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  • Writer's pictureGraham Exelby

Long Covid Part 10: The Mermaid Beach Protocol

February 2023


Introduction:


This protocol has been developed at our clinic at Mermaid Beach. It is designed to be used in association with normal guidelines as described in “RACGP. Caring for patients with post-COVID-19 conditions. 2021”(182) -below.


This protocol has evolved over 10 years of research into POTS and now the association with Long COVID. It is not a replacement for evidence-based management. It does not support using the listed tests as screening, but suggestions that we have found may be useful in individual management. This protocol does not describe management of specific problems such as neuroinflammatory or cardiac damage.


Covid enters the body via ACE2 receptors- triggers the cytokine storm after activation of the mast cells by Toll-Like Receptors, releasing cytokines, which are small proteins involved in cell signalling, as well as other inflammatory products, in particular Interleukins 6 and 8 (or IL-6 and IL-8) and Tissue Necrosis Factor alpha (or TNF). The inflammatory response can lead to lung oedema, fibrosis, inflammation that affects heart, kidneys, liver, brain etc etc, and microthromboses.


Mukherjee et(78) al found these emboli are a result of histamine receptor 1 (H1) induced fibrinogen.(78) Increased TLR expression and TLR-mediated platelet activation during COVID -19 appears to enhance vascular and coronary thrombosis.(75)


The most common brain pathology found post-mortem has been cytokine activation of microglial cells and damage by microclots, which are themselves a result of inflammatory or cytokine changes in our blood and can be found in almost any affected organ. Complicating this has been the incorporation of amyloid in some of these clots by virtue of the intensity of the inflammatory reaction in some people- amyloid better known for its association with Alzheimers disease- and makes these clots resistant to clot lysis.


Microglia account for 10% to 15% of all cells found within the brain, and as the resident macrophage cells, they act as the first and main form of active immune defence in the CNS. Inflammatory microglial activation (IL-6 and TNFa) is the most common brain pathology found in patients who died of COVID-19: 42% are affected, and another 15% have microclots in brain tissue.


Dong et al(109) demonstrated that brain inflammation plays a critical role in the pathophysiology of brain diseases. Microglia, the resident immune cells in the brain, play an important role in brain inflammation, while brain mast cells, rather than microglia, are the "first responders" to brain injury. They showed that site-directed injection of a “mast-cell degranulator” compound in the hypothalamus initiated the acute inflammatory response by inducing mast-cell degranulation, activating microglia, and triggering the production of inflammatory factors. The complex nature of the immune response and mast cell activation in now an integral part of Long Covid pathogenesis.


Dong et al demonstrated that in the brain, activation of mast cells triggers activation of microglia, whereas stabilisation of mast cells inhibits the CNS inflammation that would otherwise result from activation of microglia.(109)


The neuroinflammatory response “sensitises” the glial cells with consequent small-fibre neuropathy and from this small fibre neuropathy it is believed comes the characteristic autonomic chaos that is POTS and POTS-like Long Covid, and this includes random symptoms such as the eye pain in Covid, and the anosmia.(191)(192)


The various neurodegenerative mutations involved in Long Covid by and large have no biomarkers to measure the level of danger. Persistent inflammation can destroy brain cells. Combining MRI brain with brain SPECT scan reveals whether the impaired patient has inflammatory (hyperperfusion) or damage (hypoperfusion).


SARS-CoV-2 (is a similar way to EBV, CMV, and other viruses) affects the mitochondria, causing mitochondrial dysfunction. Mitochondria are the powerhouses of our cells and are vital to maintaining the health and even survival of cells and play a key role in maintaining homeostasis and cell-mediated immunity.


