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Wednesday, December 30, 2020

Covid-19 Vaccination — The Latest Developments


Source: @EricTopol

Latest Developments

01/24/2022

T cell responses to early variants were preserved across vaccine platforms. By contrast, significant overall decreases were observed for memory B cells and neutralizing antibodies. Functional preservation of the majority of T cell responses may play an important role as second-level defenses against diverse variants.[56] 


01/26/2021

This new work, published in the journal Science, utilizes a technology called a mosaic nanoparticle vaccine platform.[55] 
For the vaccine, Bjorkman and her colleagues used RBD proteins from up to eight viruses—including the original SARS-CoV-2 and other SARS-like coronaviruses isolated from bats—that were fused onto a nanoparticle with 60 faces. By injecting this vaccine into mice, Björkman and her colleagues found the animals produced diverse antibodies, which in follow-up experiments blocked infections caused by several SARS-like viruses, including coronavirus strains not used to create the vaccines.
The findings raise the exciting possibility that this new vaccine technology could provide protection against many coronavirus strains with a single shot.

12/26/2021

We’ve been working for years on a pan-vaccine for other viruses, like HIV-1, influenza, malaria, Epstein-Barr (NCT03186781; NCT03814720; NCT04579250; NCT04645147; NCT04296279), but no vaccine has successfully made it through clinical trials thus far. The difference for SARS-CoV-2 is that it mutates far less than HIV or influenza, making it more ideally suited for such an approach. If any universal vaccine makes it through the rigorous clinical trial process, it will be a big leap in medicine and science.

12/16/2021

Dr. Justin Groode
Science is plugging along and new vaccines will emerge that work far better because will not rely on the spike protein. My top pick is MigVax, an oral vaccine in human trials that provides IgG & IgA to spike and also 2 non-spike proteins that do not mutate, plus cell-mediated.

10/05/2021

Researchers from Royal Holloway, University of London, have now identified the first genetic link which could make people more predisposed to Cerebral Venous Thrombosis (CVT) which the condition became more prominent in the last year because of its possible link with the AstraZeneca vaccine.

The area of the human genome that strongly correlates with CVT is located in the same region as the blood group gene, the researchers said.  Here is the probability of CVT risk among different blood groups: 
  • AB blood group
    • had a 5.6 times increased risk of CVT
  • A or B blood type
    • had almost a 3 times increased risk of CVT 
compared to blood group O.[53]


08/24/2021

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a life-threatening and mysterious condition that affects a very small number of people who have received the Oxford–AstraZeneca or Johnson & Johnson (J&J) COVID-19 vaccines. It is now estimated that VITT occurred in about 1 in 50,000 people aged under 50 who received the Oxford–AstraZeneca vaccine.[51]

Since he saw the first cases in March, the United Kingdom has changed its vaccination policy, and now recommends the Oxford–AstraZeneca vaccine only for people over 40. VITT is more frequent in younger vaccine recipients, possibly because of their more-robust immune responses.

People with a history of heparin induced thrombocytopenia (HIT) or cerebral sinus vein thrombosis (CSVT) with low platelets are at increased risk of VITT; they should receive an mRNA vaccine (Pfizer or Moderna) rather than an adenoviral vector vaccine.[52]


07/16/2021

Messenger RNA vaccines against COVID-19 were not detected in human milk, according to a small study by UC San Francisco, providing early evidence that the vaccine mRNA is not transferred to the infant.[50]

07/03/2021

A Next Generation Bivalent Human Ad5 COVID-19 Vaccine Delivering Both Spike and Nucleocapsid Antigens Elicits Th1 Dominant CD4+, CD8+ T-cell and Neutralizing Antibody Responses.[49]

07/01/2021

Researchers at La Jolla Institute for Immunology (LJI) have found that T cells from people who have recovered from COVID-19 or received the Moderna or Pfizer-BioNTech vaccines are still able to recognize several concerning SARS-CoV-2 variants.[48]


05/05/2021

A study suggests that vaccination-generated antibody and/or exogenous antibody against S protein not only protects the host from SARS-CoV-2 infectivity but also inhibits S protein-imposed endothelial injury.[46]

The Pfizer-BioNTech vaccine is incredibly effective against severe disease caused by two variants, study says.[47]


04/21/2021

The Digital Green Certificate proposed by European Commission will have three certificates included within it including:
  • Vaccination certificates, stating brand of the vaccine used, data and place of inoculation and number of doses administered.
  • Negative test certificates (either a NAAT/RT-PCR test or a rapid antigen test). Self-tests will be excluded for the time being.
  • Medical certificates for people who have recovered from COVID-19 in the last 180 days.

