Covid-19 Fatal Effects: Pneumonia Types Explored

[hagopbul]

TL;DR

why covid-19 results death

Hello all:

hope you are all well .

as i am looking into reasons of death from Covid-19 i could see that pneumonia , is a major reason of death , but what kind of pneumonia ?
i couldn't find on the internet is it only viral pneumonia or mix of types ?

Best
Hagop

 

[pinball1970]

Summary:: why Covid-19 results death

Hello all:

hope you are all well .

as i am looking into reasons of death from Covid-19 i could see that pneumonia , is a major reason of death , but what kind of pneumonia ?
i couldn't find on the internet is it only viral pneumonia or mix of types ?

Best
Hagop

@jim mcnamara @Ygggdrasil @BillTre Have detailed information on this

 

[atyy]

One of the main hypotheses for deaths in Covid-19 is that the virus elicits a very strong immune reaction from the body. The strong immune reaction ("cytokine storm") is meant to defeat the virus, but unfortunately also damages the body, causing multiorgan failure leading to death. As you can see from the extracts below, cytokine storms are also hypothesized to be a cause of death in other viral infections such as SARS, MERS and influenza.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext
Early studies have shown that increased amounts of proinflammatory cytokines in serum (eg, IL1B, IL6, IL12, IFNγ, IP10, and MCP1) were associated with pulmonary inflammation and extensive lung damage in SARS patients. MERS-CoV infection was also reported to induce increased concentrations of proinflammatory cytokines (IFNγ, TNFα, IL15, and IL17). We noted that patients infected with 2019-nCoV also had high amounts of IL1B, IFNγ, IP10, and MCP1, probably leading to activated T-helper-1 (Th1) cell responses. Moreover, patients requiring ICU admission had higher concentrations of GCSF, IP10, MCP1, MIP1A, and TNFα than did those not requiring ICU admission, suggesting that the cytokine storm was associated with disease severity. However, 2019-nCoV infection also initiated increased secretion of T-helper-2 (Th2) cytokines (eg, IL4 and IL10) that suppress inflammation, which differs from SARS-CoV infection. Further studies are necessary to characterise the Th1 and Th2 responses in 2019-nCoV infection and to elucidate the pathogenesis. Autopsy or biopsy studies would be the key to understand the disease.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711683/
Severe influenza remains unusual in its virulence for humans. Complications or ultimately death arising from these infections are often associated with hyperinduction of proinflammatory cytokine production, which is also known as ‘cytokine storm’. For this disease, it has been proposed that immunomodulatory therapy may improve the outcome, with or without the combination of antiviral agents.

 

[hagopbul]

cytokine storm

that is really interesting concept the media are siting pneumonia as the major reason for death

 

[Ygggdrasil]

Here's a good article from the NY Times that discusses some of the effects of Coronavirus infection: https://www.nytimes.com/article/coronavirus-body-symptoms.html

 

[Tom.G]

And an article with a rather graphic description of how it progresses:
https://nymag.com/intelligencer/2020/03/the-story-of-a-coronavirus-infection.html

 

[Rive]

... the media are siting pneumonia as the major reason for death

It really is. Just the cytokine storm is the reason what develops that pneumonia.

It was common to compare Covid19 to (common) flu in the beginning. In that context the difference is, that in case of flu the flu usually just makes it hard to continue living with a serious pre-existing medical condition: while in case of Covid19 this kind of mortality is also present, but the main course of events is a kind of the opposite - the developed pneumonia is so serious that it is hard to survive the pneumonia if there is a (not necessarily serious) pre-existing medical condition present.

 

[atyy]

One of the differences between the 1918 flu pandemic and the current Covid-19 one is that in 1918 more young people died, but currently it is old people with underlying conditions who are most at risk. Does anyone know why?

 

[pinball1970]

One of the differences between the 1918 flu pandemic and the current Covid-19 one is that in 1918 more young people died, but currently it is old people with underlying conditions who are most at risk. Does anyone know why?