From this the PACS/ Long Covid patients have chronic fatigue, aggravated by:

  • Direct cardiac damage (eg pericarditis, myocarditis)

  • Pulmonary damage

  • Small fibre neuropathy inflammatory and very common (again IL-6 and TNFa)

  • Autonomic instability- “POTS” symptoms. Over 70% of Long-COVID have cardiovascular autonomic disorder, 30% of these with POTS (Postural Orthostatic Tachycardia Syndrome)(271)

  • Impaired cardiac function

  • Reactivation of EBV and similar viruses

  • Metabolic damage eg to phosphatidylserine and phosphatidylcholine pathwaysMicroglial damage in brain -links to Glymphatic research at Griffith Uni

Around 30% to 45% of patients continue to report an array of persistent symptoms after infection, with recent studies confirming these changes up to 2 years and ongoing in roughly 1 in 8. Commonly reported symptoms range from fatigue and dyspnoea to “brain fog” with ongoing disability and disruption of work, social, and home lives.


Major Points

  • Long Covid is not one condition.

  • The Covid may continue to be active /reactive months after contact (sustained inflammation for at least 8 months, esp if unvaccinated

  • It is a microembolic and inflammatory disease that may also add amyloid to fibrin with increased risk Alzheimers, Parkinsons, neurodegenerative disorder in infants

  • Microemboli are a result of histamine receptor 1 (H1) induced fibrinogen.(78) Increased TLR expression and TLR-mediated platelet activation during COVID -19 appears to enhance vascular and coronary thrombosis

  • Microglial activation is the most common brain pathology found in patients who died of COVID-19: 42% are affected, and another 15% have microclots in brain tissue.

  • Rauchet al(249) found phosphatidylserine was associated with increased thrombo-inflammation and vascular complications, and increasingly PEMT and similar DNA mutations may be relevant in persisting elevated D-Dimer. PEMT mutations are also associated with persisting fatigue.Cytokine-induced central sensitisation (inflammatory activation of glial/microglial cells and neuropathic inflammation) is the key driver of the autonomic and inflammatory instability in POTS and the POTS-type of PACS patients.

  • Increasing DNA evidence that multiple mutations in the Toll-Like Receptors (especially “first responders” TLR2 and TLR4) play a large role in the individual immune response, and associated with “downstream” mutations can create a domino effect responsible for the individual problems being caused by Covid. These are common and look to provide directions for management in patients not responding to the first line mast cell blockade. The TLR2 and TLR4 mutations are currently being investigated.

  • The TLR4 mutations may explain the effectiveness of Low Dose Naltrexone in chronic fatigue and cognitive impairment.

  • The TLR4 mutations appear to be potentially one of the critical “molecular connections” associated with the abnormally low “biomarkers” used to measure the inflammatory responses seen in many Covid patients. These patients have often “fallen below the radar” while in fact have an impaired immune response. Nigella Sativa (black cumin or black seed oil) is currently being looked at in the management of this with its role in modulating the TLR4 response.

  • It may reactivate earlier problems eg EBV, shingles, HSV and stay in cell nuclei

  • It appears to be co-related with aggressive malignancy (thought to be Interferon 1 and NK cell dysfunction) -no formal data as yet available. · People with cancer are at a higher risk if they contract COVID

  • There is a poor prognosis in obesity, diabetes, hypertension, and atherosclerosis

  • Increased cardiovascular or cerebrovascular event in next 12 months, doubling with a second bout of Covid. Increased dementia risk in over 65's of between 50 and 80%

  • High incidence new diabetes

  • All the POTS-type PACS patients have underlying conditions eg TOS/ neck pathology/ MALS/ Nutcracker. You can't just supplement your way out of POTS/Long Covid.

Common problems in Long COVID:

  • Fatigue, brain fog and shortness of breath

  • Over 65- 60+% increased cardiovascular or cerebrovascular event and an increased risk of dementia or between 50 to 80% in next 12 months

  • Change in microbiome

  • High incidence diabetes (30%)

  • Increased incidence of autoimmune disease

  • Neural sensitisation with autonomic dysfunction, triggering multiple problems including Postural Orthostatic Tachycardia Syndrome (POTS.) Over 70% of Long-COVID have cardiovascular autonomic disorder, 30% of these with POTS (Postural Orthostatic Tachycardia Syndrome)(271)

Red Flags:

