John J. L. Jacobs
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  • Nederlands
  • Resume
    • Science
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  • COVID-19
    • Herd Immunity Re-Revisted
      • 1 About herd immunity (HIRR).
      • 2 Three failed attempts.(HIRR)
      • 3. Calculate the costs (HIRR).
      • 4. Incomplete immunity (HIRR).
      • 5. What could possibly go wrong? (HIRR)
      • 6. How should we act? (HIRR)
      • 7. In brief. (HIRR)
    • Simple & complex
    • Epidemic Control
      • Epidemic Control Addendum
    • Summary Two years of COVID-19
    • Two years of COVID-19
      • I. Healthcare threat
      • II. Deceptive virus
      • III. Morbid tales
      • IV. Antivirus immunity
      • V. Stop the outbreak
      • VI. Dark and light reflections
      • VII. Looking forward
    • Humanitarian
    • Questions
      • Disease
      • Vaccines
      • Immunity
      • Epidemics
      • Mutation
      • Politics
    • Virus ethics
      • Transparency
      • Strife
      • Beyond Mortality
      • Special immunity
      • Vaccination
      • Prevent contamination
    • Non-sterilizing immunity
    • Immune responses and vaccines
      • Calculation of infection fatality rate
      • Various Immune responses
      • Different vaccines
      • Trials and results
      • Vaccination and next steps
    • Is it wise to vaccinate?
    • Test, trace & isolate.
    • Different tests
    • Avoid contimination
    • No herd immunity
    • A safe and efficient COVID-19 Vaccine
    • The disease and long-term effects
    • Lost at familiar property
    • Corona Dashboard. 2.0
    • How to fight COVID-19
  • ORTEC
    • P4O2 COVID-19
    • Data science leukemia
    • ​Data to improve patient care
    • Clinical decision support
    • U-Prevent
  • Federa
    • Associations of the Federa
  • Hartblik - blogs
  • Home
  • Nederlands
  • Resume
    • Science
    • Recent Research
    • Cancer immunotherapy
  • COVID-19
    • Herd Immunity Re-Revisted
      • 1 About herd immunity (HIRR).
      • 2 Three failed attempts.(HIRR)
      • 3. Calculate the costs (HIRR).
      • 4. Incomplete immunity (HIRR).
      • 5. What could possibly go wrong? (HIRR)
      • 6. How should we act? (HIRR)
      • 7. In brief. (HIRR)
    • Simple & complex
    • Epidemic Control
      • Epidemic Control Addendum
    • Summary Two years of COVID-19
    • Two years of COVID-19
      • I. Healthcare threat
      • II. Deceptive virus
      • III. Morbid tales
      • IV. Antivirus immunity
      • V. Stop the outbreak
      • VI. Dark and light reflections
      • VII. Looking forward
    • Humanitarian
    • Questions
      • Disease
      • Vaccines
      • Immunity
      • Epidemics
      • Mutation
      • Politics
    • Virus ethics
      • Transparency
      • Strife
      • Beyond Mortality
      • Special immunity
      • Vaccination
      • Prevent contamination
    • Non-sterilizing immunity
    • Immune responses and vaccines
      • Calculation of infection fatality rate
      • Various Immune responses
      • Different vaccines
      • Trials and results
      • Vaccination and next steps
    • Is it wise to vaccinate?
    • Test, trace & isolate.
    • Different tests
    • Avoid contimination
    • No herd immunity
    • A safe and efficient COVID-19 Vaccine
    • The disease and long-term effects
    • Lost at familiar property
    • Corona Dashboard. 2.0
    • How to fight COVID-19
  • ORTEC
    • P4O2 COVID-19
    • Data science leukemia
    • ​Data to improve patient care
    • Clinical decision support
    • U-Prevent
  • Federa
    • Associations of the Federa
  • Hartblik - blogs

COVID-19

I am moving my English blogs on COVID-19 and ORTEC to this site.

Nederlandse blogs over COVID-19
Two years COVID-19:Looking back and forward

II. Deceptive virus

Symptoms from the common cold give are due to the immune system, not the coronavirus causing the infection.[Proud]

Virus infection

Viruses infect cells by their receptor, in case of coronaviruses this is the Spike protein (S). SARS-2 Spike protein infects primarily cells with ACE-2.[Cowley] The virus immune pathology of coronaviruses have been known for decades: coronaviruses have a complicated relation with the immune system. [Perlman, Wong, Lee] In that light it might be less surprising that the weak in our society e.g., immunocompromised, elderly people and males, are more vulnerable.

Immune dysregulation

In brief, virus infections alarm the immune system by interferon responses but SARS-2 inhibits these.[JJ] Normally a wide arrange of immune factors collaborate against a virus infection,[JJ] and the precise tuning of immune responses determines their efficacy.[JJ] Virus interference leads to a dampened, altered and less effective immune initiation. The virus infection is not halted by the ineffective immune response and this response is amplified causing an immune overactivation of mostly innate immune cells and less specialized antigen-specific immunity. Such a response is associated with multi-organ syndrome, thrombosis and severe disease. [Schultze, Jacobs20]

The virus uses more tricks to disturb the immune response, one of these is the superantigen. Superantigens boosts immune responses specifically and are a major cause of severe and recurrent disease by bacteria and viruses.[Jacobs21] In severe disease innate immunity, antibodies and T-cells may be involved. [Toor, Davis]

Arms race

The immune system uses rocket science to eliminate virus, but coronaviruses use stealth technology to avoid neutralization by the immune system.[JJ]

