scholarly journals SARS-CoV-2 serology across scales: a framework for unbiased seroprevalence estimation incorporating antibody kinetics and epidemic recency

Author(s):  
Saki Takahashi ◽  
Michael J Peluso ◽  
Jill Hakim ◽  
Keirstinne Turcios ◽  
Owen Janson ◽  
...  

Serosurveys are a key resource for measuring SARS-CoV-2 cumulative incidence. A growing body of evidence suggests that asymptomatic and mild infections (together making up over 95% of all infections) are associated with lower antibody titers than severe infections. Antibody levels also peak a few weeks after infection and decay gradually. We developed a statistical approach to produce adjusted estimates of seroprevalence from raw serosurvey results that account for these sources of spectrum bias. We incorporate data on antibody responses on multiple assays from a post-infection longitudinal cohort, along with epidemic time series to account for the timing of a serosurvey relative to how recently individuals may have been infected. We applied this method to produce adjusted seroprevalence estimates from five large-scale SARS-CoV-2 serosurveys across different settings and study designs. We identify substantial differences between reported and adjusted estimates of over two-fold in the results of some surveys, and provide a tool for practitioners to generate adjusted estimates with pre-set or custom parameter values. While unprecedented efforts have been launched to generate SARS-CoV-2 seroprevalence estimates over this past year, interpretation of results from these studies requires properly accounting for both population-level epidemiologic context and individual-level immune dynamics.

Author(s):  
Tyler J Ripperger ◽  
Jennifer L Uhrlaub ◽  
Makiko Watanabe ◽  
Rachel Wong ◽  
Yvonne Castaneda ◽  
...  

We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.


2020 ◽  
Vol 117 (28) ◽  
pp. 16418-16423 ◽  
Author(s):  
Patricia Mateo-Tomás ◽  
Pedro P. Olea ◽  
Eva Mínguez ◽  
Rafael Mateo ◽  
Javier Viñuela

Toxicants such as organochlorine insecticides, lead ammunition, and veterinary drugs have caused severe wildlife poisoning, pushing the populations of several apex species to the edge of extinction. These prime cases epitomize the serious threat that wildlife poisoning poses to biodiversity. Much of the evidence on population effects of wildlife poisoning rests on assessments conducted at an individual level, from which population-level effects are inferred. Contrastingly, we demonstrate a straightforward relationship between poison-induced individual mortality and population changes in the threatened red kite (Milvus milvus). By linking field data of 1,075 poisoned red kites to changes in occupancy and abundance across 274 sites (10 × 10-km squares) over a 20-y time frame, we show a clear relationship between red kite poisoning and the decline of its breeding population in Spain, including local extinctions. Our results further support the species listing as endangered, after a breeding population decline of 31% to 43% in two decades of this once-abundant raptor. Given that poisoning threatens the global populations of more than 2,600 animal species worldwide, a greater understanding of its population-level effects may aid biodiversity conservation through increased regulatory control of chemical substances. Our results illustrate the great potential of long-term and large-scale on-ground monitoring to assist in this task.


2016 ◽  
Vol 82 (12) ◽  
pp. 3537-3545 ◽  
Author(s):  
Tuomas Aivelo ◽  
Juha Laakkonen ◽  
Jukka Jernvall

ABSTRACTLongitudinal sampling for intestinal microbiota in wild animals is difficult, leading to a lack of information on bacterial dynamics occurring in nature. We studied how the composition of microbiota communities changed temporally in free-ranging small primates, rufous mouse lemurs (Microcebus rufus). We marked and recaptured mouse lemurs during their mating season in Ranomafana National Park in southeastern mountainous rainforests of Madagascar for 2 years and determined the fecal microbiota compositions of these mouse lemurs with MiSeq sequencing. We collected 160 fecal samples from 71 animals and had two or more samples from 39 individuals. We found small, but statistically significant, effects of site and age on microbiota richness and diversity and effects of sex, year, and site on microbiota composition, while the within-year temporal trends were less clear. Within-host microbiota showed pervasive variation in intestinal bacterial community composition, especially during the second study year. We hypothesize that the biological properties of mouse lemurs, including their small body size and fast metabolism, may contribute to the temporal intraindividual-level variation, something that should be testable with more-extensive sampling regimes.IMPORTANCEWhile microbiome research has blossomed in recent years, there is a lack of longitudinal studies on microbiome dynamics on free-ranging hosts. To fill this gap, we followed mouse lemurs, which are small heterothermic primates, for 2 years. Most studied animals have shown microbiota to be stable over the life span of host individuals, but some previous research also found ample within-host variation in microbiota composition. Our study used a larger sample size than previous studies and a study setting well suited to track within-host variation in free-ranging mammals. Despite the overall microbiota stability at the population level, the microbiota of individual mouse lemurs can show large-scale changes in composition in time periods as short as 2 days, suggesting caution in inferring individual-level patterns from population-level data.


