Global Autoimmune Institute has stayed abreast of research on COVID-19 and its impact on those living with autoimmune disease. As the next phase of the pandemic unfolds and research on Long Covid gains traction, we would like to share answers to our most frequently asked questions regarding Long Covid and its connection to autoimmunity!

  1.  What is Long Covid?
  2.  What are the symptoms of Long COVID?
  3.  What causes Long Covid?
  4.  How can Long COVID be treated?
  5.  What treatments are under study?
  6.  What Long Covid research and clinical trials are underway?
  7.  Where can I find Long Covid resources?
  8.  What is the connection between Long Covid and autoimmune disease?


1. What is Long Covid?

Long Covid is the common name for prolonged illness occurring after COVID-19 as a result of infection. Long Covid is sometimes referred to as Post-COVID-19 Conditions (PCC) and Post-Acute Sequelae of SARS-CoV-2 infection (PASC); the umbrella term “Long Covid” does not yet have one standard definition.


 The CDC and NIH definition of Long Covid:

The Department of Health and Human Services states that “long COVID is broadly defined as signs, symptoms, and conditions that continue or develop after initial COVID-19 or SARS-CoV-2 infection. The signs, symptoms, and conditions are present four weeks or more after the initial phase of infection; may be multisystemic; and may present with a relapsing–remitting pattern and progression or worsening over time, with the possibility of severe and life-threatening events even months or years after infection”.


The WHO definition of Long Covid:

The World Health Organization developed a clinical case definition of post-COVID-19 stating that the condition is “the continuation or development of new symptoms three months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least two months with no other explanation.”



Post COVID-19 conditions are defined as “a wide range of health consequences that are due to all effects of COVID-19, including secondary and tertiary effectswhile Post-Acute Sequelae of SARS-CoV-2 infection (PASC) is “the direct and indirect consequences of SARS-CoV-2 on human health.” These definitions are functionally very similar, and which term is used depends on researcher preferences.

Prevalence & Duration

Long COVID is a new enough disease that it is not yet well understood. Current research suggests that around 22% of unvaccinated people who contract COVID-19 will have Long COVID symptoms six months after infection. About 18% still experience symptoms a year after infection, and 17% reported symptoms two years post-COVID. Fortunately, most people’s symptoms decrease in severity and frequency over time, though fatigue, loss of taste and/or smell, post-exertional malaise, difficulty breathing, and brain fog can persist. However, some people’s symptoms of Long COVID come and go, and others remain fairly steady over time


2. What are the symptoms of Long Covid?

Symptoms of Long Covid vary and often worsen after physical or mental exertionRecorded common symptoms include: 


Symptoms in Children

Symptoms may present themselves differently in children, and loss of smell and/or taste might result in loss of appetite. Brain fog may appear as a struggle with school. Many children are completely asymptomatic when infected with COVID-19 but can still develop Long Covid symptoms; this makes getting a diagnosis of Long Covid particularly challenging in this age group. For more information on Long Covid in children, check out this resource.


Diagnostic Criteria

The NIH RECOVER initiative recently published a study outlining proposed diagnostic criteria for Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Their system used 12 symptoms, each with a numerical value between 1 and 8. Patients with a symptom score of 12 or higher were classified as having Long Covid. See ‘Table 2’ below for their scoring system. 

Table 2 from Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection. JAMA. 2023;329(22):1934-1946. doi:10.1001/jama.2023.8823


3. What Causes Long Covid?

There are a variety of hypotheses about what causes Long Covid, but researchers do not yet understand the underlying mechanism that causes some people to develop Long Covid after a COVID-19 infection and others to recover. The persistence of the SARS-CoV-2 virus has been linked to Long Covid symptoms. Viral persistence occurs when the immune system does not fully clear the infection, and viruses are left in the body to replicate when they get a chance

Another hypothesis is that a COVID-19 infection reactivates other viruses present in the body, such as Epstein-Barr Virus, Human Herpes Virus-6, and Cytomegalovirus. These viruses are present in most healthy adult populations and don’t typically cause any symptoms. However, when SARS-CoV-2 infects someone, these preexisting viruses get a chance to replicate as well and can cause additional symptoms.

Autoimmunity as a cause of Long Covid has several mechanisms supported by research. Researchers have shown that the SARS-CoV-2 virus produces a protein that may be a superantigen. Superantigens are often able to evade an immune response and can cause overactivation of the immune system; it is thought that this overactivation can persist after infection, leading to an autoimmune response as well as Long Covid.

There is evidence that gut microbiome changes are associated with a typical COVID-19 infection and Long Covid. This is another possible mechanism for the autoimmune aspects of the condition.

Fibrin amyloid microclots have also been found in the blood of patients with Long Covid that contain pro-inflammatory molecules that are thought to contribute to Long Covid symptoms. The clots themselves decrease the blood flow through capillaries and thereby the oxygen reaching tissues, which may help explain the fatigue and muscle pain experienced by Long Covid patients. Within such clots there are proinflammatory molecules and antibodies which may decrease the speed at which such clots break down and contribute to the extended course of illness.

