This article provides an overview of the condition hyperferritinemia, when iron stores in the body are high, posing a risk of organ damage. This is a common event after infections, including COVID, but often overlooked by primary care providers and cardiologists as it falls under the hematology category, but can be a factor in joint pain, irregular heartbeats, liver, kidney, thyroid and eye damage and more.

Updated February 20, 2024

Case Study

December, 2020. A 57 year old woman of average weight and height, with a history of suspected COVID-19 in February 2020 and preexisting hypoferritinemia (low iron stores) presented to cardiology with complaints of abnormal heart beats and mild chest pain for two weeks. Standard cardiac bloodwork was ordered, and ferritin was added at the patient’s request. Bloodwork revealed new onset hyperferritinemia. Holter monitor, stress test and echocardiogram revealed premature atrial contractions (PACs) and premature ventricular contractions (PVCs). Iron supplements were discontinued, and patient was referred to hematology for follow up.

Overview

Iron is an essential molecule used in the transportation of oxygen through the body. It’s found in the body in the form of “free iron,” which is then converted and stored in the form of ferritin. In the acute (contagious) stage of COVID, the virus thrives on iron and sugar, depleting iron and iron stores in the body. In an effort to protect itself, the body may sequester iron in the form of ferritin. In Long COVID, the mechanism to regulate ferritin levels can be disrupted, and some people develop ferritin toxicity. This condition can damage the organs, including the thyroid, heart, liver, kidney, adrenal glands and eyes.

Iron and ferritin toxicity in long COVID can affect the lungs, gut, heart, liver and kidneys, it’s role in inflammation, hyperinflammation, blood vessel wall compromise, coagulation (blood clots) and cytokine activation (cytokine storm). It can cause cell death by interfering mitochondrial function with oxygen absorption. It can also cause cognitive impairment (brain fog), neurological issues, cardiovascular events, agueusia (taste loss) and anosmia (smell loss). Ferritin toxicity can also affect the thyroid function, and un-absorbable iron particles can deposit in the joint causing pseudo gout.

Hyperferritinemia has not received a lot of attention in the medical world in relation to COVID-19 even though it has been shown to be associated with complications in other viral diseases. It can be associated with mortality and sustained inflammatory process. High levels of free iron are harmful in tissues, especially through the redox damage that can lead to fibrosis. During infection, increased ferritin levels represent an important host defense mechanism that deprives bacterial growth of iron and protects immune cell function. It indicates the need for therapeutic intervention, aimed at controlling inflammation in high-risk patients.

COVID-19 hyperinflammation (cytokine storm) results in systemic iron dysregulation.
Intracellular ferritin excess leads to ferroptosis (a type of cell death), coagulapathy (blood clotting), and tissue damage.
Iron-generated cellular and mitochondrial free radicles augment oxidative stress and inflammation.
Hyperferritinemia from damaged tissue leakage, predicts COVID-19 mortality risk.
Iron chelators may serve as promising therapeutic targets in COVID-19 management.

Resource: Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis? - ScienceDirect

Definitions

Hyperferritinemia is an iron overload state that can cause organ damage including the liver, heart, thyroid, kidneys, adrenal glands, brain and eyes.
Hereditary hyperferritinemia is called hemochromatosis, is caused by a faulty gene that is passed from parents to children. Most people don't experience symptoms until later in life, usually after the age of 40 in men, age 60 in women.

Symptoms

Early signs and symptoms often overlap with those of other common conditions. Signs and symptoms include but are not limited to:

Joint pain
Abdominal pain
Fatigue
cognitive impairment (brain fog)
Neurological issues
Ageusia (taste loss)
Anosmia (smell loss)
Weakness
Diabetes
Loss of sex drive
Impotence
Cardiovascular events
Irregular heart rate / Heart dysrhythmia or failure
Liver failure or elevated liver enzymes
Bronze or gray skin color
Memory fog, Brain fog, confusion
Vision changes / Cataracts
Hypothyroid
High cholesterol

Diagnosis

Your doctor can order a ferritin blood test to check a full iron panel and ferritin levels. Both should be checked to assess how much iron your body is absorbing and storing. If your numbers are clinically concerning, you will be referred to a hematologist for treatment.

