Comparison of Dose-Response Relationships for Two Isolates of SARS-CoV-2 in a Nonhuman Primate Model of Inhalational COVID-19.

Background: As the COVID-19 pandemic has progressed, numerous variants of SARS-CoV-2 have arisen, with several displaying increased transmissibility. Methods: The present study compared dose-response relationships and disease presentation in nonhuman primates infected with aerosols containing an isolate of the Gamma variant of SARS-CoV-2 to the results of our previous study with the earlier WA-1 isolate of SARS-CoV-2. Results: Disease in Gamma-infected animals was mild, characterized by dose-dependent fever and oronasal shedding of virus. Differences were observed in shedding in the upper respiratory tract between Gamma- and WA-1-infected animals that have the potential to influence disease transmission. Specifically, the estimated median doses for shedding of viral RNA or infectious virus in nasal swabs were approximately 10-fold lower for the Gamma variant than the WA-1 isolate. Given that the median doses for fever were similar, this suggests that there is a greater difference between the median doses for viral shedding and fever for Gamma than for WA-1 and potentially an increased range of doses for Gamma over which asymptomatic shedding and disease transmission are possible. Conclusions: These results complement those of previous studies, which suggested that differences in exposure dose may help to explain the range of clinical disease presentations observed in individuals with COVID-19, highlighting the importance of public health measures designed to limit exposure dose, such as masking and social distancing. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, as well as to inform dose selection in future studies examining the efficacy of therapeutics and vaccines in animal models of inhalational COVID-19.

Traveling tunable laser projector for UV-blue disinfection dose determinations.

As the COVID-19 pandemic was overtaking the world in the spring of 2020, the National Institute of Standards and Technology (NIST) began collaborating with the National Biodefense Analysis and Countermeasures Center to study the inactivation of SARS-CoV-2 after exposure to different ultraviolet (UV) and blue light wavelengths. This paper describes a 1 kHz pulsed laser and projection system used to study the doses required to inactive SARS-CoV-2 over the wavelength range of 222 to 488 nm. This paper builds on NIST's previous work for water pathogen inactivation using UV laser irradiation. The design of the laser and projection system and its performance in a Biosafety Level 3 (BSL-3) laboratory are given. The SARS-CoV-2 inactivation results (published elsewhere by Schuit, M.A., et al., expected 2022) demonstrate that a tunable laser projection system is an invaluable tool for this research.

SARS-CoV-2 inactivation by ultraviolet radiation and visible light is dependent on wavelength and sample matrix.

Numerous studies have demonstrated that SARS-CoV-2 can be inactivated by ultraviolet (UV) radiation. However, there are few data available on the relative efficacy of different wavelengths of UV radiation and visible light, which complicates assessments of UV decontamination interventions. The present study evaluated the effects of monochromatic radiation at 16 wavelengths from 222 nm through 488 nm on SARS-CoV-2 in liquid aliquots and dried droplets of water and simulated saliva. The data were used to generate a set of action spectra which quantify the susceptibility of SARS-CoV-2 to genome damage and inactivation across the tested wavelengths. UVC wavelengths (≤280 nm) were most effective for inactivating SARS-CoV-2, although inactivation rates were dependent on sample type. Results from this study suggest that UV radiation can effectively inactivate SARS-CoV-2 in liquids and dried droplets, and provide a foundation for understanding the factors which affect the efficacy of different wavelengths in real-world settings.

The Stability of an Isolate of the SARS-CoV-2 B.1.1.7 Lineage in Aerosols Is Similar to 3 Earlier Isolates.

BACKGROUND: Our laboratory previously examined the influence of environmental conditions on the stability of an early isolate of SARS-CoV-2 (hCoV-19/USA/WA-1/2020) in aerosols generated from culture medium or simulated saliva. However, genetic differences have emerged among SARS-CoV-2 lineages, and it is possible that these differences may affect environmental stability and the potential for aerosol transmission. METHODS: The influence of temperature, relative humidity, and simulated sunlight on the decay of 4 SARS-CoV-2 isolates in aerosols, including 1 belonging to the recently emerged B.1.1.7 lineage, were compared in a rotating drum chamber. Aerosols were generated from simulated respiratory tract lining fluid to represent aerosols originating from the deep lung. RESULTS: No differences in the stability of the isolates were observed in the absence of simulated sunlight at either 20°C or 40°C. However, a small but statistically significant difference in the stability was observed between some isolates in simulated sunlight at 20°C and 20% relative humidity. CONCLUSIONS: The stability of SARS-CoV-2 in aerosols does not vary greatly among currently circulating lineages, including B.1.1.7, suggesting that the increased transmissibility associated with recent SARS-CoV-2 lineages is not due to enhanced survival in the environment.

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

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.

Airborne SARS-CoV-2 Is Rapidly Inactivated by Simulated Sunlight.

Aerosols represent a potential transmission route of COVID-19. This study examined effect of simulated sunlight, relative humidity, and suspension matrix on stability of SARS-CoV-2 in aerosols. Simulated sunlight and matrix significantly affected decay rate of the virus. Relative humidity alone did not affect the decay rate; however, minor interactions between relative humidity and other factors were observed. Mean decay rates (± SD) in simulated saliva, under simulated sunlight levels representative of late winter/early fall and summer were 0.121 ±â€…0.017 min-1 (90% loss, 19 minutes) and 0.306 ±â€…0.097 min-1 (90% loss, 8 minutes), respectively. Mean decay rate without simulated sunlight across all relative humidity levels was 0.008 ±â€…0.011 min-1 (90% loss, 286 minutes). These results suggest that the potential for aerosol transmission of SARS-CoV-2 may be dependent on environmental conditions, particularly sunlight. These data may be useful to inform mitigation strategies to minimize the potential for aerosol transmission.