How to keep your immune system strong?

Healthy ways to strengthen your immune system:^[1]

• Keep your kidney healthy
• Having kidney disease and kidney failure can weaken your immune system, making it easier for infections to take hold.^[10,11]
• Read Kidney Disease—All Things Considered
• 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)
• Inhibition of ferroptosis via selenium supplementation promotes the survival of follicular helper T cells, boosting the germinal center and antibody response following vaccination in mice and people.^[25]
• 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
• Exercise and its benefits
• Maintain a healthy weight
• Control your stress level
• How to manage stress
• 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
• Good night sleep
• Hours of sleep — How long is too little or too much?
• 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
• What Can Cause Depressed Immunity?
• Immune System Boosters
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

Visiting Lofoten, Norway: A Guide to This Arctic Paradise

You can view the same article with a mobile friendly version here.

Figure 1.  Lofoten, Norway

As a local guide said it well:

Lofoten is located at the 68th and 69th parallels north of the Arctic Circle in North Norway. It is known for its natural environment within Norway. 

Lofoten is a mecca for hiking, climbing, fishing, kayaking, skiing, Arctic surfing (in the summer AND winter), and cycling. The tourism scene there has a very young vibe, with lots of budget. 

Lofoten is known for excellent fishing, nature attractions such as the northern lights and the midnight sun, and small villages off the beaten track. Kayak between the islands, go fishing for the catch of your life, or look for sea eagles soaring in the sky.

Video 1.  Greetings from Norway Lofoten (YouTube link)

Lofoten

Read this good article to know about your trip:

11 things you should know about visiting the Lofoten Islands

Here are the 11 things from the article:

1. The weather is going to be crazy
2. Tourism has just recently exploded on the Lofoten Islands
3. It will be a lot easier to explore Lofoten if you have a car
4. Lofoten is perfect for outdoor adventures
5. Hiking in Lofoten in the winter can be dangerous
6. Lofoten is a photographer’s dream
7. Your chances of seeing the northern lights in Lofoten aren’t great
• If your heart is set on seeing the aurora, consider heading somewhere with clearer skies, like Abisko in Sweden.
8. The ferry from Bodø to Lofoten can be rough
9. You can also fly or drive to Lofoten
10. You’re going to smell a lot of fish
11. You’re never going to want to leave 

Figure 2. Eurail map (link)

Figure 3.  Norway Train Map

How to Get There?

Via Eurail : Copenhagen → Stockholm → Kiruna

Via Car (5h 55m): Kiruna → E10 → Lofoten

Via Train + Bus (8h 54m): Kiruna → Train (video 2) → Bromsgard (Narvik Station) → Bus → Lofoten

Via Bus (11h 4m): See detail here

Via Ferry: Bodø → Lofoten

Video 2.  The view from Narvik Norway to Abisko Sweden (YouTube link)

References

1. Experiencing a Norway Road Trip along the Atlantic West Coast
2. 20 Spots In Europe You Must See Before You Die
• Seven Sisters waterfall, Geiranger, Norway
• Preikestolen, near Stavanger, Norway
3. Norway's West: Fjords, Mountains, and Bergen (video)
4. Eurail
5. 12-Day Norway & North Cape from Hamburg B
6. Oslo, Norway
7. Driving the roof of Norway
8. USEFUL INFORMATION FOR LOM AND JOTUNHEIMEN
9. NORWAY'S TRAINS AND FJORDS
10. HOW TO GET FROM Kiruna IRF to Lofoten BY TRAIN, BUS OR CAR
11. Driving from Narvik to Lofoten (car rental)
12. 11 things you should know about visiting the Lofoten Islands
13. 20 FAMOUS LANDMARKS IN NORWAY
14. 25 Most Beautiful Destinations in Europe - Travel Video
• 4. Lofoten Islands, 17. Pulpit Rock

Witnessing the Great Migration from Above: A Balloon Safari in the Masai Mara

A Balloon Safari in the Masai Mara

You can view the same article with a mobile friendly version here.

Africa Eco Adventures Ltd offers balloon flights in Kenya’s famous Masai Mara National Reserve. The Mara is the northernmost part of the spectacular Serengeti-Mara ecosystem, home to the “Great Migration” and scores of other wildlife, including lions, cheetahs, elephants, rhinos, hippos, and crocodiles.

Maasai Mara National Reserve

Masai Mara National Reserve stretches 1,510 sq km (580 sq miles) and raises 1,500-2,170 meters above sea level. Add the conservancies and the area is at least twice the size. It hosts over 95 species of mammals and over 570 recorded species of birds.

Best Time To Visit

With the wildebeest migration in JULY – OCTOBER, this is the best time to see this incredible movement of animals. Although it is not guaranteed that the wildebeest get to Maasai Mara, it has yet to let us down. Also, December to February are great times as it is dryer and good for the Big Cats.

NOTE: The Maasai Mara is an all year round destination with the big cats, and all the big game still in the Maasai Mara Ecosystem.

See Also:

• Hot air ballooning: Joyce Beckwith flies over Maasai Mara in Kenya

Gliding over the Savannah

Ballooning with Joyce Beckwith—Captain Smiles

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)

• Involves substances found in the humors (or body fluids)
• The aspect of immunity that is mediated by macromolecules found in extracellular fluids such as:
• Secreted antibodies
• Complement proteins
• Certain antimicrobial peptides
• Contrasts with cell-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 t_1/2) observed herein were comparable to the 123d t_1/2 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:

How B Cells Adapt?

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

Asthma and Its Covid-19 Risks (or Not)

Updated 02/09/2021

Common asthma treatment reduces need for hospitalization in COVID-19 patients, study suggests

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.

Image via: ShapeAble

References

1. Understanding Asthma 
2. Rosenthal JA, Awan SF, Fintzi J, Keswani A, Ein D. Asthma is associated with increased risk of intubation but not hospitalization or death in COVID-19. Published online October 12, 2020. Ann Allergy Asthma Immunol. doi:10.1016/j.anai.2020.10.002
3. People with Certain Medical Conditions (CDC)
4. Risk of Severe COVID May Hinge on Type of Asthma
5. Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science
6. Inhaled budesonide in the treatment of early COVID-19 illness: a randomized controlled trial

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

1. Roles of Antibodies vs. T Cells in Protecting against COVID-19 
   
   

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:

• Low IFN-I and IFN-III levels and 
• Elevated chemokine expression

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 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