04/16/2021

The FDA, CDC Pause On Johnson & Johnson Covid-19 Vaccines—the pause is to give officials and scientists time to further investigate why six people in the U.S. developed cerebral venous sinus thrombosis (CVST), a rare but severe type of blood clot, after receiving the vaccine, and how to deal with this potential risk.[45]



04/02/2021

Side effect worry grows for AstraZeneca vaccine.[44]
  • The highly unusual combination of symptoms—widespread blood clots and a low platelet count, sometimes associated with bleeding—has so far been reported from at least seven countries.
  • So far, most of the clotting cases have been observed in women under age 65.

02/26/2021

Simple explainer for the potential asymptomatic carrier state after vaccines and why we still need masks for a stretch


02/24/2021

Pfizer/BioNtech And Moderna MRNA Covid-19 Vaccines Closely Mimic The Immune Response Of Natural SARS-CoV-2 Infections.[41]


02/08/2021

The optimistic mood around COVID-19 vaccine rollouts has been clouded by new variants of the virus, which could trample the efficacy of vaccines or escape them entirely.[40]

 
02/03/2021

Newborn antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination.[39]


01/29/2021

In an interim analysis of a phase 3 clinical trial conducted in the UK, the Novax vaccine has shown 89% efficacy, with 27% of participants in the trial – almost 4,000 people – older than 65. That trial suggested 95.6% efficacy against the original coronavirus and 85.6% efficacy against the more recent UK variant.[37]

The overall efficacy of J&J vaccine is 66%, but 72% in the US. That disguises some very important and exciting results. First, the vaccine had 85% efficacy against severe disease anywhere in the world – which includes South Africa where almost all participants had the variant form of the virus. That is hugely reassuring for the vaccine effort. Second, nobody in the trials who was given the vaccine was admitted to hospital or died – so 100% efficacy against the worst outcomes.[37]


01/20/2021

The new COVID-19 variant identified in South Africa can evade the antibodies that attack it in treatments using blood plasma from previously recovered patients, and may reduce the efficacy of the current line of vaccines, scientists said on Wednesday.

More than ten companies are coming together to make a digital vaccine card for Covid-19.[36]


01/17/2021

Germany says new COVID variants require new measures.[33]


01/15/2021

Norway Warns of Vaccination Risks for Sick Patients Over 80.[31]


01/14/2021

Europe Considers Vaccine Certificate to Boost Travel and Economy.[32]
Over a video conference on Jan. 21, European Union leaders will discuss the introduction of a “vaccination certificate” that would allow holders to travel freely

01/12/2021

A research showed that NSAIDs may alter the immune response to SARS-CoV-2 vaccination.[30]


01/10/2021

Japan’s Ministry of Health said the four passengers who arrived at Japan’s Haneda airport from Brazil on Jan. 2 were later diagnosed with a variant of the virus. One male in his 40s, who was asymptomatic upon arrival, was hospitalized as his respiratory system worsened.[28]

Confirmed Reinfection with SARS-CoV-2 Variant VOC-202012/01.[29]


01/04/2021

A new variant of the novel coronavirus identified in South Africa is "even more of a problem" than the highly contagious strain spreading rapidly in the United Kingdom, according to U.K. Health Secretary Matt Hancock.[27]

12/30/2020

Britain grants approval to coronavirus vaccine by Oxford and AstraZeneca[26]

12/29/2020

Spain Plans A "Registry" For Those Who Refuse COVID Vaccine[25]

