Bats host the most virulent-but not the most dangerous-zoonotic viruses

Abstract

SignificanceThe clear need to mitigate zoonotic risk has fueled increased viral discovery in specific reservoir host taxa. We show that a combination of viral and reservoir traits can predict zoonotic virus virulence and transmissibility in humans, supporting the hypothesis that bats harbor exceptionally virulent zoonoses. However, pandemic prevention requires thinking beyond zoonotic capacity, virulence, and transmissibility to consider collective "burden" on human health. For this, viral discovery targeting specific reservoirs may be inefficient as death burden correlates with viral, not reservoir, traits, and depends on context-specific epidemiological dynamics across and beyond the human-animal interface. These findings suggest that longitudinal studies of viral dynamics in reservoir and spillover host populations may offer the most effective strategy for mitigating zoonotic risk.

Keywords: bat viruses; death burden; emerging infectious diseases; virulence; zoonotic viruses.

Fig. 1.

Predictors of global CFR estimates. (A) Top 15 models ranked by AIC. Rows represent individual models, and columns represent predictor variables. Cells are shaded according to the proportion of deviance explained by each predictor. Cells representing predictor variables with a P value significance level of <0.1 are outlined in black. (B–D) Effects present in the top model, namely, reservoir host group, virus family, vector-borne transmission, and bridged spillover. Lines represent the predicted effect of the x-axis variable when all other variables are held at their median value (if numeric) or their mode (if categorical). Shaded regions indicate 95% CIs by SE, and points represent partial residuals. An effect is shaded in gray if the 95% CI crosses zero across the entire range of the predictor variable; in contrast, an effect is shaded in purple and considered “significant” if the 95% CI does not cross zero. Full model results are outlined in SI Appendix, Table S5A. (B) Reservoir host groups are ordered by increasing cophenetic phylogenetic distance from Primates (in millions of years), as indicated on the Top axis.

Fig. 2.

Predictors of capacity for forward transmission within the human population following zoonotic spillover. (A) Top 15 models ranked by AIC. Rows represent individual models and columns represent predictor variables. Cells are shaded according to the proportion of deviance explained by each predictor. Cells representing predictor variables with a P value significance level of <0.1 are outlined in black and otherwise outlined in gray. (B–E) Effects present in the top model, namely, virus family, reservoir group phylogenetic distance from Primates, vector-borne transmission, and log-transformed virus species publication count. Lines represent the predicted effect of the x-axis variable when all other variables are held at their median value (if numeric) or their mode (if categorical). Shaded regions indicate 95% CIs by SE, and points represent partial residuals. An effect is shaded in gray if the 95% CI crosses zero across the entire range of the predictor variable; in contrast, an effect is shaded in purple and considered significant if the 95% CI does not cross zero. Full model results are outlined in SI Appendix, Table S5B.

Fig. 3.

Predictors of post-1950 death burden, excluding the virus species publication count predictor. See SI Appendix, Fig. S12 for inclusion. (A) Top 15 models ranked by AIC. Rows represent individual models and columns represent predictor variables. Cells are shaded according to the proportion of deviance explained by each predictor. Cells representing predictor variables with a P value significance level of <0.1 are outlined in black and otherwise outlined in gray. (B–E) Effects present in the top model, namely, virus family, reservoir group phylogenetic distance from Primates, reservoir group species richness, and vector-borne transmission. Lines represent the predicted effect of the x-axis variable when all other variables are held at their median value (if numeric) or their mode (if categorical). Shaded regions indicate 95% CIs by SE, and points represent partial residuals. An effect is shaded in gray if the 95% CI crosses zero across the entire range of the predictor variable; in contrast, an effect is shaded in purple and considered significant if the 95% CI does not cross zero. Full model results are outlined in SI Appendix, Table S5C.

Fig. 4.

Death burden per year (cumulative post-1950 death counts divided by the length of reporting time), grouped by reservoir host group (A), virus family (B), primary transmission route (C), and CFR in humans (D). Colors indicate transmissibility between humans, with “1” indicating the lowest level of transmission (i.e., no recorded forward transmission in human population postspillover) and “4” indicating the highest level of transmission (i.e., record of endemic transmission in human populations postspillover). (A) Reservoir host groups are ordered by increasing cophenetic phylogenetic distance from Primates (in millions of years), as indicated on the Top axis.