Long-Covid
This page on long-Covid is important because long-Covid has many similarities to concussions and persistent post-concussion symptoms (PPSC). (Please refer to our page on PPSC.) Both long-Covid and concussions involve similar symptoms such as brain fog, trouble concentrating, fatigue, and more. They also result in inflammatory processes that may cause harm beyond the time frame of the initial illness or brain injury. In both, researchers are finding the elevation of the same biomarkers (markers of bodily injury).
We have in-depth information about symptoms, inflammation, and biomarkers in our section on Long-Covid in the Brain. Since the brain chemistry is similar, it’s possible that concussion treatment methods could be used with long-Covid patients, which is discussed below in Possible Treatments. Since long-Covid and concussions are similar, Concussion Alliance believes it is beneficial to dedicate a page to discuss them.
Table of Contents
What is it? | Common symptoms | Causes | Risk factors
Symptoms | Inflammation | Blood vessel damage | Tissue damage | Biomarkers
Managing expectations | Existing Treatments | Long-Covid treatment centers
Basics of Long-Covid
Disclaimer: Long-Covid is a recent illness. Some preliminary studies have been conducted; however, many are currently either in initial stages or in progress. It often takes 5+ years to complete a study and analyze its results. There is information on finding causes of long-Covid from studies in the What are the proposed causes? section. Multiple studies on this page have a small sample size and limited time, so they are considered incapable of producing conclusive results by researchers. Therefore, the information provided is tentative; however, it is as reliable as any information can be on long-Covid as of now.
What is Long-Covid?
Long-Covid is best described as having persistent symptoms or newly-onset conditions resulting from a past Covid-19 infection. According to the CDC, long-Covid is identified when symptoms persist for at least four weeks following the initial Covid-19 illness. Researchers have categorized long-Covid as patients being symptomatic from three weeks to over a year. Hence, the studies we reference have variability in how they identify long-Covid.
Long-Covid takes many different names. We chose to use ‘long-Covid,’ as it is the most frequently used to speak about the illness in the general public. While an initial (acute) Covid-19 infection has a relatively short symptomatic period, symptoms of long-Covid last, in many cases, for months after the initial Covid infection. Patients with long-Covid may have symptoms continuing from or showing up weeks after the acute phase.
Long-Covid is an invisible injury (like a concussion), with the injuries being in the brain or immune system. Since the damage cannot be physically seen, some physicians and members of the general public are questioning its credibility, causing treatment problems. However, long-Covid is a severe problem affecting many people that should be given attention and resources to resolve.
What are some common symptoms?
The symptoms of long-Covid vary – some are seen more frequently – but often include fatigue, trouble breathing, and brain fog. Brain fog is a condition in which a person may have difficulty concentrating, remembering or performing tasks, and it is also seen in concussion patients. There are other symptomatic similarities between long-Covid and prolonged or persisting concussion symptoms. The symptoms shown below are some of the more common signs of long-Covid.
A significant change in
Sleeping patterns
Taste
Smell
Digestive system
Menstrual cycle
Mental health
Any other system
Fatigue
Breathing problems
Pain within the chest
Persistent cough or cold-like symptoms
Lightheadedness or headaches
Cognitive impairment
We have listed only a few of the most common symptoms. However, there are over one hundred symptoms of the illness. As noted in this article, one international study found 203 symptoms of long-Covid in over 7,000 patient survey responses. In the United Kingdom, a tool using patient-reported symptoms was created with patient help; the tool is helping to create better objective tests for diagnosing long-Covid.
Long-Covid is also common, as the CDC states nearly one in five American adults with Covid-19 developed long-Covid.
What are the proposed causes?
A note about studies and finding causes of long-Covid from studies: Causation, proving something causes something else, is difficult to do in studies such as those done with long-Covid. However, studies can find correlations, or associations, between a proposed cause of long-Covid and the prevalence of long-Covid, which is what researchers look for. This correlation does not mean that something causes long-Covid, but something is a potential cause.
Three possible causes
The American Medical Association (AMA) has proposed three possible causes of long-Covid:
Viral remnants of the RNA from Covid-19 remain for a prolonged period in the body.
RNA fragments are pieces of code that are used to make proteins. DNA provides instructions that the RNA reads and makes proteins from; the proteins created with this process are essential to bodily functions.