12/28/2020

Vaccine overdose puts German care workers in hospital:[23]
Vorpommern-Ruegen district authorities said the workers in Stralsund city received five times the recommended dose of the BioNTech-Pfizer vaccine on Sunday. Four went to hospital for observation after developing flu-like symptoms.
Travel Insurers Likely To Make Vaccination A Requirement, New Report Finds[24]

12/24/2020

New Coronavirus Strain: Will Vaccines Still Work On Variant Found In The U.K.?[21]
The new variant has 17 mutations within it, of which 8 are affect the gene that codes for the spike protein. 
But, “relative to the size of the protein, the new variant still harbors few changes,” Professor Martin Michaelis of the University of Kent’s School of Biosciences said.

Immune responses, he added, tend to target multiple sites of a protein. So these changes aren’t expected to have a substantial impact on how well the vaccines work. But he cautioned: “only time and more research will provide a definitive answer to this question.” 
12/26/2020

Scientists Scramble To Identify Culprit Behind Covid Vaccine Allergic Reactions:[22]
For now, the CDC says people who have a history of severe allergic reactions to any component of the Pfizer-BioNTech or Moderna vaccines should not receive the vaccine, and those who have a severe allergic reaction after the first dose should not receive the second. The agency also says people who get the shots should be observed for 15 minutes after vaccination to monitor for possible adverse reactions. People with a history of anaphylaxis should be observed for 30 minutes, it says.
12/19/2020

FDA investigating five allergic reactions after Pfizer shot in U.S.[18]

12/18/2020

South Africa identifies new coronavirus strain causing surge in cases.[16]

FDA grants authorization to Moderna’s Covid-19 vaccine, the second in the U.S.[17]

12/17/2020

FDA Briefing Document — Moderna COVID-19 Vaccine (link)

Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 vaccine outweigh its risks for use in individuals 18 years of age and older?

Yes: 20 / No: 0 / Abstain: 1


12/15/2020
“Vaccination may protect the individual but not their contacts,” says Emily Hyle, an infectious disease physician at Massachusetts General Hospital in Boston. “We need more information before using vaccination status to change guidance about masking and social distancing.”[12]
A health worker in Alaska had a serious allergic reaction after getting Pfizer Inc’s coronavirus vaccine.[13]
12/13/2020

The headline news says SARS-CoV-2 Reinfection Is Rare but Possible.  So, preventive measures are important, whether you’ve had COVID-19 or not.
“We expect immunity will wane in people who have been infected, but we don’t necessarily know how long that would take. We’re not seeing tremendous numbers of reinfections, which suggests that the immune response may last a while. But it’s very important to stress to patients that reinfections can happen – and that the symptoms of reinfection may be different than the first bout of illness. It is quite possible that a reinfected person may be less symptomatic or asymptomatic and still shed the virus, infecting their friends and loved ones,” said Dr. Esper.

12/12/2020

Peru suspended trials for China’s Sinopharm COVID-19 vaccine due to a “serious adverse event” that occurred with one of the volunteers for the study, the Peruvian government said in a statement on Saturday. One volunteer was said to had experienced decreased strength in his legs among other symptoms.[10]

12/11/2020

The Sanofi/GSK protein sub-unit vaccine is said to not work well enough in older people.

Australia halts home-made COVID vaccine production on HIV false positives.[19]

12/10/2020

A Food and Drug Administration panel voted 17 to 4, with one abstention, that the benefits of a vaccine developed by Germany-based BioNTech and U.S.-based Pfizer outweigh any risks.[8]


12/09/2020

People with a significant history of allergies should not currently receive the Covid-19 vaccine from Pfizer Inc. and BioNTech SE, the U.K.’s National Health Service said, after two people experienced reactions from the shots.[5]

What exactly happened?

Two UK health care workers with a history of significant allergic reactions reported anaphylactoid reactions and are recovering well.

Anaphylactoid reactions are allergic reactions that share some of the characteristics of anaphylaxis but are less severe, said UK Drug Safety Research Unit Director Saad Shakir.  

Who Should Not Get the Vaccine? 

