What are Dangerously High Ferritin Levels in COVID-19?

Contents

What is COVID-19?

Since 2019, the phrase COVID-19 seems to be everywhere. People, news, friends and families are all talking about it. So, what is COVID-19? And what kind of illness is it? 

Signs and Symptoms

Let’s start with the signs and symptoms of Covid-19. People with Coronavirus disease (COVID-19) can have several symptoms, ranging from mild symptoms to severe illness and death.1 Some might also have an asymptomatic or presymptomatic infection where they do not display any signs or symptoms consistent with the COVID-19 illness.5 Common symptoms of people with COVID-19 include cough, fever or chills, and difficulty breathing.1 Other possible symptoms are weakness, sore throat, loss of taste or smell and muscle pain.2 Symptoms may appear 2-14 days after exposure to the virus, according to the Centers for Disease Control and Prevention.3 The detrimental effect of Covid-19 might vary depending on the individual. Older people with underlying chronic illnesses, such as lung disease, heart failure and kidney disease, have a higher risk of developing more severe complications from COVID-19 compared to younger adults.4  

Cause

Covid-19 is an illness caused by coronavirus 2 (SARS-CoV-2). The COVID-pandemic has had a disastrous impact on the world’s demographics, resulting in more than 6 million deaths as of March 2022.5 SARS-CoV-2 may have derived from an animal coronavirus, specifically from a bat host, which eventually acquired the ability for human-to-human transmission.13 The first available data about COVID-19 suggested animal-to-human transmission from wild animals in Wuhan’s Huanan Seafood Market.19, 20 Later, emerging data demonstrated the transmission of the virus between humans through droplets and direct contact.21 Several reports suggest that people who did not have direct contact with Huanan Seafood Market were infected with COVID-19.21 SARS-CoV-2 mainly attacks the respiratory and vascular systems.5 Vascular systems refer to vessels that carry blood throughout your body. The novel virus spreads through coughs and sneezes.22,23 The novel virus is highly contagious, and initially spread like wildfire across the world following the December 2019 outbreak in Wuhan, China, forcing the World Health Organization (WHO) to declare a global pandemic on 11 March 2020.5,13  

Current Treatments

Currently, studies suggest various treatments to combat COVID-19, including antiviral medications and anti-inflammatory drugs.5 Antiviral medications are prescription medicines that fight against viruses in your body.33 Meanwhile, anti-inflammatory drugs are medicines that help relieve your pain and flu symptoms.34 The effectiveness of such treatments depends on the severity of the illness and certain risk factors.5 

Several potential treatments have been proposed, authorized and approved to combat COVID-19.One of these is Paxlovid, which is a combination of two antiviral drugs.5 Research by Mahase found that patients with severe COVID-19 who received Paxlovoid treatment within three days of symptom onset have an 89% lower risk of COVID-19-related hospital admission or death compared to patients without Paxlovid treatment.6 The FDA authorized the use of Paxlovid for patients with mild to moderate Covid-19.6

Another antiviral medication potentially used for Covid-19 treatment is Remdesivir.6 Several studies elucidated the effectiveness of Remdesivir in shortening the time for adults to recover from mild-to-severe Covid-19 compared to patients who received no Remdesivir.36,37,38 However, another study suggested that Remdesivir has no significant effect on COVID-19 patients’ mortality, recovery time or length of hospital stay.39

Dexamethasone is also one of the treatments that may be effective in treating Covid-19.5 In the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial, some hospitalized patients who have or are suspected of having Covid-19 received dexamethasone (n=2104) while others received the usual care (n=4321).35 The trial demonstrated the incidence of death to be lower in the dexamethasone group compared to the usual care group on oxygen support but not in patients receiving no respiratory support. 35

Finally, the most important way to contain coronavirus is by getting vaccinated.5 Clinical researchers created several types of vaccines to combat COVID-19, such as Pfizer, Moderna, and Novavax.5 Vaccination is crucial to trigger our body to defend against disease and illnesses. 5

What is Ferritin?

Ferritin is a protein that stores iron, delivering it when the body needs it.7 Iron delivery is an essential and tightly regulated process, ensuring our body gets enough iron.8 Iron is a vital element that regulates the production of red blood cells (haemoglobin) and the transportation of oxygen in our bodies.9 Too little or too much iron may result in several diseases.8 Iron deficiency can lead to iron-deficiency anaemia. Anaemia occurs when the amount of red blood cells in the blood is low.9  Several factors can lead to anaemia, including low iron intake.9 Similarly, too much iron, termed hemochromatosis, might affect several organs such as the liver, pancreas, heart, thyroid, joints and skin.8,10 People with hemochromatosis usually do not display visible symptoms until adulthood.10 Patients often do not get diagnosed until it affects several systems in their body.10 Therefore, getting your iron status tested is crucial. A ferritin test can help your doctor measure how much iron you have in your body. Serum ferritin can act as an inflammatory marker. Your doctor will measure your serum ferritin concentration, a widely used indicator,  to determine if you have iron deficiency or excess iron in your blood.11,12 

What Happens to Ferritin Levels During COVID-19?

