Header

Showing posts with label COVID-19. Show all posts
Showing posts with label COVID-19. Show all posts

Saturday, February 6, 2021

Th1 and Th2 Responses from Different COVID-19 Vaccines: What Are They?

Table 1.  Comparison of vaccines

In the above table, list of Covid-19 vaccines are compared and one of the nonclinical results has mentioned:

  • Strong Th1 response (Moderna)
  • Strong Th1 and Th2 response (Pfizer, AstraZeneca, J&J and Sputnik V)
So, what are Th1 and Th2 responses?

Cytokines


Cytokines are the hormonal messengers responsible for most of the biological effects in the immune system, such as cell mediated immunity and allergic type responses. Although they are numerous, cytokines can be functionally divided into two groups:
  • Proinflammatory 
  • Anti-inflammatory

T Lymphocytes


T lymphocytes (or T cells) are a major source of cytokines. These cells bear antigen specific receptors on their cell surface to allow recognition of foreign pathogens. They can also recognize normal tissue during episodes of autoimmune diseases. There are two main subsets of T lymphocytes distinguished by the presence of cell surface molecules known as CD4 and CD8:

Figure 2. Schematic representation of the host immune response against microbial pathogens (Source: 18). 


Host Immunity


T helper cells (Th cells) are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of other immune cells by releasing T cell cytokines. Understanding exactly how helper T cells respond to immune challenges is currently of major interest in immunology.

There are two major subtypes of helper T cells known as Th1 and Th2:[5,6]
  • Th1
    • Th1 is the host immunity against intracellular bacteria and protozoa.  Immune stimulation promotes cellular immune system.
    • The painful, red swelling around an infected cut or pimple exemplified a Th1 response.
    • Th1 cells can be activated by IL-12 and IL-18, or Th17 cells, which respond to other cytokine stimulations such as IL-1β or IL-18 in concert with IL-23 to produce Th-17 associated cytokines.
    • COVID-19
      • One report has described a higher proportion of IFNγ-producing T helper 1 (Th1)-like cells in patients with moderate disease than in patients with severe disease.[20]
      • CD4+ T cells specific for the SARS-CoV-2 spike protein have been identified in acute infection and have a Th1 cell cytokine profile.[21]
  • Th2
    • Th2 is the host immunity against multicellular helminths (or parasitic worms) and blood-feeding insects.  Immune stimulation promotes humoral immune system.
    • The itchy red bump of a mosquito bite typified Th2.
    • COVID-19
      • A role for Th2 cell-type responses in severe COVID-19 is unclear, although patients with mild disease may have a normal TH2 cell response.[22]


Figure 3. Th1/Th2 dichotomy (Source: Wikipedia)

Discussions


The human immune system is incredibly complex. We have many types of immune cells that are orchestrated by various factors–from our encounter with microbes, to our health status, genetics, mood, and more.

The main issue with the whole Th1/Th2 theory, as some scientists have recently pointed out, is that the activity of cytokines and other immune messengers rarely fall into strict Th1 or Th2 patterns. Some cells, like non-helper regulatory T cells (Tregs), may influence both Th1 and Th2 responses.[12-14]

The optimal scenario would therefore seem to be that humans should produce a well balanced Th1 and Th2 response, suited to the immune challenge.[1]

Many researchers regard allergy as a Th2 weighted imbalance, and recently immunologists have been investigating ways to redirect allergic Th2 responses in favor of Th1 responses to try to reduce the incidence of atopy. 
Some groups have been looking at using high dose exposure to allergen to drive up the Th1 response in established disease,[2] and other groups have been studying the use of mycobacterial vaccines in an attempt to drive a stronger Th1 response in early life.[3]

An additional strategy is being used to prevent the onset of disease; this involves the study of pregnancy and early postnatal life. Both of these states are chiefly viewed as Th2 phenomena (to reduce the risk of miscarriage, a strong Th2 response is necessary to modify the Th1 cellular response in utero). The fetus can switch on an immune response early in pregnancy, and because pregnancy is chiefly a Th2 situation, babies tend to be born with Th2 biased immune responses. These can be switched off rapidly postnatally under the influence of microbiological exposure or can be enhanced by early exposure to allergens. It is also hypothesized that those who go on to develop full blown allergies may be those who are born with a generally weaker Th1 response, although it is now apparent that babies with allergies produce weak Th1 and Th2 responses.

