Long COVID in 2025: Latest Research, Symptoms, and Treatment Advances

By Editorial Team -
More than four years following the emergence of COVID-19, a subset of individuals experience persistent, multisystem symptoms extending beyond three months post-infection or post-exposure to mRNA-based COVID-19 vaccines. 

This condition, historically termed "Long COVID," has recently been redefined by some researchers as "Post-Spike Syndrome" (PSS) or "SPIKEOPATHY," emphasizing the pathogenic role of the SARS-CoV-2 Spike protein derived from both viral infection and mRNA vaccination. 

This article summarizes the most recent scientific findings and clinical advances to help patients and healthcare providers better understand and manage this complex condition.

Latest Research Insights on Long COVID

Immune System Markers and Genetic Risk Factors

A recent clinical study led by Cardiff Metropolitan University and Cwm Taf Morgannwg University Health Board identified elevated levels of the immune protein Interleukin-6 (IL-6) in people suffering from Long COVID compared to those who fully recovered1. The study also found that individuals with a particular IL-6 receptor genotype, known as the ‘AA’ genotype, have an increased risk of developing Long COVID. These findings suggest IL-6 and its receptor could serve as biomarkers to predict risk and guide future treatments.

Large-Scale Data from Electronic Health Records (EHR)

The RECOVER initiative analyzed over 6 million EHRs and found that between 10% and 26% of adults and 4% of children who had COVID-19 developed Long COVID2. Risk factors include being an adolescent or elderly, female sex, and hospitalization during acute infection. The data also showed that Long COVID incidence rises with the emergence of new SARS-CoV-2 variants, underscoring the ongoing public health challenge.


Common Symptoms of Long COVID in 2025

Long COVID symptoms vary widely and can affect multiple organ systems. Researchers have identified over 200 symptoms, but the most common and clinically relevant include34:

  • General: Fatigue, weakness, post-exertional malaise (worsening after activity), hair loss, pain, rash
  • Respiratory: Shortness of breath, chronic cough, chest pain
  • Cardiovascular: Chest tightness, heart palpitations, postural orthostatic tachycardia syndrome (POTS)
  • Neurological: Brain fog, memory loss, difficulty concentrating, headaches, dizziness, loss of smell or taste
  • Gastrointestinal: Abdominal pain, diarrhea, constipation, nausea, heartburn
  • Muscle and Bone: Muscle pain and weakness
  • Mental Health: Anxiety, depression, insomnia, psychosis symptoms
  • Others: Kidney problems, sexual dysfunction, abnormal movements
These symptoms may be ongoing, intermittent, or fluctuate in severity, making diagnosis and management challenging.


Advances in Treatment Options

Monoclonal Antibody Therapy

A promising clinical trial underway at Nova Southeastern University is testing sipavibart, a long-acting monoclonal antibody originally approved for COVID-19 prevention, as a treatment for Long COVID5. Early observational studies suggest monoclonal antibodies may reduce or eliminate Long COVID symptoms in some patients, offering hope for a targeted therapy.


Repurposed and Emerging Therapies

Several non-antiviral treatments show potential based on recent clinical evidence (6):
  • Metformin: Large phase 3 trials demonstrated a 42% to 63% reduction in Long COVID incidence when used early, making it a leading candidate for prevention.
  • Low-Dose Naltrexone (LDN): Shows significant improvements in fatigue, post-exertional malaise, and pain.
  • Dexamethasone: Reduces fatigue and shortens symptom duration by about 33%.
  • Omega-3 Fatty Acids: Moderate benefits for mental health and musculoskeletal symptoms.
  • L-Arginine with Vitamin C: High rates of symptom relief, especially fatigue and shortness of breath.
  • The COVit-2 trial, was designed to assess whether oral nicotinamide supplementation could influence recovery in newly diagnosed COVID-19 patients. Conducted across multiple centers in Germany, the study enrolled a total of 900 individuals who had recently tested positive for SARS-CoV-2. They were randomly assigned to take either nicotinamide or a placebo for four weeks, and their symptoms and progress were tracked for six months. Nicotinamide modulates gut microbial metabolic potential and accelerates recovery in mild-to-moderate COVID-19. Patients who had taken nicotinamide during the initial infection were less likely to report persistent long COVID symptoms, such as fatigue or difficulty concentrating. (7)
Other treatments under investigation include therapeutic apheresis, intravenous immunoglobulin (IVIg), N-acetylcysteine (NAC), and immunomodulators like anakinra (IL-1 receptor antagonist), fluvoxamine (SSRI with anti-inflammatory effects), and infliximab (TNF inhibitor).

How to Order Your Own Spike Antibody Test

You can order a Spike antibody (Covid-19 antibody) test from healthlabs.com to assess your risk and establish a baseline before and after starting any anti-spike protein protocol.

Another option is Attomarker's COVID Antibody Spectrum Test. Although the test is now available for sample collection in the US, the actual testing is still performed in the UK (United Kingdom). Please note that the test report takes about 2 to 3 weeks to arrive (X.com). The COVID Antibody Spectrum Test measures antibody levels & quality to Spike variants. Mapped with variant prevalence & your medical history, it offers insights into your immune profile, and has helped people with long COVID explore treatment pathways.

Looking Ahead

The complexity of Long COVID, with its multi-system involvement and varied symptoms, requires continued research and a multi-pronged treatment approach. Biomarkers like IL-6 and genetic factors may soon help identify at-risk individuals early, enabling preventive strategies. Meanwhile, ongoing clinical trials and real-world data analyses are expanding the arsenal of therapeutic options, bringing hope to millions affected worldwide.

If you or someone you know is experiencing persistent symptoms after COVID-19 infection, consult healthcare professionals for evaluation and management. Early recognition and tailored treatment can improve outcomes.


Sources:

  1. Cardiff Metropolitan University Long COVID Study, May 2025 1 
  2. RECOVER Research Update, June 2025 2
  3. Healthdirect Australia Long COVID Symptoms, Nov 2024 3 
  4. University of Washington Symptom Study, Oct 2023 4
  5. AstraZeneca Sipavibart Clinical Trial, May 2025 5 
  6. PMC Review on Long COVID Treatments, Nov 2024 6 
  7. Nature Metabolism Volume 7, Pages 1136–1149 (2025)


Related Peer Reviewed Articles and Studies:

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