Recent studies support the relationship between ferritin levels and the severity of COVID-19 illness.17 For example, a study by Bozkurt et al. found that ferritin levels were the only significant predictor determining the severity of the disease.14 In the study, patients with severe COVID-19 had a higher ferritin frequency than those with mild COVID-19.14 Another study by Zhou et al. demonstrated elevated serum ferritin levels in non-survivor patients of Covid-19 upon hospital admission and throughout the hospital stay compared to patients who survived the disease.15 Furthermore, Chen et al. found that 63 out of 99 patients with COVID-19 from Wuhan Jinyintan Hospital had a high serum ferritin level above the normal range.16 A study from New Orleans also revealed elevated serum ferritin in autopsies of ten patients who died due to COVID-19.18 Therefore, serum ferritin levels might be associated with the severity of COVID-19 disease. 

Is High Ferritin a Result of COVID-19 or a Mediator of it?

What is the Cytokine Storm in COVID-19?

First of all, what is cytokine? Cytokines are small proteins vital for the interactions and communication between cells in our body.24 They signal the immune system to do its job, which is to respond to health and disease in the body.25,26 Thus, cytokines play a vital role in protecting our bodies. There are several types of cytokines. One of them is pro-inflammatory cytokines. They play a role in producing inflammatory responses such as fever and protect our body from agents that cause disease.26

Cytokine storm also called cytokine storm syndrome(CSS), may occur when our body releases too many cytokines simultaneously into the blood.27,29 It can be harmful to our health.27 Cytokines storms are also characterized by the excessive activation of immune cells and the elevated amount of pro-inflammatory cytokines.30 If pro-inflammatory cytokines are produced in appropriate amounts, then the inflammatory responses are beneficial for our body. However, they can be harmful if they are produced in an excessive amount.26 An infection, autoimmune condition or other disease are some of the factors that can lead to a cytokine storm.27 Common signs and symptoms of a cytokine storm are high fever, inflammation (redness and swelling), severe fatigue and nausea.27 It can be fatal and lead to multiple organ failures.21, 27 Many studies have elucidated that some patients with severe COVID-19 might have cytokine storms. 28 It is hard to detect cytokines as they have a short life span and can be difficult to measure.43 Ferritin levels are possible markers widely used to detect cytokine storms.43

Does High Ferritin Cause it?

Several studies reported that patients with COVID-19 have a high level of ferritin and cytokines. A study also found elevated ferritin and cytokines in non-survivors compared to patients discharged from the hospital.15  The levels of ferritin and cytokines will increase as the patient’s condition worsens.15 Also, Liu et al. suggested that the frequency of ferritin and cytokines will decrease as patients start to recover, suggesting a relationship between the level of ferritin and cytokines.40  

There is a complex relationship between ferritin and cytokine. Research suggested that cytokines induced ferritin production, leading to inflammation that causes cell damage.32,42  Therefore, it can be concluded that high ferritin levels might be due to the accumulation of cytokines.31 However, another study also suggested a high level of ferritin might increase the production of pro-inflammatory cytokines.32, 41

What are the Implications for COVID-19 Therapy?

As mentioned before, one of the life-threatening outcomes of COVID-19 is usually accompanied by cytokine storm syndrome.28 Therefore, some COVID-19 therapy is specifically used to treat cytokine storms. However, the effectiveness of the treatment still needs further study. 

A study measuring the serum ferritin level as a marker for cytokine storm in Covid-19 patients found that their serum ferritin level was decreased when the patients were treated with Vitamin C and dexamethasone.42 The recovery rate of the patients was also found to be high.42 

Dexamethasone is used to lower the higher level of cytokines produced.5 It can also be administered to patients with Remdesivir.5  However, the National Institutes of Health (NIH) Covid-19 Treatment Guidelines Panel does not recommend that patients with mild COVID-19 take dexamethasone.5 It can be considered for patients requiring hospitalisation or oxygen support.5

Summary

COVID-19 illness is not just the ordinary flu. It has caused a pandemic and devastated communities worldwide. It could result in detrimental immune effects such as cytokine storms. Cytokine storms in COVID-19 patients are also associated with a high ferritin level. The relationship between the release of ferritin and cytokines is complex; the release of ferritin might trigger the release of cytokines and vice versa. If left untreated, it can be harmful to the patients. Thus, several treatments, such as dexamethasone, are specifically used to treat cytokine storms. 

References

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Author: Sentia Racha Keyulong

Bachelor of Science - BSc, Psychology, The University of Edinburgh, Scotland, Scotland

Sentia is an experienced Research Assistant and Medical Writer.

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