  • Unresponsive to mast cell blockade

  • New, increasing or severe shortness of breath

  • Arrhythmias

  • Unexplained chest pain

  • Syncope

  • Confusion

  • New neurological symptoms

  • Lack of response after 4 weeks of mast cell blockade

  • Increasing D-Dimer levels

Investigations:


1. Biomarkers utilized at this clinic:


Pathology which could be utilized depending on symptoms. This is not a screening profile., and are suggestions that may be useful in management

  • FBC, E’s & LFTS- high incidence liver pathology, again IL-6 driven, watch for renal dysfunction

  • HS-CRP (watch for low response). Low CRP falls under the radar

  • D-Dimer (add APTT if elevated)- elevated in around 15% for 3 months. Clear guidelines are not available. Concerns if prolonged immobilisation, previous venous thromboembolism, hormonal therapy, body weight >120 kg or BMI >35 kg/m², or in patients with an ongoing malignancy. Malignancy a possible concern in a D Dimer not improving or increasing. Can increase with stress and other factors

  • Complement C3, C4 (low C3 major prognostic value)

  • Lymphocyte subpopulations: (CD8+ lymphopaenia major prognostic value)

  • ANA, TSH, Thyroid abs (80% develop auto-immune activation- drops to 2% within 12 months

  • Tryptase -measure of mast cell degranulation (if not on antihistamines)- normals wrong, should be around 3. Low is concerning- often seen with associated low C3, and low HS-CRP (and probably shows impaired immune response -being assessed with DNA patterns at present), consider Chromogranin a (no medicare item)-useful if considering neuroendocrine tumours in hyperadrenergic patient, with HIAA and biogenic amines

  • Se ACE if cardiac and pulmonary symptoms

  • Se Troponin as appropriate

  • Homocysteine- reflects oxidative stress, as increases over 15 (ideal <8) - increasing thrombotic risk – usually MTHFR mutation, if elevated, and not responding to methylated B12 may needs SAMe- consider DNA for safety as use can be difficult in my opinion

  • B12 (normal range probably too low, ideally probably 400+), Zn, Vit D if homocysteine over 10 (“normal” of <15 not correct as increased CV risk over 9)

  • B2Microglobulin- consider if atypical lymphocyte subpopulations, FBC

  • Se Lipase if abdominal pain (if normal, often sensitized vagal compression by SMA, coeliac artery or variant, and gastroparesis can be from this or brainstem)

  • Fe studies/ Ferritin

  • APO E4- major prognostic value if cognitive impairment (marked increased risk Alzheimer’s disease, coronary artery disease and fatty liver) Not covered by Medicare, but is in full DNA if being done. Look for aneurysms, non-alcoholic fatty liver, FH early CV disease, dementia -may be managed with Candesartan, reduction of oxidative stress

  • Lipoprotein a is increasingly recognized as a prognostic factor in NASH and CV disease and may be relevant

2. Other studies that may be useful:

  • ECG lying and standing- picks up autonomic dysregulation (watch for short PR and long QT)

  • Kubo et al(190)demonstrated changes of up to 9 msec when standing (Bazett’s formula), and up to 14 msec in Framingham’s formula

  • The PR interval is the time for the electrical impulse generated in the sinus node to travel through the atria and across the AV node to the ventricles. Normal range is 0.12 to 0.20 seconds. The PR interval can be altered by changing sympathetic and parasympathetic activity. Beta blockers antagonize beta-1 and beta-2 receptors, the usual targets of the sympathetic nervous system, and can lengthen the PR interval with resultant first-degree heart block.(193)

  • Postural assessment

  • NASA Lean test if autonomic instability in lieu of tilt testing. Should be considered in all patients with autonomic dysfunction.

  • ROOS test may reproduce symptoms in thoracic outlet syndrome (should be done in all POTS-like patients given very high association)

  • Thoracic outlet scans (if positive ROOS test) Dynamic doppler needed to pick up the positional changes in Roos and Wright’s positions, and generally not seen on static MR (MRA) scans.

