The human nose organoid respiratory virus model: an ex-vivo human challenge model to study RSV and SARS-CoV-2 pathogenesis and evaluate therapeutics (preprint)

There is an unmet need for pre-clinical models to understand the pathogenesis of human respiratory viruses; and predict responsiveness to immunotherapies. Airway organoids can serve as an ex-vivo human airway model to study respiratory viral pathogenesis; however, they rely on invasive techniques to obtain patient samples. Here, we report a non-invasive technique to generate human nose organoids (HNOs) as an alternate to biopsy derived organoids. We made air liquid interface (ALI) cultures from HNOs and assessed infection with two major human respiratory viruses, respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Infected HNO-ALI cultures recapitulate aspects of RSV and SARS-CoV-2 infection, including viral shedding, ciliary damage, innate immune responses, and mucus hyper-secretion. Next, we evaluated the feasibility of the HNO-ALI respiratory virus model system to test the efficacy of palivizumab to prevent RSV infection. Palivizumab was administered in the basolateral compartment (circulation) while viral infection occurred in the apical ciliated cells (airways), simulating the events in infants. In our model, palivizumab effectively prevented RSV infection in a concentration dependent manner. Thus, the HNO-ALI model can serve as an alternate to lung organoids to study respiratory viruses and testing therapeutics.

Wastewater Analysis of SARS-CoV-2 as a Predictive Metric of Positivity Rate for a Major Metropolis (preprint)

Wastewater monitoring for SARS-CoV-2 has been suggested as an epidemiological indicator of community infection dynamics and disease prevalence. We report wastewater viral RNA levels of SARS-CoV-2 in a major metropolis serving over 3.6 million people geographically spread over 39 distinct sampling sites. Viral RNA levels were followed weekly for 22 weeks, both before, during, and after a major surge in cases, and simultaneously by two independent laboratories. We found SARS-CoV-2 RNA wastewater levels were a strong predictive indicator of trends in the nasal positivity rate two-weeks in advance. Furthermore, wastewater viral RNA loads demonstrated robust tracking of positivity rate for populations served by individual treatment plants, findings which were used in real-time to make public health interventions, including deployment of testing and education strike teams.