2009 ◽  
Vol 16 (8) ◽  
pp. 1105-1112 ◽  
Author(s):  
Richard Kennedy ◽  
V. Shane Pankratz ◽  
Eric Swanson ◽  
David Watson ◽  
Hana Golding ◽  
...  

ABSTRACT Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a β-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin.


2019 ◽  
Vol 116 (42) ◽  
pp. 20923-20929 ◽  
Author(s):  
Emma E. Garnett ◽  
Andrew Balmford ◽  
Chris Sandbrook ◽  
Mark A. Pilling ◽  
Theresa M. Marteau

Shifting people in higher income countries toward more plant-based diets would protect the natural environment and improve population health. Research in other domains suggests altering the physical environments in which people make decisions (“nudging”) holds promise for achieving socially desirable behavior change. Here, we examine the impact of attempting to nudge meal selection by increasing the proportion of vegetarian meals offered in a year-long large-scale series of observational and experimental field studies. Anonymized individual-level data from 94,644 meals purchased in 2017 were collected from 3 cafeterias at an English university. Doubling the proportion of vegetarian meals available from 25 to 50% (e.g., from 1 in 4 to 2 in 4 options) increased vegetarian meal sales (and decreased meat meal sales) by 14.9 and 14.5 percentage points in the observational study (2 cafeterias) and by 7.8 percentage points in the experimental study (1 cafeteria), equivalent to proportional increases in vegetarian meal sales of 61.8%, 78.8%, and 40.8%, respectively. Linking sales data to participants’ previous meal purchases revealed that the largest effects were found in the quartile of diners with the lowest prior levels of vegetarian meal selection. Moreover, serving more vegetarian options had little impact on overall sales and did not lead to detectable rebound effects: Vegetarian sales were not lower at other mealtimes. These results provide robust evidence to support the potential for simple changes to catering practices to make an important contribution to achieving more sustainable diets at the population level.


1999 ◽  
Vol 29 (5) ◽  
pp. 1013-1020 ◽  
Author(s):  
T. S. BRUGHA ◽  
P. E. BEBBINGTON ◽  
R. JENKINS

Psychiatric case-identification in general populations allows us to study both individuals with functional psychiatric disorders and the populations from which they come. The individual level of analysis permits disorders to be related to factors of potential aetiological significance and the study of attributes of the disorders that need to be assessed in non-referred populations (an initially scientific endeavour). At the population level valid case identification can be used to evaluate needs for treatment and the utilization of service resources (a public health project). Thus, prevalence is of interest both to scientists and to those responsible for commissioning and planning services (Brugha et al. 1997; Regier et al. 1998). The quality of case identification techniques and of estimates of prevalence is thus of general concern (Bartlett & Coles, 1998).Structured diagnostic interviews were introduced into general population surveys in the 1970s as a method ‘to enable interviewers to obtain psychiatric diagnoses comparable to those a psychiatrist would obtain’ (Robins et al. 1981). The need to develop reliable standardized measures was partly driven by an earlier generation of prevalence surveys showing rates ranging widely from 10·9% (Pasamanick et al. 1956) to 55% (Leighton et al. 1963) in urban and rural North American communities respectively. If the success of large scale psychiatric epidemiological enquiries using structured diagnostic interviews and standardized classifications is measured in terms of citation rates it would seem difficult to question. But the development of standardized interviews of functional psychiatric disorders has not solved this problem of variability: the current generation of large scale surveys, using structured diagnostic interviews and serving strictly defined classification rules, have generated, for example, 12-month prevalence rates of major depression in the US of 4·2% (Robins & Regier, 1991) and 10·1% (Kessler et al. 1994). This calls into question the validity of the assessments, such that we must reopen the question of what they should be measuring and how they should do it.