  • CTPA- chest pain and elevated D-Dimer (low pickup in microembolic cascades )

  • VQ scan in recurring chest pain and elevated D-Dimer with normal CTPA -heterogeneous pattern reflecting microembolic damage may be present.CXR (any SOB)- may need HS-CT if elevated ACE

  • Echocardiogram

  • Holter, ideally with heart rate variability (R-R interval) if any suggestion of dysautonomia or changes on ECGs.

  • RFT for any SOB after CXR subject to history

  • MRI (xray or CT) cervical spine in POTS-type -watch for loss of lordosis, C2/3 dysfunction especially where hypermobility is present.

  • MRI brain in cognitive impairment- best done with cervical spine together. Medicare compliant only with chronic headache. Look for:

  • Hyperintensities > age-associate

  • Ventricular asymmetry > expected

  • Empty/partially empty pituitary sella

  • Optic nerve change

  • Microhaemorrhages > age expected

  • MRa brain or CTa may be considered if seizures, severe headache, CVA presentation for rare cerebral infarction or less common haemorrhage, the most common site the Superior Sagittal Sinus.

  • SPECT scans brain: The various neurodegenerative mutations involved in Long Covid by and large have no biomarkers to measure the level of danger. Persistent inflammation can destroy brain cells. Combining MRI brain with brain SPECT scan reveals whether the impaired patient has inflammatory (hyperperfusion) or damage (hypoperfusion) and treatments tailored appropriately


Common Specific Problems


1. Fatigue:

  • Mitochondrial dysfunction /oxidative stress / metabolic damage ( DNA testing with Dr Valerio Vittone will provide clarity on mitochondrial and inflammatory deleterious bad gene variants that are critical to Mitochondrial dysfunction and the exaggerated immune response caused by Covid )

  • Direct cardiac damage (eg pericarditis, myocarditis)

  • Pulmonary damage- embolic, inflammatory

  • Reactivation of EBV and similar virusesSmall fibre neuropathy inflammatory and very common (again IL-6 and TNFa) -accompanying exaggerated neuropathy, rheumatoid arthritis, reactive arthritis, PMR strongly suggestive of TLR4 mutations Autonomic instability- “POTS” symptoms

  • Impaired cardiac function

  • Microglial damage in brain -link to Glymphatic research at Griffith Uni

2. Shortness of Breath / chest pain:

  • CXR

  • RFT

  • HS-CT chest / CTPA (and sometimes VQ scan for heterogeneous pattern) -no guidelines as yet but depends on level of severity

  • Echo -watch for subtle changes and EF. If LA dilatation and migraine check for PFO (Transcranial Doppler Bubble Test is gold standard)

  • D-Dimer

  • Se Troponin

  • Lying and standing ECG for excessive autonomic response

3. Dysautonomia / POTS pattern

  • All (so far) have history of other problems, but dysregulated by Covid, most common is neck injury.

  • The sensitisation has to be dealt with first.

  • Recommend lying and standing ECGs, Holter monitor (for HRV pattern and QT). Sympathetic pattern we have found best controlled by “Kiiko Matsumoto” acupuncture and with diet change- keto/low histamine and base treatment with H1/H2 blockade to get them started.

  • DNA mutations include mast cell receptor and DAO metabolism- HNMT histamine metabolism, COMT, oxidative stress, MTHFR, frequent APO E4, IL-6 and others. Clues in detailed history, especially endometriosis, migraine, syncope.

  • The POTS type ALL have mechanical components, mostly (85%) from neck and thoracic outlet (see POTS article in website). The intra-abdominal drivers are hard to assess as we can only image the arteries and veins, not the vagal compression, and unless significant enough to interest surgeons, require management of sensitization and symptoms often settle (until reactivated)

Brain Fog/cognitive impairment

  • Glymphatic flow is very important when fatigue and cognitive impairment are present (see separate article “Cervical spine with loss of lordosis and impeded glymphatics and association with Thoracic Outlet and Jugular Outlet Syndromes”) This usually improves with good posture, TOS management, LDN.

