COVID-19 and SARS-CoV2: Research Studies Related to Genetics

This is an annotated list of research studies (most are preprints) that are related to SARS-CoV2, COVID-19, and genetics.

The COVID-19 pandemic is an evolving situation with lots of data – sometimes contradictory data – being released daily.  My goal here is to keep track of the research studies on SARS-CoV2 as it relates to genetics.

COVID-19 Studies and Genetics:

Terminology:

  • SARS-CoV2 is the name of the virus that causes the disease known as COVID-19. It is a coronavirus that is genetically fairly similar to the original SARS virus that emerged in 2002-2003 in SE Asia. There are several other coronaviruses that circulate each year that cause the common cold.
  • Preprint articles are written reports of studies from universities and scientists, but they have not been through the editing and peer-review process.  Some preprints are great, some not so great.
  • SARS-CoV-2 uses the ACE2 (angiotensin-converting enzyme 2) to enter a cell and uses the cellular serine protease 2 (TMPRSS2) for S (spike) protein priming.
  • Everything has a bias – from local news to the media stories that you read online. Currently, many of the online media outlets including You Tube, Face book, Twitter, Medium, Reddit, and more are not allowing anything to be posted that contradicts the official information from the WHO. While that cuts down on the wackos, it also silences a lot of real scientific discussion. Thus, there is an inherent bias in what you are allowed to see or not see on the internet right now.
  • Have something to add? Get in touch. I’m happy to hear from you.

Research on SARS-CoV2 (with genetic connections):

Epidemic calculator — play with it and see if you can model the spread in your country/state

Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals 5/14/20
Research study published in Cell that looks at the T cells (immune system cells) that are produced in people who had moderate cases of COVID-19. The results showed that people with COVID produce CD4+ T-cells (i.e. T-helper cells) that are responsive to several different SARS-CoV2 proteins.
Of interest here is that the researchers looked at samples taken from people from 2015-2018 as controls. About half of those samples had cross-reactive CD4+ T cells that reacted to SARS-CoV2. Theoretically, this could mean that a large portion of the population already has at least partial immunity, possibly due to previous coronavirus infections (common cold).

Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors 5/17/20
This is a second study (Germany) looking at the T-helper cells (CD4+) that are part of the response in COVID-19 patients. This study also found that healthy donors had T-cells that react to SARS-CoV2 (34%).  The researchers conclude “The presence of pre-existing SARS-CoV-2-reactive T cells in healthy donors is of high interest but larger scale prospective cohort studies are needed to assess whether their presence is a correlate of protection or pathology. ”

Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune  Homeostasis and Reduces Plasma Viral Load in Critical COVID-19 5/5/20
Preprint that explains the use of an experimental HIV drug in patients who were terminally ill who had COVID-19. The research looks at the effect of a CCR5 medication, leronlimab, and examined the impact on the inflammatory cascade (IL-6, IL-1B, IL8, and CCL5). It seems like targeting CCR5 was effective at drastically dropping IL-6 and decreasing viral load.
Genetics connection: People who carry two copies of the CCR5-delta32 mutation are resistant to HIV.  (Check your genetic data here) It is not yet known if the CCR5-delta32 mutation affects susceptibility to SARS-CoV2.

Famotidine Use is Associated with Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study 5/7/20
Study of 1600+ patients in the hospital for COVID-19 (NY). about 5% of patients were receiving famotidine (aka Pepcid). Those on famotidine were at a 70% decreased risk of death even when adjusted for all the various variables. So famotidine is a histamine receptor 2 blocker.  The H2 receptors are activated by histamine and responsible for releasing stomach acid.  The study also looked at proton pump inhibitors (also used for blocking stomach acid) usage and found that they did not affect mortality.
Genetics connection:  In addition to blocking the H2 receptor, famotidine also inhibits viral replication in HIV.  But – perhaps more interestingly – H2 receptors are also found in the lungs, so perhaps the famotidine is blocking the H2 receptors in the lung.

Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system 4/30/20
A well-written and readable explanation of why nicotine may help protect against severe COVID-19 — answering the paradoxical question of why smokers are less likely to have severe COVID when they, at first glance, seem like they should be at a higher risk (comorbidities, black lungs, smoking is just bad…).  The authors tie this into the possible neurological manifestations, including the loss of smell, which is something that also happens in Parkinson’s. (Animal models show nicotine improves the loss of smell in Parkinson’s…) Interestingly, this also ties into the small blood clots seen in COVID-19. Platelets also have nicotinic cholinergic receptors. The article concludes with the idea of testing nicotine patches in addition to antivirals for severe COVID-19. Note- these researchers are not recommending smoking!
Genetic connections: The researchers note that ACE2 receptor expression does not seem to matter in severity of COVID-19 (also seen in SARS). Instead, they theorize that the nicotinic cholinergic system, which is highly polymorphic, is more important in the severe COVID cases.

COMPLEX IMMUNE DYSREGULATION IN COVID-19 PATIENTS WITH SEVERE RESPIRATORY FAILURE 4/22/20
This is a preprint published by the journal Cell, a highly respected journal. The researchers and medical doctors (EU) discuss the immune response of 54 patients with COVID-19 who had severe respiratory failure. The doctors note that there is sustained TNFα and IL6 throughout the respiratory failure, but that HLA-DR expression was really low.
Genetic Connection: This paper really interesting — and ties in with genetics research on people who got the original SARS virus. The study shows that all patients with severe respiratory failure and COVID-19 have either immune dysregulation or macrophage-activation syndrome. Researchers found that a certain HLA-DRB1 genotype, which causes overactive HLA-DR, was protective against getting SARS. Really protective (OR=0.06).  (SNP listed in article on viral immunity.)

Gut microbiota may underlie the predisposition of healthy individuals to COVID-19 – 4/26/20
Preprint article by researchers in China looking at the proteomics and gut microbiota of people with COVID-19 (small number) vs a large control group from the same population. Of particular interest here were links between specific gut microbiome species, IL-6 levels, and the age of the individuals. The researchers were using a machine-learning algorithm to predict which microbiota signatures were associated with susceptibility to severe COVID-19.
Genetic connection: Lactobacillus species were one risk factor in this Chinese population for severe COVID-19. Genetically, most people of Asian background are lactose intolerant as adults and rely on lactobacillus species to digest dairy. Additionally, this paper is notable for not finding an association with bifidobacteria, which would have possibly indicate a relationship with non-secretor status (FUT2 gene).

SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues 4/22/20
While at first glance this preprint article in Cell seemed like it just reiterated known information about the ACE2 and TMPRSS2 tissue expression (epithelial cells in lungs, nose, and intestines), the researchers also found that ACE2 expression is upregulated by interferon. This is pretty important (in my opinion). Interferon is produced by the body as a first-line defense against viral infections. So if interferon causes the cells in the lungs to produce more of the ACE2 receptors, then the body’s innate defense is actually allowing the infection to enter lung cells more easily.
Genetics connection: A lot of researchers are looking towards genetic variants in ACE2 to explain why some people are asymptomatic vs people who get more severe symptoms. So far it is just speculation – and original SARS research shows there is no genetic connection for ACE2. Instead, it may be that baseline ACE2 isn’t important and the difference is in how great the upregulation of ACE2 is due to varied interferon production.

Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring 4/25/20
In this preprint, researchers looked at the effect on QT interval for people with COVID-19 who were treated with either azithromycin or hydroxychloroquine — or the combination of both. The results showed that the QT interval was prolonged in 12% of the patients, with the biggest impact seen with the combo of drugs. Additionally, the change to QT interval was only found in men.
Genetic connection: There are several well researched genetic variants that greatly increase the risk of prolonged QT interval from hydroxychloroquine.  (No, I haven’t written the article on that yet.)

SARS-CoV-2 RNA titers in wastewater anticipated COVID-19 occurrence in a low prevalence area 4/25/20
Study out of Spain explaining the detection of SAR-CoV2 in municipal sewage treatment plants. The study shows that the SARS-CoV2 virus was detectable in sewage prior to any cases being reported in the country.
Genetics connection: Not sure that there is one…  My undergrad degree was in engineering with a minor in environmental engineering – and I find it is interesting what sewage sampling can show about diseases (and drug usage) in a city population :-)

Lack of association between genetic variants at ACE2 and TMPRSS2 genes involved in SARS-CoV-2 infection and human quantitative phenotypes 4/25/20
In this preprint out of the Netherlands, researchers looked at a bunch of genetic data and patient data from people prior to the COVID-19 outbreak. They were trying to determine if ACE2 or TMPRSS2 genetic variants were linked with any particular blood markers, but they didn’t find anything.
Genetics connection: The ACE2 and TMPRSS2 genes are implicated in the way that SARS-CoV2 enters into the cells in the lungs. While there has been some wild speculation from other genetics companies trying to sell people reports and supplements (yeah, you know who you are… ), the research from the original SARS outbreak showed that the ACE2 and TMPRSS2 genetic variants did not play a role in susceptibility to the disease.