Some people have suggested that immunization programmed (and the subsequent reduction in microbiological exposure) are responsible for the increasing incidence of atopy. There is, however, no evidence that immunization causes atopy. Moreover, this is not an argument that we should be exposing children to potentially fatal diseases again. If experiencing native diseases reduces the incidence of atopy, then the task of immunologists must be to develop vaccines that mimic the positive effects of infection.


References

  1. Th1 and Th2 responses: what are they?
  2. Gereda JE, Leung DYM, Thatayatikom A, Streib JE, Price MR, Klinnert MD, et al. Relationship between house dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet. 2000;355:1680–1683.
  3. Jones CA, Holloway JA, Warner JO. Does atopic disease start in foetal life? Allergy. 2000; 55:2–10.
  4. Can Parasites Heal the Gut?
  5. Th1 cells switch off Th2 cells and vice versa
  6. Limitations to the Th1/Th2 model
  7. CELL-MEDIATED IMMUNITY: Cell-cell interactions in specific immune responses
  8. Loke Lab - Microbiology
  9. Can Parasites Heal the Gut?
  10. Hepatitis A and Allergic Diseases
  11. Are Dogs More Protective For Children’s Health?
  12. Th1/Th2 Balance: The Hypothesis, its Limitations, and Implications for Health and Disease
  13. T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor β2
  14. Itch expression by Treg cells controls Th2 inflammatory responses
  15. All About Regulatory T cells (Tregs) & How to Increase Them
  16. Th1/Th2 model
  17. What Are the Different Types of T Cells?
  18. Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies
  19. Coronavirus Deranges the Immune System in Complex and Deadly Ways
  20. Chen, G. et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Invest. 130, 2620–2629 (2020).
  21. Weiskopf, D. et al. Phenotype and kinetics of SARS-CoV-2-specific T cells in COVID-19 patients with acute respiratory distress syndrome. Sci. Immunol. 5, eabd2071 (2020).
  22. Laing, A. G. et al. A consensus Covid-19 immune signature combines immuno-protection with discrete sepsis-like traits associated with poor prognosis.
  23. Pfizer/BioNtech And Moderna MRNA Covid-19 Vaccines Closely Mimic The Immune Response Of Natural SARS-CoV-2 Infections
  24. COVID vaccines: head-to-head comparison reveals how they stack up

Posted by at No comments:
Labels: , , , , ,

Sunday, December 27, 2020

How to keep your immune system strong?



Healthy ways to strengthen your immune system:[1]