British regulators initially responded by saying anyone with a history of a significant allergic reaction to a vaccine, medicine or food should not take the shot. An adviser to the group later said it was “tweaking” advice in part to say a food allergy was not a risk.

Pfizer had excluded people with a history of significant adverse reaction to vaccines or its vaccine’s ingredients from late stage trials.

It was crucial, Alexander Gintsburg, the Sputnik vaccine’s developer said, to refrain from alcohol three days before and after the two injections required. He said such advice was the same for anyone getting vaccinated around the world and not specific to Russia or Sputnik.[6]

References

  1. What the FDA's review reveals about Pfizer's COVID-19 vaccine
  2. FDA Briefing Document Pfizer-BioNTech COVID-19 Vaccine
  3. COVID-10 Vaccine F&Q
  4. FDA Says 2 Participants In Pfizer COVID Vaccine Trial Have Died
    • To be sure, it's unclear whether the participants who died succumbed to vaccine-related complications, or whether they even received a vaccine at all (they could have received a placebo).
  5. U.K. Says Those With Severe Allergy Should Avoid Pfizer Shot
  6. Don't mix Sputnik vaccine with alcohol, says Russian official. Some recoil
  7. Explainer: What the UK cases of allergic reaction mean for Pfizer's COVID-19 vaccine
  8. Pfizer Shot Gets FDA Advisers’ Nod as Agency Decision Nears
  9. Vaccine bootcamp (nice animation)
  10. Peru suspends Sinopharm COVID-19 vaccine trial after 'adverse event'
  11. SARS-CoV-2 Reinfection Is Rare but Possible
  12. The Coronavirus Vaccine Could Be the Ultimate Gateway Drug
  13. Health worker in Alaska had serious allergic reaction after Pfizer's vaccine - NYT
  14. Yes, people who’ve had Covid-19 can still benefit from the vaccine
  15. Vaccination is the only acceptable path to herd immunity
  16. South Africa identifies new coronavirus strain causing surge in cases
  17. FDA grants authorization to Moderna’s Covid-19 vaccine, the second in the U.S.
  18. FDA investigating five allergic reactions after Pfizer shot in U.S
  19. Australia halts home-made COVID vaccine production on HIV false positives
  20. UKvariant with 9 mutations in the Spike Protein
  21. New Coronavirus Strain: Will Vaccines Still Work On Variant Found In The U.K.?
  22. Scientists Scramble To Identify Culprit Behind Covid Vaccine Allergic Reactions
  23. Vaccine overdose puts German care workers in hospital
  24. Travel Insurers Likely To Make Vaccination A Requirement, New Report Finds
  25. Spain Plans A "Registry" For Those Who Refuse COVID Vaccine
  26. Britain grants approval to coronavirus vaccine by Oxford and AstraZeneca
  27. South Africa variant 'even more of a problem' than UK strain, health secretary says
  28. Japan Says It Found New Coronavirus Variant Similar to U.K. Strain
  29. Confirmed Reinfection with SARS-CoV-2 Variant VOC-202012/01
  30. Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection
  31. Norway Warns of Vaccination Risks for Sick Patients Over 80
  32. Europe Considers Vaccine Certificate to Boost Travel and Economy
  33. What you need to know about the coronavirus right now
  34. New COVID-19 variant defeats plasma treatment, may reduce vaccine efficacy
  35. Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States (CDC)
  36. The Big Tech Coalition Designing Digital Vaccine IDs For Covid-19
  37. Will Novavax and Johnson & Johnson Covid vaccines work against variants?
  38. Myths of Vaccine Manufacturing
  39. Newborn antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination
  40. Vaccines Versus the Mutants
  41. Pfizer/BioNtech And Moderna MRNA Covid-19 Vaccines Closely Mimic The Immune Response Of Natural SARS-CoV-2 Infections
  42. Pfizer/BioNtech And Moderna MRNA Covid-19 Vaccines Closely Mimic The Immune Response Of Natural SARS-CoV-2 Infections
  43. CD24-Exosomes (Clinical Trial)
  44. Side effect worry grows for AstraZeneca vaccine
  45. The reasons behind the FDA and the CDC pause on the Johnson & Johnson Covid-19 vaccines 
  46. SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2
  47. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants
  48. Moderna and Pfizer-BioNTech vaccines prime T cells to fight SARS-CoV-2 variants
  49. A Next Generation Bivalent Human Ad5 COVID-19 Vaccine Delivering Both Spike and Nucleocapsid Antigens Elicits Th1 Dominant CD4+, CD8+ T-cell and Neutralizing Antibody Responses
  50. No Sign of COVID-19 Vaccine in Breast Milk
  51. COVID vaccines and blood clots: what researchers know so far
  52. Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following Adenovirus Vector COVID-19 Vaccination
  53. Clot risk linked to AstraZeneca vaccine could depend on which blood group you are
  54. Pan-coronavirus "super" vaccine
  55. Mosaic RBD nanoparticles elicit neutralizing antibodies against SARS-CoV-2 and zoonotic coronaviruses . Cohen AA, Gnanapragasam PNP, Lee YE, Hoffman PR, Ou S, Kakutani LM, Keeffe JR, Barnes CO, Nussenzweig MC, Bjorkman PJ. Science. 2021 Jan 12.
  56. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron
  57. Role of drug delivery technologies in the success of COVID-19 vaccines: a perspective
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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
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Saturday, December 26, 2020