Self-reported symptoms of covid-19 including symptoms most predictive of SARS-CoV-2 infection, are heritable 4/22/20
This is a genetics study using twins in the UK who had COVID19 and took a survey on their symptoms.
Genetics Connection: The study results showed that symptoms are about 50% heritable – meaning that there is a pretty strong genetic component as to which symptoms a person has from the virus. The highest amongst the genetic results were anosmia (loss os smell), fever, and delirium.  This is a fascinating study explaining why different people have different symptoms of the same virus.

High prevalence of putative invasive pulmonary aspergillosis in critically ill COVID-19 patients 4/21/20
A study out of France showing that 33% of patients admitted to the ICU for COVID-19 had invasive pulmonary aspergillosis, a fungal infection in the lungs. Researchers knew to look for this because flu patients who die of pneumonia often also have invasive pulmonary aspergillosis.
Genetic connection: There are several genetic variants that influence susceptibility to infection by invasive aspergillosis, including NF-kappa beta variants.

Genetic analysis of the novel SARS-CoV-2 host receptor TMPRSS2 in different populations.
This preprint goes through a computer analysis of a bunch of different genetic variants in the TMPRSS2 gene and shows that one variant, rs35074065, is associated with increased gene expression. This is just an analysis of what is known about the variants and not actually looking at the variant within people with COVID-19.
Genetics Connection: Levels of TMPRSS2 vary among people due to different genetic variants — something which has been known for years. It is not known whether or not this has any bearing on COVID-19.

SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors. 4/21/20
This study out of France looked at antibody testing of people with mild-COVID19 symptoms. The results showed that antibodies were developed 5-14 days after symptoms. The researchers also tested blood bank donations and found antibodies in 3% of the population (asymptomatic) in that town in France.
Genetic connection: It is really interesting to see all the serology testing that shows a high number of people who had no symptoms from the virus. Genetically, there are mutations and genetic variants that will also influence a person’s ability to produce IgG antibodies.  (Need to write an article on this…)

ACE2 Homo-dimerization, Human Genomic variants and Interaction of Host Proteins Explain High Population Specific Differences in Outcomes of COVID19  4/24/20
A preprint from Indian researchers who were looking at computer models of how ACE2 variants could interact with SARS-CoV2. The researchers looked at different populations and how frequently the genetic variants were found in each group. And…  well, that’s about it.

A cohort study of 223 patients explores the clinical risk factors for the severity diagnosis of COVID-19 4/21/20
This preprint looked at various blood markers in people with COVID-19, comparing severe and non-severe patients. D-dimer was elevated in 87% of severe cases, vs 35% of non-severe patients. D-dimer is present in the body after a clot is dissolved — an indicator that there has been clotting. CRP levels were also elevated in lots more severe cases than non-severe.
Genetic connection: D-dimer levels are linked with a couple of genetic variants and are also linked with flu severity.  CRP levels, which indicate overall inflammation in the body, are also somewhat genetic. (Genetic Lifehacks CRP article)

Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients 4/23/20
These researchers out of France looked at 50 different COVID-19 patients (mild to severe) and did an in-depth analysis of their immune cells, whole-blood transcriptomic and cytokine production. They found that severely ill patients had a profoundly impaired interferon type I response with low production and downregulation of interferon-stimulated genes. There was also an increase in TNF-alpha and IL-6 production.
Genetics connection: There are several different polymorphisms that cause increased or decreased interferon production. There are a couple of SNPs listed in article on viral immunity, but that is just the tip of the iceberg.