  • Keep your kidney healthy
  • Keep your liver healthy
    • The liver is a key, frontline immune tissue. Ideally positioned to detect pathogens entering the body via the gut, the liver appears designed to detect, capture, and clear bacteria, viruses, and macromolecules.[14]
    • Read Risk Factors of Liver Diseases
  • Avoid toxins such as PCB, pesticide, or Arsenic 
    • PCBs are ubiquitous environmental toxicants, for which animal studies demonstrate immunotoxic effects.[12]
    • Arsenic has been shown to affect not only the immune response, but also behavior in rats.[13]
    • Read The dangers of pesticides to humans.  But, the gist is that pesticides are immunosuppressive agents.
  • Micronutrients supplementation
      • Micronutrients such as vitamin C, D, zinc, and selenium play roles in antioxidant, anti-inflammatory, antithrombotic, antiviral, and immuno-modulatory functions and are useful in both innate and adaptive immunity.[26,28,29]
    • Take selenium supplementation (especially prior to the vaccination)
  • Don't smoke or vape
  • Eat a diet high in fruits, vegetables, and whole grains
    • 30 good reasons for eating plant-based diets
    • Among COVID-19 patients, propolis and combinations of bee honey with herbal plants were associated with improved viral clearance and symptom recovery.[21]
    • The cells rely on nutrients as an energy source and for building blocks.  A study shows that nutrients are also involved in inhibitory pathways, and that deprivation of certain nutrients or metabolites might be good for adaptive immunity.[19]
  • Take a multivitamin if you suspect that you may not be getting all the nutrients you need through your diet
    • Health benefits of Vitamin D
    • Vitamin-rich foods
    • Vitamin B assists in proper activation of both the innate and adaptive immune responses, reduces pro-inflammatory cytokine levels, improves respiratory function, maintains endothelial integrity, prevents hypercoagulability and can reduce the length of stay in hospital.[23,24]
      • Therefore, vitamin B could be used as a non-pharmaceutical adjunct to the treatment of patients with COVID-19.[22]
    • A study found that taking multivitamins, omega-3, probiotics or vitamin D supplements may lessen the risk of testing positive for SARS-CoV-2. But taking vitamin C, zinc, or garlic supplements did nothing to reduce the risk of catching Covid-19.[20]
  • Exercise regularly
  • Maintain a healthy weight
  • Control your stress level
  • Control your blood pressure
  • If you drink alcohol, drink only in moderation
    • No more than one to two drinks a day for men, no more than one a day for women.
    • Alcohol can weaken the immune system and make the body more susceptible to infections.[9]
  • Get enough sleep
  • Avoid sugar or HFCS
    • Niket Sonpal, a board-certified internist and gastroenterologist, stated that the suppression of the immune system starts as soon as 30 minutes after the consumption of sugar and can last up to five hours.[16-18]
  • Take steps to avoid infection, such as washing your hands frequently and trying not to touch your hands to your face, since harmful germs can enter through your eyes, nose, and mouth.]
  • Avoid high-salt diets
    • Research has found that besides being bad for blood pressure, a high salt diet is also bad for the immune system.[27] 

References

  1. Preventing the spread of the coronavirus - Harvard Health
  2. List of Risk Factors for Covid-19
  3. Melatonin — A Promising Candidate for Prevention and Treatment of COVID-19
  4. Top Zinc-Rich Foods For Better Immunity
  5. Immunosenescence — Weaker Immune System of the Elderly Explained
  6. Hesperidin — a promising adjuvant treatment option against SARS-CoV-2 infection
  7. Immune systems are like our fingerprints
  8. Natural Immunity
  9. 6 Surprising Ways Alcohol Affects Your Health — Not Just Your Liver
  10. Chronic Kidney Disease and Pneumococcal Disease: Do You Know the Facts?
  11. The immune system and kidney disease: basic concepts and clinical implications
  12. Prenatal PCB exposure and thymus size at birth in neonates in Eastern Slovakia
  13. Arsenic ecotoxicology and innate immunity
  14. Immune Responses in the Liver
  15. Vitamin D3 — A Promising Candidate for Prevention and Treatment of COVID-19
  16. A high-sugar diet affects cellular and humoral immune responses in Drosophila
  17. Eating Sugar Can Weaken Your Immune System
  18. The Effect of Short-Term Hyperglycemia on the Innate Immune System
  19. Researchers map metabolic signaling machinery for producing memory T cells
  20. Which Vitamins Actually Reduce Your Risk Of Getting Covid-19?
  21. Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies
  22. Be well: A potential role for vitamin B in COVID-19
  23. Michele C.A., Angel B., Valeria L., Teresa M., Giuseppe C., Giovanni M., Ernestina P., Mario B. Vitamin supplements in the era of SARS-Cov2 pandemic. GSC Biol. Pharm. Sci. 2020;11(2):007–019.
  24. Zhang L., Liu Y. Potential interventions for novel coronavirus in China: a systematic review. J. Med. Virol. 2020;92(5):479–490.
  25. Selenium saves ferroptotic TFH cells to fortify the germinal center
  26. Nutritional risk of vitamin D, vitamin C, zinc, and selenium deficiency on risk andclinical outcomes of COVID-19: a narrative review
  27. A high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation
  28. The Role of Minerals in the Optimal Functioning of the Immune System
  29. Zinc Levels Affect the Metabolic Switch of T Cells by Modulating Glucose Uptake and Insulin Receptor Signaling
  30. Myths vs. Facts About Your Immune System
Posted by at No comments:
Labels: ,

