Treatment for Long Haulers Syndrome 2021

Up to 80% of patients experience prolonged illness after COVID-19. COVID long-haulers or 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. 

According to a study of Mayo Clinic patients who had COVID-19, about 75% of the people suffering long COVID symptoms — defined as persistent symptoms even six months after recovery — are women.

LHCS may persist 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. (RefRef)

Researchers are learning new details about the long-term effects of COVID-19. A study shows COVID-19 "long haulers" have a significantly higher chance of dying months after their infection.

According to the paper in Nature, COVID survivors have a 59 percent higher risk of death within six months of contracting the virus. 

Symptoms of Long Haulers Syndrome

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.


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. [Ref, Ref
• 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).[Ref

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/.

Diet and Nutrition

“Diet can be a source of inflammation, and whatever we can do to lower [inflammation] will allow the immune system to work better,” says Elizabeth Boham, MD, MS, RD, a functional-medicine physician and medical director at the UltraWellness Center in Lenox, Mass.

She recommends her patients limit their intake of refined carbohydrates and focus on whole foods rich in protein, fiber, healthy fats, and the micronutrients the immune system needs to thrive.

Supporting a good nutrient baseline is also key. “We see a significant amount of nutrient deficiencies and insufficiencies in the United States,” Boham says. Notably, insufficient levels of zinc and selenium are associated with worse outcomes from viral infections. Good sources of zinc include oysters, hemp seeds and pumpkinseeds, beans, nuts, and animal protein; sources of selenium include mushrooms, Brazil nuts, and seafood.

“Make sure you’re getting eight to 12 servings of phytonutrients a day from vegetables, fruits, spices, herbs, and tea,” she advises. Phytonutrients such as EGCG (epigallocatechin gallate, a polyphenol found in green tea) and curcumin (found in turmeric) can decrease inflammation and rebalance the immune system. 

N-Acetyl-L-Cysteine (NAC)

NAC is an amino acid that the body uses to create glutathione, the body’s master detoxifier. “Glutathione has a big impact on balancing the immune system,” explains Boham. “If we’re deficient in it, we’re more likely to get sick, and also to have a continued immune response.”

Eating plenty of cruciferous vegetables (such as kale, broccoli, and cabbage), as well as avocado, okra, spinach, and alliums, can help bolster levels of gluta­thione, as can supplementing with NAC. 

Aaron Hartman, MD, founder of the Richmond Integrative and Functional Medicine clinic in Richmond, Va., describes one patient, a 26-year-old woman, whose symptoms — persistent low oxygen and shortness of breath — following a bout of COVID resolved after treatment that included NAC as well as omega-3 fish oil.

“NAC is one of the more important nutrients for people who get shortness of breath with COVID, because of its ability to break down those really, really small blood clots called micro-emboli,” explains Hartman.

Vitamin D

Much has been written about the emerg­ing link between COVID severity and vitamin-D deficiency. A pilot study in Spain found that adding oral D3 supplementation significantly reduced the need for ICU treatment among people hospitalized after infection. 

Leo Galland, MD, a functional-medicine internist in New York City, recommends that people with long COVID supplement with up to 5,000 IU of D3 daily. Hartman advises aiming for a vitamin-D blood level in the range of 60 to 80 ng/mL.

Resveratrol

Resveratrol is a polyphenol with anti­oxidant and anti-inflammatory effects that’s found in red grapes, red wine, ­peanuts, and some berries. It’s also available as a supplement.

Galland has found it to be particularly helpful in restoring his COVID patients to health. “Resveratrol has a number of beneficial effects on coronavirus infection,” he notes. “It supports ACE-2 function, it inhibits the growth of the deadly MERS coronavirus through multiple mechanisms, and it diminishes the kind of inflammation associated with coronavirus infection.”

Galland treated a physician in her 60s who’d been sick with COVID for six weeks, continuing to run daily fevers with brain fog and fatigue. He prescribed a combination of herbs and supplements, including resveratrol, and her symptoms resolved within a couple of weeks.

He recommends long-COVID patients supplement with 200 mg of resveratrol twice a day.

Intermittent Fasting

Some functional providers believe intermittent fasting or time-restricted eating can help rejuvenate the immune system. Restricting feeding to shortened windows helps stimulate mitophagy (the removal of damaged mitochondria), Patrick Hanaway, MD, senior advisor to the CEO of the Institute for Functional Medicine, explains.

Fasting also supports the turnover of damaged cells throughout the body, making room for new, healthy mitochondria and cells to take their place.

Time-restricted eating can take a variety of forms. One of the most popular is simply eating all your day’s meals within an eight-hour window, then going 16 hours without food or calories. 

Probiotics

COVID can wreak havoc on the gut microbiome, but research on specific probiotic strains that can best restore balance following the syndrome’s particular damage is in its infancy. Galland is looking into soil-derived bacteria of the genus Bacillus because it may have natural antibiotic properties, though there’s not yet enough data to make specific recommendations.

Eating fermented foods, such as sauerkraut, yogurt, kefir, and kimchi, can help fortify and support the gut’s microbiome. And in the event of ongoing gut disturbances, working with a functional-medicine provider to design a well-rounded prebiotic and probiotic protocol can help bring the microbiome back into balance. 

Melatonin

Melatonin is an anti-inflammatory and antioxidant chemical our bodies produce to help regulate the sleep–wake cycle. It also supports the gut lining, which promotes healthy immune function.

Supplementing with 1 mg of melatonin at bedtime might benefit those whose sleep–wake cycles have become dys­regulated with long COVID.

Quercetin

Quercetin is a flavonoid found in dill, broccoli, onions, capers, apples, and berries. “Quercetin is a mast-cell stabilizer,” says Boham. “We use it with people who have allergies, asthma, and mast-cell issues.” (Mast cells, a type of white blood cell found in connective tissue throughout the body, produce allergy-related symptoms and can also be activated by SARS-CoV-2 infection.)

Quercetin appears to bind to the spike protein of the coronavirus, inhibit inflammatory pathways, and block replication of infected cells. It is also antiviral and completely safe, she adds.

In addition to emphasizing sources of quercetin in their diet, Boham says, long-COVID patients can supplement with 500 mg twice a day.

Other phytonutrients such as EGCG (epigallocatechin gallate, a polyphenol found in green tea) and curcumin (found in turmeric) can decrease inflammation and rebalance the immune system. 

Vitamin C

Vitamin C inhibits histamine. Healthcare professionals are administering vitamin C intravenously to deliver it directly into their patient’s bloodstream to be immediately available. Liposomal vitamin C is the next best option. It’s the most bioavailable form of vitamin C on the market today. The liposomal form can survive the digestive process to be up to 135% better than traditional oral vitamin C.

Long-COVID patients can supplement with vitamin C 500 mg twice a day. 

The Path Ahead

One of the pandemic’s few bright spots is the way it’s accelerated telehealth services. Patients now enjoy unprecedented access to a broad range of functional-medicine providers across the nation. (Find one near you — or one who provides virtual consulting — at www.ifm.org/find-a-practitioner.)


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