  • Variability in brain fog – intra-arterial pressure change (ref Lau, Wells et al(164))- often improves with diet change, sometimes H1/H2 blockade, LDN most effective (with care). Watch for “pressure” as research is currently looking for increased intracranial perfusion as well as the impaired flow documented by Wells et al..

  • Amyloid at present not measurable- depends on radiologist skill in interpretation -if risk contact radiology for formal Alzheimers study as may need specialist referral

  • Retinal arterial photography if camera adequate can give a clear picture of cerebral vasculature

Management:


This is a personal management protocol utilized at our clinic. Use as possible suggestions in association with RACGP Guidelines, There are no Cochrane Guidelines at this point, and all treatments are based on research from around the world.Patients need to be made aware of this. As the DNA studies reap more information the first response TLR 2 and TLR4 mutations are likely to be critical in the individual patient response.


Stop the ongoing inflammatory processes. Each area of inflammation from the Covid and pre-Covid state needs to be identified and managed if possible -but start with histamine blockade

  • H1/H2 blockade: Fexofenadine 180 bd (or alternative), Famotidine 40 bd if tolerated, but may need to be increased to 80mg bd.

  • H4 blockade: Low Dose Naltrexone -improves glymphatic function (and probably NK cell function). Recommend delay of 1 to 4 weeks before starting LDN as improvements with H1/H2 blockade can be assessed

  • If H1/H2 not tolerated, caution with Low Dose Naltrexone (H4 blockade)

  • Nigella Sativa (active ingredient Thymoquinone) increasingly looks to be a reasonable adjunct to above treatments, especially when D-Dimer remains elevated as it has anti-thrombotic activity, and may be a reasonable replacement when LRN is not tolerated. Side effects are uncommon but can include allergic reactions, nausea, diarrhoea, and can lower blood pressure. There are potential interactions with anti-clotting and diabetic medications. I believe it should be avoided if anti-clotting agents are being taken.

Deal with the mitochondrial dysfunction largely responsible for fatigue, cognitive impairment, low energy and memory loss

  • Keto /low histamine diet (low histamine major importance if has HNMT,Dao enzyme defect)

  • Consider Nicotinamide adenine dicucleotide (NAD+) or Nicotinamide mononucleotide (NMN) may help dysfunction.

  • The phytochemical sulforaphane (in nature seen in cruciferous vegetables), eg EnduraCell is being utilized to activate Nrf2 (nuclear factor erythroid 2-related factor 2,) seen as an activator of cellular defence mechanisms to induce the expression of a battery of cytoprotective genes and help repair mitochondria, induce mitochondrial biogenesis and activate Beta oxidation in the mitochondria to clear and transform fatty acids into ketone. Ketones like BHB beta hydroxybutyrate are a critical signal in the brain that upregulates Brain-derived neurotrophic factor, critical for neuroplasticity and brain health.

Support associated psychological damage


Deal with underlying metabolic damage- all the above ideally consider DNA analysis from Dr Valerio Vittone (PH.D) DNA of great importance in non-resolving symptoms.

DNA assessment can be invaluable. There is seldom- seldom only 1 mutation. More than 400 genes differentially expressed in long covid patients. Platelet and megakaryocyte gene sets seen in fatigue. Primary problems from our DNA appear to be in:


  • There is increasing DNA evidence that multiple mutations in the Toll-Like Receptors (especially “first responders” TLR2 and TLR4) play a large role in the individual immune response, and associated with “downstream” mutations can create a domino effect responsible for the individual problems being caused by Covid. These are common and look to provide directions for management in patients not responding to the first line mast cell blockade. The TLR2 and TLR4 mutations are currently being investigated

  • NLRP3 mutations look to play a major role in this neurodegenerative/inflammatory process as University of Qld researchers Woodruff et al demonstrated that SARS drives NLRP3 inflammasome activation in human microglia through spike protein.