Yes I have been wondering that.
Cytokine storm/age is also mentioned here for Spanish flu
https://simple.wikipedia.org/wiki/Influenza_pandemic_of_1918

Older immune system less of a storm lower mortality.

Covid 19 appears to be, underlying condition or age higher mortality.

Underlying condition makes sense but age being both a negative and positive factor for survival does not.

Was the Cytokine storm much more severe in younger people with Spanish flu.

Edit, this mortality graph shows the distribution.
https://en.wikipedia.org/wiki/Spanish_flu

So the very young, weaker under developed immune system high mortality. Older weaker immune system also vulnerable.
Spanish flu has that third peak at 25 compared to the 1911-17 'normal' epidemics.

 

[Rive]

A possible explanation I hear on that inverse age relation with the H1N1 active in 2009 is, that older people might had previous encounter with flu virus from the same family, while for younger it was entirely 'novel'.
Novelty might also explain the events in 1918, but not sure.

In case of Covid19 it is the BCG vaccination which is right now suspected as potential 'novelty breaker'.

Ps.: here
So people who got H1N1 in 1947-57 got the 'easy flu' in 1977-78, and both age group got it 'mild' in 2009 - but the young were affected hard both case. At least if this 'novelty theory' stands.

 

[hagopbul]

One of the differences between the 1918 flu pandemic and the current Covid-19 one is that in 1918 more young people died, but currently it is old people with underlying conditions who are most at risk. Does anyone know why?

maybe something related to alveoli ? or the lung microbiota ?

or there lung PH is lower than younger ones making the SARS-COV-2 more able to hatch on the AEC2 ?

 

[hagopbul]

found this conversation on the internet could be useful

https://www.researchgate.net/post/COVID-19_and_respiratory_distress-could_it_be_surfactant_deficiency_May_exogenous_surfactant_help

 

[Laroxe]

The 1918 flu is an interesting one, for a viral infection to enhance its own survival there is a tendency for the strains that cause less sever disease that run a longer course to be preferentially selected. This allows the virus to spread more effectively which is ultimately what it wants. A disease that has a short incubation period and has a high mortality rate interferes with its own spread, that's basically why Ebola hasn't become pandemic.
The 1918 flu is thought to have jumped species in a military staging area in France, for supplies there were pigs and a large number of poultry, there was also a military hospital treating victims of poisonous gas attacks, mustard gas causes extreme immunosuppression. This in many ways represents the "perfect storm" for both a virus with a brand new antigen profile (or mostly new, more likely) and then cross species transmission.
The first wave of flu infections was not actually that sever, soldiers that contracted it were kept near the front and usually recovered quite quickly. However there were some who developed more sever illness, these were evacuated back to their own countries for hospital care. This meant that the viral strains capable of causing the most sever infections in the young were seeded across the world and indeed it was the second wave of infections, which appeared in multiple locations similtaneously, that was the real killer.
It seems that it was the human actions in response to the first infections that not only prevented the natural selection of less sever strains but actually reversed the process.
Interestingly it may be that Ebola and HIV are following the usual evolutionary trend, in the case of Ebola this in fact is not good news. In the early outbreaks there were relatively few victims and the mortality rate was in the region of 80%, in the latest outbreak there were many more victims of the infection but the mortality rate had fallen to around 60%.

 

[hagopbul]

endoscopy or using light to effect the viral lung infection anyone knows if that idea is good to talk about ?

what i found is the following article on it but it is related to PH and never mentioned light or some thing like that

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231296/

 

[chemisttree]

Google search term Photodynamic Therapy Virus

 

[Evo]

One of the differences between the 1918 flu pandemic and the current Covid-19 one is that in 1918 more young people died, but currently it is old people with underlying conditions who are most at risk. Does anyone know why?