2020 ◽  
Author(s):  
Robin A. A. Ince ◽  
Jim W. Kay ◽  
Philippe G. Schyns

AbstractWithin neuroscience, psychology and neuroimaging, the most frequently used statistical approach is null-hypothesis significance testing (NHST) of the population mean. An alternative approach is to perform NHST within individual participants and then infer, from the proportion of participants showing an effect, the prevalence of that effect in the population. We propose a novel Bayesian method to estimate such population prevalence that offers several advantages over population mean NHST. This method provides a population-level inference that is currently missing from study designs with small participant numbers, such as in traditional psychophysics and in precision imaging. It delivers a quantitative estimate with associated uncertainty instead of reducing an experiment to a binary inference on a population mean. Bayesian prevalence is widely applicable to a broad range of studies in neuroscience, psychology and neuroimaging. Its emphasis on detecting effects within individual participants could also help address replicability issues in these fields.


Vaccines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Ariel Israel ◽  
Yotam Shenhar ◽  
Ilan Green ◽  
Eugene Merzon ◽  
Avivit Golan-Cohen ◽  
...  

Immune protection following either vaccination or infection with SARS-CoV-2 is thought to decrease over time. We designed a retrospective study, conducted at Leumit Health Services in Israel, to determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals. Antibody titers were measured between 31 January 2021, and 31 July 2021 in two mutually exclusive groups: (i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and (ii) SARS-CoV-2 convalescents who had not received the vaccine. A total of 2653 individuals fully vaccinated by two doses of vaccine during the study period and 4361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8–5644.6]) after the second vaccination than in convalescent individuals (median 355.3 AU/mL IQR [141.2–998.7]; p < 0.001). In vaccinated subjects, antibody titers decreased by up to 38% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection. This study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.


Author(s):  
Jianzhong Chen ◽  
Angela Tam ◽  
Valeria Kebets ◽  
Csaba Orban ◽  
Leon Qi Rong Ooi ◽  
...  

AbstractThe manner through which individual differences in brain network organization track population-level behavioral variability is a fundamental question in systems neuroscience. Recent work suggests that resting-state and task-state functional connectivity can predict specific traits at the individual level. However, the focus of most studies on single behavioral traits has come at the expense of capturing broader relationships across behaviors. Here, we utilized a large-scale dataset of 1858 typically developing children to estimate whole-brain functional network organization that is predictive of individual differences in cognition, impulsivity-related personality, and mental health during rest and task states. Predictive network features were distinct across the broad behavioral domains: cognition, personality and mental health. On the other hand, traits within each behavioral domain were predicted by highly similar network features. This is surprising given decades of research emphasizing that distinct brain networks support different mental processes. Although tasks are known to modulate the functional connectome, we found that predictive network features were similar between resting and task states. Overall, our findings reveal shared brain network features that account for individual variation within broad domains of behavior in childhood, yet are unique to different behavioral domains.


2019 ◽  
Vol 6 (9) ◽  
pp. 191149 ◽  
Author(s):  
Mason Youngblood

One of the fundamental questions of cultural evolutionary research is how individual-level processes scale up to generate population-level patterns. Previous studies in music have revealed that frequency-based bias (e.g. conformity and novelty) drives large-scale cultural diversity in different ways across domains and levels of analysis. Music sampling is an ideal research model for this process because samples are known to be culturally transmitted between collaborating artists, and sampling events are reliably documented in online databases. The aim of the current study was to determine whether frequency-based bias has played a role in the cultural transmission of music sampling traditions, using a longitudinal dataset of sampling events across three decades. Firstly, we assessed whether turn-over rates of popular samples differ from those expected under neutral evolution. Next, we used agent-based simulations in an approximate Bayesian computation framework to infer what level of frequency-based bias likely generated the observed data. Despite anecdotal evidence of novelty bias, we found that sampling patterns at the population-level are most consistent with conformity bias. We conclude with a discussion of how counter-dominance signalling may reconcile individual cases of novelty bias with population-level conformity.


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