Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modelling study.

BackgroundSerological surveys have been the gold standard to estimate numbers of SARS-CoV-2 infections, the dynamics of the epidemic, and disease severity. Serological assays have decaying sensitivity with time that can bias their results, but there is a lack of guidelines to account for this phenomenon for SARS-CoV-2.AimOur goal was to assess the sensitivity decay of seroassays for detecting SARS-CoV-2 infections, the dependence of this decay on assay characteristics, and to provide a simple method to correct for this phenomenon.MethodsWe performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed, unvaccinated individuals, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients).ResultsOf the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depended strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We found that a third of the included assays departed considerably from manufacturer specifications after 6 months.ConclusionsSeroassay sensitivity decay depends on assay characteristics, and for some types of assays, it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon and to assess the risk of decay for a given assay. Our analysis can guide the design and interpretation of serosurveys for SARS-CoV-2 and other pathogens and quantify systematic biases in the existing serology literature.

Assessing the burden of COVID-19 in developing countries: systematic review, meta-analysis and public policy implications.

INTRODUCTION: The infection fatality rate (IFR) of COVID-19 has been carefully measured and analysed in high-income countries, whereas there has been no systematic analysis of age-specific seroprevalence or IFR for developing countries. METHODS: We systematically reviewed the literature to identify all COVID-19 serology studies in developing countries that were conducted using representative samples collected by February 2021. For each of the antibody assays used in these serology studies, we identified data on assay characteristics, including the extent of seroreversion over time. We analysed the serology data using a Bayesian model that incorporates conventional sampling uncertainty as well as uncertainties about assay sensitivity and specificity. We then calculated IFRs using individual case reports or aggregated public health updates, including age-specific estimates whenever feasible. RESULTS: In most locations in developing countries, seroprevalence among older adults was similar to that of younger age cohorts, underscoring the limited capacity that these nations have to protect older age groups.Age-specific IFRs were roughly 2 times higher than in high-income countries. The median value of the population IFR was about 0.5%, similar to that of high-income countries, because disparities in healthcare access were roughly offset by differences in population age structure. CONCLUSION: The burden of COVID-19 is far higher in developing countries than in high-income countries, reflecting a combination of elevated transmission to middle-aged and older adults as well as limited access to adequate healthcare. These results underscore the critical need to ensure medical equity to populations in developing countries through provision of vaccine doses and effective medications.

Contact tracing-induced Allee effect in disease dynamics.

Contact tracing, case isolation, quarantine, social distancing, and other non-pharmaceutical interventions (NPIs) have been a cornerstone in managing the COVID-19 pandemic. However, their effects on disease dynamics are not fully understood. Saturation of contact tracing caused by the increase of infected individuals has been recognized as a crucial variable by healthcare systems worldwide. Here, we model this saturation process with a mechanistic and a phenomenological model and show that it induces an Allee effect which could determine an infection threshold between two alternative states-containment and outbreak. This transition was considered elsewhere as a response to the strength of NPIs, but here we show that they may be also determined by the number of infected individuals. As a consequence, timing of NPIs implementation and relaxation after containment is critical to their effectiveness. Containment strategies such as vaccination or mobility restriction may interact with contact tracing-induced Allee effect. Each strategy in isolation tends to show diminishing returns, with a less than proportional effect of the intervention on disease containment. However, when combined, their suppressing potential is enhanced. Relaxation of NPIs after disease containment--e.g. because vaccination--have to be performed in attention to avoid crossing the infection threshold required to a novel outbreak. The recognition of a contact tracing-induced Allee effect, its interaction with other NPIs and vaccination, and the existence of tipping points contributes to the understanding of several features of disease dynamics and its response to containment interventions. This knowledge may be of relevance for explaining the dynamics of diseases in different regions and, more importantly, as input for guiding the use of NPIs, vaccination campaigns, and its combination for the management of epidemic outbreaks.

Age-specific rate of severe and critical SARS-CoV-2 infections estimated with multi-country seroprevalence studies.

BACKGROUND: Knowing the age-specific rates at which individuals infected with SARS-CoV-2 develop severe and critical disease is essential for designing public policy, for infectious disease modeling, and for individual risk evaluation. METHODS: In this study, we present the first estimates of these rates using multi-country serology studies, and public data on hospital admissions and mortality from early to mid-2020. We combine these under a Bayesian framework that accounts for the high heterogeneity between data sources and their respective uncertainties. We also validate our results using an indirect method based on infection fatality rates and hospital mortality data. RESULTS: Our results show that the risk of severe and critical disease increases exponentially with age, but much less steeply than the risk of fatal illness. We also show that our results are consistent across several robustness checks. CONCLUSION: A complete evaluation of the risks of SARS-CoV-2 for health must take non-fatal disease outcomes into account, particularly in young populations where they can be 2 orders of magnitude more frequent than deaths.

Redundancy between spectral and higher-order texture statistics for natural image segmentation.

Visual texture, defined by local image statistics, provides important information to the human visual system for perceptual segmentation. Second-order or spectral statistics (equivalent to the Fourier power spectrum) are a well-studied segmentation cue. However, the role of higher-order statistics (HOS) in segmentation remains unclear, particularly for natural images. Recent experiments indicate that, in peripheral vision, the HOS of the widely adopted Portilla-Simoncelli texture model are a weak segmentation cue compared to spectral statistics, despite the fact that both are necessary to explain other perceptual phenomena and to support high-quality texture synthesis. Here we test whether this discrepancy reflects a property of natural image statistics. First, we observe that differences in spectral statistics across segments of natural images are redundant with differences in HOS. Second, using linear and nonlinear classifiers, we show that each set of statistics individually affords high performance in natural scenes and texture segmentation tasks, but combining spectral statistics and HOS produces relatively small improvements. Third, we find that HOS improve segmentation for a subset of images, although these images are difficult to identify. We also find that different subsets of HOS improve segmentation to a different extent, in agreement with previous physiological and perceptual work. These results show that the HOS add modestly to spectral statistics for natural image segmentation. We speculate that tuning to natural image statistics under resource constraints could explain the weak contribution of HOS to perceptual segmentation in human peripheral vision.

Flexible contextual modulation of naturalistic texture perception in peripheral vision.

Peripheral vision comprises most of our visual field, and is essential in guiding visual behavior. Its characteristic capabilities and limitations, which distinguish it from foveal vision, have been explained by the most influential theory of peripheral vision as the product of representing the visual input using summary statistics. Despite its success, this account may provide a limited understanding of peripheral vision, because it neglects processes of perceptual grouping and segmentation. To test this hypothesis, we studied how contextual modulation, namely the modulation of the perception of a stimulus by its surrounds, interacts with segmentation in human peripheral vision. We used naturalistic textures, which are directly related to summary-statistics representations. We show that segmentation cues affect contextual modulation, and that this is not captured by our implementation of the summary-statistics model. We then characterize the effects of different texture statistics on contextual modulation, providing guidance for extending the model, as well as for probing neural mechanisms of peripheral vision.