Tuberculosis has been repeatedly cited.

https://www.berkeley.edu/news/media/releases/2000/10/25_flu.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139993/

 

[hagopbul]

Google search term Photodynamic Therapy Virus

I saw it , a PhD student in Aleppo university tried them using solid state laser on some tumours , but never heard them using it on lung . I only saw on the internet a 2016 news article talking about a company researching it as an option for lung infection , don't know if it is useful against viruses

hope you all safe

 

[Laroxe]

There is increasing attention being paid to the effects of the virus on the endothelial lining of blood vessels, while many viral infections have an impact on the heart and circulation in Corvid 19 it seems to have an increased significance. In one study 71% of non survivors were found to have disseminated intravascular coagulation at post mortem, often with indicators of pulmonary embolism. These changes are rarely seen in survivors with indicators in around 0.6%. (Tang et al. 2020)
Monitoring blood clotting factors and the use of anticoagulants has become a routine part of care in severely ill patients.

Its thought that COVID-19 may trigger rupture or erosion of coronary plaques in patients with underlying coronary artery disease, but this is also seen in other infections causing a systemic inflammatory response. Certain cardiac arrhythmia's are also common in the severely ill though its not clear whether this is due to a direct effect of the virus or hypoxia. These effects might explain why previous cardiovascular disease and hypertension increase risk

Another observation that is a useful predictor of mortality is that the most severely ill tend to have suppression of the lymphocyte count, there are lots of potential explanations offered but as these cells play a central role in defence against virus infections its not surprising its an important finding.

 

[hagopbul]

about the blood vessel , could we say that because the SARS-COV-2 effecting ACE2 population or concentration , it may effect the blood pressure also creating turbulence , would that have effects on blood clotting

the effect on pressure even if it is localized may create small micro bubbles better say micro cavitation that may or may not effect the clotting mechanism

https://www.mcnallyinstitute.com/01-html/turbulence_cavitation.htm

https://www.ahajournals.org/doi/pdf/10.1161/01.RES.35.4.608

best
H.B.

 

[Laroxe]

about the blood vessel , could we say that because the SARS-COV-2 effecting ACE2 population or concentration , it may effect the blood pressure also creating turbulence , would that have effects on blood clotting

the effect on pressure even if it is localized may create small micro bubbles better say micro cavitation that may or may not effect the clotting mechanism

https://www.mcnallyinstitute.com/01-html/turbulence_cavitation.htm

https://www.ahajournals.org/doi/pdf/10.1161/01.RES.35.4.608

best
H.B.

To be honest the direct role of ACE2 receptors on the clinical course of the infection is still very confusing, while the receptor facilitates viral entry to cells it might also play a significant role in protecting from some of its damaging effects. This seems to be a reasonable review of what remains a poorly understood process.

https://heart.bmj.com/content/early/2020/04/30/heartjnl-2020-317056

 

[jim mcnamara]

@Laroxe - I had similar issues. This is a series of youtube lessons, part of Med Cram - meant for clinicians and med students. It was a good fit for my level of understanding in Biochem and some other areas. The clinical part was interesting. I am NOT a physician, so I probably missed lots of important things in that area.

@hagopbul - this might be useful for you but I do not know. It does explain clearly what the ACE model now is believed to be.

[overly simplified to help you understand]
It has a series of explanations based on clinical evidence and autopsies.

The root cause of pneumonia is the virus disrupts (reduces) the removal of superoxides that are "waste" products of the metabolic process that creates energy. These superoxides are nasty and trigger responses from the immune system.

The other part of pathogenesis(how disease gets going) , blood clots in dangerous places, revolves around cells that line the arteries. These cells are attacked by the virus -> leading to a flood of chemicals that force nearby blood to coagulate. This creates all kinds of symptoms, and often fatal conditions. This is why low molecular weight heparin has been given to patients - with success. It "undoes" clotting.
[/end overly]
Warning 67 videos...
Big list of programs:

 

[BillTre]

With all the different sets of symptoms that the virus seems to cause in different people, I am wondering if the differences between people cold be due to differences in the expression (presence) of the virus in different places.
In some cases it would not be surprising if the ACE2 receptor is present in different places at different ages.
Being aware of genetic variability, it would not surprise me if different people's differing genetic constiution cause the virus to be expressed in different places in the body due to smeothing like differences in the control sequences for the ACE2 gene.
Anyone know anything about this?

