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Exercise and Clinical Immunology > COVID - L7 > Flashcards

COVID - L7 Flashcards

1
Q

Name symptoms of COVID-19.

A
  • Fever or chills
  • Cough
  • Shortness of breath
  • Fatigue
  • Muscle or body aches
  • Headache
  • Loss of taste
  • Loss of smell
  • Sore throat
  • Congestion or runny nose
  • Nausea or vomiting
  • Diarrhea
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2
Q

It has been shown that ACE2 receptors are linked to viral entry of the corona virus. What is ACE2?

A

ACE2 is an enzym involved in the Renin-Angiotensin-Aldosterone System (RAAS) that catalyzes the conversion from angiotensine I to angiotensine II and is known to have a direct influence on the cardiovascular system.

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3
Q

Describe the Renin-Aniogentensin-Aldosterone System (RAAS) and briefly describe its pathway.

A

RAAS is a endocrine system that regulated blood pressure, fluid and electrolyte balance, and systemic vascular resistance. The system is activated when there is a decrease in (renal) blood flow, where the following occurs:

  • Juxtaglomerular kidney cells sense the decrease in blood flow and secrete renin in a response.
  • Angiotensinogen produced by the liver is converted by renin into angiotensin I, which is converted to angiotensin II by ACE in the lungs.
  • Angiotensin II causes vasoconstriction of aterioles and stimulates the adrenal cortex to produce aldosterone. The latter results in increased Na+ and water reabsorption and increased secretion of K+ and H+ into urine.
  • All together, blood volume and blood pressure increase intil it returns to normal.
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4
Q

Severe covid infection is linked to cytokine storm. What is this?

A

A cytokine storm is defined as an acute overproduction and uncontrolled release of pro-inflammatory markers.

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5
Q

What determines the severity of the disease?

A
  • Number of virus particles and cytokine storm
  • Comorbidities (e.g. low grade inflammation or ACE2 expression)
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6
Q

What is post-intensive care syndrome (PICS) or intensive care acquired weakness (ICU-AW)?

A
  • PICS: health problems that remain after critical illness.
  • ICU-AW: A skeletal muscle disorder that can occur following sepsis, mobility restriction, hyperglycemia, and use of glucocorticoids or neuromuscular blocking agents.
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7
Q

Name factors that can lead to intensive care acquired weakness (ICU-AW) (i.e. muscle atrophy) in the context of SARS-CoV-2 infection.

A
  • SARS-CoV-2 infection -> forced inactivity due to hospitalization -> muscle weakness (vice versa muscle weakness leads to more inactivity).
  • SARS-CoV-2 infection -> forced inacitivity due to hospitalization -> malnutrition -> muscle weakness
  • SARS-CoV-2 infection -> viral infiltration -> muscle weakness
  • SARS-CoV-2 infection -> systemic inflammation and immune cell infiltration -> motorneuron degeneration -> muscle weakness
  • Comorbidities that enhance systemic inflammation
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8
Q

Complete the sentences.

  • … intensity regular exercise is associated with a reduction in respiratory infection compared to … intensity regular exercise.
  • Exhaustive exercise before or during an infectious condition such as COVID-19, can trigger severe illness due to increased OR decreased …, …, and … cells.
A
  • Moderate intensity regular exercise is associated with a reduction in respiratory infection compared to low (i.e. sedentary) intensity regular exercise.
  • Exhaustive exercise before or during an infectious condition such as COVID-19, can trigger severe illness due to decreased B, T, and NK cells.
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9
Q

What is the Takotsubo Syndrome?

A

A neurocardiac condition that is also known as stress cardiomyopathy or broken heart syndrome and is characterized by a sudden temporary weakening of the muscles of the heart. It usually appears after a significant physiological or physical stressor. During the COVID pandemic, this syndrome was also observed in people watching an anxiety-provoking evening news progrom on COVID-19.

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10
Q

A study investigated MRI images of the heart of patients that had covid-19 infection and either had a home recovery or were hospitalized as a result of infection (compared to healthy controls and risk factor-matched controls). What was shown with this study?