Sunday, November 29, 2020

Immunological Memory — The Source of Protective Immunity from a Subsequent Infection

While many successful vaccines act primarily by generating antibodies, there is also a clear need for vaccines that generate populations of highly-specific T cells, especially against infectious agents that successfully escape antibody responses.[1]

Latest Developments


Based on a latest research, it stated that:[16]

These results provide further evidence that a three-dose vaccine regimen benefits the induction of optimal functional T cell immune memory.

Table 1. Vaccines do generate populations of highly-specific T cells (Source @erictopol)

Innate Immune System vs Adaptive Immune System


The innate immune system is a conserved defense strategy critical for the initial detection and restriction of pathogens and later activation of the adaptive immune response. Effective activation of innate immunity relies on the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) .

The adaptive immune system, also called acquired immunity, uses specific antigens to strategically mount an immune response. Unlike the innate immune system, which attacks only based on the identification of general threats, the adaptive immunity is activated by exposure to pathogens, and uses an immunological memory to learn about the threat and enhance the immune response accordingly. The adaptive immune response is much slower to respond to threats and infections than the innate immune response, which is primed and ready to fight at all times.

Figure 1.  Steps in adaptive immune process (see [11] for more details)
Note that after monocytes enter the tissue, they become known as macrophages

Antibody-Mediated Immunity (or Humoral Immunity)


Humoral immunity (or is antibody-mediated immunity)
Figure 2.  An APC engulfs and digests a foreign bacterium (Source: [15])
An antigen from the bacterium is presented on the cell surface
in conjunction with an MHC II molecule.
Lymphocytes of the adaptive immune response interact with
antigen-embedded MHC II molecules to mature into functional immune cells.


Figure 3.  Antigen presentation stimulates T cells to become 
either "cytotoxic" CD8+ cells or "helper" CD4+ cells 
(Source: Wikipedia)

Immune Memory


Immune memory (or immunological memory), from either primary infection or immunization, is the source of protective immunity from a subsequent infection.[3-5] Thus, COVID-19 vaccine development is closely tied to the topic of immunological memory.[6,7]

A thorough understanding of immune memory to SARS-CoV-2 requires evaluation of its various components, including:[2]
  • Antigen Presenting Cells (APCs which includes macrophages, dendritic cells, B cells)
    • In the steady state, and when the body is challenged by injury and infection, dendritic cells (one type of APCs)  travel from body surfaces to immune or lymphoid tissues, where they home to regions rich in T cells. There, dendritic cells deliver two types of information: 
      • they display antigens, the substances that are recognized by T cells, 
      • they alert these lymphocytes to the presence of injury or infection. 
      This directs the T cells to make an immune response that is matched to the challenge at hand.
  • B Cells (aka B lymphocytes)
    • Function in the humoral immunity component of the adaptive immune system by secreting antibodies
    • Present antigens and secrete cytokines
    • Express B cell receptors (BCRs) on their cell membrane. 
      • BCRs allow the B cell to bind to a specific antigen, against which it will initiate an antibody response.
  • CD8+ T Cells (aka killer T-cells or cytotoxic T cells)
    • Are T lymphocytes that kill cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways
    • Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen
  • CD4+ T Cells (i.e., T helper cells)
    • Help the activity of other immune cells by releasing cytokines, small protein mediators that alter the behavior of target cells that express receptors for those cytokines. 
    • Help to polarize the immune response into the appropriate kind depending on the nature of the immunological insult (virus vs. extracellular bacterium vs. intracellular bacterium vs. helminth vs. fungus vs. protist). 
    • Are essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils.
as these different cell types may have immune memory kinetics relatively independent of each other. 