  • Mast cells- membrane, HNMT, Dao enzyme function

  • TRP mutations- TRPM3 appears critical in NK (Natural Killer) immune cell function (Griffith CIFS research) and glymphatic function

  • COMT (impaired processing of catecholamines, 2 types, fast and slow COMT- clue is family history breast cancer, autism, ADHD, POTS/dysautonomia)

  • MTHFR, PEMT, CHKA and other methylation mutations

  • Oxidative stress and mitochondrial mutations eg eNOS

  • IL-6 and other Interleukins

  • APO E4, (and LPa also appears likely) in resistant cognitive impairment

https://www.mcmc-research.com/post/long-covid-part-2-dna-mutations-that-underpin-pots-and-long-covid-1


Watch for under-responders- low HS-CRP, Tryptase, C3- (research underway at present)·


Consider IV protocol for severe fatigue and possible addition of NMN for mitochondrial repair :

  • IV Vitamin C 15g with IV B dose in 100 ml Saline 1-3 times per week

  • Glutathione 500 mgs in 10 mls in 100ml saline bag weekly- Glutathione infusions- powerful antioxidant provides significant immune system support. Consider weekly x 3 or 4

  • B12 can be added in these periodically depending on the homocysteine (ideal below 7-8) and B12 (ideal 400+) levels

With IVs, if/when they plateau after a few weeks, until proficient chasing these -consider refer to Valerio for DNA. Valerio Vittone advice: “when the IV is most critical to do as a “reset” depending on the genetics so when they see Mitochondrial dysfunction of even “intermediate” nature they should consider DNA to validate IV with the genetics when possible”


LDN -for fatigue, TLR4 stabilisation, reducing small fibre neuropathy. (personal experience as no effective guidelines as yet available)

  • When effective, in combination with H1/H2 blockade, fatigue and brain fog usually lift at around 3 mg on average.

  • A significant percentage are having reactions, mostly sleep disorders but I have seen a serotonin syndrome when used with a tricyclic antidepressant- cause ultimately an adrenal adenoma. With a dramatic deterioration it can be another Covid infection.

  • A clue to potential poor responders so far are those that react adversely to antidepressants or H1/H2 blockade.

  • Start low 0.5 mg, maximum 4.5 mg, taken once daily, increasing weekly. Cease immediately if any side effects-common is insomnia- it may increase and hold or reduce dose. Sometimes change timing. Can reduce dose to 0.1 mg and go slower.

  • I cannot find anything more than observational studies on LDN, and it is being used liberally with few safeguards. —Information sheet for patients on website.

  • Beware of supplements they are taking esp SAMe – danger with anti-depressants, although it can be extremely beneficial and psychiatrists use it liberally in addition to other psychotropic agents. I believe should not be used unless skilled in its use.

  • Use with caution in bipolar disorder.

  • Consider referral to Dr Valerio Vittone who understands the complex interplay and how it potentially affects the body. SAMe may have positive benefits, best I can find is imported Klaire Labs SAMe 200mg (needs script in Australia and hard to source, but no script needed if imported)

If neuropathy present, diet is very important, along with mast cell blockade. TLR4 thought to be a major factor and LDN becomes very useful after initial stabilization with diet and H1 and H2 blockade. Then DNA to source the underlying metabolic defects. Assess traditional pathways –NAD/NMN, LDN and SAMe may be helpful. Clinical improvements with H1/H2/H4 blockade as above. At this stage hard to quantify what gives best relief, but my impression is that it is the H2 blockade with famotidine, but best results are found when used in combination.


Red flags includes :

  • lack of response within 4 weeks of mast cell blockade- look for other factors, especially for autonomic instability. POTS has mechanical drivers that require sorting.

  • If watching an elevated D Dimer that will not settle, check for inflammatory problems elsewhere driving this

  • Be wary of occult malignancy. Observational reports are of increased malignancy but as yet no published data

  • Sustained stress

  • Mechanical factors – may need to assess for POTS (ECG instability /NASA lean test).