*Note to Providers: Serum ferritin concentrations are often measured to investigate fatigue, possible liver disease, anemia, malignancy, or other conditions. Many clinicians interpret the serum ferritin concentration together with TS to determine if iron overload, iron deficiency, or subnormal iron mobilization for erythropoiesis is present. Thus, many clinicians rely on inferences made from TS measurements as an aid to the diagnosis of a variety of abnormalities.

Typical Treatment

This condition is usually treated by a hematologist. Iron chelation is the treatment for iron overload and has been proven to have an anti-viral and anti-fibrotic activity. Although phlebotomy therapy is effective in removing excess iron in hereditary hemochromatosis, chelation therapy is required in the treatment of many patients. The use of the oral chelator deferiprone remains controversial, and work is continuing on the development of new orally effective iron chelators.

Is hyperferritinemia curable?

Hyperferritinemia, the type seen in Long COVID, is treatable with chelation therapy or in mild cases, a low iron diet.

Hereditary hyperferrinemia is not curable, but can be managed medically.

Limit foods high in iron if you have elevated ferritin levels

Talk to your doctor

If you are concerned about any of the symptoms listed in this article, ask your MD to check a full iron panel, ferritin levels, a full thyroid panel including reverse T3 and reverse T4, Vitamin D, platelets, coagulation factors, liver & kidney function, lipid panel.

Things you can do to help yourself

Minimizing physical & psychological stressors is essential in recovery from Long COVID.

Nutrition: Try to eat protein and fresh vitamin rich foods daily and avoid chemicals, preservatives, sugars, fast foods, prepared foods and high histamine foods.
Don’t skip meals. Your body needs protein, vitamin C, and vitamin D to heal from any injury or illness. A low histamine or low carbohydrate (sugar) diet is recommended by doctors treating Long COVID (PASC), and many people report a reduction in symptoms within 1-3 days of the diet change, including decreases in sneezing, itching or hives, irritable bowel syndrome, body pain, along with a reduction in swelling and inflammation.
Hydration: A minimum of eight 8 oz glasses of plain water daily is recommended.
Avoid drinks with chemical additives. You can easily make a fresh electrolyte drink yourself by adding a dash of mineral rich Epsom salt and a piece a fruit like a raspberry for flavor instead of spending money on commercial drinks like Gatorade that contain chemicals and sit in plastic bottles for long periods of time. Remember that caffeine and alcohol have dehydrating effects.
Sleep hygiene: Getting 7-9 hours of sleep so your body can repair itself. You need at least 4 hours of uninterrupted sleep to get into the restorative phase of sleep.
Avoid stimulating activities after dinner like thrilling movies or books, arguments, negative news or frustrating stimuli.
If you wake up frequently or with a startle, you may be experiencing drops in your oxygen level, which signal your brain to release adrenaline to force you to take a breath. This could be a temporary inflammation issue or more enduring sleep apnea. Ask your doctor for a sleep study to evaluate your need for a CPAP or BiPAP, a machine that pushes air into your lungs when it senses an apneic episode (periods of not breathing).
Stress management: Stress effects every component of your life.
The only thing you can control about stress is your reaction to it. Try to avoid or minimize your exposure to stressful situations: Turn off the news, make family visits that end unpleasantly short, wait for the morning to have intense discussions, let go of things that annoy you but don’t really matter in the big scheme of things, avoid intense conversations or entertainment in the evening.
Exercise within tolerance: Pace yourself and do not push your body to extremes in any way.
For some this may mean seated breathing exercises, walking to the mailbox. Rest when your body says to slow down. Gradually build on your activity endurance as your body cues you to progress. This can be hard to gauge, because when you feel good you naturally do more, but if you do too much you may experience symptom flare ups 1-3 days later as the post exertion inflammation builds. Some people describe this as post exertional malaise, others experience severe recovery set backs.
Breathwork: You can literally stop the fight or flight reaction by taking slow deep breaths.
Deep slow breathing shuts down the adrenaline flow, slows your heart rate, lowers your blood pressure and decreases stress related histamine release. When you do this, your blood reroutes back to your brain and nervous system to allow you to think clearly. It also allows your body to use its energy and oxygen to heal your inflamed nerves and organs.

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