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area 4/22/20
This is an article in the Journal of the American Medical Association (JAMA) outlining the characteristics of 5700 patients in NY hospitals with COVID-19. 94% of the hospitalized patients had a chronic health condition — hypertension (56%), obesity (41%), and diabetes (34%) top the list.
Genetics connection: I was going to go into all the genetic connections with hypertension, obesity, and diabetes to see why these would increase the risk of severe COVID-19.  But then I decided to look at the numbers for the population of New York City and see how far out of the norm these chronic health conditions are…  Turns out that 65% of people in NYC over age 65 have high blood pressure. So the 56% hypertension as a co-morbidity is actually less than the population average for older adults.  In people over age 65, the diabetes rate was 28%  and obesity was at 37% in 2017.  (source: NY state gov)

Coast-to-coast spread of SARS-CoV-2 during the early epidemic in the United States
Researchers at Yale looked at the genome of the SARS-CoV2 virus in 9 people who had the virus in CT with samples all collected before March 14th. For those 9 people, the genome of the virus matched with the virus genome out of Washington state. The researchers concluded that initial COVID-19 cases in CT were from people traveling within the US rather than internationally.

Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine 4/24/20
This Letter printed in BMJ explains the course of COVID-19 infection in 17 patients who had lupus and had been on hydroxychloroquine for an average of 7+ years. The conclusion was that the symptoms and clinical progression of COVID-19 were similar to patients who had not been on hydroxychloroquine.

JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy 4/9/20
This preprint from the Down Syndrome institute at CU looks at the inhibition of JAK1 to stop the hypersensitivity of the immune system and cytokine storm that is causing mortality in people with COVID-19. They found that inhibiting JAK1 would attenuate the cytokine storm.
Genetics connection: This was noted to be of particular importance for people with Down syndrome, due to carrying an extra copy of the interferon gene on Chromosome 21.

Mast Cells Contribute to Coronavirus-induced Inflammation: New anti-inflammatory strategy 2/4/20
This article explains how mast cells in the lungs are activated in coronavirus infections and how they add to the severe inflammatory response.
Genetics connectionarticle on genetics and mast cell activation syndrome  – plus see theory section below

Heightened innate immune responses in the respiratory tract of COVID-19  patients 4/17/20
This preprint in Cell shows the results from testing broncheoalveolar lavage fluid (lung gunk) of 8 COVID-19 patients, 146 pneumonia patients, and 20 healthy controls. It is interesting – go read the paper.  Check out Figure 4 at the bottom for the increases in mast cells and neutrophils and decreases in macrophages and natural killer cells.

Antibody/Serology testing results:

Antibody and serology testing is showing the larger portions of the population who have developed antibodies to SARS-CoV2 without having symptoms of COVID-19.

  • Antibodies show up about two weeks after infection, so keep in mind that the antibody results are showing the percentage of the population that had the virus at least two weeks prior.
  • There is a lot of discussions around these results, in part because the logical conclusion to be drawn from the numbers shows that the infection fatality rate is a whole lot lower than expected (e.g. 0.1 – 0.6% instead of the 1-6% that initial numbers showed).
  • Another reason for controversy are questions on whether the antibody testing is accurate enough (false negative and false positive rates).  There were also initial questions on whether previous coronavirus infections would show up in the results, but it seems that those fears have been laid to rest.

Quick overview – Most of these published antibody test results are showing 10 – 40 fold higher antibody results than positive tests in an area. This leads to the conclusion that 90-99% of people have either no symptoms or very mild symptoms from the SARS-CoV2 virus. (assuming here that people with mild symptoms didn’t get a COVID-19 active test)

The infection fatality rate of COVID-19 inferred from seroprevalence data – 5/19/20
Preprint of a study from Stanford looking at the data from 12 population serology studies that had at least 500 people in each study.  The results showed that there is a lot of difference in different areas of the world. The resulting infection fatality rates were between 0.02% (Japan) to 0.50% (Geneva). Over half of the IFRs were less than 0.1%. It makes sense that the IFR would be different between different population groups, different environmental conditions, and different hospital systems.

Estimating the true (population) infection rate for COVID-19: A Backcasting Approach with Monte Carlo Methods 5/17/20
This is a mathematical model looking at case numbers in 15 different countries. The researchers conclude that worldwide, the number of cases is about 18-fold higher than what is being shown through testing. Note that if the case rate is 18-fold higher that would put the case fatality rate around 0.3% (current data, my calculation). This seems to be in line with antibody studies from various places.

