.
Article in English | MEDLINE | ID: covidwho-1388077

ABSTRACT

The extent and duration of immunity following SARS-CoV-2 infection are critical outstanding questions about the epidemiology of this novel virus, and studies are needed to evaluate the effects of serostatus on reinfection. Understanding the potential sources of bias and methods to alleviate biases in these studies is important for informing their design and analysis. Confounding by individual-level risk factors in observational studies like these is relatively well appreciated. Here, we show how geographic structure and the underlying, natural dynamics of epidemics can also induce noncausal associations. We take the approach of simulating serologic studies in the context of an uncontrolled or a controlled epidemic, under different assumptions about whether prior infection does or does not protect an individual against subsequent infection, and using various designs and analytic approaches to analyze the simulated data. We find that in studies assessing the efficacy of serostatus on future infection, comparing seropositive individuals to seronegative individuals with similar time-dependent patterns of exposure to infection, by stratifying or matching on geographic location and time of enrollment, is essential to prevent bias.

5.
Clin Infect Dis ; 2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1376286

ABSTRACT

Seven cases of COVID-19 SARS-CoV-2 reinfection from the NBA 2020-2021 occupational testing cohort are described including clinical details, antibody test results, genomic sequencing, and longitudinal RT-PCR results. Reinfections were infrequent and varied in clinical presentation, viral dynamics, and immune response.

7.
Health Aff (Millwood) ; 40(8): 1321-1327, 2021 08.
Article in English | MEDLINE | ID: covidwho-1337565

ABSTRACT

Early in the COVID-19 pandemic, outpatient clinics throughout the US shifted toward virtual care to limit viral transmission in the office. However, as health care facilities have reopened, evidence about the risk of acquiring respiratory viral infections in medical office settings remains limited. To inform policy for reopening outpatient care settings, we analyzed rates of potential airborne disease transmission in medical office settings, focusing on influenza-like illness. We quantified whether exposed patients (that is, those seen in a medical office after a patient with influenza-like illness) were more likely to return with a similar illness in the next two weeks compared with nonexposed patients seen earlier in the day. Patients exposed to influenza-like illness in the medical office setting were more likely than nonexposed patients to revisit with a similar illness within two weeks (adjusted absolute difference: 0.7 per 1,000 patients). Similar patterns were not observed for exposure to urinary tract infection and back pain as noncontagious control conditions. These results highlight the potential threat of reopening outpatient clinics during the pandemic and the value of virtual visits for patients with suspected respiratory infections.


Subject(s)
COVID-19 , Respiratory Tract Infections , Humans , Infection Control , Outpatients , Pandemics , Physicians' Offices , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , SARS-CoV-2
8.
PLoS Biol ; 19(7): e3001333, 2021 07.
Article in English | MEDLINE | ID: covidwho-1305572

ABSTRACT

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season. For 46 individuals with acute infections, we inferred the peak viral concentration and the duration of the viral proliferation and clearance phases. According to our mathematical model, we found that viral RNA concentrations peaked an average of 3.3 days (95% credible interval [CI] 2.5, 4.2) after first possible detectability at a cycle threshold value of 22.3 (95% CI 20.5, 23.9). The viral clearance phase lasted longer for symptomatic individuals (10.9 days [95% CI 7.9, 14.4]) than for asymptomatic individuals (7.8 days [95% CI 6.1, 9.7]). A second test within 2 days after an initial positive PCR test substantially improves certainty about a patient's infection stage. The effective sensitivity of a test intended to identify infectious individuals declines substantially with test turnaround time. These findings indicate that SARS-CoV-2 viral concentrations peak rapidly regardless of symptoms. Sequential tests can help reveal a patient's progress through infection stages. Frequent, rapid-turnaround testing is needed to effectively screen individuals before they become infectious.


Subject(s)
COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19/diagnosis , RNA, Viral/genetics , SARS-CoV-2/genetics , Virus Replication/genetics , Virus Shedding/genetics , Adult , Athletes , Basketball , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Convalescence , Humans , Male , Prospective Studies , Public Health/methods , SARS-CoV-2/growth & development , Severity of Illness Index , United States/epidemiology
9.
Elife ; 102021 05 18.
Article in English | MEDLINE | ID: covidwho-1232679

