Long COVID Investigations

This is a personal methodology in Long COVID and similar in POTS

A Clinical Guide for GPs

Dr Graham Exelby May 2025

Checklist:

1.     Functionality Scales

2.     Timeline of illness/trauma

3.     Symptoms

4.     Family history

5.     Radiology

6.     Holter

7.     Pathology

8.     Retinal Photography

Radiology

 Spectral CT: 

The very important radiology breakthroughs have been made on the Gold Coast at Mermaid Beach Radiology, currently the only location in Australia with the technology.  In particular the Spectral CT angiogram/venogram will show the various compression regions that are responsible for many of the symptoms.

These are often present but asymptomatic until sensitized by Covid.   In some we have documented collagen change from the virus and post-viral inflammation 

• There are usually clues in their timeline eg “eating disorders” may in reality be an SMA or MALS.  

• Endometriosis is commonly a marker for a Nutcracker.    

• These scans pick up a long of Covid-associated malignancy, but should not be used for general malignancy screening as adenocarcinomas may not be apparent.  

• Spectral CT can be used for an opportunistic non-compression breast screen .  This is very useful in at risk patients.   We found so many abnormal scans for breast carcinoma/fibroadenoma, the scan has been tweaked as an “add-on” at the beginning of the normal scan to differentiate between them.

MRI brain with venography 

Vital to assess possible damage to the venous sinuses, pituitary flattening, hyperintensities, low-lying cerebellar tonsils in the brain rather than a normal MRI.   You are best to have a neuroradiologist to discuss issues with, and general radiologists have a high “miss” rate.    The MRI at Mermaid Beach has the highest resolution currently available (limited by lack of medicare rebate)

Echocardiogram (with ascending aorta) if shortness of breath, POTS-like symptoms.   Be watchful of RA dysfunction and IVC flattening

SPECT scan brain if there is any brain fog.  The MRI at Mermaid Beach obviates the need for separate Spect scanning

Spectral CT Chest:

If a full Spectral scan is not needed, but there are chest symptoms the Spectral CT is set up for a more complete assessment, far superior to a CXR    If a D-Dimer is positive and there is chest pain/ SOB and CTPA negative (usual occurrence), the older VQ scan may show diffusion dysfunction, but I do find the spectral does the job very well.

Dynamic Vascular Scans- especially if symptoms are when erect as CT is supine.    The supine scans miss the TOS which is very posture-dependent.  Two places only can do these: Gold Coast available at Australian Ultrasound Specialists at Miami (and Brisbane)(1300 388 000), and Brisbane Precision Vascular Imaging at Greenslopes  on 07 3847 9144.  If you need IJV valve studies you need the AUS scans.

24 hr holter monitor with HRV (QML ONLY please) as these are the only ones routinely doing heart rate variability.   You need the full results, not the abbreviated ones normally sent to GPs)   Apple watches do give an idea but inadequate for tracking the autonomic instability in POTS and Long Covid.    Ones from cardiologists very seldom provide this information.  

Pathology

• FBC

• HS-CRP- most GPs order CRP (measures IL-6 which is a critical assessment, but the more accurate HS-CRP is needed unless Sullivan & Nicolaides pathology who do this now routinely)

• E’s & LFTs- electrolytes, liver , kidney function

• ANA -tests for autoimmune disease activation (ENA if Sjogrens suspected), other auto-immune studies that have been done, dSDNA and ANCA may also be needed. 

• Complement C3, C4.   Complement C3 is a vital biomarker in Long Covid – the combination of C3 with C4 and ANA exclude SLE

• Se Homocysteine (measure oxidative stress in the MTHFR mutations that are in all POTS patients)   DNA for MTHFR is generally not required as it is a small part of the overall problem

• TSH, Thyroid antibodies- basic test for thyroid function and if any inflammation

• Se Tryptase (before any anti-histamines) to assess mast cell responses

• Lymphocyte sub-populations- for T cell status

• D-Dimer, VITAL if chest pain

Second round tests if appropriate

• ·       Beta 2 microglobulin -a protein shed by B cell lymphocytes- this may elevate in immune system dysfunction.  This is very important if there are abnormal full blood counts, especially after Covid

• Fe studies

• Pl Zn (Zinc) Cu (copper)

• Se B12 (normal > 400)

• Se B6 -watch for excess in peripheral neuropathy- can be from diet/supplements of metabolic dysfunction

• Red cell Mg (magnesium)

• Red cell folate if Se Homocysteine > 9 in young people -older people have higher levels of acceptance

• Se ACE if granulomas in lungs

Third round tests if appropriate

• Se PTH looks at parathyroid function

• Se Lipase- pancreatic function

• Hormone assays (important if there is PCOS)- Testosterone, SHBG, FAI, FSH, LH, fasting glucose, Se Insulin, TSH

• Pituitary tests if brain fog and pressure are present (TSH, FSH, LH, Prolactin, Growth hormone, Cortisol).    If abnormal Se cortisol, proceed to 24 hr salivary cortisol

• Vitamin D3

More if elevated D-Dimer: These are useful if chest pain and shortness of breath are present

• Fibrinogen

• PTT

• APTT

• Complement C3 (and C5 if persistent D Dimer elevation)

Regarding pituitary testing:

The normal anterior pituitary secretes six main hormones from five separate cell lineages:   These tests may be quite important in those with brain fog and associated pressure.

• adrenocorticotrophic hormone (ACTH) from corticotrope cells

• thyroid stimulating hormone (TSH) from thyrotroph cells

• growth hormone (GH) from somatotroph cells

• prolactin from lactotroph cells

• follicle stimulating hormone (FSH) and luteinising hormone (LH) from gonadotroph cells.

• The posterior pituitary releases two hormones, which are synthesised in the hypothalamus – arginine vasopressin (also known as antidiuretic hormone) and oxytocin.

Retinal photography is a vital component in the investigation process.  Not all retinal cameras are of sufficient quality.