COVID-19 Autopsy Pathology Findings

Summary

In this detailed presentation, pathologist Dr. Andrea Gilbert shares autopsy findings of a patient who died from COVID-19. The patient, a young to middle-aged woman with obesity and possible asthma, presented with severe respiratory failure and was diagnosed with acute respiratory distress syndrome (ARDS) due to the virus. Autopsy revealed extensive lung damage with large areas of consolidation, pulmonary edema, and desquamation of pneumocytes. Notable was the presence of diffuse alveolar damage, perivascular lymphocytic infiltrates suggestive of vasculitis, and rare multinucleated giant cells. The heart showed signs of takotsubo cardiomyopathy and edema without evidence of viral myocarditis. Acute kidney injury was also observed. Dr. Gilbert emphasizes the importance of ventilator use in severe cases and cautions against the misuse of hydroxychloroquine. This comprehensive analysis provides valuable insights into the pathogenesis of COVID-19, highlighting the need for serious consideration of the disease, even among younger individuals.

Takeaways

• 🧬 The patient, a young to middle-aged woman with obesity and possible asthma, presented with COVID-19 and experienced severe respiratory failure, leading to acute respiratory distress syndrome (ARDS) and death.
• 🩺 Clinically, the patient showed signs of heart dysfunction with elevated cardiac markers, low oxygen levels, and a diagnosis of septic shock and cardiogenic shock, indicative of the multi-system impact of COVID-19.
• 🔍 Autopsy findings revealed extensive lung damage with large areas of consolidation, severe pulmonary edema, and desquamation, which are consistent with the patient's clinical hypoxia and respiratory distress.
• 🔬 Microscopic examination showed evidence of viral cytopathic effects, suggesting direct damage to lung cells by the virus, and the presence of multinucleated giant cells and hyaline membranes, characteristic of diffuse alveolar damage.
• 🫀 The heart showed no signs of ischemic injury, but there was evidence of a rare congenital condition affecting the right atrium, which may have contributed to cardiac abnormalities during the severe lung infection.
• 🩸 Peripheral blood smear showed atypical lymphocytes and a left shift, indicating the body's active response to infection, but no clear evidence of thrombosis.
• 💊 The patient had received hydroxychloroquine, a drug with a narrow therapeutic window, which requires close monitoring due to its potential toxicity.
• 🧠 The neuropathology findings were not discussed in the script, but the presenter mentioned presenting such findings in other episodes, highlighting the multi-organ impact of the virus.
• 📉 The kidneys showed no signs of primary infection or inflammatory disorder but had focal areas of acute tubular injury, potentially linked to severe hypoxia from the lung injury.
• ⚖️ The autopsy findings underscore the severe impact of COVID-19 on the respiratory system and the importance of understanding the pathogenesis of the disease for clinical management.
• ⚠️ The presenter emphasized the importance of not dismissing the use of ventilators in severe cases, as they are often necessary to prevent patients from drowning in their own fluids due to lung failure.

Q & A

What is the significance of sharing autopsy results for a patient who was positive for COVID-19?

The significance lies in the limited pathology data available for COVID-19. Autopsy results can provide valuable insights into the disease's impact on the body, which is crucial for clinicians in ICUs and emergency departments to better understand and combat the virus.

What was the patient's clinical presentation before her death?

The patient, a young to middle-aged woman, presented with a one-week history of fever, cough, and dyspnea (difficulty breathing). She had obesity and a possible history of asthma. In the emergency room, she experienced severe respiratory failure and hypotension.

What was observed in the patient's lung during the autopsy?

The lungs were heavy, boggy, and consolidated, with a firm or rubbery consistency instead of the normal spongy feel due to air. There was significant pleural edema and areas of consolidation. Microscopically, there was diffuse consolidation, pulmonary edema, and desquamation of pneumocytes.

What is the 'viral cytopathic effect' mentioned in the autopsy?

Viral cytopathic effect refers to the changes in the appearance of cells that have been infected by a virus. Infected cells often appear abnormal and different from healthy cells, which can be observed under a microscope.

What was the patient's cardiac condition?

The patient was diagnosed with reverse takotsubo cardiomyopathy, also known as 'broken heart syndrome,' which is not an ischemic type of cardiomyopathy. She also experienced cardiogenic shock and had elevated cardiac markers indicating concern about her heart function.

What was found regarding the patient's kidney condition?

The patient had acute kidney injury with evidence of acute tubular injury and necrosis, which could be related to severe hypoxia due to her lung injury.

What is the role of hydroxychloroquine in the treatment of COVID-19 as mentioned in the script?

Hydroxychloroquine was mentioned as a treatment the patient received. However, it's noted that it's not a benign drug and requires close monitoring due to its narrow therapeutic window, meaning the margin between effective dosage and toxicity is small.

What was the patient's vascular condition as observed during the autopsy?

There was a perivascular lymphocytic infiltrate observed around the blood vessels in the lungs, which in some areas resembled vasculitis. However, the patient tested negative for ANCA, which is typically associated with vasculitis.

What are the implications of the autopsy findings for the understanding of COVID-19 pathology?

The autopsy findings provide detailed pathological insights into the effects of COVID-19, particularly the extensive lung damage, which aligns with the clinical presentation of acute respiratory distress syndrome (ARDS). It also suggests potential cardiac and renal involvement.

What is the importance of not jumping to conclusions about micro thrombi in COVID-19 cases?

