Evaluating SARS-CoV-2 airborne quanta transmission and exposure risk in a mechanically ventilated multizone office building.

The world has faced tremendous challenges during the COVID-19 pandemic since 2020, and effective clean air strategies that mitigate infectious risks indoors have become more essential. In this study, a novel approach based on the Wells-Riley model applied to a multizone building was proposed to simulate exposure to infectious doses in terms of "quanta". This modeling approach quantifies the relative benefits of different risk mitigation strategies so that their effectiveness could be compared. A case study for the US Department of Energy large office prototype building was conducted to illustrate the approach. The infectious risk propagation from the infection source throughout the building was evaluated. Different mitigation strategies were implemented, including increasing outdoor air ventilation rates and adding air-cleaning devices such as Minimum Efficiency Reporting Value (MERV) filters and portable air cleaners (PACs) with HEPA filters in-room/in-duct germicidal ultraviolet (GUV) lights, layering with wearing masks. Results showed that to keep the risk of the infection propagating low the best strategy without universal masking was the operation of in-room GUV or a large industrial-sized PAC; whereas with masking all strategies were acceptable. This study contributes to a better understanding of the airborne transmission risks in multizone, mechanically ventilated buildings and how to reduce infection risk from a public health perspective of different mitigation strategies.

Ultrafine and Fine Particulate Matter Inside and Outside of Mechanically Ventilated Buildings.

The objectives of this study were to measure levels of particulate matter (PM) in mechanically ventilated buildings and to improve understanding of filtration requirements to reduce exposure. With the use of an Ultra High Sensitivity Aerosol Spectrometer and an Aerodyne Mass Spectrometer, ultrafine (0.055-0.1 µm) and fine (0.1-0.7 µm) indoor and outdoor PM was measured as a function of time in an office, a university building, and two elementary schools. Indoor particle levels were highly correlated with outdoor levels. Indoor and outdoor number concentrations in Denver were higher than those in Boulder, with the highest number concentrations occurring during summer and fall. The ratio of indoor-to-outdoor (I/O) PM was weakly but positively correlated with the amount of ventilation provided to the indoor environment, did not vary much with particle size (ranged between 0.48 and 0.63 for the entire size range), and was similar for each period of the week (weekend vs. weekday, night vs. day). Regression analyses showed that ultrafine indoor PM baseline concentrations were higher at night from nighttime infiltration. A lag time was observed between outdoor and indoor measurements. Weekday days had the shortest lag time of 11 min, and weekend nighttime lags when the HVAC was not in use were 50 to 148 min. Indoor-outdoor PM concentration plots showed ultrafine PM was more correlated compared to fine, and especially when the HVAC system was on. Finally, AMS data showed that most of the PM was organic, with occasional nitrate events occurring outdoors. During nitrate events, there were less indoor particles detected, indicating a loss of particulate phase nitrate. The results from this study show that improved filtration is warranted in mechanically ventilated buildings, particularly for ultrafine particles, and that nighttime infiltration is significant depending on the building design.

Pharmacokinetics of obinutuzumab in Chinese patients with B-cell lymphomas.

AIM: The Phase Ib GERSHWIN study (NCT01680991) assessed the pharmacokinetic (PK) profile of obinutuzumab following multiple intravenous (i.v.) doses to Chinese patients with B-cell lymphomas, and compared findings with previous obinutuzumab PK studies in mainly Caucasian (non-Chinese) patients. METHODS: GERSHWIN was an open-label, single-arm intervention study. Patients aged >18 years with CD20+ relapsed/refractory chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) were enrolled from four centres in China. The treatment period was 24 weeks; patients received obinutuzumab 1000 mg i.v. on Days (D)1, 8 and 15 of Cycle (C)1 (CLL patients: first infusion split over 2 days) and on D1 of C2-8 (all cycles: 21 days). PK parameters were estimated using non-compartmental analysis (NCA), and a population PK analysis was used to determine whether observed GERSHWIN PK data were in accordance with previous obinutuzumab PK studies in non-Chinese patients. RESULTS: The PK analysis population included 48 patients: 28 patients completed all treatment cycles. NCA showed a similar PK profile in Chinese patients with FL, DLBCL and CLL. Steady-state concentrations of obinutuzumab appeared to be reached at the start of C2 irrespective of histology. There was no apparent relationship between body weight and systemic exposure. Most PK profiles observed in GERSHWIN lay within the 90% prediction interval of simulated profiles. CONCLUSIONS: Obinutuzumab exposure was comparable in CLL, DLBCL and FL patients. NCA and population PK analysis indicate that PK characteristics of Chinese patients with B-cell lymphomas are similar to those in non-Chinese patients.