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BackgroundOutpatient COVID-19 monoclonal antibody (mAb) treatment via subcutaneous delivery, if effective, overcomes the logistical burdens of intravenous administration.MethodsACTIV-2/A5401 was a randomized, masked placebo-controlled platform trial where participants with COVID-19 at low risk for progression were randomized 1:1 to subcutaneously administered BMS-986414 (C135-LS) 200 mg, plus BMS-986413 (C144-LS) 200 mg, (BMS mAbs), or placebo. Coprimary outcomes were time to symptom improvement through 28 days; nasopharyngeal SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) on days 3, 7, or 14; and treatment-emergent grade 3 or higher adverse events (TEAEs) through 28 days.ResultsA total of 211 participants (105 BMS mAbs and 106 placebo) initiated study product. Time to symptom improvement favored the active therapy but was not significant (median 8 vs 10 days, P=0.19). There was no significant difference in the proportion with SARS-CoV-2 RNA ConclusionsWhile safe, the BMS mAbs delivered subcutaneously were not effective at treating COVID-19 at low risk for progression. The lack of clinically significant activity may relate to the pharmacokinetics of subcutaneous administration of mAbs.

Cells are the most basic structural and functional unit of living organisms. In recent years, people have paid more attention to cell heterogeneity. In order to characterize the heterogeneity of cells and prevent the life information in an individual cell from being overwhelmed by the average level of the population gained from traditional cell biology research, many new analytical techniques have been developed for single-cell analysis. However, single-cell analysis is extremely challenging due to the minimal cell volume, low content and wide variety of analytes in single cells, some of analytes change rapidly in cells and others may interfere with each other during analysis. Mass spectrometry has gradually become an ideal tool for single-cell analysis due to its high sensitivity, high resolution and high selectivity. In this review, several techniques of single-cell analysis based on mass spectrometry in the recent five years were systematically summarized and discussed including electrospray ionization mass spectrometry (ESI-MS), laser desorption ionization mass spectrometry (LDI-MS), secondary ion mass spectrometry (SIMS) and inductively coupled plasma mass spectrometry (ICP-MS). Finally, this review also looked into future developments of these mass spectrometry-based techniques. With the development of cell biology, the requirement for single-cell analysis technology is increasing as well. In the meanwhile, single-cell analysis, which focuses on studying the mechanisms of cellular and molecular behavior, has aroused more and more attention from various branches of life sciences in recent years. Although higher spatial resolution and detection sensitivity have become the development trends for single-cell mass spectrometry, none of these mass spectrometry-based techniques can be recognized flawless, which means they all have certain flaws to some extent. Consequently, single-cell analysis technology based on mass spectrometry is developing towards methodological diversification. On the one hand, it is of great importance to choose one suitable mass spectrometry-based technique according to the research purpose and actual conditions. On the other hand, it should be also emphasized that different methods can complement each other and jointly provide a more comprehensive analysis environment for single-cell mass spectrometry, thereby improving and innovating existing single-cell analysis techniques based on mass spectrometry. This review will provide insights into better understanding on and development of single-cell analysis by mass spectrometry.

AZD7442 (Evusheld) is a combination of two human anti-severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) monoclonal antibodies (mAbs), tixagevimab (AZD8895) and cilgavimab (AZD1061). Route of administration is an important consideration to improve treatment access. We assessed pharmacokinetics (PKs) of AZD7442 absorption following 600 mg administered intramuscularly (i.m.) in the thigh compared with 300 mg intravenously (i.v.) in ambulatory adults with symptomatic COVID-19. PK analysis included 84 of 110 participants randomized to receive i.m. AZD7442 and 16 of 61 randomized to receive i.v. AZD7442. Serum was collected prior to AZD7442 administration and at 24 hours and 3, 7, and 14 days later. PK parameters were calculated using noncompartmental methods. Following 600 mg i.m., the geometric mean maximum concentration (Cmax ) was 38.19 μg/mL (range: 17.30-60.80) and 37.33 μg/mL (range: 14.90-58.90) for tixagevimab and cilgavimab, respectively. Median observed time to maximum concentration (Tmax ) was 7.1 and 7.0 days for tixagevimab and cilgavimab, respectively. Serum concentrations after i.m. dosing were similar to the i.v. dose (27-29 μg/mL each component) at 3 days. The area under the concentration-time curve (AUC)0-7d geometric mean ratio was 0.9 for i.m. vs. i.v. Participants with higher weight or body mass index were more likely to have lower concentrations with either route. Women appeared to have higher interparticipant variability in concentrations compared with men. The concentrations of tixagevimab and cilgavimab after administration i.m. to the thigh were similar to those achieved with i.v. after 3 days from dosing. Exposure in the i.m. group was 90% of i.v. over 7 days. Administration to the thigh can be considered to provide consistent mAb exposure and improve access.