A Cross-Sectional Study


Understanding the complexities of immune memory to SARS-CoV-2 is key to gain insights into the likelihood of durability of protective immunity against 
  • Re-infection with SARS-CoV-2 
  •  2° COVID-19 disease
In the study of Shane Crotty et al,[2] they assessed immune memory of all three branches of adaptive immunity (CD4+ T cell, CD8+ T cell, and humoral immunity) in a cross-sectional study of 185 recovered COVID-19 cases, extending out to greater than six months post-infection. 

Here are the summary of their results on SARS-CoV-2-specific memory of:
  • B cells
    • Overall, based on the observations, development of B cell memory to SARS-CoV-2 appeared to be robust and likely long-lasting
  • CD8+ T cells 
    • The memory CD8+ T cell half-lives (or t1/2) observed herein were comparable to the 123d t1/2 observed for memory CD8+ T cells within 1-2 years after yellow fever immunization.[10]
    • Overall, the decay of circulating SARS-CoV-2-specific CD8+ T cell is consistent with what has been reported for another acute virus.
  • CD4+ T cells
    • Circulating SARS-CoV-2 memory CD4+ T cell responses were quite robust
      • 94% of subjects with detectable circulating SARS-CoV-2 memory CD4+ T cells at 1 month PSO
      • 89% of subjects with detectable circulating SARS-CoV-2 memory CD4+ T cells at≥ 6 months PSO

Their findings have implications for immunity against 2° COVID-19, and thus the potential future course of the pandemic.[8,9]

Hybrid Immunity


Based on a new article on Science Magazine, it states that:[13]
Hybrid vigor can occur when different plant lines are bred together and the hybrid is a much stronger plant. Something similar happens when natural immunity is combined with vaccine-generated immunity, resulting in 25 to 100 times higher antibody responses, driven by memory B cells and CD4+ T cells and broader cross-protection from variants.
Why does this pronounced neutralization breadth occur?  Memory B cells are a primary reason.  They have two major functions:
  1. To produce identical antibodies upon reinfection with the same virus
  2. To encode a library of antibody mutations, a stock-pile of immunological variants
These diverse memory B cells, created in response to the original infection, appear to be preemptive guesses by the immune system as to what viral variants may emerge in the future.  This brilliant evolutionary strategy is observed clearly for immunity to SARS0CoV-2:
A substantial proportion of memory B cells encode antibodies  that are capable of binding or neutralizing VOCs, and the quality of these memory B cells increase over time.  Thus the increase in variant-neutralizing antibodies after vaccination of previously SARS-CoV-2-infected persons reflects recall of diverse and high-quality memory B cells generated after the original infection.
Also read this companion article on:


References

  1. Human T Cell Memory: A Dynamic View
  2. Immunological memory to SARS-CoV-2 assessed for greater than six months after infection
  3. W. A. Orenstein, R. Ahmed, Simply put: Vaccination saves lives. Proc National Acad Sci. 114, 4031–4033 (2017).
  4. P. Piot, H. J. Larson, K. L. O’Brien, J. N’kengasong, E. Ng, S. Sow, B. Kampmann, Immunization: vital progress, unfinished agenda. Nature. 575, 119–129 (2019).
  5. S. Plotkin, W. Orenstein, P. Offit, Plotkin’s vaccines, 7th edition (Elsevier, 2018), Elsevier.
  6. D. S. Stephens, M. J. McElrath, COVID-19 and the Path to Immunity. Jama. 324 (2020), doi:10.1001/jama.2020.16656.
  7. F. Krammer, SARS-CoV-2 vaccines in development. Nature, 1–16 (2020).
  8. S. M. Kissler, C. Tedijanto, E. Goldstein, Y. H. Grad, M. Lipsitch, Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period. Science. 368, 860–868 (2020).
  9. C. M. Saad-Roy, C. E. Wagner, R. E. Baker, S. E. Morris, J. Farrar, A. L. Graham, S. A. Levin, M. J. Mina, C. J. E. Metcalf, B. T. Grenfell, Immune life history, vaccination, and the dynamics of SARS-CoV-2 over the next 5 years. Science, eabd7343 (2020).
  10. R. S. Akondy, M. Fitch, S. Edupuganti, S. Yang, H. T. Kissick, K. W. Li, B. A. Youngblood, H. A. Abdelsamed, D. J. McGuire, K. W. Cohen, G. Alexe, S. Nagar, M. M. McCausland, S. Gupta, P. Tata, W. N. Haining, M. J. McElrath, D. Zhang, B. Hu, W. J. Greenleaf, J. J. Goronzy, M. J. Mulligan, M. Hellerstein, R. Ahmed, Origin and differentiation of human memory CD8 T cells after vaccination. Nature. 552, 362–367 (2017).
  11. Vaccine bootcamp (nice animation)
  12. Human Coronavirus: Host-Pathogen Interaction
  13. Hybrid Immunity
  14. Understanding the Basics of Memory B Cells—The Antibody Factory
  15. Antigen-Presenting Cells
  16. Resilient T cell responses to B.1.1.529 (Omicron) SARS-CoV-2 variant