SARS-CoV-2 seroprevalence trends in healthy blood donors during the COVID-19 Milan outbreak 5.18.20
Study on healthy blood donors in Milan. The results show that 4% of the population had antibodies to SARS-CoV2 in Feb. prior to the outbreak in Milan. This increased through April to about 10% of the population having antibodies. Of note here – these were healthy blood donors, screened for all signs of COVID-19 prior to giving blood. This shows about a 20-fold higher rate of asymptomatic cases (e.g. about 95% of people who get SARS-CoV2 are asymptomatic).

Results released for antibody testing in Boston residents 5.18.20
This is a press release from the Boston gov’t website explaining that 10% of the population of Boston have antibodies for COVID-19. The study also found that 2.6% of the population was currently asymptomatic and positive for current COVID-19 infection. Note that this is concurrent with being locked down and with masks being mandatory for everyone.

Asymptomatic infection and herd immunity of COVID-19 in Wuhan and Japan 5/6/20
This is a Japanese study (preprint) that looks at the inconsistencies in the high reproductive number not correlating with the data from Wuhan and Japan. These researchers applied a ‘susceptible–infected–recovery model with the proportion of asymptomatic patients among infected people (q) as a key parameter for estimation, along with the basic reproduction number (R0).’  Basically, they are adjusting the R0 value for the initial period, the period when the infection was peaking, and a post-peak rate. Basically, they came up with asymptomatics comprising around 99% of the population in Wuhan, and 99.9% of the population in Japan. The conclude that for Japan and Wuhan “for every symptomatic patient confirmed, approximately 150 or 9000 asymptomatic cases are presumed to exist.”

Estimation of SARS-CoV-2 infection fatality rate by real-time antibody screening of blood donors 4/28/20
A preprint of a study in Denmark using blood donations from April 6th – 17th. Researchers did antibody tests on about 9,500 blood donations. The donors were all healthy adults, ages 17-69. Results showed that about 1.7% of the Danish population had positive antibodies for SARS-CoV2. This is 21-fold higher than the reported number of cases in Denmark.  The researchers published the infection mortality rate at 0.08% which is really low — but noted that this is just for people under age 70, which was their population group of blood donors. There is a higher infection mortality rate (not given) for people over 70.

Article: Cuomo Says 21% of Those Tested in N.Y.C. Had Virus Antibodies 4/24
This is a NY Times article reports on the press conference in which NY Gov. Cuomo announced that an estimated 21% of New Yorkers have previously had the SARS-CoV2 virus and developed antibodies. He said if their numbers are correct, the mortality rate for COVID-19 is around 0.5% in NY.  (This was about 20-fold higher than case numbers at that time, thus leading to about a 95% rate of people being either asymptomatic or too mild to go get tested.

COVID-19 Antibody Seroprevalence in Santa Clara County, California 4/11/20
Preprint of the Stanford testing of residents of Santa Clara county for antibodies. The results showed around 3% of the population was estimated to have antibodies, which would be 50-85 fold higher than published cases for the county. Although the lead researcher on the study is a highly respected leader in the field, there has been a lot of criticism of the study, in part because the study participants were recruited via Facebook and may not be representative of the population as a whole.   (NOTE – this study has now been revised by the author and shows that antibodies in that are were more like 20-50 fold higher than published cases.)

Article: Early antibody testing results reveal more COVID-19 infections than confirmed cases 4/23/20
Neuroscience News article explaining the USC test results for antibodies in a sample population in Los Angeles.  The results showed approximately 4% of the population has previously had SARS-CoV2 and developed antibodies — which was 28 to 55 times higher than confirmed cases. There is a margin of error on the estimate, though, so it is more likely that somewhere between 3% and 5% of the population has had the virus. Los Angeles County had 600 deaths at the time of the article. (Doing the math, that would put the fatality rate between 0.1- 0.3% in LA – although that figure is not included in the article.)

SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors. 4/21/20
This is a preprint from the Oise region in France looking at antibodies in people with cold-like symptoms, hospitalized COVID-19 patients, and blood donors (assumed asymptomatic). The antibodies were found in hospitalized patients 5-14 days after the onset of symptoms. A total of 3% of healthy blood donors in the area had antibodies without symptoms, and 29% of people who had previously mild cold-like symptoms had antibodies. Importantly, the researcher tested blood from 491 donors from 2019 to make sure that the antibodies test wasn’t picking up previous coronavirus antibodies.