The importance is to avoid misinterpretation of findings that could lead to inappropriate treatment. Micro thrombi can occur in the context of diffuse alveolar damage with acute lung injury, not necessarily indicating a systemic prothrombotic state.

What was the patient's age and medical history?

The patient was a young to middle-aged woman with a past medical history significant for obesity and a questionable history of possible asthma.

What was the patient's condition that led to the autopsy?

The patient passed away due to complications from COVID-19 infection, which resulted in acute respiratory distress syndrome (ARDS), septic shock, cardiogenic shock, and acute kidney injury.

Outlines

00:00

👩‍⚕️ Introduction to a Special Presentation on COVID-19 Autopsy Findings

Dr. Andrea Gilbert, a board-certified pathologist, introduces a special presentation on the autopsy findings of a patient who died from COVID-19. She emphasizes the importance of sharing such pathology data, which is scarce compared to the abundant clinical reports, to better understand the disease's impact on the body and to assist medical professionals in managing the pandemic.

05:03

📋 Clinical Presentation and Autopsy Findings of a COVID-19 Patient

The video presents the case of a young to middle-aged woman with obesity and possible asthma, who died from COVID-19 after experiencing fever, cough, and dyspnea. The autopsy revealed severe lung damage, including dullness, redness, and consolidation, with pleural effusion and lymphocytic pleuritis. Microscopic examination showed diffuse consolidation and air space filling, indicating impaired gas exchange due to fluid and cellular infiltrate.

10:03

🔬 Viral Cytopathic Effects and Lung Tissue Analysis

The autopsy findings suggest extensive pulmonary edema and the presence of viral cytopathic effects, which are visible changes in cell morphology due to viral infection. The video highlights the severe impact on the lungs, with cells appearing abnormally enlarged and reactive, indicative of the virus's effect on lung tissue. The desquamation pattern observed suggests a significant loss of normal lung function.

15:04

🩺 Lung Pathology and Gas Exchange Impairment

The video discusses the lung pathology observed in the autopsy, including areas of blocked alveoli and a desquamation pattern where pneumocytes are falling off, preventing gas exchange. The presence of hyaline membranes, a characteristic feature of diffuse alveolar damage, is also noted. These membranes line the alveolar spaces and further impede gas exchange, contributing to the patient's severe hypoxia.

20:07

🧫 Diffuse Alveolar Damage and Inflammatory Response

The autopsy case shows evidence of diffuse alveolar damage with edema, fibrin exudates, and a significant inflammatory response characterized by the presence of numerous neutrophils and lymphocytes. The patient's lung tissue exhibited features consistent with viral pneumonia, including lymphocytic infiltration and the formation of hyaline membranes, indicating an active inflammatory process.

25:09

🩸 Caution Regarding Thrombosis and Coagulopathy in COVID-19

Dr. Gilbert advises caution regarding the use of anticoagulant therapy in COVID-19 patients, given the risk of thrombosis and the potential for diffuse alveolar damage to cause microthrombi formation. She did not observe microthrombi in this particular case but acknowledges the need for further research on the topic. The discussion also touches on the vascular findings within the lung, including perivascular lymphocytic infiltrates and possible vasculitis.

30:12

🫀 Cardiac Findings in the Autopsy Patient

The video describes cardiac findings in the patient, including a thin right atrium with areas lacking myocardium and suspected congenital issues. Despite concerns for viral myocarditis, the autopsy did not reveal evidence of inflammation indicating the presence of the virus in the heart tissue. However, edema and rare focal lymphocytic infiltrates were observed, raising questions about the cause of the cardiac abnormalities.

35:16

💊 Considerations on Hydroxychloroquine and Cardiac Function

Dr. Gilbert discusses the potential effects of hydroxychloroquine, noting that it is not a benign drug and requires close monitoring due to its narrow therapeutic window. She suggests that the drug's administration might have influenced the cardiac findings, but there was no clear evidence of myocarditis in the patient. The video emphasizes the importance of considering all factors when managing patients with COVID-19.

40:16

🧵 Kidney Pathology and Acute Tubular Injury

The autopsy revealed unremarkable kidney tissue with no signs of primary infection or inflammatory disorders. However, focal areas of acute tubular injury were identified, which could explain the patient's elevated creatinine levels and acute kidney injury. The video suggests that severe hypoxia due to lung injury might have contributed to this renal damage, but a direct viral effect on the kidneys was not evident.

45:17

📝 Conclusion and Thanks for the Educational Presentation

Dr. Gilbert concludes the presentation by thanking the family for allowing the case to be shared and emphasizing the educational value of the autopsy findings. She highlights the importance of understanding the pathogenesis of COVID-19 through pathology and encourages healthcare professionals to stay informed about the disease's effects on various organs.

Keywords

💡Neuropathology

Neuropathology is the study of diseases that affect the nervous system, including the brain, spinal cord, and peripheral nerves. In the video, Andrea Gilbert, a pathologist, discusses her expertise in neuropathology and how it applies to the autopsy findings of a patient who was positive for COVID-19.

💡Autopsy

An autopsy, also known as a post-mortem examination, is a medical procedure that involves a thorough examination of a deceased person's body to determine the cause of death and to understand the disease's effects. In the video, Dr. Gilbert shares the autopsy results of a young to middle-aged woman who died from complications related to COVID-19.

💡COVID-19

COVID-19 is a disease caused by the SARS-CoV-2 virus, which emerged in late 2019 and led to a global pandemic. The video focuses on the pathology data regarding COVID-19, which is crucial for understanding the disease's impact on the human body beyond clinical reports.