ABSTRACT

Background: The impact of variable infection risk by race and ethnicity on the dynamics of SARS-CoV-2 spread is largely unknown. Methods: Here, we fit structured compartmental models to seroprevalence data from New York State and analyze how herd immunity thresholds (HITs), final sizes, and epidemic risk change across groups. Results: A simple model where interactions occur proportionally to contact rates reduced the HIT, but more realistic models of preferential mixing within groups increased the threshold toward the value observed in homogeneous populations. Across all models, the burden of infection fell disproportionately on minority populations: in a model fit to Long Island serosurvey and census data, 81% of Hispanics or Latinos were infected when the HIT was reached compared to 34% of non-Hispanic whites. Conclusions: Our findings, which are meant to be illustrative and not best estimates, demonstrate how racial and ethnic disparities can impact epidemic trajectories and result in unequal distributions of SARS-CoV-2 infection. Funding: K.C.M. was supported by National Science Foundation GRFP grant DGE1745303. Y.H.G. and M.L. were funded by the Morris-Singer Foundation. M.L. was supported by SeroNet cooperative agreement U01 CA261277.


Subject(s)
COVID-19/epidemiology , Health Status Disparities , Models, Statistical , Pandemics/statistics & numerical data , African Americans/statistics & numerical data , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Cost of Illness , Humans , Immunity, Herd , Minority Groups/statistics & numerical data , New York/epidemiology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , /statistics & numerical data
10.
JAMA Intern Med ; 181(7): 960-966, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1196360

ABSTRACT

Importance: Clinical data are lacking regarding the risk of viral transmission from individuals who have positive reverse-transcription-polymerase chain reaction (RT-PCR) SARS-CoV-2 test results after recovery from COVID-19. Objective: To describe case characteristics, including viral dynamics and transmission of infection, for individuals who have clinically recovered from SARS-CoV-2 infection but continued to have positive test results following discontinuation of isolation precautions. Design, Setting, and Participants: This retrospective cohort study used data collected from June 11, 2020, to October 19, 2020, as part of the National Basketball Association (NBA) closed campus occupational health program in Orlando, Florida, which required daily RT-PCR testing and ad hoc serological testing for SARS-CoV-2 IgG antibodies. Nearly 4000 NBA players, staff, and vendors participated in the NBA's regular and postseason occupational health program in Orlando. Persistent positive cases were those who recovered from a documented SARS-CoV-2 infection, satisfied US Centers for Disease Control and Prevention criteria for discontinuation of isolation precautions, and had at least 1 postinfection positive RT-PCR test(s) result. Exposures: Person-days of participation in indoor, unmasked activities that involved direct exposure between persistent positive cases and noninfected individuals. Main Outcomes and Measures: Transmission of SARS-CoV-2 following interaction with persistent positive individuals, as measured by the number of new COVID-19 cases in the Orlando campus program. Results: Among 3648 individuals who participated, 36 (1%) were persistent positive cases, most of whom were younger than 30 years (24 [67%]) and male (34 [94%]). Antibodies were detected in 33 individuals (91.7%); all remained asymptomatic following the index persistent positive RT-PCR result. Cycle threshold values for persistent positive RT-PCR test results were typically above the Roche cobas SARS-CoV-2 limit of detection. Cases were monitored for up to 100 days (mean [SD], 51 [23.9] days), during which there were at least 1480 person-days of direct exposure activities, with no transmission events or secondary infections of SARS-CoV-2 detected (0 new cases). Conclusions and Relevance: In this retrospective cohort study of the 2020 NBA closed campus occupational health program, recovered individuals who continued to test positive for SARS-CoV-2 following discontinuation of isolation were not infectious to others. These findings support time-based US Centers of Disease Control and Prevention recommendations for ending isolation.


Subject(s)
Antibodies, Viral/analysis , Basketball/statistics & numerical data , COVID-19/transmission , Disease Transmission, Infectious/statistics & numerical data , Pandemics , SARS-CoV-2/immunology , Adolescent , Adult , COVID-19/epidemiology , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , United States/epidemiology , Young Adult
11.
Nat Rev Immunol ; 21(5): 330-335, 2021 05.
Article in English | MEDLINE | ID: covidwho-1164868

ABSTRACT

When vaccines are in limited supply, expanding the number of people who receive some vaccine, such as by halving doses or increasing the interval between doses, can reduce disease and mortality compared with concentrating available vaccine doses in a subset of the population. A corollary of such dose-sparing strategies is that the vaccinated individuals may have less protective immunity. Concerns have been raised that expanding the fraction of the population with partial immunity to SARS-CoV-2 could increase selection for vaccine-escape variants, ultimately undermining vaccine effectiveness. We argue that, although this is possible, preliminary evidence instead suggests such strategies should slow the rate of viral escape from vaccine or naturally induced immunity. As long as vaccination provides some protection against escape variants, the corresponding reduction in prevalence and incidence should reduce the rate at which new variants are generated and the speed of adaptation. Because there is little evidence of efficient immune selection of SARS-CoV-2 during typical infections, these population-level effects are likely to dominate vaccine-induced evolution.


