Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19

Abstract

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23–363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102–603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.

Oral and intranasal Ad5 SARS-CoV-2 vaccines decrease disease and viral transmission in a golden hamster model

“…3). Similar dose-dependent disease severity findings have been shown by others in hamsters, mice, ferrets and nonhuman primates [12][13][14][15][16] .…”

Mathematical Modeling of Vaccines That Prevent SARS-CoV-2 Transmission

“…We previously estimated the relationship between viral load and transmission probability for SARS-CoV-2 [35]. The emergent transmission response curve has a similar sigmoidal shape to empirically-derived curves for SARS-CoV-1 in a controlled set of murine experiments [64] and SARS-CoV-2 in non-human primates [65], and resembled the relationship between quantitative viral PCR and probability of culture positivity in humans infected with SARS-CoV-2 [66].…”

“…A valid viral load surrogate cannot currently be inferred from human cohorts as the exposure viral load is rarely documented between transmission pairs, though formal surrogate endpoint analysis will ultimately be necessary if sufficient data emerges. Animal models of infection are ideal for this purpose and the necessary transmission dose could be inferred with a relatively small number of non-human primates or mice [64,65].…”

Modelling airborne transmission of SARS-CoV-2 using CARA: Risk assessment for enclosed spaces

“…a more recent study with nonhuman primates showed an exposure of 52 TCID 50 was enough to cause seroconversion and 256 TCID 50 for the presence of fever [19], with a dose-response curve likely to equally fit an exponential model.…”

“…As discussed above and at the time of writing, a dose-response model for SARS-CoV-2 has yet to be developed. In this study we've adopted the findings by Watanabe et al [18] for the SARS-CoV virus, where an exponential fit to a dose-response for SARS has been derived, and most recently a similar approach was adopted for a SARS-CoV-2 exposure to primates [19]. Assuming a human dose-response for SARS-CoV-2 also fits an exponential model, the probability of a COVID-19 infection is represented by where P (I|vD total , ID 50 ) denotes the conditional probability of event I (infection) for given values of the absorbed and infection doses vD total and ID 50 , respectively.…”