The body attacks itself following infection.
The body attacking itself is called autoimmunity, which can happen due to changes to the immune system.
Changes to the body’s natural microbiome after infection can cause drastic changes to how the body reacts to the environment.
The microbiome includes a complex set of microorganisms, such as bacteria. They live all over the body, but most of them are in our gut, helping digestion.
Microclots and RNA remnants
In a Science article, researchers reported blood clots and damage to tiny blood vessels in the lungs are causing long-Covid patients’ breathing problems. However, these clots are quite small (called microclots), so they are challenging to detect with imaging. It could be possible that Covid causes microclots in the brain, which lead to cognitive issues such as brain fog.
The Science article mentions a preliminary study that found viral RNA remnants of Covid-19 in respiratory and cardiovascular tissue in almost all of the study’s 44 participants – along with remnants in many other types of tissue (including lymphoid, endocrine, and brain tissue). The study suggests that RNA remnants could contribute to long-term symptoms; however, these findings have not been peer-reviewed or published. Some other studies with fewer participants have found the same RNA remnants.
Immune system changes
There is also evidence that, following infection of Covid-19, the immune system has changed. Specifically, there is an increase in systemic inflammation. Levels of some cytokines (proteins involved in the immune system) are significantly increased in long-Covid patients compared to acute Covid patients. This increase in cytokines was also seen by Allison Grossberg, a Ph.D. student at the University of Denver working on a long-Covid study. She says, “In [Covid] patients who are hospitalized, they have this really strong inflammatory response to viral infection, and those cytokines do a lot of damage. And so you end up with basically your immune system kind of going haywire, and it's not really able to shut off. And then your own immune system is damaging your tissue.”
Microbiome changes
Recent studies have found that changes in the microbiome are correlated with long-Covid. One study found that 19 oral bacteria species were elevated in patients with long-Covid compared to acute Covid patients. Another study found that patients with long-Covid have different gut microbiota than those without Covid. The gut microbiome differences included either significantly greater or fewer amounts of different types of bacteria. This result did not vary significantly if the patient was on antibiotics or not.
One study compared patients with Covid to healthy controls and found that both oral and gut microbiomes were significantly different between the two groups. Some studies have been conducted on lung microbiota; however, they provide varying results about whether lung bacteria changes with long-Covid. Researchers are still working on finding viable treatment options for resetting and replenishing the microbiome.
What are some potential risk factors?
If you do not get infected with Covid, you cannot get long-Covid, so the best way to not get long-Covid is to use preventative measures that reduce your chance of Covid infection. Some measures include getting vaccinated and boosted, wearing a mask, and washing or sanitizing your hands. One study found that getting vaccinated and boosted leads to lower rates of long-Covid infections in a cohort of 2,560 healthcare workers in Italy.
Currently, Omicron’s subvariant, BA.5, is causing the most Covid cases, and travel could be one of the causes of the spike in cases, especially with mask requirements lifted (the CDC still recommends wearing one while traveling). However, BA.5 is also highly transmissible, making it easy to spread.
The BA.5 variant has evolved spike proteins that are harder to recognize by the body’s immune system. People who are vaccinated are protected against the unevolved spike proteins of the earlier variants but not against the BA.5 spike proteins. Spike proteins are unique ‘keys’ that are located on the outside of the Covid virus. Spike proteins, given time, can change what they look like, which is what happened with the Delta and Omicron variants. The video in this section has more information about this change to the spike protein. The more evolved the Covid virus and spike protein gets, the greater the chance of being infected.
There are some groups of people who are more likely to get long-Covid. According to the CDC, older adults are less likely to have long-Covid than younger adults. Nearly three times as many adults ages 50-59 currently have long-Covid than those age 80 and older. The CDC also states that almost 9% of Hispanic adults currently have long-Covid, higher than non-Hispanic White (7.5%) and Black (6.8%) adults and over twice the percentage of non-Hispanic Asian adults (3.7%). The AMA finds that children are less affected by long-Covid than adults are.