  • Metabolic damage/ DNA mutations

Particularly when POTS / dysautonomia predominate my management starts with:


  • Desensitizing the “sensitization” that characterizes the underlying microglial activation -Link to protocol- this is an inexpensive regime based on the use of H1 + H2 blockade as used by Lawrence Afrin and cohorts, and this has been expanded in our clinic, using usually fexofenadine or cetirizine for H1 blockade twice daily and famotidine for H2 blockade at higher than normal doses, often up to 4 daily, adding H4 blockade subject to response. Low Dose Naltrexone is a H4 blocker, and clinically appears to reduce the cytokine response from TLR4 as well as having positive results with chronic fatigue. If pericarditis or other processes are occurring, the treatments are continued until the inflammatory response is subdued. Nigella Sativa has around a 30% significant improvement in symptoms when used alone, but best appears to be when used as an addition, studies currently assessing this against Krill Oil.Calming the autonomic instability (usually with acupuncture although some medication may be needed. 70% of Long COVID had autonomic dysfunction, and 30% of these have POTS, mostly undiagnosed (271)

  • Assessing persisting problems, eg most POTS have an underlying problem with their upper cervical spine, often with a thoracic outlet syndrome, or a MALS, and control these until desensitization is completed. Fatigue is the predominant problem but using mitochondrial “support” and appropriate supplementation, almost all can be recovered.- link to protocol

  • Recovery program. This is vital and needs to be paced to individual patients. Poor posture is a significant problem for most, aligned with phone and increased laptop use and deconditioning. This includes attention to diet and mitochondrial repair. All post-COVID needs a progressive return to physical activity and exercise as deconditioning causes deterioration- start assessment at 6 to 8 weeks post infection. Same as POTS deconditioning program -needs good exercise physiologist if there is significant impairment.

  • When using this simple mast cell blockade, either to prevent Covid-related disease, or to treat the fatigue and cognitive impairment, it comes with a warning that lack of improvement may represent more serious damage, and should be actively pursued.

  • As mentioned earlier, personalized DNA provides a pathway that helps in the management of those Long Covid patients that do not fully respond to the management protocols that we have put in place.


RACGP Recommended Management Guidelines(182) “The most common scenario: Non-specific multisystem post-viral symptoms


Common symptoms include:

  • fatigue

  • dyspnoea

  • joint pain

  • chest pain

  • cough

  • change in sense of smell or taste

  • cognitive disturbances

  • hoarse voice

Less common symptoms include:

  • insomnia

  • low-grade fevers

  • headaches

  • neurocognitive difficulties

  • myalgia and weakness

  • gastrointestinal symptoms

  • rash

  • depression”

The guidelines describe “Management of these presentations will usually be pragmatic and symptomatic. Management should be guided by the patient’s specific clinical circumstances and be evidence based. Specialist referral should be undertaken, as required.

  • Support your patient to maximise their personal wellbeing through diet, exercise and sleep.

  • Consider and exclude serious complications and possible alternative causes of ongoing symptoms, such as anaemia.

  • Investigate new or worsening symptoms that could indicate delayed sequelae, such as venous thromboembolism (VTE), cardiac complications or pneumonia.

  • Where possible, optimise the management of the patient’s other chronic conditions.

  • Identify other social factors that could intersect with their personal health and wellbeing, including smoking, alcohol intake, drug use, risk of mental health issues, risk of family and intimate partner violence, and risk of social isolation.

  • Consider current recommendations for management of specific symptoms

Breathlessness:

  • Optimise management of pre-existing respiratory conditions

  • Recommend respiratory muscle conditioning (pulmonary rehabilitation)

  • Consider chest X-ray at 12 weeks for patients who have had significant respiratory illness

  • Corticosteroids could be considered for inflammatory lung disease on the advice of a respiratory physician

  • Recommend gradual commencement or return to symptom-limited exercise guided by tertiary-trained exercise professionals

  • Referral to a speech pathologist for management of chronic cough, hoarse voice or dysphagia

  • Consider home pulse oximetry measurement

  • Referral to an Accredited Practising Dietitian if symptoms interfere with nutrition, and speech pathology if dysphagia is present

