Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans.

It is often presented as common knowledge that, in the human body, bacteria outnumber human cells by a ratio of at least 10:1. Revisiting the question, we find that the ratio is much closer to 1:1.

The global biomass of wild mammals.

Wild mammals are icons of conservation efforts, yet there is no rigorous estimate available for their overall global biomass. Biomass as a metric allows us to compare species with very different body sizes, and can serve as an indicator of wild mammal presence, trends, and impacts, on a global scale. Here, we compiled estimates of the total abundance (i.e., the number of individuals) of several hundred mammal species from the available data, and used these to build a model that infers the total biomass of terrestrial mammal species for which the global abundance is unknown. We present a detailed assessment, arriving at a total wet biomass of ≈20 million tonnes (Mt) for all terrestrial wild mammals (95% CI 13-38 Mt), i.e., ≈3 kg per person on earth. The primary contributors to the biomass of wild land mammals are large herbivores such as the white-tailed deer, wild boar, and African elephant. We find that even-hoofed mammals (artiodactyls, such as deer and boars) represent about half of the combined mass of terrestrial wild mammals. In addition, we estimated the total biomass of wild marine mammals at ≈40 Mt (95% CI 20-80 Mt), with baleen whales comprising more than half of this mass. In order to put wild mammal biomass into perspective, we additionally estimate the biomass of the remaining members of the class Mammalia. The total mammal biomass is overwhelmingly dominated by livestock (≈630 Mt) and humans (≈390 Mt). This work is a provisional census of wild mammal biomass on Earth and can serve as a benchmark for human impacts.

The total mass, number, and distribution of immune cells in the human body.

The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. Here, we estimated the abundance of the primary immune cell types throughout all tissues in the human body. We conducted a literature survey and integrated data from multiplexed imaging and methylome-based deconvolution. We also considered cellular mass to determine the distribution of immune cells in terms of both number and total mass. Our results indicate that the immune system of a reference 73 kg man consists of 1.8 × 1012 cells (95% CI 1.5-2.3 × 1012), weighing 1.2 kg (95% CI 0.8-1.9). Lymphocytes constitute 40% of the total number of immune cells and 15% of the mass and are mainly located in the lymph nodes and spleen. Neutrophils account for similar proportions of both the number and total mass of immune cells, with most neutrophils residing in the bone marrow. Macrophages, present in most tissues, account for 10% of immune cells but contribute nearly 50% of the total cellular mass due to their large size. The quantification of immune cells within the human body presented here can serve to understand the immune function better and facilitate quantitative modeling of this vital system.

Inferring the differences in incubation-period and generation-interval distributions of the Delta and Omicron variants of SARS-CoV-2.

Estimating the differences in the incubation-period, serial-interval, and generation-interval distributions of SARS-CoV-2 variants is critical to understanding their transmission. However, the impact of epidemic dynamics is often neglected in estimating the timing of infection-for example, when an epidemic is growing exponentially, a cohort of infected individuals who developed symptoms at the same time are more likely to have been infected recently. Here, we reanalyze incubation-period and serial-interval data describing transmissions of the Delta and Omicron variants from the Netherlands at the end of December 2021. Previous analysis of the same dataset reported shorter mean observed incubation period (3.2 d vs. 4.4 d) and serial interval (3.5 d vs. 4.1 d) for the Omicron variant, but the number of infections caused by the Delta variant decreased during this period as the number of Omicron infections increased. When we account for growth-rate differences of two variants during the study period, we estimate similar mean incubation periods (3.8 to 4.5 d) for both variants but a shorter mean generation interval for the Omicron variant (3.0 d; 95% CI: 2.7 to 3.2 d) than for the Delta variant (3.8 d; 95% CI: 3.7 to 4.0 d). The differences in estimated generation intervals may be driven by the "network effect"-higher effective transmissibility of the Omicron variant can cause faster susceptible depletion among contact networks, which in turn prevents late transmission (therefore shortening realized generation intervals). Using up-to-date generation-interval distributions is critical to accurately estimating the reproduction advantage of the Omicron variant.