💡Acute Respiratory Distress Syndrome (ARDS)

ARDS is a severe lung condition characterized by sudden onset of diffuse inflammation in the lungs, leading to difficulty in oxygenating the blood. In the context of the video, the patient was diagnosed with ARDS due to COVID-19 infection, which was a significant factor in her death.

💡Viral Cytopathic Effect

Viral cytopathic effect refers to the visible changes in host cells caused by viral infections. Dr. Gilbert discusses the presence of this effect in the lung cells of the patient, suggesting that the cells appeared abnormal due to the viral infection.

💡Pulmonary Edema

Pulmonary edema is a condition where fluid accumulates in the lungs, causing difficulty in breathing. The video describes how the patient's lungs were consolidated with severe pulmonary edema, which is a critical finding in the context of COVID-19 pathology.

💡Lymphocytic Infiltrate

Lymphocytic infiltrate refers to the presence of lymphocytes (a type of white blood cell) in tissues where they are not normally found. In the video, Dr. Gilbert notes a lymphocytic perivascular infiltrate, suggesting an immune response in the blood vessels of the lungs.

💡Vasculitis

Vasculitis is the inflammation of blood vessels, which can be caused by various conditions, including infections. The video mentions the possibility of vasculitis in the patient's lungs, indicating another layer of complexity in the pathological effects of COVID-19.

💡Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy, also known as 'stress cardiomyopathy' or 'broken heart syndrome,' is a temporary heart failure condition that can be triggered by severe stress. The video discusses the patient's diagnosis of reverse takotsubo cardiomyopathy, which is linked to the severe stress her body underwent due to COVID-19.

💡Acute Kidney Injury

Acute kidney injury, also known as acute renal failure, is a sudden loss of kidney function. In the video, Dr. Gilbert describes the patient's elevated creatinine levels and the autopsy findings of acute tubular injury, indicating kidney damage as a result of the disease process.

💡Hydroxychloroquine

Hydroxychloroquine is a medication originally used to treat malaria and later, certain autoimmune diseases. It was discussed in the video as a treatment that the patient received, and Dr. Gilbert emphasizes the need for close monitoring due to its narrow therapeutic window and potential side effects.

Highlights

Andrea Gilbert, a pathologist, discusses an autopsy of a COVID-19 positive patient to provide insights into the pathology of the virus.

The patient was a young to middle-aged woman with obesity and possible asthma, presenting with fever, cough, and dyspnea.

The patient experienced severe respiratory failure, hypotension, and hypoxia, leading to intubation and ventilation.

Laboratory findings included low lymphocyte count, elevated cardiac markers, and positive antinuclear antibody (ANA), with negative ANCA.

Autopsy revealed extensive lung damage with consolidation, pulmonary edema, and desquamation, impeding gas exchange.

Microscopic examination showed viral cytopathic effects in lung cells, indicating direct damage from the virus.

Diffuse alveolar damage was present, characterized by hyaline membranes and fibrin exudates, typical in acute lung injury.

Perivascular lymphocytic infiltrates were observed, suggesting a possible vasculitis associated with COVID-19.

The patient had acute kidney injury with evidence of acute tubular necrosis, potentially linked to severe hypoxia from lung injury.

Heart pathology showed no signs of viral myocarditis, but there was evidence of edema and areas of the right atrium with thinned myocardium.

The patient's cardiac issues might be related to the lung involvement and not directly to viral myocarditis.

Andrea Gilbert emphasizes the importance of ventilators in treating severe respiratory failure in COVID-19 patients.

The case highlights the severe clinical course and potential for acute organ damage in patients without significant comorbidities.

Hydroxychloroquine treatment in the patient is discussed, noting the need for close monitoring due to its narrow therapeutic window.

The autopsy findings provide valuable data for understanding the pathogenesis of COVID-19 and its impact on various organs.

Gilbert dispels myths about the dangers of ventilators, stressing their necessity in life-threatening respiratory conditions.

The presentation concludes with a reminder of the seriousness of COVID-19 for all age groups and the importance of taking preventive measures.

Transcripts

[Music]