A

That patients who had COVID-19, especially when hospitalized, had higher ‘chances’ of cardiac inflammation and/or fibrosis.

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11
Q

Name factors that enhance the risk of COVID-19-induced cardiac dysfunction.

A
  • Systemic inflammation
  • Hypoxemia or lung failure
  • Direct myocardial injury
  • Cytokine storm
  • Disseminated Intravascular Coagulation (DIC)
  • Stress induced cardiomyopathy
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12
Q

How is post-covid condition characterized?

A
  • viral persistence
  • microclots
  • post-exertional malaise
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13
Q

What is the problem with the current definition of post-covid-19 condition?

A

That there is overlap in the definition with other processes such as comorbidity and aging or hospitalization.

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14
Q

Name potential immunopathological mechanisms that lead to post-acute covid-19.

A
  • Hidden viral reservoirs
  • Immune exhaustion
  • Viral-induced autoimmunity
  • Abnormal immunometabolism
  • Altered microbiome
  • Imbalance in RAS
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15
Q

Name risk factors of long covid.

A

Obesity, diabetes mellitus, hypertension, ischemic heart disease, COPD, chronic kidney disease.

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16
Q

Describe how SARS-CoV-2 uses the ACE2 pathway to infect cells and what consequences viral infection has on the cell via ACE2 entry.

A
  • SARS-CoV-2 infects cells harboring ACE2 and is subsequently endocytosed. With this, ACE2 is also endocytosed, decreasing overall ACE2 levels.
  • Normally, activated ACE2 converts angiotensin IIto angiotensin 1-7. But since ACE2 is endocytosed by viral entry of SARS-CoV-2, angiotensin II levels increase.
  • (High levels of) angiotensin II interacts with its receptor AT1-Rs, which causes the accumulation of free radicals (ROS, RNS). This leads to hypertension and inhibiton of vasodilation.
  • This process is stimulated even further by mitochondrial dysfunction that results in the production of even more free radicals.
  • Angiotensin 1-7 bind to MasR, which mediates vasorelaxation and decreases free radical production.
17
Q

What is post-exertional malaise (PEM)?

A

A worsening of COVID symptoms that occurs after exertion (e.g. exercise). It usually begins 12-48 hours after the activity that triggered PEM and can last for days.

18
Q

What is chronic fatigue syndrome?

A
  • A condition that causes fatigue, exercise intolerance, sleep problems, and brain fog.
  • It may be triggered by genetic mutations and certain viruses or toxins.
  • It is diagnosed by first ruling out similar conditions.
  • Treatment includes lifestyle changes and OTC medications.
19
Q

What is persistent exertional intolerance after (long) COVID-19?

A

A peripheral, rather than central (i.e. involving the muscles, blood vessels and other tissues rather than the cardiovascular and respiratory system) cardiac limit to exercise characterized by diffusion defect in oxygen delivery in patients who have recovered from COVID-19. Patients also exhibit an exaggerated hyperventilatory response during exercise.

20
Q

Description of a study:

  • Patients with long-covid (experimental group) and patients who had covid but without long covid (control) were included in the study.
  • Throughout 14 days, questionnaires, muscle biopsies, venous blood draw, and a bike exertion test were performed.
  • Data was collected regarding: patient characteristics, medical history, questionnaires, outcomes, and symptoms.
  • Outcome measured was skeletal and mitochondrial dysfunction post-exertion.

What was found regarding the skeletal dysfunction post-exertion?

A

The main finding was that exercise intolerance has a peripheral contribution, meaning that effects/explanations of exercise intolerance were found outside the lungs and/or the heart. For example, they found that the following parameters were decreased in the long-COVID group compared to the control group:

  • VO2 max
  • Peak power output
  • Gas exchange threshold
  • Muscle deoxygenation
  • Fiber type distribution
21
Q

Description of a study:

  • Patients with long-covid (experimental group) and patients who had covid but without long covid (control) were included in the study.
  • Throughout 14 days, questionnaires, muscle biopsies, venous blood draw, and a bike exertion test were performed.
  • Data was collected regarding: patient characteristics, medical history, questionnaires, outcomes, and symptoms.
  • Outcome measured was skeletal and mitochondrial dysfunction post-exertion.