Population group studies:

Theodore Roosevelt testing results – NavyTimes article
The whole crew of the USS Theodore Roosevelt were tested for COVID-19, and 20% were found to be positive. While several sailors were hospitalized, no one amongst the crew ended up in the ICU nor were there any deaths. (Mainly younger population group, lots of outdoor time and physically in good shape.)

What I find interesting /wonder about — why in what should have been the perfect conditions to spread the virus to everyone on the ship did only 20% get the virus (have you seen those bunk rooms?). It seems like even in the most ideal condition, spread of this virus doesn’t top 40% — are some people immune? previous coronavirus or genetic difference?

COVID-19 outbreak at a large homeless shelter in Boston: Implications for universal testing
A Boston homeless shelter found that 36% of the 408 homeless individuals tested were positive for COVID-19. Interestingly, almost none of the individuals had any symptoms.

In four U.S. state prisons, nearly 3,300 inmates test positive for coronavirus — 96% without symptoms  (news article – can’t find any publication of the raw data)
This is an article covering testing in several different prison populations. One prison with 2500 inmates and found that 2,028 were positive for COVID-19 and 95% had no symptoms. Of note here is that the prison had a lot of older inmates with pre-existing health conditions.  While the news account seems to worry that prisons are vastly undercounting cases, the glass-half-full side is that if huge swaths of a population of prisoners can have COVID-19 and be asymptomatic, there won’t be an over-run of prison hospitals.

The epidemiological studies of prison populations and homeless shelters raise a lot more questions than they answer. Why is it that 96% of prisoners and almost 100% of homeless people who tested positive for COVID-19 were asymptomatic? These two population groups seem like they should be in overall worse health than the rest of the population.

Estimating the burden of SARS-CoV-2 in France 4/24/20
This is a preprint from researchers involved in the mathematical modeling of infectious diseases in France. The researchers estimate that 2.6% of infected individuals end up hospitalized and 0.5% end up dying. (This was estimates based on data from the Princess Diamond along with information from French hospitals — so not based on actual data in France.) The mortality rate ranged from 0.001% for younger people to 8% in people over age 80. They are projecting that by May 11, 5.7% of the population will have been infected.

 

Mast Cell Theory…

Everyone has a theory and a viewpoint on COVID-19, right? Not sure whether this theory is right or not…

My thoughts (and no – I’m not an MD):

  1. Interleukin-6 (IL-6) is greatly increased in cases of severe COVID-19 compared to non-complicated cases. [ref]
  2. IL-6 (interleukin-6)  is an inflammatory cytokine secreted by macrophages in response to PAMPs (pathogen-associated molecular patterns) And…. mast cells release IL-6.
  3. IL-6 can also feedback and cause more mast cells to be differentiated. In addition to IL-6, mast cells release histamine (vasodilator), proteases to break down proteins, and other inflammatory mediators. All of this causes swelling, fluid moving into the area.   [ref]
  4. Looking at other lung infections that cause ARDS:  Influenza A viruses have been shown to directly activate mast cells in the lungs, which “participate in the excessive inflammatory and pathological response observed during influenza A infections.” [ref]
  5. Mast cell degranulation increases IL-6 and TNF-alpha levels in community-acquired pneumonia — and it inhibits the clearance of Streptococcus pneumoniae. [ref]
  6. Mouse studies show that influenza A infection  “stimulates a massive increase in the number” of mast cells in the lungs (from day 6 onward in the mice).
    Even after the infection has passed, it takes a while for the mast cell numbers to go back down to normal. at 10-days post-infection, mast cells were 29 times higher than normal.  [ref]
  7. Mast cells in the lungs produce both tryptase and chymase – enzymes that break down proteins. (Interestingly, mast cells in the alveoli don’t express FcεRI, the IgE receptor that cross-links with allergens or pathogens. )[ref]
  8. “Chymase is the most efficient Ang II (angiotensin II)–forming enzyme in the human body and has been implicated in a wide variety of human diseases that also implicate its many other protease actions.”   [ref]
  9. Questions that I have (legit questions, I don’t have the answers):
    Are mast cells a big part of the acute respiratory distress syndrome seen in severe cases? If so, would blocking the proliferation early on be helpful – or would this be detrimental to fighting off the virus? (This would take controlled studies to answer)
    Does the formation of angiotensin II cause any of the severe problems associated with COVID-19 in regards to the cardiovascular system?
    Does the nasal mist vaccine for the flu increase mast cells in the lungs of people who have had the vaccine recently? (I doubt it, but it is a question…)
    Does air pollution in the region cause increased mast cells in the lungs, priming them for ARS?