Subject(s)
COVID-19/prevention & control , Off-Label Use , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Vaccination/methods , Vaccines/administration & dosage , Biological Evolution , COVID-19/immunology , Humans , Immune Evasion/genetics , Immune Evasion/immunology , Vaccination/psychology
12.
Elife ; 102021 03 05.
Article in English | MEDLINE | ID: covidwho-1119624

ABSTRACT

Establishing how many people have been infected by SARS-CoV-2 remains an urgent priority for controlling the COVID-19 pandemic. Serological tests that identify past infection can be used to estimate cumulative incidence, but the relative accuracy and robustness of various sampling strategies have been unclear. We developed a flexible framework that integrates uncertainty from test characteristics, sample size, and heterogeneity in seroprevalence across subpopulations to compare estimates from sampling schemes. Using the same framework and making the assumption that seropositivity indicates immune protection, we propagated estimates and uncertainty through dynamical models to assess uncertainty in the epidemiological parameters needed to evaluate public health interventions and found that sampling schemes informed by demographics and contact networks outperform uniform sampling. The framework can be adapted to optimize serosurvey design given test characteristics and capacity, population demography, sampling strategy, and modeling approach, and can be tailored to support decision-making around introducing or removing interventions.


Subject(s)
COVID-19/epidemiology , Adolescent , Adult , Age Factors , Aged , Bayes Theorem , COVID-19/diagnosis , COVID-19 Serological Testing , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Middle Aged , Pandemics , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Uncertainty , Young Adult
13.
medRxiv ; 2020 Mar 08.
Article in English | MEDLINE | ID: covidwho-829788

ABSTRACT

BACKGROUND: Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases, such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible, and broader mitigation measures must be implemented. METHODS: To estimate the comparative efficacy of these case-based interventions to control COVID-19, we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit to the incubation period distribution and each of two sets of the serial interval distribution: a shorter one with a mean serial interval of 4.8 days and a longer one with a mean of 7.5 days. To assess variable resource settings, we consider two feasibility settings: a high feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and low feasibility setting with 50% of contacts traced, a two-day average delay, and 50% effective isolation. FINDINGS: Our results suggest that individual quarantine in high feasibility settings where at least three-quarters of infected contacts are individually quarantined contains an outbreak of COVID-19 with a short serial interval (4.8 days) 84% of the time. However, in settings where this performance is unrealistically high and the outbreak continues to grow, so too will the burden of the number of contacts traced for active monitoring or quarantine. When resources are prioritized for scalable interventions such as social distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. INTERPRETATION: Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission in order to make data-driven policy decisions regarding the cost-benefit comparisons of individual quarantine vs. active monitoring of contacts. To the extent these interventions can be implemented they can help mitigate the spread of COVID-19.

14.
Nat Rev Immunol ; 20(11): 709-713, 2020 11.
Article in English | MEDLINE | ID: covidwho-834892

ABSTRACT

Immunity is a multifaceted phenomenon. For T cell-mediated memory responses to SARS-CoV-2, it is relevant to consider their impact both on COVID-19 disease severity and on viral spread in a population. Here, we reflect on the immunological and epidemiological aspects and implications of pre-existing cross-reactive immune memory to SARS-CoV-2, which largely originates from previous exposure to circulating common cold coronaviruses. We propose four immunological scenarios for the impact of cross-reactive CD4+ memory T cells on COVID-19 severity and viral transmission. For each scenario, we discuss its implications for the dynamics of herd immunity and on projections of the global impact of SARS-CoV-2 on the human population, and assess its plausibility. In sum, we argue that key potential impacts of cross-reactive T cell memory are already incorporated into epidemiological models based on data of transmission dynamics, particularly with regard to their implications for herd immunity. The implications of immunological processes on other aspects of SARS-CoV-2 epidemiology are worthy of future study.