hello and welcome to Adventures in

neuropathology

I have a very special presentation for

you all today a little bit of background

my name is Andrea Gilbert I am a

pathologist I am a physician I am board

certified in anatomic pathology clinical

pathology and neuropathology and usually

on this platform I share with you guys

the neuropathology part of my practice I

am also the autopsy director at my

institution and I wanted to share with

you the results of an autopsy that we

did for a patient who was positive for

kovat 19 I think that this is very

important because we don't have a lot of

pathology data out there regarding kovat

19 we do have quite a few clinical

reports coming out of how these patients

are doing in a clinical perspective but

we don't really have a lot of reports

out there based on pathology studies and

so I just want to say thank you so much

to the family for allowing me to present

this I think it gives a lot of

information to our clinical colleagues

in the ICUs and in the emergency

departments so that we have a more

informed position when trying to fight

this virus on the on the global stage

okay so let's get started okay this is a

clinical presentation fortunately we

haven't had

that many deaths yet in the San Antonio

area so I don't want to share with you

her exact age but she was a young to

middle-aged woman and she presented six

days before she passed away with a

one-week history of fever cough and

dyspnea which means difficulty breathing

her past medical history was significant

for just obesity there was a

questionable history of possible asthma

my impression was that she would puff on

an inhaler every once in a while

especially during allergy season but as

far as having pulmonary function testing

that she didn't have that official

diagnosis in the emergency room she was

noted to have severe respiratory failure

and hypotension she had some serious

hypoxia meaning that her oxygen levels

were very low and so she immediately had

a breathing tube stuck down her throat

to help her breathe and was put on a

ventilator so here are some labs and

again this is a pathology presentation

so this is going to be very brief to the

non pathologist non-medical folks out

there her white blood cell count had a

normal range but the peripheral

lymphocyte count the absolute lymphocyte

count was a little bit low and this has

been described in other patients with

Kovan and the reason for that is not

clear her cardiac markers which is the

troponin and the BNP her cardiac markers

were elevated so there was concern about

her heart function the d-dimer was

elevated interleukin 6 was undetectable

that did increase throughout her stay of

note ANCA was negative

I will show you a little bit of

vasculitis in the future here in just a

little bit but ANCA was negative she did

have a positive a na for the non-medical

folks we see a na in disease processes

like SLE lupus and a few other things so

the the meaning for this as far as how

much it was implicated in her disease

process that is unclear but ultimately

throughout her medical admission she was

diagnosed with a RDS which is acute

respiratory distress meaning you're

having some severe difficulty breathing

requiring ventilation requiring her to

be on a ventilator and this was believed

to be secondary to

Kovan 19 infection and she was positive

for the the kovat 19 virus which is

called the SARS copa 2 virus she did

have an instant me what that means is a

myocardial infarction she had not enough

oxygen getting to the muscle tissues she

developed septic shock

cardiogenic shock and she also had this

reverse tuck asobu cardiomyopathy

colloquially this is called broken heart

syndrome it means that it's not an

ischemic type cardiomyopathy she also

had shock liver acute kidney injury and

then the possibility of SLE with the

positive a na so this patient passed

away and she had an autopsy done for the

non-medical folks out there as part of

an autopsy what we do is we open the

chest and we open the abdomen and we

look at the the organs and looking at

them with the naked eye this is called

the gross examination and then we take

small little pieces of tissue and we cut

them very small and we put them under a

microscope okay so let's take a look at

her lung this is what it looks like here

on the outer surface

where the lung should look like is a

lung should be very very shiny and we've

got a bit of glare here but we can see

that this if you look in the areas of

this lung that does not have the glare

to it we can see that there is a

dullness to it here on the pleural

surface and then if we look right around

here this area of the lung is very red

it's very eerie thinness and it was

actually this area of the pleura that

I'm showing here was underlying large

areas of consolidation and when we took

little sections of this long to look for

to look at under the microscope I'd see

that there was a lot of pleural deema

that had this blood-tinged fluid to it

on the surface of the lung we could see

that there were these flat tan smooth

little lesions kind of like macules on

the on the pleural surface

microscopically these did correlate with

a lymphocytic pleuritis the lungs were

very heavy

they were very boggy they were very

consolidated and and so what that means

is that when when you feel the lungs it

should have this very kind of spongy

like consistency to it because it's full

of air but this month was not it was

very very much of a firm or kind of a

rubbery consistency and then when you

cut into it there's all this pleural

edema so if we take a look at what the

lung tissue looked like on the the lung

on the left side of the screen this is

what generally lungs should look like

relatively speaking we see that there's

a lot of these clear looking spaces here

and those clear looking spaces they

should have air in them so what we've

done is we've taken this this big piece

of tissue and we've sliced it into these

very very very very thin slices and when

we take those thin slices and we

down on the glass slide and we look at

it through the microscope what we're

seeing is a lot of clear spaces because

those clear spaces should be filled with

air in the living person so on the right

side of the screen what we're seeing is

that there is this diffuse consolidation

the air spaces that we see on the left

side of the screen on the right side of

the screen they're completely filled up

and so I'm gonna focus in right about

here in the center here and so on the

left side of the screen it's relatively

less involved on the right side of the

screen we can see that the air spaces

are really really filled up and they've

got a lot of cells in them which I'll go

into in just a second for the

non-medical people out there take a look

at the the septal walls here at the

alveoli the alveoli are supposed to be

very very thin essentially they contain

a capillary vessel running through with

blood and then the Numa site which is

the lung cell that the cell lining of

the alveoli and that is a very very thin

border and the reason why it's so thin

is that it allows for the diffusion of

oxygen coming from the alveolar space

into the capillaries where the blood is

so that we can oxygenate the blood the

