Covid-19 described pathology: a new extent

[jim mcnamara]

TL;DR Summary

Covid-19 is very different from influenza because it was first described as a cardio-pulmonary disease, then vascular was added, now a third modality: neurologic. Sort of a triple (or quadruple)whammy.

https://www.nbcnews.com/health/heal...ave-neurological-symptoms-study-says-n1242143
https://onlinelibrary.wiley.com/doi/full/10.1002/acn3.51210

The scope of pathological effects of a Covid-19 infection is very diverse, ranging from asymptomatic to three or four major organ system pathologies.

Objective:
Covid‐19 can involve multiple organs including the nervous system. We sought to characterize the neurologic manifestations, their risk factors, and associated outcomes in hospitalized patients with Covid‐19.

Results:
Neurologic manifestations were present at Covid‐19 onset in 215 (42.2%), at hospitalization in 319 (62.7%), and at any time during the disease course in 419 patients (82.3%). The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), ... [snip]

Physicians specialize in, say, pulmonary disease and are board certified specialists in that area. Neurologists do the same. The paper above is a fairly comprehensive review of neurologic of Covid-19 effects. Some are persistent after recovery, others transient. 82.3% of all patients in the study had one (or more) neurologic symptoms. Encephalopathies in patients with other comorbidities appear to associate with decreased patient survival.

This overall pathology has been known was seen frequently, but this paper shows how commonly the neurologic problems arise in patients. Which may be associated with the patients who have long term ( possibly lifetime) problems, from the disease process. So-called 'long haulers'

 

[Ygggdrasil]

82.3% of all patients in the study had one (or more) neurologic symptoms. Encephalopathies in patients with other comorbidities appear to associate with decreased patient survival.

I would not focus on the figure that 82% of hospitalized patients experienced neurologic symptoms since they include headaches as neurologic symptoms. The observation that ~30% of patients experienced encephalopathy (altered mental function), however, is the more salient takeaway from the study, especially since encephalopathy correlated poorly with survival and recovery. For example,

After they were discharged, only 32% of the patients with altered mental function were able to handle routine daily activities like cooking and paying bills, said Dr. Igor Koralnik, senior author of the study and chief of neuro-infectious disease and global neurology at Northwestern Medicine. In contrast, 89% of patients without altered mental function were able to manage such activities without assistance.

https://www.chicagotribune.com/coro...0201005-hxwwj2bnkzhnnozkx3skq46hye-story.html

 

[aheight]

Just under a third of patients developed a more serious type of neurological problem: encephalopathy, or altered brain function.

Any possibility this is a new type of prion-manifestation? Neurologic symptoms do seem a little similar. Here are prion disease symptoms:

• Rapidly developing dementia
• Difficulty walking and changes in gait
• Hallucinations
• Muscle stiffness
• Confusion
• Fatigue
• Difficulty speaking

 

[jim mcnamara]

I see nothing to support that hypothesis.

Known diseases like CJD (mad cow disease) are caused by prions and are a spongiform encephalopathy - at autopsy the brain looks like swiss cheese under the microscope. No report of that in a large number of autopsies.

 

[ChinleShale]

A couple of related questions:

1) Not all viruses have vaccines e.g. HIV. What makes this virus a good candidate?
2) Some viruses have effects that appear after many years e.g. cancer. What science is there to predict this and what very long term effects are likely with this corona virus?

 

[Ygggdrasil]

A couple of related questions:

1) Not all viruses have vaccines e.g. HIV. What makes this virus a good candidate?

We know that we should be able to develop a vaccine for COVID-19 because:
a) We can develop short term immunity to other coronaviruses. There are four other coronaviruses known to circulate in human populations, all of which cause colds. Studies of these viruses have shown people infected with these viruses are resistant to infection for ~6 months to a few years.
b) Most people infected with the Coronavirus develop antibody and T-cell responses.
c) Studies with animals show that prior infection with the SARS-CoV-2 Coronavirus protects against re-infection.
d) Animal studies of vaccines and early clinical trial results for vaccine candidates are promising (e.g. we know that the vaccines seem to elicit antibodies against the virus).

As for what features of the SARS-CoV-2 virus that allow us to develop a successful vaccine versus viruses like HIV, I'm not sure there is a very clear answer. Here's a popular press article that looks at the question. Something that the article does not mention is the differing life cycles of the viruses. SARS-CoV-2 appears to propagate fairly rapidly in the body, which may aid the body in mounting a strong immune response against the virus. In contrast, HIV replicates much more slowly and throughout a lot of its life cycle it can stay latent and hidden within cells inside of the body. These features could help it better hide from and evade the body's immune responses than other viruses.

2) Some viruses have effects that appear after many years e.g. cancer. What science is there to predict this and what very long term effects are likely with this corona virus?

This is something I don't think we know much about yet, unfortunately.

 

[Astronuc]

September 24, 2020 - In Deadly COVID-19 Lung Inflammation, BU Researchers Discover a Culprit in NFkB Pathway
https://www.bu.edu/articles/2020/in...searchers-discover-a-culprit-in-nfkb-pathway/

According to their findings, published online last week in Cell Stem Cell, the trouble starts soon after the air sacs in the lungs are infected with SARS-CoV-2, when the virus activates one of the body’s biological pathways known as NFkB (the k is pronounced “kappa”). As that’s happening, the virus also suppresses the lungs’ ability to call in the help of the immune system to fight off the viral invaders.
. . . .