Risk Factors for Covid-19

Transmission of the Covid virus occurs via respiratory secretions and saliva. Droplets are expelled through the mouth or nose and can directly land on the mucous membranes (mouth, nose, eyes) of another person. Indirect transmission is also possible either from droplets landing on the skin of another person who then touches his or her mucous membranes or from touching a surface that has been infected.

Inter-individual clinical variability after respiratory infection with SARS-CoV-2 is immense.  Most infected individuals (>98%) remain asymptomatic or develop mild, ambulatory disease. 
"Patients with COVID-19 display a wide array of clinical manifestations and degrees of severity, ranging from flu-like symptoms to acute respiratory distress," said Robert E. Gerszten, MD. "While pre-existing conditions, particularly cardiovascular and metabolic disease, are risk factors for disease severity and outcomes, the underlying reasons that some people develop life threatening disease while others remain asymptomatic are not well understood."

Different Post-Infection Symptoms & Outcomes


What is it that makes some people very sick and other people hardly sick at all? 
There are two major possibilities from the genetics perspective:[23]
  1. The genetic sequence of the virus itself: that some strains make people sicker than others
  2. The unique genetics of each person who catches the disease.

After COVID-19 infection, some people[5]
  • Requires hospitalization (<2%)
    • Some people develop pneumonia 1 to 2 weeks post infection and require hospitalization 
  • Require intensive care (<0.5%)
    • Because of acute respiratory distress syndrome (ARDS) and/or the failure of other organs
  • Develop a severe systemic inflammatory response syndrome (SIRS)  (<0.01%)
Figure 1.  Various outcomes due to different timing and dose of IFN response (courtesy: @BioRender & @annsea_park)


Risk Factors


The diseases and health factors that, according to a study done in Denmark, have the most influence on whether a patient ends up on a respirator after being infected with COVID-19 are in order of priority: BMI, age, high blood pressure, being male, neurological diseases, COPD, asthma, diabetes and heart disease.[38]

Wang said the immunological factors the researchers have identified — a sluggish neutralizing-antibody response, deficient fucose levels on antibody-attached sugar chains, and hyperabundant receptors for fucose-deficient antibodies — were each, on their own, modestly predictive of COVID-19 severity. But taken together, they allowed the scientists to guess the disease’s course with an accuracy of about 80%.

