Driving research of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS),
Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia and Post COVID .

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Long COVID Clinic Studies

Study AIM

The newly established clinic in Uppsala will continue the work of the OMF-Funded MultiCenter Collaborative Study on COVID to ME/CFS progression.

LEAD INVESTIGATORS
  • Jonas Bergquist, MD, PhD, Prof, Director ScD
Updates and Potential

Studies A & B: IRB protocol has been approved, and patients are being recruited.

 

STUDY HYPOTHESIS AND DESCRIPTION

The clinic provides an opportunity to continue studying  the disease process as it develops, and hopefully better understand ME/CFS.  A subset of the previously critically ill patients will be monitored for disease progression over time alongside non-critically ill Long Covid patients who will also visit the clinic for continuing symptoms.

As with the previous study investigators will use genomics, proteomics, metabolomics, and immunology to recover as many immune cells as possible, and to characterize their evolution to ME/CFS. Furthermore, we are studying the plasma and cerebrospinal fluid (CSF) to identify proteins and large molecules (e.g., antibodies) as well as small molecules that appear or disappear in association with the development of ME/CFS.

OBJECTIVES

Study A:

  • Recruit approximately 50 patients with confirmed mild COVID infection (confirmed by antibody analysis or positive PCR test) and long-term symptoms over 12 weeks after infection, recruited via Postcovid clinic. 50 gender- and age-matched controls who have undergone confirmed COVID infection but who have no long-term symptoms or sequelae of the infection are invited. 
  • Patients and controls will be asked to perform various psychometric tests and complete questionnaires: Fatigue severity scale FSS, MADRS, MOCA test, 1 minute sit-to stand test, orthostatic test, RAND-36, BANS, EQ-5D- SL and DePaul’s PEMS scale.
  • Patients and controls should leave a total of 30 ml of EDTA plasma tube. lsolated blood cells (PBMC) as well as extracted DNA and RNA will be analyzed at SciLife Labs Technology Platform for Sequencing for sequencing of the entire transcriptome. 
  • Run proteomics using high ­resolution mass spectrometry and metabolomics analysis using high-resolution mass spectrometry and NMR. Alternatively, we can supplement the protein analysis with an inflammatory Olink panel.

Study B:

  • Study persistent symptoms after 24 and 36 months in patients (selected from the COMBAT study, 150 in total) after mild confirmed covid-19 infection and how the possible symptoms affect the daily activities and ability to work as well as sick leave. 
  • Study whether patients with persistent symptoms have affected physical ability and muscle strength 
  • Study whether those patients with persistent symptoms have elevated levels of inflammatory biomarkers (proteins, metabolites) and/ or autoantibodies compared to those without symptoms at the time 24 months after mild covid-19. 
  • Identify whether people with persistent symptoms 24 months after covid-19 have any specific HLA types in comparison with those who have no symptoms at the time of 24 months. 
  • Study how the intestinal microbiome is affected by mild infection compared to a healthy control group and in some individuals compared to baseline. We will receive biobank samples for a healthy control group from the SCAPIS (Swedish Cardiopulmonary bio-Image study) study.

 

NMR Metabolomics
NMR (Nuclear Magnetic Resonance) is an instrument/tool used to perform metabolic studies, metabolic profiling, and metabolomics in biofluids and tissues for more than 40 years using magnetic fields. There is a very close connection between metabolic measurements and NMR. This connection has flourished because of NMR’s many unique strengths for characterizing complex mixtures’ chemical composition.
Proteomics
The large-scale study of proteins, which are large, complex molecules that are required for structure, function, and regulation of the human body's tissues and organs.
Microvesicles and viral sequencing
Microvesicles are a type of extracellular vesicle that is released from the cell membrane. Vesicles are small, fluid-filled sacs or vacuoles within the body. Sequencing is a technique used to determine the exact sequence of bases (A, C, G, and T) in a DNA (or viral) molecule.
Micro RNA
Cells use Micro RNA to control whether a particular gene is making too much, too little or the normal amount of its protein at a particular time.
Autoantibodies
Antibodies that react with self-molecules and that occur in healthy individuals and are referred to as natural antibodies or autoantibodies.
Extracellular DNA for viral reactivation and Mitochondrial DNA
exDNA (extracellular DNA), exDNA is often secreted actively and is used to perform several tasks, thereby offering an attractive target or tool for biotechnological, medical, environmental, and general microbiological applications. Viruses are intracellular parasites that rely to a significant extent on the host cell for replication. Viral reactivation occurs when an active replication of the viral genome results in a lytic (degradation of the cell) infection characterized by the release of new progeny (descendant) virus particles.
Immune cell profiling
The immune system has many important regulatory roles in disease development and progression. Given the emergence of effective immune therapies, reliable predictors of response are needed. Immune cell profiling determines response by evaluating immune cell populations from treated and untreated samples. For our purposes, we will evaluate the white blood cell response to the viral infection using a process called “Cytof.”
Leukocyte Genomics
A leukocyte is a colorless cell circulating in the blood and body fluids and is involved in counteracting foreign substances and disease. A genome is all genetic material of an organism. Genomics is a biology field focusing on the structure, function, evolution, mapping, and editing of genomes. Therefore, leukocyte genomics is the study of all genetic material of leukocytes.
Metabolomics
Metabolomics is a way to study metabolism – that is, through measuring amounts of the metabolites (small molecules) produced by our bodies as we convert food into energy and other molecules that our cells need to survive. Metabolomics technology is ‘large-scale,’ meaning that several thousand metabolites can be measured from a single sample of e.g., blood or urine.