Long-Covid in the Brain
Related symptoms
Since long-Covid is such a recent illness, researchers are not clear about what exactly is causing its symptoms. However, it is theorized that brain damage could be one of the causes of symptoms. Some long-Covid symptoms that may be brain-related include
Brain fog
Headaches
Changes in sleep, smell, taste, or mental health
These symptoms might be caused by various sources of Covid damage that may affect the brain directly or indirectly, such as inflammation, blood vessel damage, and tissue damage, but researchers are not entirely sure. For comparison, concussions also trigger an inflammatory response. Researchers are working to develop viable blood-based biomarkers for concussions; some potential biomarkers they are studying for concussions may eventually be effective in diagnosing long-Covid.
Inflammation
Covid results in an inflammatory response in the central nervous system, which includes the brain and spinal cord. A healthy inflammatory response is triggered to fight off infection and involves the activation of microglia, cells that destroy unwanted things in the brain. With Covid, researchers are finding the microglia are behaving abnormally, and there is an increase in cytokines, molecules that regulate inflammation.
Increased cytokine release can harm the immune system and abnormally behaving microglia may be destroying neurons— which could be contributing to the feeling of brain fog. Essentially, the microglia and cytokines are harming neurons and the protective layer (myelin sheath) of neurons, so the brain is getting damaged. Researchers found this in mice and then did another analysis with humans to test whether humans have the same inflammatory response. They found that Covid patients with cognitive difficulties, such as brain fog, had a greater number of cytokines than Covid patients without cognitive difficulties. The same inflammatory response, release of harmful cytokines and activation of microglia, is seen in patients with concussions due to the inflammation from the head/body impact.
Treatment of inflammation can be difficult since “inflammation is a really good thing acutely. And with both injury and viral infection, the time course looks different for everyone. So variability really is the rule, not the exception. It's really hard to know when you would give someone a drug that would decrease inflammation,” according to Allison Grossberg.
Blood vessel damage
A study found damaged blood vessels in some brains of patients who had passed away due to Covid. The researchers identified microvascular injury (small, injured blood vessels) in their brains. In these areas of injury, there were lesions and fibrinogen leakage. Lesions are areas of damaged tissue, which could be a product of damage to parts of neurons (brain cells). Fibrinogen is a protein that induces clotting in the blood, which helps restrict the blood flow in injured tissue. However, fibrinogen in the brain could mean the blood-brain barrier (BBB) is compromised or leaky.
The BBB needs to stay intact to protect the brain from harmful immune cells that could damage neurons. The brains in the study also had activated microglia (cells that destroy unwanted material in the brain) around neurons, indicating that the microglia are trying to harm the neurons. The study found severe damage to the patients’ brains; however, the study’s small sample size and extreme sample population (patients who have died of Covid-19) limit the clinical relevance of the findings.
Tissue Damage
A study looking at Covid-positive patients found changes in brain structure, including a thinner gray matter layer, greater signs of tissue damage in olfactory regions, and a smaller overall brain size. The researchers also found that Covid-positive patients had an increased time to complete tasks compared to participants who tested Covid-negative. Gray matter is a layer of neurons in the brain's outermost layer. It is essential to retain memories, motor control/balance, respond to stimuli, and other functions. If damaged, it could result in difficulty with motor control or cognitive difficulties. Covid also damages olfactory (smelling) regions, particularly injury to neurons and small blood vessels. This damage could be contributing to problems with smell and taste. Smaller brain size was also found, even in mild Covid cases. The increased time to complete tasks could be due to the overall tissue damage.
Biomarkers
Biomarkers are biological markers that provide information about what is going on in a cell or organism. One example of a blood-based biomarker, the type that researchers are primarily focused on, is blood glucose (sugar). Researchers are working towards identifying biomarkers that will detect if a person has a concussion. Please refer to our blog post with Allison Grossberg to learn more about these.
Similarly, biomarkers may also someday be used in diagnosing and treating long-Covid. Currently, researchers are finding elevated biomarkers that indicate neuronal injury and injury to other supporting brain cells (glia and astrocytes) in hospitalized Covid patients compared to healthy controls. The elevated levels of biomarkers in these Covid patients were also greater than the biomarkers in patients with mild cognitive impairment and Alzheimer’s disease. This distinction is important because the biomarkers could potentially be an objective way to correctly diagnose patients with long-Covid.