Based on other researches, list of risk factors for Covid-19 also includes:[1,3,6,7,12,13]

  • 3 Immunological factors identified 
    • A sluggish neutralizing-antibody response, deficient fucose levels on antibody-attached sugar chains, and hyperabundant receptors for fucose-deficient antibodies — were each, on their own, modestly predictive of COVID-19 severity. 
    • But taken together, they allowed the scientists to guess the disease’s course with an accuracy of about 80%.[53]
  • Air pollution
    • Dr. Anita Shallal of Detroit's Henry Ford Hospital said long-term exposure to air pollution may impair the immune system and make it more susceptible to viral infections, while fine particles in air pollution may also act as a carrier for the virus and help it spread.[47]
  • Blood type
    • A multivariate linear model confirmed the significance of the “B+” frequency predictor as protective against death by COVID-19.[51]
  • High viral load environment (i.e., hospitals)[41]
    • Japanese are advised to avoid crowds, clubs, and close contact in closed spaces, especially if it involves talking and singing.[33]
  • Age (major risk)
    • Both mortality and critical disease are frequently reported in subjects >65 years of age but rarely in those <20 years of age.
  • Pre-existing conditions
    • See the next sub-section for details
  • Deficiency of Vitamin D
    • Among hospitalized COVID-19 patients, pre-infection deficiency of vitamin D was associated with increased disease severity and mortality.[54]
  • Male[3,6]
    • The risks for critical illness and mortality in male were estimated to be 1.5 times and 1.3 times higher than female.
      • The studies in early 1940s ascertained that females have enhanced capability of producing antibodies. This enhanced immune reactivity in females helps mount an effective resistance to infection and therefore females are less susceptible to viral infections.
    • The most high-risk group includes older males (see Fig. 2) with underlying chronic health conditions such as diabetes, cardiovascular conditions, obesity, and hypertension.
    • Male coronavirus patients with low testosterone levels are MORE likely to die from COVID-19, German hospital finds[24]
      • However, the role of testosterone played in COVID-19 patients is a double-edged swords[30]
        • Low testosterone levels in males have a direct correlation with the high probability of ICU admission and the worse disease outcome. 
        • On the contrary, however, high testosterone levels can lead to thrombosis which is also one of the fatal manifestations in COVID-19 patients.
      • Testosterone is known to help regulate the body's immune response but when a man has low levels of testosterone, the immune system is not kept in check and can go haywire (i.e., cytokine storm) following infection. 
  • Genetic variations[11]
    • A higher risk in blood group A than in other blood groups and a protective effect in blood group O as compared with other blood groups.
    • A 3p21.31 gene cluster was identified as a genetic susceptibility locus in patients with Covid-19 with respiratory failure.
    • The genetic variants in the NKG2C/HLA-E axis have a significant impact on the development of severe SARS-CoV-2 infections[40] 
    • The major genetic risk factor for severe COVID-19 is inherited from Neanderthals[29] 
  • Compromised antiviral responses
    • Early robust IFN response is crucial[13,14]
      • In the best case scenario, a rapid and robust induction of Interferon type I (IFN-I) should result in viral control and mild disease. (see Figure 1)
        • This may happen in young people, or with low viral exposure settings.
      • Neutralizing autoantibodies  (auto-Abs) to IFN-I underlie life-threatening COVID-19 pneumonia.
        • A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.  
        •  In these patients, adaptive autoimmunity impairs innate and intrinsic antiviral immunity. 
      • Individuals that lack specific IFNs can be more susceptible to infectious diseases.
    • The timing of early antibody response is crucial[12] 
      • A delay in antibody responses could lead to more severe COVID-19 symptoms or even death.
      • Patients who developed neutralizing antibodies (NAb) before 14 days of symptom eventually recovered, while those who made NAb after 14 days developed severe disease and sustained higher viral load (i.e., viral load went out of control).
    • Neuro-COVID
      • This group of patients can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease
        • It is more prevalent in patients with severe COVID-19
      • The cerebrospinal fluid (CSF) of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells, which suggest compromised antiviral responses.
    • Increased plasma D-dimer level
      • There exists a significant correlation between increased plasma D-dimer level with an increased proportion of COVID-19 case severity. 
      • A systematic review shows that a level of 3.48 μg/mL, which is over five times higher than in non-severe/survival cases, could result in poor outcomes in hospitalized COVID-19 patients.[52]
    • Autoantibodies to immune-related or tissue-specific self antigens
      • The more severe the disease, the more autoantibodies COVID patients had.[31] 
        • There are many unanswered questions. How long do these autoantibodies last? What damage do they cause? How are they induced? Do they occur in #LongCovid?
      • Immune-related antigens
        • Some antibodies bound to interferons, chemokine and cytokines, while others bound to proteins expressed on the surface of immune and non-immune cells. Such antibodies could dampen body's immune response.
      • Tissue-specific antigens
        • Antibodies to various tissue-specific antigens were also found in organs like the central nervous system, vascular, connective tissues, liver, GI tract, etc. Such antibodies could drive damage in target tissues.
Figure 2.  Older males with the highest risk