SARS-CoV-2 has been shown to infect the mitochondria of cells and lead to their dysfunction; this in turn can cause metabolic problems and excess inflammation, which are thought to contribute to Long Covid symptoms.

Risk & Protective Factors

Risk factors for developing Long Covid are not yet fully understood. Studies suggest that the severity of Covid symptoms, pre-existing health problems, female sex, hypertension, smoking, cardiovascular disease, diabetes, and obesity are all risk factors. A recent study found differences in symptoms of Long Covid among ethnicities/races, with Black patients at higher risk of headaches, diabetes, and pulmonary embolism and Hispanic patients at a greater risk of experiencing headaches and difficulty breathing. Another study assessed the prevalence of Long Covid and risk factors associated with Long Covid among pediatric COVID-19 survivors.

Having B+ blood is thought to be a protective factor. There is also evidence that vaccination for COVID-19 protects against Long Covid. Treatment with remdesivir is considered protective for hospitalized patients.


4. How can Long COVID be treated?

Treatment recommendations for long COVID typically follow a symptoms management approach. Different authorities’ recommendations vary slightly; however, all focus on individualized treatments specific to the symptoms of the patient. Doctors are advised to rule out other causes first, but not dismiss a patient’s symptoms if their vitals and labs appear normal.


Recommendations by organization:

Centers for Disease Control and Prevention (CDC)
Veterans Affairs (VA)
American Academy of Physical Medicine and Rehabilitation (AAPM&R)
World Health Organization (WHO)
National Institute for Health and Care Excellence (NICE)
Substance Abuse and Mental Health Services Administration (SAMHSA)

Recommendations by presentation of symptoms:

Anosmia and dysgeusia (loss of taste and smell)

The VA recommends smell/olfactory training as the main treatment for the loss of taste and smell. The olfactory training regimen outlined by the VA is as follows: 

Actively smell or sniff four familiar scents. Think about your memory of the odor while smelling the odor. In random order, sniff for a total of 20-60 seconds for each odor. Rest for 30 seconds between each scent. Sniff the four scents 2 to 4 times daily, each, for 24-36 weeks. Change the odorants used every 12 weeks. The stimulating smells used are often in commercially available smell kits [and] are often selected from major smell categories, such as aromatic, flowery, fruity, and resinous.


Unless there are other nasal symptoms (congestion, rhinitis), they do not recommend intranasal steroids; they recommend against the use of antibiotics and vitamin A drops.


The AAPM&R also recommends olfactory training, with the addition of mouth moisturization and referral to an ENT if symptoms persist for more than three months. The WHO also recommends olfactory training, but they are clear that there is little evidence of its efficacy, though also little risk.



Autonomic Nervous System Dysregulation

The VA and AAPM&R suggest treatment for POTS as such: hydration (64 oz of water daily), limiting alcohol, increasing sodium intake (between 3000-5000 mg daily), compression stockings, slowly getting out of bed, taking care when standing, small frequent meals, and biofeedback


The VA advises against strenuous activity in hot weather but encourages a gradual return to exercise, starting with recumbent activities such as rowing, swimming, and cycling and progressing to upright activities, walking, jogging, and using an elliptical. Working with a cardiologist, physical therapist, and occupational therapist may be needed


The AAPM&R suggests medication (low-dose beta blockers, fludrocortisone, midodrine, pyridostigmine, ivabradine, clonidine, methyldopa, modafinil, methylphenidate, SSRIs, or SNRIs) for patients whose symptoms do not improve with the measures outlined above


Chest Pain

Once other causes of chest pain (cardiac, gastrointestinal, etc.) have been ruled out, the VA recommends diaphragmatic breathing, stretching, and one or two weeks of low-dose non-steroidal anti-inflammatory drugs (NSAID). Working with a cardiologist, physical therapist, or chiropractor may also be needed



Fatigue and Activity Intolerance

The VA, AAPM&R, and WHO suggest a titrated return to activity and patient education on strategies for conserving energy. The VA also recommends dietary supplementation with B12, vitamin D, fish oil, and Cognitive Behavioral Therapy for insomnia and diaphragmatic breathing. Consults with physical therapy, occupational therapy, Cardiology, Pulmonology, and mental health can also be helpful.


Dyspnea (difficulty breathing)  

The VA and AAPM&R recommend supplemental oxygen and consultation with a pulmonologist if needed. The VA also advises working with cardiology, pulmonary rehabilitation, ENT or speech-language pathology, physical therapy, and/or occupational therapy. The Asthma and Allergy Association of America recommends focused deep breathing exercises, relaxation techniques, pulmonary rehabilitation, and consultation with a pulmonary or asthma specialist if symptoms persist.


Cognitive Impairment

The VA recommends diaphragmatic breathing, occupational therapy, and consultation with a neurologist. The AAPM&R recommends consulting with an occupational therapist, speech-language pathologist, and/or neuropsychologist. They also suggest counseling patients on sleep hygiene and gradually returning to activity and aerobic exercise. The WHO recommends cognitive exercises as well as environmental modifications to improve the ease of everyday activities. The SAMHSA recommends cognitive rehabilitation, cognitive behavioral therapy, metacognitive strategies, attention processing training, mindfulness-based stress reduction, and modifications to routines such as recording lectures and minimizing distractions.



