COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.

One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed 1-3 . Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals 4-6 . Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo , a neutralizing antibody isolated from a convalescent patient 7 and highly potent against the B.1.1.7. isolate 8,9 . In both prophylactic and therapeutic settings, SARS-CoV-2 remained undetectable in the lungs of COVA1-18 treated hACE2 mice. Therapeutic treatment also caused a dramatic reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg - 1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 had a very strong antiviral activity in the upper respiratory compartments with an estimated reduction in viral infectivity of more than 95%, and prevented lymphopenia and extensive lung lesions. Modelling and experimental findings demonstrate that COVA1-18 has a strong antiviral activity in three different preclinical models and could be a valuable candidate for further clinical evaluation.

Tritium dynamics in soils and plants grown under three irrigation regimes at a tritium processing facility in Canada.

The dynamics of tritium released from nuclear facilities as tritiated water (HTO) have been studied extensively with results incorporated into regulatory assessment models. These models typically estimate organically bound tritium (OBT) for calculating public dose as OBT itself is rarely measured. Higher than expected OBT/HTO ratios in plants and soils are an emerging issue that is not well understood. To support the improvement of models, an experimental garden was set up in 2012 at a tritium processing facility in Pembroke, Ontario to characterize the circumstances under which high OBT/HTO ratios may arise. Soils and plants were sampled weekly to coincide with detailed air and stack monitoring. The design included a plot of native grass/soil, contrasted with sod and vegetables grown in barrels with commercial topsoil under natural rain and either low or high tritium irrigation water. Air monitoring indicated that the plume was present infrequently at concentrations of up to about 100 Bq/m(3) (the garden was not in a major wind sector). Mean air concentrations during the day on workdays (HTO 10.3 Bq/m(3), HT 5.8 Bq/m(3)) were higher than at other times (0.7-2.6 Bq/m(3)). Mean Tissue Free Water Tritium (TFWT) in plants and soils and OBT/HTO ratios were only very weakly or not at all correlated with releases on a weekly basis. TFWT was equal in soils and plants and in above and below ground parts of vegetables. OBT/HTO ratios in above ground parts of vegetables were above one when the main source of tritium was from high tritium irrigation water (1.5-1.8). Ratios were below one in below ground parts of vegetables when irrigated with high tritium water (0.4-0.6) and above one in vegetables rain-fed or irrigated with low tritium water (1.3-2.8). In contrast, OBT/HTO ratios were very high (9.0-13.5) when the source of tritium was mainly from the atmosphere. TFWT varied considerably through time as a result of SRBT's operations; OBT/HTO ratios showed no clear temporal pattern in above or below ground plant parts. Native soil after ∼20 years of operations at SRBT had high initial OBT that persisted through the growing season; little OBT formed in garden plot soil during experiments. High OBT in native soil appeared to be a signature of higher past releases at SRBT. This phenomenon was confirmed in soils obtained at another processing facility in Canada with a similar history. The insights into variation in OBT/HTO ratios found here are of regulatory interest and should be incorporated in assessment models to aid in the design of relevant environmental monitoring programs for OBT.

In situ measurements of tritium evapotranspiration (³H-ET) flux over grass and soil using the gradient and eddy covariance experimental methods and the FAO-56 model.

The behaviour of tritium in the environment is linked to the water cycle. We compare three methods of calculating the tritium evapotranspiration flux from grassland cover. The gradient and eddy covariance methods, together with a method based on the theoretical Penmann-Monteith model were tested in a study carried out in 2013 in an environment characterised by high levels of tritium activity. The results show that each of the three methods gave similar results. The various constraints applying to each method are discussed. The results show a tritium evapotranspiration flux of around 15 mBq m(-2) s(-1) in this environment. These results will be used to improve the entry parameters for the general models of tritium transfers in the environment.

Canadian inter-laboratory organically bound tritium (OBT) analysis exercise.

Tritium emissions are one of the main concerns with regard to CANDU reactors and Canadian nuclear facilities. After the Fukushima accident, the Canadian Nuclear Regulatory Commission suggested that models used in risk assessment of Canadian nuclear facilities be firmly based on measured data. Procedures for measurement of tritium as HTO (tritiated water) are well established, but there are no standard methods and certified reference materials for measurement of organically bound tritium (OBT) in environmental samples. This paper describes and discusses an inter-laboratory comparison study in which OBT in three different dried environmental samples (fish, Swiss chard and potato) was measured to evaluate OBT analysis methods currently used by CANDU Owners Group (COG) members. The variations in the measured OBT activity concentrations between all laboratories were less than approximately 20%, with a total uncertainty between 11 and 17%. Based on the results using the dried samples, the current OBT analysis methods for combustion, distillation and counting are generally acceptable. However, a complete consensus OBT analysis methodology with respect to freeze-drying, rinsing, combustion, distillation and counting is required. Also, an exercise using low-level tritium samples (less than 100 Bq/L or 20 Bq/kg-fresh) would be useful in the near future to more fully evaluate the current OBT analysis methods.