What is Long Covid?
Long Covid is the range of new returning or ongoing health problems that people experience four or more weeks following SARS-CoV-2 infection.
There are more than 200 different symptoms, including:
- shortness of breath
- memory loss fatigue and nausea
- GI distress
- loss of sense or taste
How many people in the UK are affected by Long Covid?
- In the UK as of June 2022, the prevalence of ongoing long COVID following SARS-CoV-2 infection was 2 million people and still on the rise.
- 405,000 infected less than 12 weeks following SARS-CoV-2 infection
- 1,400,000 more than 12 weeks following SARS-CoV-2 infection 807,000 more than one year following SARS-CoV-2 infection
- 403,000 (21%) more than two years following SARS-CoV-2 infection
- All SARS-CoV-2 variants were involved, but omicron variant more than others
Therefore close to 1.2 million individuals still have Long Covid symptomatology from a year to two years after initial infection with SARS-CoV-2
Source: Immuno 2022, 2, 512–533. https://doi.org/10.3390/immuno2030033
What are the early factors that are detected in Long Covid?
- Presence of antibodies in the blood of long COVID patients:
- Antibody to receptor binding domain of spike protein; this antibody level correlated with acute disease severity
- Titers of antibody against EBV Early Antigen Detection and EBNA (Epstein Barr Nuclear Antigen) correlated with the disease
- Anti-nuclear antibodies as a result of tissue damage Anti-nucleolar (SSA, SSB, Sm, RNP, Jo-1) antibodies
- Anti-actin and mitochondrial antibodies
- Overall, notable connections between autoantibodies and hyperinflammation in long COVID are observed
Five major hypotheses about Long Covid
- Viral persistence in various tissues
- Reactivation of latent viruses, particularly EBV and HHV-6
- Multiple tissue damage and autoimmunity
- Disturbance in the gut microbiota and release of bacterial toxins that cause damage to the gut
- Multi-tissue damage and autoimmunity
Overall, viral persistence in various tissues, reactivation of latent viruses (such as EBV and HHV-6) can result in multiple tissue damage, gut dysbiosis, and damage to gut and blood brain barriers that may result in poly autoimmunity, and consequently long Covid.
1) Viral persistence in various tissues
When we get infected with SARS-CoV-2, five days later, 10 days later, we are well but that doesn't mean the virus is gone or remnants of the virus is gone. The virus still may be in the brain, GI tract, muscle and possibly everywhere in the body. This is called viral persistence.
2) Reactivation of latent viruses, particularly EBV and HHV-6
Reactivation of latent viruses, particularly EBV and HH-V six contributes to severity of Long Covid.
3) Multiple tissue damage and autoimmunity
Multiple tissue damage is caused by different variants of SARS-CoV-2’s direct damage to the tissue. Immune response against tissue antigens can result in autoimmunity.
4) Gut dysbiosis
Gut dysbiosis results in release of bacterial toxins. Bacterial toxins cause damage to the gut barrier and entry of unwanted molecules, including inflammatory cytokines into the blood, damaging the blood brain barriers, leading to inflammation in the brain
5) Poly autoimmunity
Due to the host’s immune reactions to the virus and to our self tissue antigens, poly autoimmunity involves many organs and tissues.
Exploration of each of the five major hypothesis about long Covid
The contribution of Epstein Barr to Long Covid
Research has proven that Covid-19 reactivates Epstein Barr virus, which contributes to Long Covid.
- 66.7% of long Covid subjects were positive for EBV reactivation based on positive titers for EBV EA-D IgG or EBV VCA IgM.
Source: Investigation of Long Covid Prevalence and its relationship to Epstein-Barr Virus Reactivation, Pathogens 2021, 10, 763. https://doi.org/10.3390/pathogens10060763
An awareness of the association between SARS-Cov-2 and EBV reactivation creates new opportunities for long Covid diagnosis that we can measure in the laboratory
The contribution of HHV-6 to Long Covid
Research has shown that Covid-19 reactivates HHV-6, which contributes to Long Covid.
- Viremia with EBV, CMV, and HHV-6 was detected in 28 (82%), 5 (15%), and 7 (22%) patients, respectively IgG or IgM antibodies against HHV-6 are detected at high levels in patients with long Covid
Source: High Incidence of EBV, HHV-6, reactivations in critically ill patients with Covid-19
- Patients with post-COVID manifestations presented with reactivation of EBV in 42.6%, HHV6 in 25.0%, and EBV plus HHV6 in 32.4%.
