Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present with different disease severity. Here, we determined 171 microRNAomes from 58 hospitalised COVID-19 patients (Cohort 1) and levels of 25 cytokines and chemokines (CC) in the same samples. Combining microRNA (miRNA) and CC measurements allowed for discrimination of severe cases with greater accuracy than using miRNA or CC levels alone. Severity group-specific associations between miRNAs and COVID-19-associated CC (e.g. IL6, CCL20) or clinical hallmarks of COVID-19 (e.g. neutrophilia, hypoalbuminemia) separated patients with similar CC levels but different disease severity. Analysis of an independent cohort of 108 patients from a different centre (Cohort 2) demonstrated feasibility of CC/miRNA profiling in leftover hospital blood samples with similar severe disease CC and miRNA profiles, and revealed CCL20, IL6, IL10, and miR-451a as key correlates of fatal COVID-19. These findings highlight that systemic miRNA/CC networks underpin severe COVID-19.

BackgroundNon-medical devices such as the handheld fan (fan), mobility aids (wheeled walkers with seats) and inspiratory muscle training (IMT) devices offer benefits for patient management of chronic breathlessness. We examined the published evidence regarding patient, carer and clinician use of the fan, mobility aids and IMT devices for chronic breathlessness management, and the potential barriers and facilitators to day-to-day use in a range of settings.MethodsMEDLINE, Embase, Scopus, EBSCO and the Cochrane Database of Systematic Reviews were searched. Papers were imported into EndNote and Rayyan for review against a priori eligibility criteria. Outcome data relevant to use were extracted and categorised as potential barriers and facilitators, and a narrative synthesis exploring reasons for similarities and differences conducted.ResultsSeven studies met the inclusion criteria (n=5 fan, n=2 mobility aids and n=0 IMT devices). All of the studies presented patient use of non-medical devices only. Patients found the fan easy to use at home. Mobility aids were used mainly for outdoor activities. Outdoor use for both devices were associated with embarrassment. Key barriers included: appearance; credibility; self-stigma; technical specifications. Common facilitators were ease of use, clinical benefit and feeling safe with the device.ConclusionThe efforts of patients, carers and clinicians to adopt and use non-medical devices for the management of chronic breathlessness is impeded by lack of implementation research. Future research should improve knowledge of the barriers and facilitators to use. This would enhance understanding of how decision-making in patient–carer–clinician triads impacts on non-medical devices use for breathlessness management.

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