Subject(s)
Antibodies, Viral/biosynthesis , Betacoronavirus/immunology , Coronaviridae Infections/prevention & control , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Adaptive Immunity/drug effects , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , COVID-19 , COVID-19 Vaccines , Coronaviridae/drug effects , Coronaviridae/immunology , Coronaviridae Infections/epidemiology , Coronaviridae Infections/immunology , Coronaviridae Infections/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cross Reactions , Humans , Immunity, Herd/drug effects , Immunologic Memory , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Rhinovirus/drug effects , Rhinovirus/immunology , SARS-CoV-2 , Viral Vaccines/administration & dosage , Viral Vaccines/biosynthesis
15.
Nat Commun ; 11(1): 4674, 2020 09 16.
Article in English | MEDLINE | ID: covidwho-772965

ABSTRACT

SARS-CoV-2-related mortality and hospitalizations differ substantially between New York City neighborhoods. Mitigation efforts require knowing the extent to which these disparities reflect differences in prevalence and understanding the associated drivers. Here, we report the prevalence of SARS-CoV-2 in New York City boroughs inferred using tests administered to 1,746 pregnant women hospitalized for delivery between March 22nd and May 3rd, 2020. We also assess the relationship between prevalence and commuting-style movements into and out of each borough. Prevalence ranged from 11.3% (95% credible interval [8.9%, 13.9%]) in Manhattan to 26.0% (15.3%, 38.9%) in South Queens, with an estimated city-wide prevalence of 15.6% (13.9%, 17.4%). Prevalence was lowest in boroughs with the greatest reductions in morning movements out of and evening movements into the borough (Pearson R = -0.88 [-0.52, -0.99]). Widespread testing is needed to further specify disparities in prevalence and assess the risk of future outbreaks.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Residence Characteristics/statistics & numerical data , Transportation/statistics & numerical data , Adolescent , Adult , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Female , Health Status Disparities , Humans , Middle Aged , New York City/epidemiology , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pregnant Women , Prevalence , SARS-CoV-2 , Young Adult
17.
Lancet Infect Dis ; 20(9): 1025-1033, 2020 09.
Article in English | MEDLINE | ID: covidwho-324298

ABSTRACT

BACKGROUND: Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible and broader mitigation measures must be implemented. METHODS: To estimate the comparative efficacy of individual quarantine and active monitoring of contacts to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit a model to the incubation period distribution (mean 5·2 days) and to two estimates of the serial interval distribution: a shorter one with a mean serial interval of 4·8 days and a longer one with a mean of 7·5 days. To assess variable resource settings, we considered two feasibility settings: a high-feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and a low-feasibility setting with 50% of contacts traced, a 2-day average delay, and 50% effective isolation. FINDINGS: Model fitting by sequential Monte Carlo resulted in a mean time of infectiousness onset before symptom onset of 0·77 days (95% CI -1·98 to 0·29) for the shorter serial interval, and for the longer serial interval it resulted in a mean time of infectiousness onset after symptom onset of 0·51 days (95% CI -0·77 to 1·50). Individual quarantine in high-feasibility settings, where at least 75% of infected contacts are individually quarantined, contains an outbreak of SARS-CoV-2 with a short serial interval (4·8 days) 84% of the time. However, in settings where the outbreak continues to grow (eg, low-feasibility settings), so too will the burden of the number of contacts traced for active monitoring or quarantine, particularly uninfected contacts (who never develop symptoms). When resources are prioritised for scalable interventions such as physical distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. Even under the shorter serial interval, if physical distancing reduces the reproductive number to 1·25, active monitoring of 50% of contacts can result in overall outbreak control (ie, effective reproductive number <1). INTERPRETATION: Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission to make data-driven policy decisions regarding the cost-benefit comparisons of individual quarantine versus active monitoring of contacts. To the extent that these interventions can be implemented, they can help mitigate the spread of SARS-CoV-2. FUNDING: National Institute of General Medical Sciences, National Institutes of Health.


Subject(s)
Betacoronavirus/isolation & purification , Contact Tracing , Coronavirus Infections/prevention & control , Disease Outbreaks/prevention & control , Models, Theoretical , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Quarantine , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Epidemiological Monitoring , Humans , Monte Carlo Method , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , SARS-CoV-2 , Voluntary Programs
18.
Science ; 368(6493): 860-868, 2020 05 22.
Article in English | MEDLINE | ID: covidwho-57045

ABSTRACT

It is urgent to understand the future of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission. We used estimates of seasonality, immunity, and cross-immunity for human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1 using time-series data from the United States to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether critical care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Additional interventions, including expanded critical care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serological studies are urgently needed to determine the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained because a resurgence in contagion could be possible as late as 2024.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/virology , Models, Biological , Pneumonia, Viral/virology , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus OC43, Human/physiology , Disease Outbreaks , Disease Transmission, Infectious , Humans , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , SARS-CoV-2 , Seasons
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