Source: Herpes Virus Infections and Post-Covid Manifestations: A Pilot Observational Study
The contribution of gut microbiota to long Covid
Post Covid-19, bad bacteria gets enraged, and good bacteria gets depleted. This depletion of good bacteria versus enriched bad bacteria, contributes to neurological fatigue, respiratory, gastrointestinal, and muscular skeletal tissue damage.
Therefore, we have to pay attention to some of the measurements associated with leaky gut and leaky brain syndrome.
The influence of poly autoimmunity
Autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.
- Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively.
Source: Autoimmunity is a hallmark of Post-Covid Syndrome
The earlier we detect the autoimmunity, the better we can help patients. This is because auto immunity has several stages.
If you suspect that there is an autoimmune picture emerging with Long Covid, it is advisable to run Immunoscience's Labs Auto Immune Panel Comprehensive.
The autoimmune biomarkers it analyses are:
ANA (Anti-Nuclear Antibodies)
These are antibodies that attack normal proteins in the nucleus of the body cells. Overall abnormal levels of ANA serve as a screening for many autoimmune diseases. High levels of ANA is detected in patients with rheumatoid arthritis, scleroderma, lupus, vasculitis, Sjögren’s syndrome, and mixed connective tissue disease (MCTD).
ENA (Extractable Nuclear Antigen)
These are antibodies that attack normal proteins called ribonucleoprotein or proteins that do not contain DNA. Elevated ENA can contribute significantly to the diagnosis and prognosis of a variety of connective tissue diseases such as scleroderma, polymyositis, Sjögren’s syndrome, and systemic lupus erythematosus.
dsDNA (Double Stranded Deoxyribonucleic Acid) Antibody
These antibodies are ANAs that target double stranded DNA. Autoantibodies to double stranded DNA are detected in different autoimmune disorders that include SLE, drug-induced lupus, MCTD, RA, scleroderma and Sjögren’s syndrome.
RF (Rheumatoid Factor)
This IgM antibody was the first autoantibody found in Rheumatoid Arthritis. It is produced by the immune system and works against our own IgG when it aggregates. Elevated RF is also detected in the blood of patients with parasitic diseases, liver disease, sarcoidosis, EBV and SLE.
Anti-Actin or Smooth Muscle Antibody
Actin is a major component of smooth muscle. Antibodies are usually directed against the actin component of the cytoskeleton. Anti-actin antibodies are found in 52-85% of patients with autoimmune hepatitis or chronic active hepatitis, and in 22% of patients with primary biliary cirrhosis.
The mitochondrial (M2) antigen is part of the pyruvate dehydrogenase (PDH) complex of tightly organized polypeptides and cofactors. Anti-mitochondrial antibodies are detected in patients with primary biliary cirrhosis. Certain chemical xenobiotics used in different cosmetics and as food additives share homology with PDH and mitochondrial antigen, and thus mitochondrial antibodies may also be detected in the blood of individuals exposed to these chemicals.
Circulating Immune Complexes (CIC) - Immune complexes are macromolecules consisting of antibodies bound to different antigens. They play a variety of roles in the activation and regulation of phagocytes. Circulating immune complexes that bind C1q complement are present in human serum in small quantities that are removed by the liver.
Advanced functional testing recommendations
To detect Long Covid, Dr Vodjani recommends testing for antibodies against EBV, SARS-CoV-2 and HHV-6, and in turn to assess for autoimmune reactivity and gut dysbiosis.
Long Covid Panel
The Long Covid Panel assesses antibodies against:
- SARS Cov-2
- Epstein Barr Virus
The Auto Immune Panel Comprehensive
As EBV and HHV-6, and SARS-CoV-2 cause autoimmunity, the auto immune panel comprehensive is recommended, as it includes:
- anti nuclear antibody
- anti extractable nuclear antigen antibody
- double stranded DNA antibody
- rheumatoid factor,
- immune complexes,
- smooth muscle
- actin antibody
- mitochondrial antibody
The Cyrex Essential Barrier Screen Panel
- Array 2 screens for intestinal antigenic permeability
- Array 22 analyses irritable bowel and SIBO
- Array 20 assesses if there’s a breakdown in blood brain barrier
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