What is the connection between COVID-19 and mast cells?

Mast cells are a type of white blood cell that are found in the connective tissue and in every organ system throughout the body. Mast cells guard the doorways at the places where the human body comes into direct contact with the environment—the skin, respiratory system (airways), GI system, and more. They are also found in the brain.

Mast cells are part of our immune system and when they detect a germ or virus they become activated. When a mast cell becomes activated, it degranulates—crumbles—which starts an inflammatory response by releasing and setting free hundreds of different chemicals—called mediators—especially histamine. All of this protects our body from germs and infections.

Mast cells do a lot. They regulate the function of all sorts of different cells, organs, tissues. They play a part in the disease process of many illnesses.

Current research has shown that the COVID-19 process of infection is linked to an over-response of immune cells including mast cells (see here and here). The research has shown an elevated number of mast cells as well as significantly higher levels of specific chemicals indicating systemic mast cell activation in the people with COVID-19 who were studied (see here).

Current research has shown that mast cells are involved in COVID-19 and Long COVID (also called Post COVID), in their mechanisms of action, and in their symptoms (see herehere, and  here). COVID-19 and Long COVID come under the heading of environmental illnesses due to their involving airborne pathogens in the spread of the infection and, (as evidenced through the results of research studies), the emerging role of mast cell activation.

But what is Long COVID?

Long COVID (sometimes also called post COVID or post acute COVID syndrome or “long haulers”) is an array of symptoms that some people experience after having COVID. Many of the people who have had COVID develop a variety of mid- and long-term effects that include but are not limited to fatigue, breathlessness, and cognitive dysfunction such as confusion, brainfog, forgetfulness, physical pain, anxiety, depression, lack of mental focus and clarity. Symptoms can occur as part of a person’s initial illness or can develop after a person has had COVID and recovered—regardless of how severe or mild their case may have been. Symptoms can come and go, and can relapse over time (see here and here).

Recent studies have shown that as many as 50% of people who have had COVID-19, regardless of the severity of their COVID experience, have been reported to exhibit Long COVID symptoms even months after their COVID infection, presenting with symptoms such as brainfog, malaise, fatigue, joint pain, chest tightness, shortness of breath, “which are very similar to the symptoms observed in Mast Cell Activation Syndrome (MCAS) patients,” (see here).

What are Long COVID symptoms?

The most common symptoms of long COVID include:

  • Fatigue
  • Shortness of breath or difficulty breathing
  • Memory and/or concentration problems
  • Sleep problems
  • Persistent cough
  • Chest pain
  • Trouble speaking
  • Muscle aches
  • Loss of smell or taste
  • Depression
  • Anxiety
  • Fever

(see here and here).

When do Long COVID symptoms show up?

The symptoms of Long COVID can persist from a person’s initial COVID illness. They can also begin after a person recovers from their COVID illness, regardless of how mild or severe a case of COVID a person may have had.

Long COVID is usually diagnosed three months after a person has had COVID-19. The three month window allows for a person’s doctor or healthcare provider to rule out COVID’s normal recovery process as well as rule out any other medical conditions that could account for the symptoms. The symptoms themselves and their effects, however, need to have been present and lasting for at least two months (see here).

I feel terrible, I know something is wrong—but all my tests come back normal. Why?

It can be challenging for many healthcare professionals to recognize symptoms of a possible mast cell activation issue or disorder. It can be equally as challenging for healthcare professionals to know what tests to administer to screen for possible mast cell activation problems. These are disorders that appear to be without biomarkers and whose symptoms can be misleading because they often can include what seem to be prominent psychiatric complaints as well as strange or atypical physical complaints about multiple organ systems that don’t seem to respond to traditional treatments and interventions (see here).

An example of the challenge:

A person goes to their doctor with complaints of physical pain. They are experiencing pain that can often be severe in their hands, arms, sides, and legs. The pain can sometimes travel up their neck into their jaw. It can also include migraine or migraine-like head pain. Happening at the same time as the pain, the person complains of feeling tingling and numbness in the areas where the pain is present and all over their bodies—sometimes even when the pain isn’t there. This person has had COVID.

Typically, when a person presents with these types of pain, they will be sent to be checked by a neurologist. The neurologist will perform a neurological exam (also called a neuro exam.) Neuro exams evaluate a person’s nervous system and will assess many areas including motor skills, sensory skills, balance, coordination, mental status, reflexes, and the functioning of the nerves and nervous system.

The nervous system controls many parts of the body and includes the brain, spinal cord, 12 nerves that come from the brain, and the nerves that come from the spinal cord. If a person has a complaint of, for example, headaches, blurry vision, fatigue, changes in behavior, change in balance or coordination, numbness or tingling in the arms or legs, weakness, fever, tremor, slurred speech, seizures, a doctor might order a neuro exam to be done to see if there may be a problem with some aspect of the person’s nervous system (see here).

If the problem is not neurological and is a mast cell activation related issue, typically the results of the neuro exam will be within normal ranges. A neurological exam tests for neurological problems.

Mast cells communicate with nerve cells and several of the chemicals—histamine being one of them—released by mast cells when they are activated (and degranulate) modulate nerve fiber functions (see here). The symptoms of mast cell activation can appear highly similar to the symptoms associated with a neurological issue or disorder. However, the tests involved in a neuro exam typically do not include those for assessing for a possible mast cell activation issue or disorder (see here, here, and here).

Then what’s the difference between Long COVID symptoms and mast cell symptoms?

Current Research by Leonard Weinstock, MD, (see here) has shown a high prevalence of mast cell activation symptoms in Long COVID patients prior to mast cell activation syndrome (MCAS) treatment. Mast cell activation symptoms were found to be significantly increased in Long COVID.

The World Health Organization (see here) lists as Long COVID symptoms: fatigue, shortness of breath or difficulty breathing, memory and/or concentration problems, sleep problems, persistent cough, chest pain, muscle aches, brainfog, depression, anxiety, fever, and more.

The British Heart Foundation (see here) lists as Long COVID symptoms: fatigue, difficulty concentrating, shortness of breath or breathlessness, muscle aches, chest tightness or pain, muscle and joint pain, brainfog, headaches, dizziness, pins and needles, anxiety, difficulty sleeping, depression, ringing in the ears (tinnitus), feeling hot and cold, and more.

The Mast Cell Disease Society (see here) lists as mast cell activation symptoms: shortness of breath, fatigue, headaches, body aches, brainfog, cognitive dysfunction, anxiety, depression, abdominal pain, bone pain, muscle pain, light-headedness, fainting, chest pain, flushing, and more. Their listed potential mast cell triggers includes: stress (emotional, physical including pain, environmental); heat, cold, or sudden temperature changes; fatigue; exercise; sun/sunlight; and more.

The Mastocytosis Society Canada (see here) lists 58 different symptoms of mast cell activation/degranulation: joint pain, bone pain, headaches, numbness and tingling, cognitive impairment, chest pain, shortness of breath, neuropathic pain, unexplained anxiety, vertigo, persistent fatigue, ringing in the ears (tinnitus), temperature (hot/cold) sensitivity, and more.

What do I do?

If you feel that you may have a mast cell related issue or disorder, please contact a physician to receive medical help. The information presented here is not medical advice and is in no way a substitute for receiving medical advice and treatment from a doctor and mast cell specialist.