ABSTRACT
The biology driving individual patient responses to SARS-CoV-2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data, covering a year post disease onset, from 215 SARS-CoV-2 infected subjects with differing disease severities. Our analyses revealed distinct "systemic recovery" profiles with specific progression and resolution of the inflammatory, immune, metabolic and clinical responses, over weeks to several months after infection. In particular, we found a strong intra-patient temporal covariation of innate immune cell numbers, kynurenine- and host lipid-metabolites, which suggested candidate immunometabolic pathways putatively influencing restoration of homeostasis, the risk of death and of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery on the patient level, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-systemic-recovery-prediction-app, designed to test our findings prospectively. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/22276437v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@e410cforg.highwire.dtl.DTLVardef@10bad79org.highwire.dtl.DTLVardef@1a9ebadorg.highwire.dtl.DTLVardef@afb5f7_HPS_FORMAT_FIGEXP M_FIG C_FIG
ABSTRACT
AIM: Children and adolescents with functional neurological disorder (FND) present with physical impairment and mental health comorbidities. Specialist physiotherapy programs for treating FND have been developed over the last two decades. This article reports outcome data from three cohorts of children treated with a multidisciplinary rehabilitation intervention - the Mind-Body Program - in which a psychologically informed physiotherapy intervention, known as the wellness approach to physiotherapy, was a key component. METHODS: For three cohorts of children (n = 57, n = 60 and n = 25, respectively) treated in the Mind-Body Program, data about functional impairment and mental health concerns were collected at presentation and at follow-up (4 years, 12 months and 18 months, respectively). RESULTS: Outcome data show that FND symptoms resolved in 54/57 (95%), 51/60 (85%) and 22/25 (88%) of children in the three cohorts, and that 31/57 (61%), 32/60 (53%) and 13/25 (52%) of children returned to full health and to full-time school attendance. Changes in Global Assessment of Function (GAF) were significant (t(54) = 21.60, P < 0.001; t(55) = 9.92, P < 0.001; t(24) = 6.51, P < 0.001). Outcomes were less favourable for children with chronic FND symptoms at presentation; those whose comorbid mental health disorders or other (comorbid) functional somatic symptoms did not resolve; and those who subsequently developed chronic mental health problems. CONCLUSIONS: Implementation of a multidisciplinary rehabilitation intervention - with psychologically informed physiotherapy as one of the key treatment components - resulted in resolution of FND symptoms and return to health and well-being in the large majority of patients.