 

[Laroxe]

With all the different sets of symptoms that the virus seems to cause in different people, I am wondering if the differences between people cold be due to differences in the expression (presence) of the virus in different places.
In some cases it would not be surprising if the ACE2 receptor is present in different places at different ages.
Being aware of genetic variability, it would not surprise me if different people's differing genetic constiution cause the virus to be expressed in different places in the body due to smeothing like differences in the control sequences for the ACE2 gene.
Anyone know anything about this?

I believe the Ace2 receptor is fairly common in the body and other possible co receptors have been implicated in allowing entry. There was a lot of interest in the effects of antihypertensive drugs that bind to this receptor and it was suggested that chronic treatment with these drugs caused an over expression of this receptor, some people thought this might allow the virus easier access to the cells others thought blocking the receptor might stop entry. Apparently neither effect is seen.
The severity of the illness can be linked to the direct effects of the virus on the lungs, kidneys, liver, heart, vascular endothelium and brain or it might occur as a consequence of the immune response, generally in sever disease the recovery is generally prolonged beyond when the virus itself should be the problem. The virus itself is known to modify our immune responses and the new presentation in children suggests an autoimmune element
I think there are simply too many variables to consider in trying to understand the differences in peoples responses, I expect there will be a range of genetic, physiological, and socio/cultural differences that effect the outcomes. The virus certainly seems quite picky about its victims but there are still quite a few that don't fit the usual risk groups. Still if nothing else we do seem to be learning a great deal about the complexity of viral infections from this one.

 

[Astronuc]

Tuberculosis has been repeatedly cited.

https://www.berkeley.edu/news/media/releases/2000/10/25_flu.html

From the Berkeley article: "In the early 20th century, however, tuberculosis was a major killer of men in that age group, apparently because of transmission in factories where men worked in densely-packed, poorly-ventilated conditions, Noymer said."

Congregations of people and poor/inadequate ventilation in conjunction with folks not wearing masks seems to be factors in the transmission of SARS-Cov-2 virus.

 

[Astronuc]

I was looking for mortality due to influenza and found the following regarding pneumonia, influenza and Covid.

https://www.cdc.gov/flu/weekly/index.htm

 

[Laroxe]

Tuberculosis has been repeatedly cited.

https://www.berkeley.edu/news/media/releases/2000/10/25_flu.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139993/

Apparently it's down to the way our immune system works, our first exposure to the influenza virus seems to imprint a particular antibody response. Exposure to a new strain causes the memory cells coded for a particular response to become active and multiply, but the antibodies they produce are coded for their first infection, the body then has to start the process of refining the antibody response to the new variant. Apparently it is the memory cells for the first infection that persist in the system, this means these guide the antibody response over a persons' lifetime.

It's suggested that for people born before 1890 their first exposure was to a H1 like influenza virus and this immunological memory provided some protection from the pandemic strain and to the likelihood of secondary bacterial infections, which were the primary cause of death. In 1889 a pandemic of the so called Russian flu spread around the world and then from 1890 to around 1900, widespread epidemics of influenza-like illness recurred. (note: interestingly, a Coronavirus has been implicated, these are associated with aberrant immune responses). This strain would therefore become the first exposure of people born during that period, and it's suggested that this predisposed people to an aberrant first immune response to infection characterised by a rapid over production of cytokines.

If we discount the problems of the very young and the very old in response to any infection, this idea fits perfectly with the strange mortality data. People between 30 and 60 would have been exposed to the prevailing influenza strains prior to 1889/1890 and were relatively protected, as were those under 17 who 's exposure was to the viruses that followed the Russian flu. So, in 1918, people born between 1875–1900 so would be aged 18 to around 40 would have had the 1889–90 pandemic strain as their first exposure been exposed to the 1889–90 pandemic influenza strain. In this group the disease was characterised by a rapid onset of what is now known as a cytokine storm.

https://www.sciencedaily.com/releases/2019/03/190320110619.htm
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310443/