way that that should normally work is

that the alveolar spaces the alveolar

sacs and the alveolar ducts they should

be clear they should be full of air on

the left side of the screen it's

relatively what we should be seeing on

the right side of the screen it is not

okay so let's take a look here what

we're seeing here is a really markedly

severe and very extensive edema so if

you take a closer look here you can see

that there's this kind of reticulated

pattern here what we're seeing there is

that is where the alveolar septa are

this this is where the alveoli are we

can make out these little circles here

and here and here and here and here and

basically what that is show

this is where the alveolar spaces were

and that is the alveolar wall bordering

that space but instead of seeing the

clear space like we should be seeing

we're seeing that it's filled massively

filled up with this pulmonary edema and

so for the for the non-medical folks out

there what this means is that that she

was unable to perform gas exchange in

the alveolar spaces because they were

they were filled up with fluid and this

cellular infiltrate which we'll see in

just a second okay so we've got a lot of

findings here and I'm just gonna list

these as we go through them so we're

seeing large areas of consolidation

there's markedly severe pulmonary edema

again filling up those air spaces with

that fluid and so if we think back to

her clinical presentation of how she

presented before she passed away

you will remember that she had a really

bad hypoxia in hypoxemia which means

that there's not enough oxygen in the

blood and this is why because her her

alveolar sacs and the air spaces were

filled up with fluid and you're not able

to get oxygen and carbon dioxide out so

if we continue on here we can see we'll

go back to this example that we just

looked at previously let's zoom in in

this area right here and we already saw

this slide there's a relatively

uninvolved lung on the left side and

much more involved lung on the right

side and let's zoom in right here where

that box is some of you might be

wondering what this is we can see that

there are these little cilia here this

is respiratory epithelium it probably

got lodged in there during section so

don't worry about that the thing that I

really want to point out here is this

cell right here now if you take a

comparison between this cell and the

cell

around it you can see that this cell is

massively enlarged we've got a scale bar

right here to me this is very convincing

for viral cytopathic effect so for a

viral psychopathic effect well what is

that it is the effect that the virus has

on the cytologic appearance of a cell so

if you think about things like herpes

add no virus

cytomegalovirus there's a bunch of

different viruses out there that when

the virus infects the cells it looks

abnormal so the the cell that is

infected by the virus looks very

different from the cells that are not

affected by the virus and so this I

believe is a Numa site and I believe

that this it may be a very reactive Numa

site but I think it's very convincing

for viral psychopathic effect another

cell that's very convincing Perseid

viral psychopathic effect is this one

look at the size here it's a massively

enlarged cell now this cell is really

prominent it catches the eye you can see

it from a mile away but if you look

around you can see that there's other

cells very similar to it that aren't are

not as enlarged or not as prominent but

they do have what looks like to be an

abnormal appearance to them this guy

over here and so I think what we have

here is a viral psychopathic effect with

there being some cells that are

massively affected but other cells they

do show this this change to the to the

nuclear appearance and to the

cytoplasmic appearance that is is very

suspicious very very suspicious so okay

so if we take a closer example we can

see here's another example of what I

believe to be a viral psychopathic

effect other people out there might

think that oh maybe that's just a really

reactive Numa site and that's totally

possible but to me that this is very

convinced

so just to recap what have we seen so

far I've put the new findings in red

here in here that we just described as

this viral psychopathic effect and some

people might think is a really reactive

Newman site but I think it's very

convincing okay so moving on here we've

moved to another part of the lung we can

see here here is the pleura here if this

is the peripheral aspect of the lung

here and I'm gonna focus in in just a

little bit but I want to show how on the

bottom left-hand side of the screen we

can see that there's a lot of clear

space this is where the air is able to

get into and on the bottom right-hand

part of the screen we can see that

there's really no spaces there and those

alveoli have been blocked up and are not

able to do gas exchange here let's take

a focus in here and let's take a closer

look there so what we can see here is

this is a higher power image and I've

made a an outline of the alveolar

linings here okay so this is where the

alveolar wall is these little black

areas so that everybody can see what I'm

talking about so if we take a look here

here's the little capillaries it's a

little bit congested within the alveolar

wall and look at the pneuma sites that

have come off of the alveolar wall so

this is kind of a desquamation type

pattern so for the non-medical folks out

there if you if you rub your hand up

against your skin you'll see it gets

really ashy because there's little skin

cells that are falling off

that's called desquamation so basically

the the cells of the that normally lined

the lung tissue they seem to be falling

off of their basilar attachments which

is not a good thing

you don't want those cells to be falling

off because you're not going to be able

to get good gas exchange so in this area

where we actually have air within this

area within the alveolar spaces but

there's no gas

going on here because the cells have

come off of their baler attachment so

here is where the alveolar wall should

be and then here is where the pneuma

sites are so basically what I'm saying

here is that the the large areas of the

lung were filled up with this fluid this

pulmonary edema and then even in the

areas of lung that we're able to get air

into them you're not able to get gas

exchange because of this desk womate of

type pattern that we're seeing with the

pneuma sites that seem to be falling off

of their alveolar walls and as we go

through here we if you take a look at

the nuclear features of these cells we

can see that some of these cells they

have these very eosinophilic nuclei that

are very suspicious for viral cytopathic

effect okay

so if we move forward we can see in a

higher power view that these Numa sites

were disassociating from the alveolar

wall and they form these sensational

aggregates if you look through the

medical literature of the very few

autopsy cases that have been reported

for the current novel coronavirus that

we're seeing today and then you also

look at the literature for the SARS

virus we can see that there are these

multinucleated giant cells that have

been reported in the literature

multinucleated giant cells when you