Remdesivir, a broad-use antiviral, has already been used clinically in Coronavirus patients. Camostat, an antiviral and cancer drug sometimes used to treat pancreatitis, has previously been tested in a type of cell found higher up in the lungs, in the airway, and found to be effective. With the BU team’s experiments confirming it also works to treat Coronavirus infection in the lungs’ air sac cells, Kotton says camostat is a good candidate for clinical trials.
. . . .

SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response
https://www.sciencedirect.com/science/article/pii/S1934590920304598?via=ihub

 

[ChinleShale]

@Astronuc

So according to this paper, the corona virus suppress the body's immune response. That would seem to be a survival trait that could have been selected for. Are there other known mechanisms for this in other viruses?

 

[Ygggdrasil]

@Astronuc

So according to this paper, the corona virus suppress the body's immune response. That would seem to be a survival trait that could have been selected for. Are there other known mechanisms for this in other viruses?

Most viruses have evolved some way to evade or suppress the host's immune responses, which can range from evading antibodies and the adaptive immune response to interfering with antiviral signaling molecules in the body (such as interferons or cytokines) to stopping infected cells for being destroyed by the body. See this review for more detail: https://www.cell.com/imto/pdf/S0167-5699(00)01699-6.pdf

 

[Astronuc]

Are there other known mechanisms for this in other viruses?

I don't know the answer, but I hope not.

An interesting paragraph in the Boston U article,

“It was scary to see how much damage the virus does to these cells,” Mühlberger says. “It disrupts the [membrane surrounding the cell nucleus], and causes significant changes to the cell’s organelles,” which are the internal parts of a cell that carry out essential functions. “The cells really suffer,” she says, and not even Ebola or Marburg viruses have as much impact on the cell’s internal organelles as the novel Coronavirus does, she adds.

Viruses and bacteria evolve by surviving. So if a mechanism develops that let's the virus be more successful, that line of virus will continue. We certainly don't need Coronavirus (Cov-2) to pick up traits like that of Ebola or Marburg, or other haemorrhagic viruses.

 

[Laroxe]

Really we have found out a great deal about this virus in quite a short time. We know it can target a wide range of cells in the body, viruses often target multiple cell types, but knowing this makes the symptoms more understandable.
It does seem to have a number of effects that have a direct effect on our immune system, stimulating over reactions, the ability to infect T cells and its ability to limit the number of effective targets for antibodies to name a few. However these were all issues that were used to inform vaccine design, its thought that the vaccines will induce an immune response that is both more effective and more persistent even than the natural disease.
Developing new vaccines always involves understanding the pathogen and they can be very different, several HIV vaccines have been produced but even the most effective only had a small effect. HIV is a primitive virus that's very sloppy in the way in copies itself, its protein coat varies all the time, they now think they have identified an area that is stable and a new vaccine is in trials. They now have to show that antibodies that target this protein stop the infection. This was an issue with Covid 19, they identified around 40 different antibodies that react with the virus but only the ones that targeted the spike protein were protective.
Remember a successful virus isn't one that kills its host, there has been no Ebola pandemic because it kills its victims so quickly it stops its own spread. Currently its thought that Covid 19 mutates very slowly but it may be that it could become less serious that would make it more successful, this might be happening with HIV.
I am confident we will have an effective vaccine and over time even more effective ones but we still need the trials to report to confirm this, we may even have a choice in 2021.

 

[ChinleShale]

I don't know the answer, but I hope not.

An interesting paragraph in the Boston U article, Viruses and bacteria evolve by surviving. So if a mechanism develops that let's the virus be more successful, that line of virus will continue. We certainly don't need Coronavirus (Cov-2) to pick up traits like that of Ebola or Marburg, or other haemorrhagic viruses.

So this virus supposedly came from bats. Why would it have a way to suppress human immune response? Are the mechanisms for immune response more or less the same across species?

 

[Astronuc]

HIV is a primitive virus that's very sloppy in the way in copies itself, its protein coat varies all the time, they now think they have identified an area that is stable and a new vaccine is in trials. They now have to show that antibodies that target this protein stop the infection. This was an issue with Covid 19, they identified around 40 different antibodies that react with the virus but only the ones that targeted the spike protein were protective.

HIV apparently has less than 10,000 bases in its genome according to an article in SciAm.

The SARS-CoV-2 genome is a strand of RNA that is about 29,900 bases long--near the limit for RNA viruses. Influenza has about 13,500 bases, and the rhinoviruses that cause common colds have about 8,000. (A base is a pair of compounds that are the building blocks of RNA and DNA.) Because the genome is so large, many mutations could occur during replication that would cripple the virus, but SARS-CoV-2 can proofread and correct copies. This quality control is common in human cells and in DNA viruses but highly unusual in RNA viruses. The long genome also has accessory genes, not fully understood, some of which may help it fend off our immune system.

https://www.scientificamerican.com/interactive/inside-the-coronavirus/

The genome consists of 9,200-9,600 nucleotides in the case of HIV-1 and approximately 9,800 nucleotides in the case of HIV-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924471/