DYNamic Assessment of Multi Organ Level Dysfunction in Patients Recovering From Covid-19

NCT05060497 | Completed

• 1 other identifier: 20050
• Study Type: observational
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

In this study the investigators are hoping to the find out what changes occur within the body of people recovering from Covid-19 at 5-7 months and 11-13 months following discharge from hospital, compared to healthy controls, and whether these changes can help explain why some patients may experience fatigue. Measurements will be taken using state-of-the-art MRI imaging at rest and also during low intensity exercise, to mimic everyday activity. In doing so it is expected that this will inform ways to adapt exercise rehabilitation programmes, making them better suited for Covid-19 survivors.

Conditions

Covid19

Outcome Measures

Primary Outcomes (15)

• Resting state brain structural measures - white matter and grey matter volumes

  Use of MRI sequences to assess grey matter and white matter volume in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Resting state brain structural measures - white matter microstructure

  Use of MRI sequences to assess white matter tract distribution in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Resting state cardiac structural integrity - cardiac output

  Use of MRI sequences to assess cardiac output at rest in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Resting state cardiac structural integrity - cardiac fibrosis

  Use of MRI sequences to look for the degree of fibrosis at rest in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Resting state whole-body fat and muscle volumes

  Use of MRI sequence (mDixon) to assess whole-body fat and muscle content in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Resting state myocellular fat content

  Use of MR spectroscopy sequence to assess intramyocellular and extramyocellular lipid content in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cerebral blood flow

  MRI sequences will be carried out at rest, during steady-state low level in-bore supine exercise and recovery to assess changes in cerebral blood flow in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cerebral perfusion

  MRI sequences will be carried out at rest, during steady-state low level in-bore supine exercise and recovery to assess changes in cerebral perfusion in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cerebral oxygen extraction

  MRI sequences will be carried out at rest, during steady-state low level in-bore supine exercise and recovery to assess changes in cerebral oxygen extraction in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cardiac output

  MRI sequences will be carried out at rest, during steady-state low level in-bore supine exercise and recovery to assess changes in cardiac output in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Recovery kinetics of skeletal muscle phosphocreatine

  Recovery kinetics of phosphocreatine (Pcr) in the gastrocnemius will be measured following its depletion using MR spectroscopy to assess skeletal muscle quality in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Muscle mRNA

  Muscle mRNA expression will be determined in skeletal muscle samples obtained from a micro biopsy of the vastus laterals in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Whole body glucose disposal - glucose and insulin concentrations

  Oral glucose tolerance test will be used to measure glucose and insulin concentration for whole body glucose disposal in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Whole body glucose disposal - resting energy expenditure

  Indirect calorimetry will be used to measure resting energy expenditure for whole body glucose disposal in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

• Motor unit size

  Intramuscular electromyography will be used to measure motor unit size in the vastus lateralis in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5-7 months post hospital discharge for patients

Secondary Outcomes (19)

• Clinical and demographic data

  5-7 months post hospital discharge for patients

• muscle strength and function

  5-7 months post hospital discharge for patients

• hand grip strength

  5-7 months post hospital discharge for patients

• Short Physical performance battery test (SPPB)

  5-7 months post hospital discharge for patients

• Physical activity

  5-7 months post hospital discharge for patients

Study Arms (2)

Covid patients

Participants who were treated in hospital with laboratory diagnosed Covid-19 requiring high flow oxygen, non invasive ventilation or intubation and have now recovered. They will be recruited 5-7 months post discharge from their local hospital Trust

Healthy control volunteers

Participants who are otherwise healthy, who have not had Covid-19 infection and are age, gender, BMI and ethnicity matched to patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

recruiting 30 patients and 10 controls

You may qualify if:

• Covid patients -
• Adults aged 18 years and over,
• Severe, laboratory confirmed Covid-19 infection that required hospital admission,
• months post discharge from local hospital Trusts.
• Controls -
• No active or previous Covid infection, ie no previous positive Covid PCR test and absence of active symptoms
• Matched for age, gender, BMI and ethnicity.