typically see that you typically think

about TB fungus foreign body reaction

sarcoid etc etc but I don't think that's

any of the processes that we're seeing

here in my opinion what has been

reported as multinucleated giant cells

are actually these social groups of Numa

sites that have been decimated their

work come off of of the alveolar wall

and if we look further if we look a

little bit closer some of these are very

suspicious for a viral site

Pathak effect if we correlate our lung

findings that we've seen thus far the

the areas that are listed in light we've

already talked about the the areas that

are listed in red these are new findings

that we're discussing so the new Messiah

desquamation are swapping off where

those the the lining of the lung alveoli

are just kind of coming off in droves

kind of like in a DI pee sort of pattern

but not really

and then the multinucleated giant cells

like aggregations which I believe are

just these soft Numa sites that form

these sensational groups what we were

also seeing was bona fide Highland

membranes so this is a characteristic

feature of diffuse alveolar damage also

notice that we've got a ton of

inflammatory cells here and here and

here and here and so this is a

characteristic of diffuse alveolar

damage where we get the formation of

these highland membranes that line the

alveolar spaces and of course you can't

get any gas exchange through these

highland membranes so that kind of

worsens the picture here's another

example of the highland membranes is

this very eosinophilic kind of dense

looking material that lines the alveolar

walls this image is also showing how

these Numa sites that are just kind of

falling off of their basilar attachments

they're filling up into the alveolar

spaces some of them have kind of

enlarged nuclear features and ample

cytoplasm very suspicious for a viral

psychopathic effect

this is alveolar fibrin and again this

was a very prominent finding throughout

the the lung this this amorphous pink

material they were quite a few areas

that were looking like maybe it was

Highland membranes versus fiber and

deposition

it was a little bit hard to tell which

was which so this was a pretty extensive

finding all right so basically what we

were seeing is conducive or congruent

with what is so far reported in the

literature this is just another example

showing that there is edema here here's

the Hyland membranes associated with

diffuse alveolar damage and I'd like to

take a moment just to point out the

massive amount of inflammatory cells so

to the medical folks out here all of

these little purple dots here this is

all inflammatory cells inflammatory

cells so this is a this is a very

extensive inflam inflammatory process so

when we think about inflammation in the

lung if you see a whole bunch of

neutrophils in the lung then we call

that in acute pneumonia and that's

usually associated with bacteria and

things like that

for pneumonias that have a lot of

lymphocytic infiltration which is what

we see here the lymphocytic infiltration

goes along more with a viral pneumonia

and so that's what we have here so far

what we've been seeing is very

consistent with a viral pneumonia so

just going back to the diffuse alveolar

damage to the pathology residents out

there diedi can be basically separated

into two parts an early phase in the

later stage the early phase is called

the exudative stage because you get

these edema and the fibrin s exudates

that we've just been talking about the

later stage is called a proliferative

phase or organizing phase and then a

fibrosis stage so in this and and these

are not completely black and white it's

a spectrum so what we're seeing here is

the early stage of diffuse alveolar

damage with these Highland membranes and

the fitness exudates and lots of edema

and then in the later stages you'll

start to get organization proliferation

and fibrosis now we don't have any

fibrosis here but we do have a few areas

that had increased mitosis ie

proliferation and things like that so so

I think we're starting to move into the

organizing phase but this for the vast

majority this patient was kind of in the

early stages of the proliferative phase

and very much in the exudative stage

again we can see these kind of

multinucleated giant cells like groups

of the numa sites here is a nice

alveolar wall here and all of the numa

sites are just kind of falling off and

in these newest sites they they're much

thicker they have this reactive

appearance so basically what I'm saying

here is that there is a really bad viral

type pneumonia and even though there

were some parts of her lungs that were

aerated they weren't getting good gas

exchange because of the damage to the

pneuma sites that we were seeing okay so

what are lung findings so far we had the

Highland membranes which is a very very

characteristic of the diffuse alveolar

damage and this is consistent with her

clinical presentation of the acute

respiratory distress syndrome or a RDS

okay so when I was first looking through

this lung and scanning in at 10,000 feet

I thought that originally I thought that

this was a fibrin thrombus but when you

get up on higher power you can see that

no it's not a fibrin thrombus

it's just coagulum and you can see

separation of the erythrocytes here and

the fibrin there so to the pathologist's

in the group if you're looking at these

things from 10,000 feet before you start

calling micro thrombi please go in and

take a closer look I know that

obvious but please do that okay and then

to the clinicians in the group there

have been some very convincing reports

of a possible coagulopathy type

situation associated with a throat

prothrombotic propensity of these

patients forming clots and things like

that so as far as whether or not micro

thrombi are present in covent 19

patients I think the jury is still out I

didn't see any in this autopsy case but

that's not to say that it's not present

in other patients so I would offer a

word of caution to the clinicians out

there who are managing these patients as

you all know by Brent oolitic therapy is

not an innocuous thing and it does have

its risks so before administering that

you know you just gotta take it in

context of the of what's going on with

your patient so I do want to make a note

though that any time you have a diffuse

alveolar damage type situation with

acute lung injury that in and of itself

can cause can cause fibrin thrombi to

form so you can always get a little bit

of micro thrombi anytime you have a

diffuse alveolar damage situation with

acute lung injury and so you have to

take that with a grain of salt if you're

only seeing micro thrombi within the

lung tissue that doesn't necessarily

mean that is a pro thrombotic since

systemic situation there so that's

something to be taken into account okay

so this is an extensive evaluation of

the lung findings here we just have the

the lung parenchymal findings I want to

move forward with you guys and talk

about the vascular findings within the

lung and so this is the blood vessels

and I've labeled it here the the blood

vessels are filled up with red blood

cells as the oxygen carrying cells but

notice on the periphery of these blood

cells the periphery of the blood vessels