The total number and mass of SARS-CoV-2 virions.

Quantitatively describing the time course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within an infected individual is important for understanding the current global pandemic and possible ways to combat it. Here we integrate the best current knowledge about the typical viral load of SARS-CoV-2 in bodily fluids and host tissues to estimate the total number and mass of SARS-CoV-2 virions in an infected person. We estimate that each infected person carries 109 to 1011 virions during peak infection, with a total mass in the range of 1 µg to 100 µg, which curiously implies that all SARS-CoV-2 virions currently circulating within human hosts have a collective mass of only 0.1 kg to 10 kg. We combine our estimates with the available literature on host immune response and viral mutation rates to demonstrate how antibodies markedly outnumber the spike proteins, and the genetic diversity of virions in an infected host covers all possible single nucleotide substitutions.

Revised Estimates for the Number of Human and Bacteria Cells in the Body.

Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg.

What fraction of cellular DNA turnover becomes cfDNA?

Cell-free DNA (cfDNA) tests use small amounts of DNA in the bloodstream as biomarkers. While it is thought that cfDNA is largely released by dying cells, the proportion of dying cells' DNA that reaches the bloodstream is unknown. Here, we integrate estimates of cellular turnover rates to calculate the expected amount of cfDNA. By comparing this to the actual amount of cell type-specific cfDNA, we estimate the proportion of DNA reaching plasma as cfDNA. We demonstrate that <10% of the DNA from dying cells is detectable in plasma, and the ratios of measured to expected cfDNA levels vary a thousand-fold among cell types, often reaching well below 0.1%. The analysis suggests that local clearance, presumably via phagocytosis, takes up most of the dying cells' DNA. Insights into the underlying mechanism may help to understand the physiological significance of cfDNA and improve the sensitivity of liquid biopsies.

The unmitigated profile of COVID-19 infectiousness.

Quantifying the temporal dynamics of infectiousness of individuals infected with SARS-CoV-2 is crucial for understanding the spread of COVID-19 and for evaluating the effectiveness of mitigation strategies. Many studies have estimated the infectiousness profile using observed serial intervals. However, statistical and epidemiological biases could lead to underestimation of the duration of infectiousness. We correct for these biases by curating data from the initial outbreak of the pandemic in China (when mitigation was minimal), and find that the infectiousness profile of the original strain is longer than previously thought. Sensitivity analysis shows our results are robust to model structure, assumed growth rate and potential observational biases. Although unmitigated transmission data is lacking for variants of concern (VOCs), previous analyses suggest that the alpha and delta variants have faster within-host kinetics, which we extrapolate to crude estimates of variant-specific unmitigated generation intervals. Knowing the unmitigated infectiousness profile of infected individuals can inform estimates of the effectiveness of isolation and quarantine measures. The framework presented here can help design better quarantine policies in early stages of future epidemics.

The distribution of cellular turnover in the human body.

We integrated ubiquity, mass and lifespan of all major cell types to achieve a comprehensive quantitative description of cellular turnover. We found a total cellular mass turnover of 80 ± 20 grams per day, dominated by blood cells and gut epithelial cells. In terms of cell numbers, close to 90% of the (0.33 ± 0.02) × 1012 cells per day turnover was blood cells.

The total number and mass of SARS-CoV-2 virions.

Quantitatively describing the time course of the SARS-CoV-2 infection within an infected individual is important for understanding the current global pandemic and possible ways to combat it. Here we integrate the best current knowledge about the typical viral load of SARS-CoV-2 in bodily fluids and host tissues to estimate the total number and mass of SARS-CoV-2 virions in an infected person. We estimate that each infected person carries 109-1011 virions during peak infection, with a total mass in the range of 1-100 µg, which curiously implies that all SARS-CoV-2 virions currently circulating within human hosts have a collective mass of only 0.1-10 kg. We combine our estimates with the available literature on host immune response and viral mutation rates to demonstrate how antibodies markedly outnumber the spike proteins and the genetic diversity of virions in an infected host covers all possible single nucleotide substitutions.