In concussion patients, the biomarkers GFAP, NfL, and UCH-L1 could potentially be used for concussion diagnostics or prognostics since they may indicate inflammation or damage to brain tissue. However, researchers still need to do more research to determine if these or other biomarkers may be helpful. There is more information on these in various blog posts linked below, in Extra Resources.
Possible Treatments
While Concussion Alliance has resources for long-Covid because of its neurological similarities to concussions, we recommend finding the most up-to-date information from a reliable source such as the CDC. If you need help understanding and learning to live with your long-Covid, we recommend Body Politic and Survivor Corp— both organizations have support groups. Survivor Corp has a page with guidelines for best practices for Post-Covid Care Centers and an interactive map that links to Post-Covid Care Centers by state.
With Covid-19, every case is unique in its signs, symptoms, and treatment— and long-Covid is no different. It may be hard to explain to friends and family how long-Covid affects you because it is an invisible injury. Visit our page on invisible injuries to learn more about how others work towards treatment and keep a positive mindset.
Managing Expectations in Treatment
It is important to note that all treatments listed are not in any way a cure for long-Covid. These treatment methods are all being tested to help relieve the worst parts of the condition, and researchers and clinicians are trying to understand the most successful treatments. A typical long-Covid patient will have symptoms of long-Covid for months and, in some cases, even over a year, so it is vital to manage expectations for healing and treatment. It is essential to take the treatment process one step at a time and to celebrate small progress, similar to recovering from a concussion.
Cognitive Behavioral Therapy
Cognitive behavioral therapy or CBT is a type of psychological therapy that aims to help the patient develop their own coping skills and has been described as “teaching the patient to be their own therapist.” One promising study is the Covid Mind Study at Yale, which will study long-Covid patients for five years after their acute Covid-19 infection. Dr. Spudich, a lead researcher in the study, has stated that he has “seen improvement” in patients who receive CBT. In an article for the Wall Street Journal, Dr. Spudich says that CBT is “not solving the underlying problems but helping them develop tricks and techniques to manage things that they’re having trouble with.”
Graded Exercise Therapy
Graded exercise therapy (or graduated exercise therapy) is a form of therapy that has been proven effective in treating concussion patients. Graded exercise therapy involves a treadmill (or stationary bicycle) test that pushes the patient to the point of exercise where symptoms become present and measures the heart rate at this stage. Then, the physical therapist will plan future workouts to improve that symptomatic limit by performing an exercise just below the symptomatic range. While there is limited and conflicting research on how this can be applied to treating long-Covid, some researchers warn to stay away from any graded exercise therapy as it could set a patient back in their recovery.
Rehabilitation
Rehabilitation is generally the most recommended and widely used treatment for those diagnosed with long-Covid. Rehabilitation clinics (like those targeting concussion) typically include physical therapy, occupational therapy, speech therapy, rehab psychology, and vocational rehabilitation. The easiest way to find out which forms of rehabilitation best suit you is by visiting a long-Covid rehabilitation or treatment center.
Acupuncture
Acupuncture has shown positive results in those dealing with the symptoms of long-Covid. One study states, “Medical acupuncture can shorten posthospitalization recovery time, improve symptoms, and influence many of the causes of Long-Covid.” Acupuncture has been proven to reduce stress, promote healthy sleep, and support viral immunity. The study also notes that recovering from long-Covid is difficult because of how complicated the condition is. See our resource on acupuncture for additional information.
What are long-Covid treatment centers?
There are many long-Covid treatment centers that are popping up across the United States. If a person is experiencing disabling symptoms of long-Covid, it is likely that the primary care physician will refer the patient to a long-Covid treatment center. Considering long-Covid is a relatively new condition, there is little research surrounding the best treatments, but some treatment centers have demonstrated success in alleviating symptoms.
If you are interested in visiting a long-Covid treatment center, there is a helpful article on Becker’s Hospital Review website that lists some of the most prevalent treatment centers in the United States. Survivor Corp lists Post-Covid Care Centers by state.
Extra Resources
In this interview, Allison Grossberg talks about her current study about long-Covid and its connection to brain injury. She discusses her personal history, the background of the study, a potential treatment option, the usefulness of biomarkers in long-Covid diagnosis and other applications, and the connections between long-Covid and concussions.