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PubMed This is a summary of 23 peer-reviewed journal articles Updated
Primary Care · Post-Acute Sequelae of SARS-CoV-2

Understanding Long COVID (PASC)

At a Glance

Long COVID, or PASC, can cause persistent or new symptoms after even a mild COVID-19 infection. Evaluation rules out other conditions, while care focuses on pacing, symptom-specific treatment, support for problems such as POTS, and carefully considered clinical trials.

If you are struggling with health problems months after a COVID-19 infection, you are dealing with a recognized clinical condition. Many patients feel dismissed or told their symptoms are “just anxiety,” but medical research has confirmed that Post-Acute Sequelae of SARS-CoV-2 (PASC), commonly known as Long COVID, is a complex multisystem disease with likely biological contributors that remain under investigation [1][2].

Defining Long COVID

Health organizations use specific timeframes to define this condition for research. The World Health Organization (WHO) research definition describes symptoms that usually begin within 3 months of the initial infection, last for at least 2 months, and cannot be explained by any other diagnosis [1][2]. However, you do not have to wait a rigid amount of time to seek clinical evaluation.

Importantly, you do not need to have had a “severe” case of COVID-19 to develop Long COVID [3]. It can follow mild or even asymptomatic infections [3]. Furthermore, a positive PCR or antibody test is not always required for a diagnosis if your clinical history strongly suggests a prior infection [4].

How Common Is It?

Estimates of how many people develop Long COVID vary widely—ranging from roughly 8% to nearly 40% of adults—depending on which definition is used and when the study was conducted [5][6]. These numbers vary because:

  • Definitions: Some studies count anyone with one lingering symptom, while others require multiple symptoms and functional impairment [6].
  • Vaccination: Evidence suggests that being vaccinated and boosted before infection may lower the risk of developing Long COVID [6][7].
  • Variants: Different versions of the virus (like Omicron vs. Delta) may result in different rates of long-term symptoms [5].

Proposed Research Hypotheses

Scientists are investigating several hypotheses for why symptoms persist. These remain active research areas, and different mechanisms may apply to subsets of patients:

  • Viral Persistence: The virus or “pieces” of it (proteins or genetic material) may remain in certain tissues. Detecting viral material does not establish replicating virus or causation, but it supports viral persistence as a plausible contributor [8][9].
  • Immune Dysregulation: The immune system may become overactive or “confused,” attacking the body’s own tissues (autoimmunity) or showing signs of chronic inflammation [10][11].
  • Microclots and Vascular Damage: Researchers are investigating whether endothelial injury and tiny, abnormal blood clots (microclots) contribute to symptoms. However, there is no validated routine clinical test for “microclots” and they do not have a universally accepted treatment pathway [12][13].
  • Mitochondrial Dysfunction: The “powerhouses” of your cells (mitochondria) may not be producing energy correctly, which is a proposed mechanism being studied for profound fatigue and “brain fog” [14][15].

Managing Your Symptoms

Currently, there is no single “cure” for Long COVID, so care focuses on managing specific symptoms and improving function [1]. Standard care often involves:

  1. Individualized Assessment: Your doctor should rule out other conditions (like thyroid disease or anemia) that could cause similar symptoms [16].
  2. Addressing Autonomic Issues: Many patients experience Postural Tachycardia Syndrome (POTS), where the heart rate jumps significantly upon standing. This can often be managed with specific hydration, compression garments, or specific medications, under strict medical supervision [17][18].
  3. Pacing and Energy Management: If you experience Post-Exertional Malaise (PEM)—a crash in energy after physical or mental effort—standard care emphasizes “pacing” to stay within your “energy envelope” and avoid flares [19][20].
  4. Experimental Treatments: Some doctors may discuss “off-label” treatments like low-dose naltrexone (LDN), which is being studied for its potential to reduce inflammation and fatigue, though large-scale proof is still developing [21][22].

Clinical Trials and Research

Clinical trials are research studies evaluating new interventions. They carry unknown risks and are not guaranteed treatments. Current trials are investigating:

  • Antivirals: Testing if drugs like Paxlovid can affect Long COVID symptoms [23].
  • Anti-inflammatories: Investigating if specific immune-modulating drugs can calm inflammation [21].
  • Neurological Rehab: Programs exploring cognitive exercises or brain stimulation (like rTMS) [NCT07278206][NCT06095297].

If you are interested in participating, review the risks, interactions, and eligibility with your clinician and search for “Long COVID” or “PASC” at ClinicalTrials.gov [NCT06511050].