You may not qualify if:

• Absolute contraindications for MR scan
• Pre-Covid diagnosed chronic respiratory, renal, cardiovascular or cerebrovascular disease or diabetes
• BMI\<20kg/m2
• Pregnancy
• Those requiring oxygen therapy or non-invasive ventilation
• Those on anticoagulation will be included but will not have a muscle biopsy
• Active arthritis
• Overt muscle damage, e.g. plasma creatine kinase \> 300
• Any other conditions in addition to the above that the investigators consider may affect study measurements or safety

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

NIHR Nottingham BRC Respiratory Theme, University of Nottingham and NUH Trust

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

Related Publications (7)

• Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, Holden KA, Read JM, Dondelinger F, Carson G, Merson L, Lee J, Plotkin D, Sigfrid L, Halpin S, Jackson C, Gamble C, Horby PW, Nguyen-Van-Tam JS, Ho A, Russell CD, Dunning J, Openshaw PJ, Baillie JK, Semple MG; ISARIC4C investigators. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020 May 22;369:m1985. doi: 10.1136/bmj.m1985.

  PMID: 32444460 BACKGROUND

• Ronco C, Reis T, Husain-Syed F. Management of acute kidney injury in patients with COVID-19. Lancet Respir Med. 2020 Jul;8(7):738-742. doi: 10.1016/S2213-2600(20)30229-0. Epub 2020 May 14.

  PMID: 32416769 BACKGROUND

• Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 2020 May-Jun;14(3):247-250. doi: 10.1016/j.dsx.2020.03.013. Epub 2020 Mar 25.

  PMID: 32247212 BACKGROUND

• Narici M, Vito G, Franchi M, Paoli A, Moro T, Marcolin G, Grassi B, Baldassarre G, Zuccarelli L, Biolo G, di Girolamo FG, Fiotti N, Dela F, Greenhaff P, Maganaris C. Impact of sedentarism due to the COVID-19 home confinement on neuromuscular, cardiovascular and metabolic health: Physiological and pathophysiological implications and recommendations for physical and nutritional countermeasures. Eur J Sport Sci. 2021 Apr;21(4):614-635. doi: 10.1080/17461391.2020.1761076. Epub 2020 May 12.

  PMID: 32394816 BACKGROUND

• Forster HV, Dempsey JA, Thomson J, Vidruk E, DoPico GA. Estimation of arterial PO2, PCO2, pH, and lactate from arterialized venous blood. J Appl Physiol. 1972 Jan;32(1):134-7. doi: 10.1152/jappl.1972.32.1.134. No abstract available.

  PMID: 5007005 BACKGROUND

• Piasecki M, Ireland A, Jones DA, McPhee JS. Age-dependent motor unit remodelling in human limb muscles. Biogerontology. 2016 Jun;17(3):485-96. doi: 10.1007/s10522-015-9627-3. Epub 2015 Dec 14.

  PMID: 26667009 BACKGROUND

• Meyerspeer M, Boesch C, Cameron D, Dezortova M, Forbes SC, Heerschap A, Jeneson JAL, Kan HE, Kent J, Layec G, Prompers JJ, Reyngoudt H, Sleigh A, Valkovic L, Kemp GJ; Experts' Working Group on 31P MR Spectroscopy of Skeletal Muscle. 31 P magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations. NMR Biomed. 2020 Feb 10;34(5):e4246. doi: 10.1002/nbm.4246. Online ahead of print.

  PMID: 32037688 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples: Full blood count, renal function including eGFR, troponin, brain natriuretic peptide, glycosylated haemoglobin, liver function, ferritin, creatine kinase (CK), clotting and international normalized ratio (INR), TNF-alpha, IL-6 and CRP Muscle biopsy: citrate synthetase

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Charlotte E Bolton, Prof

  NIHR Nottingham Biomedical Research Centre, Respiratory theme

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: September 29, 2021
• Study Start: October 27, 2020
• Primary Completion: February 24, 2022
• Study Completion: February 24, 2022
• Last Updated: March 27, 2023

Record last verified: 2023-03

Locations

GB (1)