Posted by at No comments:
Labels: , , , ,

Thursday, November 26, 2020

Asthma and Its Covid-19 Risks (or Not)

Updated 02/09/2021

Without much ado, I'll refer you to read [1] to understand Asthma (see also the infographic provided in this article).

Figure 1.  Endothelial dysregulation by SARS-CoV-2. [5]

What's ACE2 Receptor?


The SARS-CoV-2 virus that causes COVID-19 enters lung cells by engaging with a type of protein on their surface called an ACE2 receptor.  Normally, this cell-surface receptor functions to regulate blood pressure, but SARS-CoV-2 has co-opted it as a means to gain entry into cells in the lungs and other organs. 

Patients in conditions like diabetes or hypertension, this receptor (i.e., ACE2) expression is increased. That's a possible reason why those comorbid diseases are at especially high risk for this infection.[4]

Allergy-driven asthma vs non-allergic asthma


Allergy-driven asthma

"In the setting of an allergic type of inflammation, the expression of the ACE2 receptor appears to be downregulated. It appears to be lower. There's not as much receptor," Dr. Sandhya Khurana said.[4]

Because there aren't as many ACE2 receptors available, people with allergic asthma might not be as vulnerable to severe infection, Khurana said.

Non-allergic asthma

Some studies have suggested that people who have asthma (or non-allergic asthma) caused by something other than allergies -- exercise, stress, air pollution, weather conditions -- might have an increased risk of severe COVID-19.

However, their asthma could be caused by other lung ailments (e.g., COPD) that are associated with more serious cases of COVID, for instance, said Dr. Mitchell Grayson.

Everything that came out of the initial epidemic in China suggested that asthma was not a risk factor for life-threatening COVID, Grayson said, and the data continued to confirm that as the coronavirus spread across the globe.

Wrap It Up


The CDC[3] does list moderate-to-severe asthma as a possible risk factor for severe COVID-19 disease, but there are no published data to support that at this time.

 "It's good practice to observe the recommended guidance on hand hygiene and social distancing and masking and avoiding any situation where you could be exposed, even though it's obviously welcome to see that allergic asthma is not as high-risk as some of the other comorbid diseases," Khurana said.

Posted by at No comments:
Labels: , , ,

Wednesday, November 25, 2020

Akiko Iwasaki—Immune Response to SARS-CoV-2

Video 1.  Akiko Iwasaki—Immune Response to SARS-CoV-2 (11/17/2020; YouTube link)


The eleventh lecture in the COVID-19, SARS-CoV-2 and the Pandemic Series, presented by the MIT Department of Biology. Akiko Iwasaki of Yale Medical School gave a talk titled "Immunology: antibodies." 

For more information on the class, visit “COVID-19, SARS-CoV-2 and the Pandemic” (7.00). 

Slides from the Lecture





















See Also

Posted by at No comments:
Labels: , , ,

Sunday, November 15, 2020

Coronavirus—What Makes Some Patients Sicker than Others?

COVID-19 typically causes fever and a dry cough. One may have aches in the body—the muscles—and if it's severe enough, there would be shortness of breath.

Gastrointestinal symptoms can occur and are an indication of more severe disease. It's not very common to have a runny nose or the sniffles, and a sore throat is not common either.