Pre-existing Conditions 


Adults of any age with the following conditions are at increased risk of severe illness from the virus that causes COVID-19:[17]
  • Cancer
  • Chronic kidney disease
  • Respiratory issues 
  • Heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
  • Moderately to severely immunocompromised (weakened immune system) people[49]
    • Been receiving active cancer treatment for tumors or cancers of the blood
    • Received an organ transplant and are taking medicine to suppress the immune system
    • Received a stem cell transplant within the last 2 years or are taking medicine to suppress the immune system
    • Moderate or severe primary immunodeficiency (such as DiGeorge syndrome, Wiskott-Aldrich syndrome)
    • Advanced or untreated HIV infection
    • Active treatment with high-dose corticosteroids or other drugs that may suppress your immune response
  • Obesity (body mass index [BMI] of 30 kg/m2 or higher but < 40 kg/m2)
  • Severe Obesity (BMI ≥ 40 kg/m2)
  • Pregnancy
    • Based on what we know at this time, pregnant people are at an increased risk for severe illness from COVID-19 compared to non-pregnant people.[44]
  • Sickle cell disease
  • Smoking
    • Cigarette smoke induces expression of angiotensin-converting enzyme 2 (ACE2), which allows SARS-CoV-2 to enter cells, and could possibly influence viral invasion beyond its negative effects on overall lung function.
    • A study from Cleveland Clinic’s Respiratory Institute is among the first to look at the cumulative effect of smoking on COVID-19 outcomes.  And, it found that the more a patient was exposed to smoking, the more likely they were to have worse outcomes from COVID-19.[46]
  • Thyroid abnormalities[48]
    • Abnormal thyroid and hypothyroidism, but not hyperthyroidism, were associated with poor COVID-19 outcomes.
  • Type 2 diabetes mellitus
    • DM is a risk factor for a worse prognosis for COVID-19, which may be related to impaired innate immune response and greater susceptibility of patients with DM to a cytokine storm.[8,9]
  • Pre-existing psychiatric diagnosis[1]
    • The researchers at Univ. of Oxford have found that people with a pre-existing psychiatric diagnosis were 65% more likely to be diagnosed with COVID-19 than those without, even when the known risk factors for COVID-19 were taken into account.
  • Dementia
    • People with dementia had significantly greater risk of contracting the coronavirus, and they were much more likely to be hospitalized and die from it, than people without dementia, a new study of millions of medical records in the United States has found.[39]