Relevant research:

High rate of increased level of plasma Angiotensin II and its gender difference in COVID-19: an analysis of 55 hospitalized patients with COVID-19 in a single hospital, WuHan, China  5/1/20
Study in Wuhan showing that angiotensin II levels were higher in people with severe COVID-19 symptoms. 32% of the critically ill patient group had high angiotensin II levels, compared with only 9% of the non-critically ill group. Angiotensin II levels were also higher in males than females, pointing to another reason for the gender differences noted in mortality rate.

Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis 4/3/20
A preprint of a meta analysis that shows that IL-6 levels are almost 3-fold higher on average in people with complicated or severe COVID-19.

Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients 4/10/20
Another study pointing to the high levels of IL-6 as being the one factor that differentiated people who needed mechanical ventilation. IL-6 levels over 80 pg/ml predicted respiratory failure with high accuracy (22-fold increased risk of respiratory failure).

Article: Anti IL-6 For Coronavirus Patients: Does It Work, or Not? 4/27/20
This is a blog article in Science that discusses all the ongoing clinical trials on IL-6 inhibitors. The results have been mixed – some positive and some showing no benefit.

Article: New York clinical trial quietly tests heartburn remedy against coronavirus 4.26.20
This clinical trial is testing famotidine, an H2 (histamine) receptor blocker known as Pepcid. Histamine is released by mast cells, but it can also be a signal to trigger degranulation on other mast cells.

COVID-19: towards understanding of pathogenesis
Article in Cell Research discussing the different stages of COVID-19 infection (viremia – when the virus is multiplying in the cells; pneumonia – lungs are battling fluid; and severe). The doctors suggest high-dose IV immunoglobulin or anti-IL6R antibodies – along with heparin if needed to prevent blood clots.

Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19 5/1/20
A preprint of a study in Wuhan that showed that hydroxychloroquine decreased hospital stays and decreased mortality. Interesting here – IL-6 levels were significantly lowered by the end of the treatment (7 – 10 days).

Where can you get a Covid-19 antibody test for yourself?

LabCorp has announced it is offering antibody tests through Walgreens walk-in clinics. You can also order online through their website. It looks like a $10 copay, with an online doctor’s visit included.

Quest now offers antibody tests direct to the consumer for $119 without the need for a doctor’s order.

There are also local testing companies popping up everywhere with COVID-19 antibody tests. I suggest googling ‘COVID-19 antibody testing’ along with the name of your city or state. Do your due diligence to make sure that the antibody test that they are using is one that has a low false-positive rate.

 

Longevity Science – why are the elderly more susceptible to COVID-19?

Inflamm-Aging: Why Older Men Are the Most Susceptible to SARS-Cov-2 Complicated Outcomes 4/9/20

Inflamm-aging is a term used to describe the systemic inflammation that comes with aging. Along with chronic, systemic inflammation, the immune system becomes impaired (immune senescence). This preprint is an overview of why older people’s immune system becomes impaired and why a lack of the initial interferon I response allows the coronavirus to flourish. The researchers explain that high IL-6 levels are common in aging individuals and that persistently high Il-6 causes lung tissue inflammation and injury. The article also explains why a lower ACE2 expression can lead to increased lung inflammation.

COVID-19 is an emergent disease of aging
This is an interesting point of view preprint that examines the idea that COVID-19 is a disease of aging. It also explains that elevated levels of inflammation and exhausted immune system (due to thymus involution?) are precipitating factors for diseases of aging, including COVID-19. The thymus is a lymphoid organ where T-cells mature. T-cells are critical for fighting off pathogens. Thymus involution refers to the atrophy of the thymus during aging and how it is replaced by fibrotic tissue.  The paper looks at the data out of Italy for Covid-19 fatalities and age structure.

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.