we can see that there

a somewhat of a concentration of these

little purple dots which are lymphocytes

and other inflammatory cells and so this

is a peri vascular distribution so if we

look in another section here we can see

that again I've labeled the vessels here

and here and we can see that there's a

little bit of an accentuation of the

inflammatory cells right around the

blood vessels so this is a peri vascular

distribution a lymphocytic peri vascular

infiltrate and in some areas it really

starts to look like vasculitis and so we

can see here that the peri vascular

inflammatory infiltrate and what we can

appreciate here on higher power is how

these inflammatory cells they look like

they're really extending through the

wall now I wasn't seeing anything that

looked like fibrin oeid necrosis which

would be a slam-dunk vasculitis but I

think it is pretty convincing where we

have these perivascular lymphocytes and

some of them look like they're really

starting to go through the walls here

and so this is on higher power if we

look on lower power we can see that in

and I've circled this for the for the

non-medical folks but we can see on

lower power we can see how the blood

vessels here and here and here and here

are surrounded by these little purple

dots which are the lymphocytes the

inflammatory cells and so we've got this

pretty prominent peri vascular

lymphocytic infiltrate we can see the

exact same thing here and I've circled

these for you

this peri vascular lymphocytic

infiltrate in in an area of the lung

that's a little bit more aerated than

what we were seeing in other areas in

addition we can also see lymphocytes

inflammatory cells within the pleura and

and this corresponds to what we're

seeing on the gross examination with the

little flat tan Mac you'll like lesions

on the gross surface okay so in addition

to everything that we've just talked

about there were large areas of a

pulmonary infarction and so basically

what we can see here is that

there are these really consolidated

areas that are not aerated they don't

have any air in them and and this tissue

has has died so we've got a pulmonary

infarction if you look up close there

isn't a necrosis there and so we've got

a necrotizing infarction with hemorrhage

in addition to what I believed to be is

vasculitis a lymphocytic vasculitis with

a very prominent and very extensive

perivascular lymphocytic huffing i don't

think that this has been described in

other

Cobin 19 patients in addition of note

she did have a positive a na so i don't

know what exactly that means as far as

relating that to this vasculitis here

her ANCA was negative and is it possible

that maybe there might be an autoimmune

sort of situation here I'm not sure so

so the lung findings were really really

extensive and very severe so I just want

to get on a soapbox for a little bit and

and let you guys know that there have

been some reports out there especially

in the lay media talking about how

ventilators cause harm and that

ventilators are bad etc etc and I just

want to say that that is not the case so

ventilators do have the capacity to

cause Barrow trauma but as with anything

you have to weigh the risks and the

benefits in patients who are basically

drowning in their own fluids and they're

not able to breathe and they're gasping

for breath ventilator is absolutely

necessary to be clear I didn't see

anything in this lung that looked like

Barrow trauma I didn't see anything in

this patient that looked like there was

injury from the ventilator all of this

is associate

with the with the with the virus with

the inflammatory infiltrate and with the

infection of the virus and another

interesting thing about this case is

that this patient was not an older

patient she was not elderly she had

obesity maybe this possible history of

asthma but really didn't have much in

the way of comorbidities and she was

relatively young and and she had a very

severe a very severe clinical course so

just a note to all of you young people

out there if you think that you're

invincible you're not so please take it

seriously okay so I'm off my soapbox

let's continue so these were the lung

findings that I was showing you guys I

wanted to continue on to some other

aspects of this case and so if we move

forward here's the peripheral smear this

comes back to the discussion about the

possibility of micro thrombi and a

prothrombotic sort of situation here

basically what we're seeing were these

atypical lymphocytes and then a left

shift so what does that mean the left

shift is where the cells are getting

pushed out of the bone marrow a little

bit earlier than when they're ready and

usually you see this when a person is

fighting an infection and they're trying

to get as many of those an infection

fighting immune cells out as quickly as

possible so we were seeing the left

shift and some atypical lymphocytes and

we can see that here so basically what I

wanted to point out is that this blood

smear is really not all that super

exciting there's there's some atypical

lymphocytes and the left shift but for

the most part we weren't seeing anything

that looked like thrombosis we weren't

seeing shifts the sites we weren't

seeing di sea we weren't seeing anything

like that so alright and so there's some

more okay now we get into the heart okay

so I will remind you

that this patient had a reverse

takotsubo cardiomyopathy she had severe

hypokinesis of part of the the wall of

her heart and so that means that the

heart was not able to beat properly and

to the point where there was actually

quite the question of whether or not

this represented a viral myocarditis so

I wanted to show with you the heart

findings here and these are the coronary

vessels we can see that the coronary

vessels are really clear they're widely

open widely paitent and so whatever

cardiomyopathy issues that she was

having was not due to an ischemic type

injury and on cuts section the heart

looked pretty good there was a little

bit of staining here but that wasn't

anything microscopically and then here

what we have is a little bit of formalin

fixation artifact but for the most part

she didn't have any areas of ischemic

looking injury the right ventricle is a

little bit dilated she did have a lot

going on in her lungs and so the right

ventricle pumps blood to the lungs so if

you've got a lot of increased pressure

in the lungs that can cause a back up in

the in the right ventricle so it's not

able to pump blood out as well but for

the most part the the gross impression

of the heart was not all that it wasn't

that bad this was really interesting

though this heart the right atrium this

is the right atrium it was very thin and

there were areas of the right atrium

that looked like the the myocardium was

partially missing here and here and so

there were areas where the epicardium

was basically bare and did not have

myocardium underlying it and so I think

that this is probably a congenital

process for this patient where can Jenna

congenitally she didn't have enough

myocardium with

the right ventricle but that never

really caused her any problems because

she was relatively healthy but when you

have a severe lung injury and a severe