SARS-2 has a major impact on the host immune system. It produces 16 non-structural proteins, that have interactions with 300 host proteins. At least 10 SARS-2 proteins inhibit interferon responses, the default antiviral strategy, and this pattern differs from other coronaviruses (Figure 1).[Belizário, Suryawansh, Kasuga] Vitamin D has a role in an alternative immune activation route.[Peng] By interfering with the normal antiviral immune response, SARS-2 strongly deregulates the immune system. [Oshiumi, Carty]

Administration of interferon might have a positive effect in early stage of disease but negative in severe disease,[Sodeifian] since interferons also upregulate ACE2, the receptor for SARS-2.[Busnadiego]
Picture
Figure 1. Inhibition of cellular responses by SARS-2.[Kasuga]


Superantigen

SARS-2 has a superantigen in the Spike protein.[NG, Huang, Giamarellos-Bourboulis, Jacobs21] Superantigens derive their name from their ability to induce extreme strong immune responses, many bacteria have superantigens. Superantigens recognize antigen-specific receptors on T-cells (TCR) or B-cells (antibodies) from the outside and not from the antigen-biding domain. Therefore, superantigens can activate a large proportion of these lymphocytes, more than any normal antigen would.

Superantigens are the main cause of sepsis, which somewhat resembles the clinical picture of severe COVID-19. Such an immune response is in potential deadly, if not down-regulated. The strength of superantigen is related in the concomitant activation of multiple T-cell clones, irrespective of their antigen specificity. At first glance, it might appear counterintuitive that a pathogen provokes extreme strong immune responses.

But although superantigens produce strong immune responses, they do not mature to a high degree of specificity and these responses wane rapidly. Firstly due to tolerogenic immune responses that counteract the otherwise lethal, self-destructive immune responses. Secondly because the vast number of memory B- and T- lymphocytes are not maintained by cytokine support. Thus superantigen provoke a dangerously strong but temporary immune response against disease.

Metabolic diseases

Vitamin D deficiency is strongly associated with diseases-related mortality.[Kumar] Normalizing vitamin D levels seems to be one of the easiest interventions to protects from severe COVID. [Heine] Also, other metabolic dysregulations, like obesity, hypertension, dyslipidemia, hyperglycemia, or diabetes, can have major impact on the severity of COVID-19 (Figure 2).[Yan] Various metabolites influence the strength and direction of immune responses.[Wege] Similar effects can be noticed from air pollution, nitrogen dioxide (NO2 ), ozone (O3 ), and particulate matter (PM).[Woodby] So it seems likely that air pollution could also be an important risk factor for sever COVID-19, especially in the lower social-economic groups.

Picture
Figure 2. The influence of obesity and other metabolic disorders on disease progression. [Yan]

Complicated immune effects

Some patients with immune deficiencies are protected from severe COVID-19 while others are more vulnerable.[Bucciol] The immunological regulation is very delicate, and minor disturbances, low-grade chronic inflammation, could greatly influence the outcome after SARS-2 infection.[Suárez-Reyes]

When the immune response is ineffective, disease progression is counteracted with a stronger immune response i.e., hyperinflammatory syndrome, which leads to severe disease.[Gustine] Vitamin D might be also needed to resolve hyperinflammatory responses. [Hu, Chiu]

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John. J.L. Jacobs. 30.11.2021

Two years of COVID-19
  • I. Healthcare threat
  • II. Deceptive virus
  • III. Morbid tales
  • IV. Antivirus immunity
  • V. Stop the outbreak
  • VI. Dark and light reflections
  • VII. Looking forward
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  • Home
  • Nederlands
  • Resume
    • Science
    • Recent Research
    • Cancer immunotherapy
  • COVID-19
    • Herd Immunity Re-Revisted
      • 1 About herd immunity (HIRR).
      • 2 Three failed attempts.(HIRR)
      • 3. Calculate the costs (HIRR).
      • 4. Incomplete immunity (HIRR).
      • 5. What could possibly go wrong? (HIRR)
      • 6. How should we act? (HIRR)
      • 7. In brief. (HIRR)
    • Simple & complex
    • Epidemic Control
      • Epidemic Control Addendum
    • Summary Two years of COVID-19
    • Two years of COVID-19
      • I. Healthcare threat
      • II. Deceptive virus
      • III. Morbid tales
      • IV. Antivirus immunity
      • V. Stop the outbreak
      • VI. Dark and light reflections
      • VII. Looking forward
    • Humanitarian
    • Questions
      • Disease
      • Vaccines
      • Immunity
      • Epidemics
      • Mutation
      • Politics
    • Virus ethics
      • Transparency
      • Strife
      • Beyond Mortality
      • Special immunity
      • Vaccination
      • Prevent contamination
    • Non-sterilizing immunity
    • Immune responses and vaccines
      • Calculation of infection fatality rate
      • Various Immune responses
      • Different vaccines
      • Trials and results
      • Vaccination and next steps
    • Is it wise to vaccinate?
    • Test, trace & isolate.
    • Different tests
    • Avoid contimination
    • No herd immunity
    • A safe and efficient COVID-19 Vaccine
    • The disease and long-term effects
    • Lost at familiar property
    • Corona Dashboard. 2.0
    • How to fight COVID-19
  • ORTEC
    • P4O2 COVID-19
    • Data science leukemia
    • ​Data to improve patient care
    • Clinical decision support
    • U-Prevent
  • Federa
    • Associations of the Federa
  • Hartblik - blogs