Fatigue:

  • Maximise self-care, sleep, relaxation and nutrition

  • Recommend that patients pace and be selective when prioritising daily activities

  • Recommend caution with return to exercise (reduce if there is any increase in symptoms)

  • A monitored return to exercise can be supported by an exercise physiology, physiotherapy or rehabilitation referral

  • If fatigue is causing difficulty with activities of daily living (ADLs), recommend energy conservation techniques and home visits by an occupational therapist or rehabilitation service

Chest pain:

  • Exclude acute coronary syndrome, myocarditis, pericarditis, pulmonary effusion or pulmonary embolism, and arrhythmia

  • Provide education regarding symptoms of concern

  • Patients who have had myocarditis or pericarditis as a component of their acute illness should abstain from vigorous exercise for 3–6 months, and athletes should have cardiology supervision for return to training

  • Refer for graded increase in low-to-moderate activity to increase mobility, exercise capacity and quality of life; this should be facilitated by a physiotherapist or exercise physiologist, or cardiac rehabilitation program

Headaches, low-grade fevers and myalgia:

  • Exclude COVID-19 reinfection or recrudescence

  • Prescribe simple supportive measures and analgesia or antipyretics, as needed

  • Check for secondary infections and prescribe antibiotics, as appropriate

Neurocognitive difficulty:

  • Provide supportive management

  • If severe enough to cause difficulty with ADLs, consider cognitive testing, occupational therapy support and speech pathology support for cognitive communication impairment

Depression/anxiety:

  • Provide information about post–COVID-19 recovery

  • Use existing standardised screening tools

  • Address multifactorial contributors that might require assistance with pain management, independence with ADLs, financial and other social supports, and loneliness

  • Facilitate access to mental health services or online support if patient is unwilling to access face-to-face counselling

  • Encourage individualised moderate-intensity exercise initiated and supervised by a tertiary trained exercise professional

  • Refer to an Accredited Practising Dietitian for nutrition support and access to food services

Thrombosis risk and contraceptive choice:

  • COVID-19 causes a hypercoagulable state in some people, which might worsen the VTE risk associated with combined hormonal contraception. The incidence of VTE in biological females of reproductive age with COVID-19 infection is currently not known

  • Patients should be advised of this risk to allow informed choice of contraceptive option

  • For biological females who have had mild or moderate COVID-19 and stopped oral menopausal hormone therapy, also known as hormone replacement therapy, if recommencing, consider using a transdermal preparation

  • For biological females who have had COVID-19 and who are taking oestrogen-containing contraception, manage these medications as per usual care

  • For biological females who have stopped or suspended contraception when they have contracted COVID-19, contraception can be restarted when acute symptoms have resolved(182)”

Traditional management of POTS


Traditional management, while sound and proven, unfortunately is limited in its effectiveness as it is based on symptom-management.


1. Established conservative/lifestyle measures

  • ·Avoid situations that can exacerbate symptoms

  • Large heavy meals

  • Alcohol intake

  • Heat exposure

  • Liberal intake of salt and water

  • Sleep with head of bed elevated—bed head raised 10 cm

  • Use of compression garments

  • Hose to top of abdomen

  • Abdominal binder

  • Physical counter manoeuvres

  • Leg crossing

  • Squatting

  • Drinking water before getting up in the morning

  • Strategies to avoid upright exercise

  • Seated rower

  • Swimming

  • Recumbent bike

2. Established therapeutics

  • Fludrocortisone (mineralocorticoid/aldosterone analogue- 100- 200 mcg mane

  • Midodrine (a1 agonist)- 2.5 to 10 mg tds

  • b blockers in hyperadrenergic state (metoprolol or propranolol)

  • Pyridostigmine (acetylcholinesterase inhibitor – cholinergic agonist)- 30- 60 mg tds

  • Clonidine (central sympatholytic)- useful in hyperadrenergic POTS or hypertensive response- 100 mcg twice daily

  • Ivabradine (IST and POTS)- 2.5- 10 mg bd


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