COVID-19 Long-haul Syndrome (Post COVID Syndrome): Symptoms, Treatment and I-RECOVER Protocol
Up to 80% of patients experience prolonged illness after COVID-19. LHCS (Long
Haul COVID Syndrome) is not only seen after the COVID infection but it is
being observed in some people that have received vaccines.
LHCS may persistent
for months after the acute infection and almost half of patients report
reduced quality of life. Patients may suffer prolonged neuropsychological
symptoms, including multiple domains of cognition. (Ref, Ref)
What are some common symptoms of post COVID syndrome? Their typical symptoms can include:
- Headaches
- Sleep difficulties
- Hair loss
- Smell disorder
- Decreased appetite
- Cognitive (ability to think) issues
- Erratic heartbeat
- Chest pain
- Fatigue
- Gastrointestinal issues
- Intolerance to physical or mental activity
- Low-grade fever
- Muscle and joint pain
- Shortness of breath
NB: A syndrome is not a disease. It’s a group of signs and symptoms that
may accompany more than one specific disease. In this case, the syndrome
affects some people who have contracted the virus that causes COVID-19 and
can mimic the symptoms of other, seemingly unrelated diseases.
In one Italian study, COVID-19 long-haulers experienced fatigue, shortness of
breath, joint pain, and chest pain, in that order. None of the patients in
that study had a fever after their acute illness had passed. However nearly
half of them reported their quality of life had suffered.
A puzzling feature of the LHCS syndrome is that it is not predicted by initial
disease severity; post-COVID-19 frequently affects mild-to-moderate cases and
younger adults that did not require respiratory support or intensive care.
[411] The symptom set of LHCS is in majority of the cases very similar to the
chronic inflammatory response syndrome (CIRS)/ myalgic
encephalomyelitis/chronic fatigue syndrome.[411] An important differentiating
factor from CIRS is the observation that LHCS continues to improve on its own
albeit slowly in majority of the cases. Another important observation is that
LHCS includes more young people compared to severe COVID that affects older
people or persons with comorbidities. Furthermore, the similarity between the
mast cell activation syndrome and LHCS has been observed, and many consider
post-COVID to be a variant of the mast cell activation syndrome.[413]
The LHCS syndrome in highly heterogenous and likely results from a variety of
pathogenetic mechanisms. The following theories have been postulated to
explain LHCS: [411]
1. Ongoing respiratory symptoms (SOB, cough, reduced effort tolerance) may be
related to unresolved organizing pneumonia (activate pulmonary
macrophages).
2. Monocyte activation syndrome. Persistence of viral debris in monocytes
results in an ongoing immune response in an attempt by the immune system to
clear the offending protein(s) and viral RNA fragments.
3. The neurological symptoms may be related micro- and/or macrovascular
thrombotic disease which appears to be common in severe COVID-19 disease.[414]
Brain MRIs’ 3 months post-infection demonstrated micro-structural changes in
55% of patients. [415] In addition, features of encephalopathy may be related
to encephalitis and auto-reactive brain antibodies [416] as well as severe
cerebral vasoconstriction. [417] The brain microvasculature expresses ACE-2
receptors and SARS-CoV-2 “pseudovirons” may bind to the microvascular
endothelium causing cerebral microvascular inflammation and
clotting.[418].
4. An unmasking of mast cell activation syndrome (MCAS), or triggering of mast
cell activation syndrome. Mast cells are present in the brain, especially in
the median eminence of the hypothalamus, where they are located perivascularly
close to nerve endings positive for corticotrophin releasing hormone.[419]
Following stimulation, mast cells release proinflammatory mediators such as
histamine, tryptase, chemokines and cytokines which may result in
neurovascular inflammation.[419] The “brain-fog”, cognitive impairment and
general fatigue reported in long-COVID may be due to mast cell related
neurovascular inflammation.
Clinical signs and symptoms can be grouped in the following clusters. The
reason for this grouping is to allow organ specific targeted
therapy/individualized therapy.
1. Respiratory: shortness of breath, congestion, persistent cough, etc.
2. Neurological/psychiatric: brain fog, malaise, tiredness, headaches,
migraines, depression, inability to focus/concentrate, altered cognition,
insomnia, vertigo, panic attacks, tinnitus, anosmia, phantom smells,
etc.
3. Musculoskeletal: myalgias, fatigue, weakness, joint pains, inability to
exercise, post-exertional malaise, inability to perform normal activities of
daily life (ADL’s).
4. Cardiovascular: Palpitations, arrhythmias, Raynaud like syndrome,
hypotension, and tachycardia on exertion.
5. Autonomic: Postural tachycardia syndrome (POTs), abnormal sweating.
6. GIT disturbance: Anorexia, diarrhea, bloating, vomiting, nausea, etc.
7. Dermatologic: Itching, rashes, dermatographia
8. Mucus membranes: Running nose, sneezing, Burning and itchy eyes.
FLCCC I-Recover Protocol
Given the lack of clinical trials of long-haul COVID-19 syndrome, these
recommendations are based on the abnormal changes within the body associated
with the COVID-19 disease and post viral illnesses along with the collective
experience of FLCCC members.
