Abstract Background Bronchiolitis obliterans syndrome (BOS) is a late complication after allogeneic hematopoietic cell transplantation (HCT). While retrospective evidence shows symptomatic respiratory viral infections (RVI) may contribute to the development and progression of BOS, a similar role for asymptomatic RVI is unknown. This study aims to assess the incidence of asymptomatic and symptomatic RVI in a high-risk population. Methods Allogeneic HCT recipients with new-onset chronic graft-versus-host disease (cohort 1, at risk for BOS) and new onset BOS (cohort 2) were enrolled in an ongoing multi-center prospective longitudinal study (NCT05250037) to assess the role of RVI in development of BOS. Participants conducted weekly handheld home spirometry, weekly symptom surveys, and submitted self-administered nasal swabs for respiratory viral PCR testing every two weeks; additional swabs were prompted if symptom survey score reached ≥2. An asymptomatic episode was defined as one or more consecutive positive viral swab with a symptom score of 0-1 and no positive symptoms in the 2 weeks before or after. A symptomatic RVI episode was defined as the first positive PCR to the final positive PCR with any associated symptom score ≥2, allowing no more than ≥4 weeks or 2 negative samples between any 2 consecutive positive PCR samples. Results From March 2022 to July 2023, 73 participants were enrolled (cohort 1: n=50; cohort 2: n=23), with 47 completing one year of follow-up. Compliance was 68% for surveys and 62% for nasal swabs. Twenty percent of 744 swabs tested positive for ≥1 virus. Of 43 participants who tested positive for RVI, 21% (9/43) had 1 episode, 21% (9/43) had 2 episodes, and 52% (25/43) had ≥3 episodes. Ninety-five percent of RVI episodes (104/109) were symptomatic, most commonly rhinovirus (22%), followed by SARS-CoV-2 (21%), seasonal coronavirus (18%), parainfluenza (14%), RSV (6%), adenovirus (5%), and influenza (4%). Only 5% (5/109) of RVI episodes were asymptomatic with 2 episodes of SARS-CoV-2, 2 episodes of seasonal coronavirus, and 1 episode of parainfluenza. The median duration of a symptomatic episode was 1 week (range 1-18 weeks). During the follow-up period, 3 participants in cohort 1 satisfied diagnostic criteria for BOS, of which 2 had antecedent RVI. Conclusion The first year of this observational study revealed frequent symptomatic RVIs and a low rate of asymptomatic RVIs in patients at high risk for BOS. Ongoing follow-up and analyses will evaluate the impact of common RVI on BOS development and progression after HCT.

Electrochemical biosensors have shown great potential for simple, fast, and cost-effective point-of-care diagnostic tools. However, direct analysis of complex biological fluids such as plasma has been limited by the loss of sensitivity caused by biofouling. By increasing the surface area, the nanostructured electrode can improve detection sensitivity. However, like a double-edged sword, a large surface area increases the nonspecific adsorption of contaminating proteins. The use of nanoporous structures may prevent fouling proteins. However, there is no straightforward approach for creating nanostructured and nanoporous surfaces compatible with microfabricated thin-film electrodes. Herein, the preferential etching of chloride and surfactant-assisted anisotropic gold reduction to create homogeneous, nanostructured, and nanoporous gold electrodes is demonstrated, yielding a 190 ± 20 times larger surface area within a minute without using templates. This process, "surfactant-based electrochemical etch-deposit interplay for nanostructure/nanopore growth" (SEEDING), on electrodes enhances the sensitivity and antibiofouling capabilities of amperometric biosensors, enabling direct analysis of tumor-derived extracellular vesicles (tEVs) in complex biofluids with a limit of detection of 300 tEVs µL^-1 from undiluted plasma and good discrimination between patients with prostate cancer from healthy ones with an area under the curve of 0.91 in urine and 0.90 in plasma samples.