What's the Difference?


In comparison to other respiratory viruses, SARS-CoV-2 infection drives a lower antiviral transcriptional response that is marked by:

which could explain the proinflammatory disease state associated with COVID-19.


Risk Factors


“Most people coronavirus affects in a mild way, so they can spread the infection, but there is a subset of the population that gets seriously ill. It is both highly contagious and highly lethal.” 

— Kári Stefánsson comments on "The Bad Combination"

How the COVID-19 affects each individual could be different based on individual's 

  • Genes,[30,31]  
  • Age and pre-exiting health conditions 
  • Individual’s immune system[29]   
Figure 1. Pie charts show the minor allele frequency at rs35044562

Genes


Certain genetic variants, especially in genes that influence the immune system, seem to predispose people to a host of other infectious diseases.[35]

Researchers of Covid-19 have already begun to get some sense of who is most vulnerable. Some are honing in on the immune system and its response to infection as a potential trigger for severe disease.

Increasing evidence suggests that a significant minority of Covid-19 patients get very ill because of:
  • Low IFN-I and IFN-III levels[33]
    • Once the virus has invaded the cell, a host defense-mediated response is triggered, which involves the induction of a family of IFNs (interferons). These IFNs constitute a heterogeneous group of proteins and are best known for their ability to induce cellular resistance to virus infection.
      • People with severe COVID-19 had mutations in genes that encode components of this process. (see Figure 2)
      • Individuals with genetic mutations in the IFN-I-induction pathway (Figure 2.a) might benefit from therapy that provides interferon, but such treatment would not help those with mutations in the genes encoding IFNAR (Figure 2.b).  
      • People who have neutralizing antibodies to IFN-α and IFN-ω might benefit from therapy that provides other types of interferon, such as IFN-β and IFN-λ, if given early during infection.
      • For more information, read NIH's recommendation for guidance.
  • More ACE2 receptors on the host cells
    • The receptor coronavirus uses to penetrate host cells, called ACE2, can be present in varying numbers in different people based on their genetics and on environmental factors, such as what medicines they take.
  • Elevated chemokine expression
    • See the below section of Individual’s immune system for details
  • Neanderthal core haplotype[31]
    • The major genetic risk factor (i.e., the haplotypes that carry the risk allele at rs35044562) for severe COVID-19 is inherited from Neanderthals.
      • The risk variant in this region confers an odds ratio for requiring hospitalization of 1.6
    • The haplotype is carried by around 50% of people in south Asia and around 16% of people in Europe (see Figure 2).

Figure 2.  A defective antiviral signaling pathway (details)

Age and Pre-Exiting Health Conditions 


Those in the harm’s way of Covid-19 are older adults and people with conditions that are tied to inflammation. Many of these conditions also have a genetic component.
New York state, which is closely tracking people who died from Covid-19, found that almost 90% had other health conditions. The most common are high blood pressure, found in 56% of the 10,834 deaths through April 13, diabetes, high cholesterol and heart disease.

Summary

All factors below play a large role in determining how people fare once they’ve contracted Covid-19:
  • High blood pressure, obesity and diabetes
    • Three of the most-powerful risk factors for severe disease all have a genetic component.
    • Overweight patients who were under age 60 were twice as likely to be hospitalized as their thinner peers, while those who were obese were three times as likely to need intensive care.
      • The results make sense because obesity is a pro-inflammatory state: People who carry extra weight have higher levels of immune response and inflammation.
  • Low oxygen levels and signs of inflammation on lab tests 
    • Patients with such test results are most likely to be critically ill
  • Low testosterone levels[36]
    • Testosterone may be able to stop the body's immune system from going haywire 
    • Low levels of the sex hormone are unable to regulate the body's immune response, leading to a 'cytokine storm' which can be fatal.

Individual’s Immune System


“If we can understand why some people experience cytokine storms, we can better treat the Covid-19 patients”
— Akiko Iwasaki, a Yale University immunologist

As the body mounts an intense effort to fight off the previously unknown pathogen, the immune system can kick into overdrive — what’s known as a cytokine storm — causing collateral damage that may do more harm than the virus itself.