Common questions in this guide

What is Long COVID (PASC), and how is it defined?
Long COVID, also called PASC, is a condition in which symptoms continue or develop after a COVID-19 infection and may affect several body systems. The WHO research definition generally describes symptoms that begin within three months, last at least two months, and are not better explained by another diagnosis. You should not wait for a rigid timeline before asking a clinician about persistent symptoms.
Can I develop Long COVID after a mild infection without a positive test?
Yes. Long COVID can follow a mild or asymptomatic infection, and a positive PCR or antibody test is not always required when your clinical history strongly suggests that you had COVID-19. A clinician will consider your history and evaluate other possible explanations for your symptoms.
What symptoms can Long COVID cause?
Symptoms vary, but commonly discussed problems include fatigue, brain fog, post-exertional malaise, a racing or rapidly increasing heart rate when standing, and dizziness. Symptoms can fluctuate and may interfere with work, social activities, or self-care. A clinician should assess new, severe, or worsening symptoms.
What treatment is available for Long COVID?
There is no single established cure, so care is tailored to the symptoms and focuses on improving function. Evaluation may include checking for other causes such as thyroid disease or anemia, while management can include pacing for post-exertional malaise and hydration, compression garments, or supervised medication for POTS. Treatment choices should be individualized with a clinician.
What does pacing mean for Long COVID fatigue?
Pacing means balancing physical, mental, and emotional activity with available energy so you stay within your energy envelope. It is used when exertion triggers post-exertional malaise, a delayed crash that can occur 12 to 48 hours after overexertion. A symptom diary can help you and your clinician identify limits and patterns.
How is POTS related to Long COVID, and how is it managed?
Postural tachycardia syndrome, or POTS, can cause a marked heart-rate increase after standing and may occur in people with Long COVID. Clinicians may assess symptoms and heart-rate changes with an appropriate stand test, while management may include individualized hydration, compression garments, and medication under medical supervision. Your clinician should also consider other causes of dizziness or rapid heart rate.
Are there clinical trials or off-label treatments for Long COVID?
Clinical trials are studying antivirals such as Paxlovid, anti-inflammatory or immune-modulating medicines, and neurological rehabilitation approaches including cognitive exercises or repetitive transcranial magnetic stimulation. These studies have unknown risks and are not guaranteed treatments. Off-label options such as low-dose naltrexone have limited or developing evidence and should be discussed with a clinician for interactions and monitoring.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is your experience in managing Long COVID or PASC, and do you work with a multidisciplinary team?
  2. 2.Based on my symptom history, which of the proposed biological mechanisms seem most relevant to my case?
  3. 3.Are there any routine tests, such as a 'stand test' for my heart rate or basic inflammatory markers, that we should perform to baseline my symptoms?
  4. 4.Can you help me differentiate my symptoms from other conditions like thyroid issues, anemia, or sleep disorders?
  5. 5.What are the risks, interactions, and monitoring requirements of trying 'off-label' treatments for my specific symptoms?
  6. 6.How can we monitor my progress, and what are the specific 'red flags' that should prompt an urgent visit?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (23)
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    Long COVID or Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) and the Urgent Need to Identify Diagnostic Biomarkers and Risk Factors.

    Parums DV

    Medical science monitor : international medical journal of experimental and clinical research 2024; (30()):e946512 doi:10.12659/MSM.946512.

    PMID: 39289865
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    Post COVID fatigue: Can we really ignore it?

    Sharma P, Bharti S, Garg I

    The Indian journal of tuberculosis 2022; (69(2)):238-241 doi:10.1016/j.ijtb.2021.06.012.

    PMID: 35379408
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    Considerations in Children and Adolescents Related to Coronavirus Disease 2019 (COVID-19).

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    Long COVID incidence in adults and children between 2020 and 2023: a real-world data study from the RECOVER Initiative.

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    Sleep and long COVID: preexisting sleep issues and the risk of post-acute sequelae of SARS-CoV-2 infection in a large general population using 3 different model definitions.

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    Intrinsic factors behind long COVID: III. Persistence of SARS-CoV-2 and its components.

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    Journal of cellular biochemistry 2024; (125(1)):22-44 doi:10.1002/jcb.30514.

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    Early biological markers of post-acute sequelae of SARS-CoV-2 infection.

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    Persistent Immune Dysregulation during Post-Acute Sequelae of COVID-19 is Manifested in Antibodies Targeting Envelope and Nucleocapsid Proteins.

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    bioRxiv : the preprint server for biology 2025; doi:10.1101/2025.08.18.670908.

    PMID: 40894595
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    Long-term SARS-CoV-2-specific immune and inflammatory responses in individuals recovering from COVID-19 with and without post-acute symptoms.

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    PMID: 34358460
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    Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches.

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    The Journal of clinical investigation 2022; (132(15)).

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    Tissue injury and leukocyte changes in post-acute sequelae of SARS-CoV-2: review of 2833 post-acute patient outcomes per immune dysregulation and microbial translocation in long COVID.

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    Journal of leukocyte biology 2023; (113(3)):236-254 doi:10.1093/jleuko/qiac001.

    PMID: 36807444
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    Plasma proteomics show altered inflammatory and mitochondrial proteins in patients with neurologic symptoms of post-acute sequelae of SARS-CoV-2 infection.

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    Longitudinal NMR-Based Metabolomics Study Reveals How Hospitalized COVID-19 Patients Recover: Evidence of Dyslipidemia and Energy Metabolism Dysregulation.

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    Clinical Characteristics of Patients Initially Suspected of Long COVID: A Case Series From a Specialized Outpatient Clinic.

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    Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know?

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    Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence.

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This Long COVID page is for informational purposes only and does not constitute medical advice. Speak with a clinician to evaluate your symptoms, rule out other conditions, and discuss safe treatment or clinical-trial options for your situation.

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