What was found regarding mitochondrial dysfunction post-exertion?

A
  • There was decreased succinate dehydrogenase (SDH) activity post-exercise, an enzymes important in the TCA cycle.
  • There was decreased oxidative phosphorylation post-exercise (both at baseline as post-exercise).

Therefore: metabolic and mitochondrial dysfunction in long COVid patients, which worsens with post-exertional malaise.

22
Q

Description of a study:

  • Patients with long-covid (experimental group) and patients who had covid but without long covid (control) were included in the study.
  • Throughout 14 days, questionnaires, muscle biopsies, venous blood draw, and a bike exertion test were performed.
  • Data was collected regarding: patient characteristics, medical history, questionnaires, outcomes, and symptoms.
  • Outcome measured was skeletal and mitochondrial dysfunction post-exertion.

What was found regarding blood vessels?

A

There were no alterations in capillarization (no differences in capillary density or capillary-to-fiber ratio).

23
Q

Another theory that could explain the cause of long COVID are microclots. What are these microclots?

A

These microclots are thought to block capillaries and potentially affect blood and oxygen flow. The microclots contain amyloid and fibrin(ogen).

24
Q

Description of a study:

  • Patients with long-covid (experimental group) and patients who had covid but without long covid (control) were included in the study.
  • Throughout 14 days, questionnaires, muscle biopsies, venous blood draw, and a bike exertion test were performed.
  • Data was collected regarding: patient characteristics, medical history, questionnaires, outcomes, and symptoms.
  • Outcome measured was skeletal and mitochondrial dysfunction post-exertion.

The study also measured amyloid-containing deposits in skeletal muscle in both groups. What was found?

A

That the long-covid group at baseline and post-exertion showed an increased number of amyloid deposits compared to the control group.

25
Q

Another study investigated whether these microclots in capillaries resulted in blockage of the capillaries during rest and post-exertion. What was found?

A

That there was no blockage of capillaires by microclots.

26
Q

Description of a study:

  • Patients with long-covid (experimental group) and patients who had covid but without long covid (control) were included in the study.
  • Throughout 14 days, questionnaires, muscle biopsies, venous blood draw, and a bike exertion test were performed.
  • Data was collected regarding: patient characteristics, medical history, questionnaires, outcomes, and symptoms.
  • Outcome measured was skeletal and mitochondrial dysfunction post-exertion.

Post-covid is also characterized by viral persistance. The study also investigated whether there was a difference in the amount of nucleocapsid protein present between the two groups at baseline and 1-day after PEM. What was found?

A

That nucleocapsid protein was present in almost all participants, but was not more abundant in long COVID.

27
Q

Description of a study:

  • Patients with long-covid (experimental group) and patients who had covid but without long covid (control) were included in the study.
  • Throughout 14 days, questionnaires, muscle biopsies, venous blood draw, and a bike exertion test were performed.
  • Data was collected regarding: patient characteristics, medical history, questionnaires, outcomes, and symptoms.
  • Outcome measured was skeletal and mitochondrial dysfunction post-exertion.

The study identified pathological features of long COVID in the skeletal muscle of these patients. Describe what was found.

A

Differences between the two groups at baseline and 1-day after PEM were found regarding:

  • atrophy (more atrophy for long-covid)
  • internal nuclei (more internal nuclei for long-covid) -> indicators of ongoing muscle regeneration
  • necrosis (more necrosis for long-covid)
  • regeneration (more regeneration for long-covid)
28
Q

Just read

Long-covid patients show signs of myopathy, particularly one day after exercise.

A
29
Q

Name the pathological features after post-exertional malaise.

A
  • Severe muscle fiber atrophy
  • Regenerating fibers
  • Fibers with central nuclei
  • Necrosis
  • Immune cell infiltration (T cells and macrophages)
  • Abnormal round cells

Exercise and Clinical Immunology (16 decks)

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