lung involvement that right ventricle

sorry that right atrium would not be

able to contract as as as well as it

should have so I think that this

probably contributed some to her cardiac

abnormalities that were noted in the

ante-mortem time period okay so let's

take a closer look at the myocardium

just as a reminder the the clinicians in

this case were very concerned about a

viral myocarditis she had this very

severe hypokinesis or decreased wall

movement of the of the wall of her heart

she wasn't able to push blood as well as

she should have been and so the the

clinicians in this case were very

concerned about a fulminant viral

myocarditis we did not see that what we

did find was edema so there was this

very interesting mix oeid edema that we

were seeing in the heart and I don't

know if this is an intrinsic part of the

covent process or if this was something

different so just as a bit of background

there have been increased reports of

koban 19:00 and patients with kovin 19

having a cardiomyopathy cardiac issues

and for the most part this has been

complicated because a lot of the the

patients who have been passing away they

have other cardiac issues that were

pre-existing prior to them getting sick

so it's kind of hard to say okay what

was the pre-existing cardiovascular

disease compared to the the current

COBIT infection and but in this patient

this patient had no history of

underlying cardiovascular disease this

patient had

very clear coronary arteries that

grossly and microscopically did not have

any [ __ ] erotic disease and she was a

young to middle-aged adult so we're

seeing this mix oeid type edema which is

kind of strange but I'm not sure the

exact cause of that is this a process of

the virus but we weren't seeing

inflammatory infiltrates that would

indicate presence of the virus in the

heart tissue perhaps maybe this might be

due to the hydroxychloroquine that she

received when she had about a leak of it

so let me take a moment to get on my

little soapbox about hydroxychloroquine

so hydroxychloroquine is not a benign

drug it's not like popping an aspirin or

taking an ibuprofen it's not a benign

drug so so people who take it they need

to be closely monitored the therapeutic

window for hydroxychloroquine is very

narrow so what does that mean it means

that the amount that it takes to have

effect versus the amount that it takes

to have toxicity is very close together

so that therapeutic range between having

an effect and then having toxicity is

very narrow and so these patients they

really need to be monitored it needs to

be under a physician's management okay

done with a hydroxychloroquine spiel

let's move on so this patient has a

relatively good-looking heart there was

this edema this kind of mix oeid edema I

apologize the blue really isn't coming

out but it had these kind of mix oyd

like spaces there and again the

clinicians were very concerned about a

fulminant viral myocarditis we were not

seeing a fulminant myocarditis we did

see very very rare areas of very focal

very mild lymphocytes and so these

little purple guys right here these are

little lymphocytes we did do an

immunohistochemical

saying that highlights lymphocytes and

this is as exciting as it gets a very

rare faux sigh of very few scattered

lymphocytes were present this was in the

papillary muscle of the left ventricle

we did not see lymphocytes anywhere else

and so that clinical impression of a

fulminant viral myocarditis was not

substantiated on the on the pathologic

findings so for the clinicians out there

who are in the ICUs and treating these

patients we're seeing that there's these

very abnormal kind of EKG functional

processes within the heart the hearts

not beating as well as it should be and

there's a question about a viral

myocarditis and that's not what we're

seeing in this autopsy patient so so

what is responsible for those cardiac

abnormalities I don't know but it's not

a viral myocarditis them and maybe

perhaps the virus is involving the

electrical conduction system within the

heart but I don't see evidence of a

viral myocarditis in this autopsy case

okay so moving on when it talked to you

about the kidneys here so this is the

kidneys the the kidneys grossly they

they looked pretty okay and

microscopically this is what we were

seeing it was a pretty unremarkable

kidney for the most part so so just a

brief review these are the glomeruli

here this is the the part that makes the

urine and it has a normal size normal

cellularity normal architecture okay and

so for this patient she did have

elevated creatinine that was going up

throughout the the hospital course and

so there was a concern for acute kidney

injury and looking through the remainder

of this kidney and browsing through we

saw a lot of autolytic change and this

is what autologous and the kidney looks

like where there's basically this kind

of

rotation of the the tissue here and what

autologous means is that after a person

passes away the the membranes start to

lose their structure the cells they

start to degrade and that's basically

what Hollis's is but what was very

interesting was in focal areas we could

see evidence of acute tubular injury and

so what we were seeing was these cells

the the tubules cells so here the TBL

cells here and here and here and here

okay and these tubular cells we start to

get this proteinaceous material the TAM

horsfall protein within the the to be

lumen we're also starting to get

granular casts within the tubular lumen

and then here is this necrotic debris

within the the tubules basically we were

seeing this very focal acute tubular

necrosis which would explain the

clinical impression of acute kidney

injury there have been reports out there

showing that patients are having kidney

disease sometimes the kidney disease

gets worse even after the pulmonary

disease gets better so I think the

jury's still out there on this one I

mean I could hypothesize that she did

have a very severe hypoxia due to her

sit very severe lung injury and so maybe

the severe hypoxia might be responsible

for this acute tubular necrosis that's

possible but I didn't see anything that

looked like a primary an infection

inflammatory disorder here I didn't see

anything that looked like a viral

nephritis or an interstitial nephritis

anything like that all right so that

completes the tour of this autopsy case

again I want to say thank you so much to

the family for allowing me to present

this case I think that it has the

potential to teach us a lot about what's

going on with the Co

19 virus and what are the pathologic

effects of this virus again we've had a

lot of clinical reports coming out

talking about what they're seeing in

patients and ICUs and emergency rooms

but I think it gives a lot of

information to us if we can look at the

pathology and see what's going on in the

pathogenesis of this disease so that

completes our discussion this is autopsy

findings I also present neuropathology

findings on adventures in their

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that I've ever made before sorry about

the length but I think it's important to

present these findings so people know

what we're dealing with so that's it

join us next time on adventures in

neuropathology thanks