References

  1. New Research Published in The Lancet Psychiatry Finds COVID-19 Associated with Increased Risk for Developing Psychiatric Disorders
  2. Long-Haul COVID-19: Putative Pathophysiology, Risk Factors, and Treatments
  3. Androgen deprivation strategies could help mitigate SARS-CoV-2 infection
  4. Life-Threatening COVID-19: Defective Interferons Unleash Excessive Inflammation
  5. Casanova J.L., Su H.C., COVID Human Genetic Effort—A Global Effort to Define the Human Genetics of Protective Immunity to SARS-CoV-2 Infection. Cell. 2020; 181: 1194-1199
  6. Life-Threatening COVID-19: Defective Interferons Unleash Excessive Inflammation
  7. Coronavirus: what it means for you if you have heart or circulatory disease
  8. Huang I., Lim M.A., Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia–A systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020;14:395–403.
  9. Guo W., Li M., Dong Y., Zhou H., Zhang Z., Tian C. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020.
  10. Researchers reveal how genetic variations are linked to COVID-19 disease severity
  11. Genomewide Association Study of Severe Covid-19 with Respiratory Failure
  12. What aspects of antibody responses determine the outcome of #COVID19? 
  13. The role of type I interferons (IFN) in #SARS_CoV_2 infection?
  14. Autoantibodies against type I IFNs in patients with life-threatening COVID-19
  15. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
  16. COVID-10 and pregnancy (CDC)
  17. People with Certain Medical Conditions (CDC)
  18. Even Mild Covid-19 Infections Can Make People Sick for Months
  19. Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact
  20. As evidence builds that COVID-19 can damage the heart, doctors are racing to understand it
  21. A perspective on potential antibody-dependent enhancement of SARS-CoV-2
  22. COVID-19 survivors suffer long term heart conditions
  23. Your Risk of Getting Sick From Covid-19 May Lie in Your Genes
  24. Male coronavirus patients with low testosterone levels are MORE likely to die from COVID-19, German hospital finds
  25. Covid Doctors Find a Turning Point in Life-Threatening Cases
  26. Strokes and mental state changes hint at how COVID-19 harms the brain
  27. Death Rate of Covid-19 by Age / Prior Illness / Ethnic Group
  28. COVID's cognitive costs? Some patients' brains may age 10 years
  29. The major genetic risk factor for severe COVID-19 is inherited from Neanderthals
  30. Role of testosterone in COVID-19 patients – A double-edged sword?
  31. Diverse and functional autoantibodies in #COVID patients found
  32. Skin Symptoms in Most Children with Multi-System Inflammatory Syndrome Related to COVID-19
  33. Ventilation and viral loads: the key misunderstandings of how coronavirus spreads
  34. Vitiligo and Covid-19 risk
  35. Immune determinants of COVID-19 disease presentation and severity
  36. How COVID-19 Is Transmitted and Who Is Most at Risk
  37. Sex differences in immune responses
  38. Computer can determine whether you’ll die from COVID
  39. People With Dementia Are Twice as Likely to Get Covid, Huge Study Finds
  40. Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19
  41. Tracking smell loss to identify healthcare workers with SARS-CoV-2 infection
  42. Coronavirus Deranges the Immune System in Complex and Deadly Ways
  43. Sex differences in immune responses that underlie COVID-19 disease outcomes
  44. Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface
  45. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
  46. More Smoking Pack Years Can Mean Worse Outcomes of COVID-19 Infection
  47. Dirty air makes COVID worse, beta variant deadlier than original
  48. Thyroid disease and hypothyroidism are associated with poor COVID-19 outcomes: A systematic review, meta-analysis, and meta-regression
  49. COVID-19 Vaccines for Moderately to Severely Immunocompromised People
  50. Brain Injury in COVID-19 is Associated with Autoinflammation and Autoimmunity
  51. Country-level factors dynamics and ABO/Rh blood groups contribution to COVID-19 mortality
  52. Roy, Molay (2020-09-14). "Elevated D-dimer is Associated with Severity of COVID-19 | Science Trend
  53. Antibodies in blood soon after COVID-19 onset may predict severity
  54. Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness
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Friday, December 25, 2020

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:

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
    1. Norway's West: Fjords, Mountains, and Bergen (video)
    2. Eurail
    3. 12-Day Norway & North Cape from Hamburg B
    4. Oslo, Norway
    5. Driving the roof of Norway
    6. USEFUL INFORMATION FOR LOM AND JOTUNHEIMEN
    7. NORWAY'S TRAINS AND FJORDS
    8. HOW TO GET FROM Kiruna IRF to Lofoten BY TRAIN, BUS OR CAR
    9. Driving from Narvik to Lofoten (car rental)
    10. 11 things you should know about visiting the Lofoten Islands
    11. 20 FAMOUS LANDMARKS IN NORWAY
    12. 25 Most Beautiful Destinations in Europe - Travel Video
      • 4. Lofoten Islands, 17. Pulpit Rock




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