Approach to Treatment:
The treatment approach should be individualized according to the grouping of
clinical signs and symptoms. However, in general, it is likely that patients
who received inadequate antiviral treatment (ivermectin) during the acute
symptomatic phase and inadequate anti-inflammatory/macrophage repolarization
therapy (corticosteroids, statins, omega-3 fatty acids, fluvoxamine,
ivermectin, etc) during the acute phase of COVID are much more likely to
develop the post-COVID syndrome. In patients with ongoing respiratory symptoms
chest imaging is suggested (preferably a chest CT scan). Those with unresolved
pulmonary inflammation (organizing pneumonia) should be treated with a course
of corticosteroids (prednisone) and closely followed. A CRP should be
measured, and extended corticosteroids (titrated to the CRP) offered to these
patients. Similar to patients who have recovered from septic shock, [420] a
prolonged (many months) immune disturbance with elevated pro- and
antiinflammatory cytokines may contribute to the LHCS. This is likely the
consequence of monocyte activation syndrome and monocyte repolarization
therapy is therefore indicated. In addition, a cytokine panel may allow
targeted anti-inflammatory therapy (Maraviroc in patients with high CCR5
levels) . It should be noted that much like omega-3 fatty acids,
corticosteroids have been demonstrated to increase expression of pro-resolving
lipids including Protectin D1 and Resolvin D4.[421] An unknown number of
patients who have recovered from COVID-19 organizing pneumonia will develop
pulmonary fibrosis with associated limitation of activity. Pulmonary function
testing demonstrates a restrictive type pattern with decreased residual volume
and DLCO.[406] These patients should be referred to a pulmonologist with
expertise in pulmonary fibrosis. Anti-fibrotic therapy may have a role in
these patients, [380-383] however additional data is required before this
therapy can be more generally recommended. As discussed above, the serotonin
receptor blocker cyproheptadine may reduce the risk of pulmonary fibrosis.
[256]
How to treat COVID long haulers symptoms: FLCCC I-Recover Protocol
Although numerous reports describe the epidemiology and clinical features of
post-COVID syndrome, studies evaluating treatment options are glaringly
sparse. Indeed, the NICE guideline for managing the long-term effects of COVID-19 provide no specific
treatment recommendations. In general, while the treatment of ‘Long COVID”
should be individualized, the following supplements may have a role in the
treatment of this disorder.
First-line treatment based on the
FLCCC I-Recover Protocol.
- Ivermectin has been reported to have a role in the treatment of post-COVID-19 syndrome. A dose of 0.2-0.4 mg/kg day for 3-5 days, followed by once or twice weekly dosing for ongoing symptoms for up to 4 weeks. Discontinue after 2 - 4 weeks if all symptoms have resolved. A repeat course is recommended in those who respond poorly or relapse once the treatment is stopped. The anti-inflammatory properties of ivermectin may mediate this benefit.
- If inadequate response to ivermectin: Prednisone 0.5mg/kg daily for 5 days, 0.25mg/kg for 5 days followed by 0.12 mg/kg for 5 days. Patients with persistent organizing pneumonia may require higher doses for a more prolonged period of time.
- If presenting with neurological symptoms i.e. poor concentration, mood disturbance. Fluvoxamine 50 -100 mg day for 15 days. Monitor response closely as some patients will respond poorly to this medication. Teens and young adults who are prescribed fluvoxamine can experience acute anxiety which needs to be monitored for and treated by the prescribing clinician to prevent rare escalation to suicidal or violent behavior.
Supplements recommended to support the therapy
• Omega-3 fatty acids: Vascepa, Lovaza or DHA/EPA 4 g day. Omega-3 fatty acids
play an important role in the resolution of inflammation by inducing resolvin
production. [154,155]
• Melatonin 2- 5 mg at night (slow release/extended release) with attention to
sleep hygiene.
• Vitamin D3 1000-3000 u/day
• Vitamin C 500 mg BID (vitamin C inhibits histamine).[62]
Other Supportive Therapies
• Functional rehabilitation with light aerobic exercise paced according to
individual capacity.[411]
• Behavioral modification and psychological support may help improve
survivors’ overall well-being and mental health. [423]
Second-line approach (after poor response to first-line protocol) and
treatment of suspected mast cell activation
Choose a type 1 (loratadine or cetrizine) and type II antihistamine
(famotidine) along with a mast cell stabiliser (rupadatadine, quercetin or
luteoline).
Second line:
- montelukast 10 mg/day (for mast cell activation syndrome). Caution as may cause depression in some patients.
- SSRIs (selective serotonin reuptake inhibitors) e.g. fluvoxamine, fluoxetine (prozac).
Find health care providers (US): https://covidlonghaulers.com/.
COVID long haulers chances of dying
Researchers are learning new details about the long-term effects of COVID-19. A new study shows COVID-19 "long haulers" have a significantly higher chance of dying months after their infection.References:
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