The VA and AAPM&R suggest using albuterol as needed, inhaled corticosteroid (ICS), and ICS/long-acting beta-agonist (LABA) medications for two or three months. They also suggest hydration, expectorants, and other airway-clearing devices if needed. The VA also recommends diaphragmatic breathing. Consultation with a pulmonologist is recommended.



The AAPM&R recommends over-the-counter painkillers, acupuncture, relaxation therapies, deep breathing exercises, and biofeedback. They suggest supplementing with magnesium, melatonin, coenzyme Q10, riboflavin, and/or feverfew as a preventative measure. Referral to a neurologist is specified as important for managing migraines.

The VA suggests over-the-counter and/or prescription painkillers, hydration (64 oz. of water daily) as well as counseling on lifestyle factors such as sleep, exercise, and nutrition, regulating glucose, supplementing with Riboflavin and Magnesium Oxide, and diaphragmatic breathing. They also suggest referral to a neurologist if symptoms persist.


Mental Health (Anxiety, Depression, Obsessive Compulsive Disorders, Substance Use Disorders, Psychotic Disorders, PTSD)

The VA suggests patient education on stress management and sleep, guided meditation, and supplementation with fish oil. Antidepressants are not a blanket recommendation but should be considered in specific cases. They also recommend attending long Covid support groups (see ‘Where can I find Long Covid resources?’ section below). The WHO recommends psychological support, mindfulness, exercise, and support groups. The Substance Abuse and Mental Health Services Administration advises Individual and/ or group psychotherapy, peer support groups, and the use of SSRIs for certain patients with OCD or PTSD. They also advise referral to a psychiatrist



Swallowing Difficulty

The WHO recommends dietary modifications and swallowing exercises. The AAPM&R recommends referral to speech therapy.



5. What treatments are under study?

The FDA has not approved any drugs for treating Long Covid, but many are under investigation.


Thompson et al. suggest that “long-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.” Further clinical trials will be needed to determine the efficacy definitively. A recent study suggests that low-dose naltrexone can improve symptoms of Long Covid. Researchers found that the drug improved “6 of 7 parameters measured: recovery from COVID-19, limitation in activities of daily living, energy levels, pain levels, levels of concentration and sleep disturbance (p ≤0.001), improvement in mood approached but was not significant (p = 0.054).”


Though not helpful for those currently suffering from Long Covid, a recent study found that the drug 68 Metformin may help prevent the development of Long Covid in patients when given after COVID-19 infection. These study results are preliminary. 


Several other drugs and supplements have shown promise for treating the symptoms of Long Covid, including palmitoylethanolamide and luteolin (PEALUT) and vitamin D3 for loss of smell, ivabradine for heart palpitations, probiotics for fatigue, and Sulodexide for chest pain and palpitations

Vaccination against COVID-19 has been shown to lower the risk of developing Long Covid.



6. What Long Covid research and clinical trials are underway?

One of the main programs aimed at understanding long Covid is the government funded RECOVER initiative. Their website is continually updated with results of RECOVER studies. 


There are currently over 400 clinical trials related to Long Covid on the clinicaltrials.gov website. A few of particular interest are:


To find more studies to participate in check out:

NIH Long Covid Clinical Trials


MAYO Clinic

CDC Science behind Long COVID



7. Where can I find Long Covid resources?

Find Care

Currently, most patients with long Covid receive treatment from their primary care physician, though there are post-COVID care centers around the country where larger teams of specialists treat patients (https://www.survivorcorps.com/pccc). 


Enroll in a Clinical Trial

Interested in enrolling in a clinical trial for long Covid? Check out the CDC webpage, RECOVER initiative, clinicaltrials.gov website or the mayo clinic website.

Find a Support Group

The CDC has links to a few Long Covid support groups, including:


A group offered through the Mayo clinic: https://connect.mayoclinic.org/group/post-covid-recovery-COVID-19/


A list provided by Long Covid Support of support groups around the world


Long Covid Families has lots of resources, including a support group for families.



8. What is the connection between Long Covid and Autoimmune Disease?

While a COVID-19 infection has been shown to increase the risk of developing an autoimmune disease, the connection between Long Covid and autoimmune conditions remains unclear. However, symptoms of Long Covid are similar to those of many autoimmune diseases, and many Long Covid patients have rheumatic disease symptoms. At this point, autoimmune diseases have not been indicated as a risk factor for developing Long Covid.


COVID timeline updates related to Long Covid


Our articles related to Long Covid:

Patient-Powered Surveys Help Generate New Data About Long COVID

Understanding Long COVID

Global Perspectives on Long COVID

Is Long COVID a New Autoimmune Disease?

Global Autoimmune Institute Mini LogoThis content is accurate to the best of our knowledge, is for educational and informational purposes only, and is not intended as a substitute for advice from a qualified medical professional. Information shared on this page is not intended to serve as diagnosis, treatment, or prevention of disease. Seek professional medical advice regarding your medical condition or any symptoms you may be experiencing, and for best practices pertaining to your medical plan.


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