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.

Live virus vaccines are a critical component of worldwide vaccination strategy for reducing disease burden but often require complex biological production processes that are sensitive to many different factors, both known and often unknown. Prior application of high‐throughput process development (HTPD) approaches to these processes has been hampered by a complex design space, low‐throughput analytics, and challenges inherent in biosafety level 2 containment and asepsis in laboratory automation. In 2013, we initiated a project with HighRes Biosolutions to design and install an integrated high‐throughput screening platform to enable HTPD for biosafety level 2 upstream process development studies. The system incorporates the necessary tools for performing cell and virus culture studies in microplates, as well as advanced analytical capabilities necessary for assessment of cell phenotype, product quality, and antigen yield. To date, we have applied this system to screen optimal media formulations and viral production conditions in support of two viral vaccine programs, with phenotypic assays performed as an integrated part of the workflow. This case study illustrates the power of HTPD in addressing large‐scale biological screening challenges by narrowing a vast design space and identifying parameter interactions in live virus production processes.

From the beginning of the COVID-19 pandemic, researchers assessed the impact of the disease in terms of loss of life, medical load, economic damage, and other key metrics of resiliency and consequence mitigation; these studies sought to parametrize the critical components of a disease transmission model and the resulting analyses were informative but often lacked critical parameters or a discussion of parameter sensitivities. Using SARS-CoV-2 as a case study, we present a robust modeling framework that considers disease transmissibility from the source through transport and dispersion and infectivity. The framework is designed to work across a range of particle sizes and estimate the generation rate, environmental fate, deposited dose, and infection, allowing for end-to-end analysis that can be transitioned to individual and population health models. In this paper, we perform sensitivity analysis on the model framework to demonstrate how it can be used to advance and prioritize research efforts by highlighting critical parameters for further analyses.

Objective. To assess the validity of SARS-CoV-2 Antigen (Ag) detection for the diagnosis of SARS-CoV-2 infection in mildly infected or asymptomatic patients. Material and methods. Observational study to evaluate diagnostic tests. Non-hospitalized patients with indication for diagnostic testing for SARS-CoV-2 infection were included. The diagnostic test to be evaluated was the determination of Ag and as a reference standard to determine the presence of viral RNA the RT-PCR was used. Results. A total of 494 patients were included. Of these 71.5% (353/494) had symptoms and 28.5% (141/494) were asymptomatic (presurgery screening (35/494) and confirmed case-contact (106/494). The overall sensitivity of the Ag test was 61.1% and the specificity was 99.7%. The sensitivity and specificity in the asymptomatic group were 40% and 100% respectively, and in the symptomatic group 63.5% and 99.6% respectively. In turn, the sensitivity and specificity in the group of symptomatic patients varied according to the time of symptom evolution: in patients with recent symptoms, they were 71.4% and 99.6% respectively, while in patients with symptoms of more than 5 days of evolution, they were 26.7% and 100% respectively. In all groups studied, the presence of antigen is associated with a high viral load (Ct<30 cycles). Conclusions. The use of Ag detection test is not indicated for the diagnosis of SARS-CoV-2 infection in asymptomatic patients or with symptoms of more than 5 days of evolution, but it could be useful in patients with symptoms of 1-5 days of evolution.