Children with less-developed immune systems could be less vulnerable. Evidence from deCODE suggests women also may experience severe symptoms less frequently. 

Figure 1. Long-term symptoms
Figure 2.  Covid-19 survivors report a wide range of long-term symptoms


References

  1. The Tip of the Iceberg: Virologist David Ho (BS '74) Speaks About COVID-19
  2. Even Mild Covid-19 Infections Can Make People Sick for Months
  3. [WEBCAST REPLAY] COVID-19 Pandemic Update: Analysis From Neil Howe & Daryl Jones
  4. Why U.S. hospitals see promise in plasma from new coronavirus patients
  5. Virus May Spread Twice as Fast as Earlier Thought, Study Says
  6. What Does Your Cough Say About Your Illness?
  7. The COVID-19 vaccine development landscape
  8. She spent 9 days in a coma and relearned how to walk. What this Covid-19 survivor wants protesters to know
  9. If you’re hoping a vaccine is going to be a knight in shining armor saving the day, you may be in for a disappointment. SARSCOV2 is a highly contagious virus. A vaccine will need to induce durable high level immunity, but coronaviruses often don’t induce that kind of immunity (link)
  10. Mutations map holds the key to bringing coronavirus under control
  11. Virus Likely to Keep Coming Back Each Year, Say Top Chinese Scientists (Bloomberg)
    • “The virus is heat sensitive, but that’s when it’s exposed to 56 degrees Celsius for 30 minutes and the weather is never going to get that hot,” said Wang Guiqiang, head of the infectious diseases department of Peking University First Hospital. “So globally, even during the summer, the chance of cases going down significantly is small.”
  12. All the Covid-19 Symptoms You Didn’t Know About
  13. Coronavirus: Can it affect eyesight?
  14. What Troponin Tells Us About Myocardial Injury in COVID-19
    • Clinicians then assess potential causes of troponin elevation, including hyperinflammation, which may respond to immunosuppressive therapy.
  15. Strokes and mental state changes hint at how COVID-19 harms the brain
  16. A family physician’s COVID story
  17. A COVID-19 vaccine: 5 things that could go wrong
  18. Studies detail conjunctivitis in kids, adults with COVID-19
  19. A perspective on potential antibody-dependent enhancement of SARS-CoV-2
  20. COVID-19 survivors suffer long term heart conditions
  21. As evidence builds that COVID-19 can damage the heart, doctors are racing to understand it
  22. Novel coronavirus survives 28 days on glass, currency, Australian researchers find
  23. CDC Expands Covid Risk Warning to Include Overweight People
    • Nearly 72% of American adults are overweight (25 < BMI < 30) or obese (BMI ≥ 30)
  24. CDC Says Virus Can Spread Indoors in Air Beyond Six Feet
  25. Covid may cause sudden, permanent hearing loss – UK study
  26. 29-Year-Old Overcomes COVID-19, Cardiac Arrest While On Ventilator
  27. Hospitalised COVID-19 patients can have ongoing symptoms for months -study
  28. What Will Not Change
  29. Common cold antibodies hold clues to COVID-19 behavior
  30. Your Risk of Getting Sick From Covid-19 May Lie in Your Genes
  31. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals
  32. 'Breakthrough finding' reveals why certain Covid-19 patients die
  33. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19
  34. Bench-to-bedside review: Understanding genetic predisposition to sepsis
  35. Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections
  36. Male coronavirus patients with low testosterone levels are MORE likely to die from COVID-19, German hospital finds
  37. Black And Asian People More Likely To Catch Covid-19 In U.S. And U.K., Study Finds
  38. Covid19 and the immune system — the good, the bad and the ugly 
  39. Interferon deficiency can lead to severe COVID (Nature)
  40. Researchers reveal how genetic variations are linked to COVID-19 disease severity
  41. Akiko Iwasaki—Immune Response to SARS-CoV-2
  42. Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19
  43. If Your Eye Does This, You May Have COVID, Says Study
Posted by at No comments:
Labels: , ,
Subscribe to: Posts (Atom)