Alterations of Pulmonary Function

Week 6

Why is infectious disease a significant cause of death and morbidity? (3)

• reemergence of old infections thought to be controlled

• emergence of previously unknown infections

• development of infections resistant to multiple antibiotics

Communicability

ability to spread disease from person to person

immunogenicity

ability to produce an immune response

infectivity

ability to invade and multiply in the host

MOA

how microorganism damages tissue

pathogenicity

ability to produce disease

portal of entry

route microorganism takes

toxigenicity

production of toxins

virulence

capacity to cause severe disease/potency

ID50

estimated number of organisms or virus particles required to produce infection in 50% of population

endemic

diseases with relatively high, but constant, rates of infection in a population

epidemic

number of new infections in a population that greatly exceeds number usually observed

pandemic

an epidemic that spreads over a large area such as a continent or worldwide (covid-19)

what does covid-19 stand for? (SARS-COV-2)

Severe Acute Respiratory Syndrome Coronavirus 2

Where/when did covid-19 begin?

Wuhan, China, 2019

What was the reasoning behind covid-19s name?

the virus has distinctive spikes on its surface, making it look like a solar corona, thus its name coronavirus

Where did it orignate from?

virus may have originated in bats and may have been transferred. to humans through exposure to an unidentified animal vector

genomic studies have identified related coronaviruses in bats in Chima, Cambodia, Thailand and Laos

Human to human transmission of COVID-19 led to

hundreds of millions of cases worldwide and milllions of deaths

Viral mutations of covid-19 led to emergence of variants and this caused…

increased infectivity

What are the 3 variants mentioned?

B.1.1.7 (alpha) - emerged in UK

B.1.1.351 (beta) - emerged in South Africa

B.1.1.33 (P1) - emerged in Brazil

What are the two new variants that emerged in 2021 that have infectivity and have been teh cause of surges in new infections worldwide?

1. B.1.617.2 (delta) variant

2. B.1.1529 (omricon) variant

T/F - are more variants of covid 19 emerging?

Yes

What are the stages of viral infection of host cell? (Covid-19 but this is pretty much the same process for other viruses)

1. recognition and attachment of virus to host receptor or cell wall molecule

2. penetration into host cell by fusion or endocytosis

3. uncoating of viral genome within cell cytoplasm

4. replication of viral genome using host or viral transcriptases and polymerases

5. translation with viral structural protein synthesis in host cell endoplasmic reticulum and Golgi apparatus

6. assembly of virus

7. release of virus by budding or exocytosis

Where are the highest levels of covid-19 bacteria found? (3)

sputum, pharyngeal swabs, feces

what is the method of transmission (2)

droplet and airborne (aerosol)

• droplets released during cough,sneezing, talking

T/F it is rare to get transmission of virus from someone who is infected that is asymptomatic

true

What is a major contributor to spread of virus?

presymptomatic transmission

During the 3 to 7 days between infection and symptoms, shedding of virus can be high from respiratory tract. But infected individuals do not realize they are ill.

This means someone can have COVID-19 and spread it to others BEFORE they even develop symptoms.

What is the viral shedding peak

when the virus is most transmissable (symptomatic illness this usually occurs 3-5 days after symptom onset)

After 5-7 days the viral shedding declines so…

the virus is no longer readily transmissble

when is the risk of transmission highest? (3)

• indoor environments

• poor ventilation

• close contact (less than 6ft)

T/F - COVID-19 spreads easily through contaminated surfaces!

False

Covid 19 Pathophysiology: Step 1: Virus evades the immune system

virus evades early innate responses, especially interferons'

Unopposed viral replication and slows initiation of adaptive immune response

COVID-19 weakens interferons (proteins that warn cells about viruses), allowing the virus to multiply more easily and delaying adaptive immunity (B and T cells that fight specific infections).

Covid 19 Pathophysiology: Step 2: Immune cell dysfunction

As disease progresses neutrophil and natural killer cell dysfunction develops

Also effective in killing T cells resulting in a profound lymphopenia

- Neutrophils (infection-fighting white blood cells) become dysfunctional, NK cells (kill infected cells) become less effective, and T cells decrease, causing lymphopenia (low count).

Covid 19 Pathophysiology: Step 3: Excessive inflammatory response

Once infection is established powerful inflammatory response is initiated, sometimes progressing to a “cytokine storm”

Numerous interleukins (Il-1, IL-6, IL-8, IL-17), TNFα, and other inflammatory cytokines are produced at high levels

- The immune system overreacts and releases too many cytokines (chemicals that trigger inflammation), potentially causing a cytokine storm (severe, uncontrolled inflammation that can damage tissues).

Hyperinflammatory response causes (3)

increased permeability of vascular and epithelial membranes, edema, and tissue necrosis, especially in lung tissue

Covid 19 Pathophysiology: Step 4:Blood vessel damage and clotting

Hyperinflammatory response causes endothelial injury, microangiopathic changes, and platelet activation.

Hypercoagulable state like disseminated intravascular coagulation (DIC) characterized by clotting but without bleeding.

- Excessive inflammation damages the endothelium (blood vessel lining), causing microangiopathy (small blood vessel damage) and platelet activation (cells that help form clots).

- This causes hypercoagulability (increased clotting), similar to DIC (widespread abnormal clotting). Unlike classic DIC, COVID-19-related clotting may occur without obvious bleeding.

Covid 19 Pathophysiology: Step 5:Lung damage (ARDS)

Severe inflammation of lung tissue results in acute respiratory distress syndrome (ARDS).

-Severe lung inflammation damages the alveoli (tiny air sacs), causing fluid buildup and difficulty getting oxygen into the blood.

-This can lead to ARDS (severe lung injury causing low blood oxygen).

Covid 19 Pathophysiology: Step 6: Heart and brain damage

• Inflammatory and immune changes in myocardium.

• Contributes to cardiomyocyte death.

• Neuroinflammation is common.

• Damage to brain parenchyma and cerebral vasculature.

-Heart: Inflammation damages the myocardium (heart muscle), causing cardiomyocyte death (death of heart muscle cells), which can weaken heart function.

-Brain: Neuroinflammation (inflammation of the nervous system) can damage brain parenchyma (brain tissue) and cerebral vasculature (brain blood vessels), increasing the risk of neurological complications.

Covid 19 Pathophysiology: Step 7: Kidney damage

• AKI may occur, especially in critically ill clients.

• Nephropathy characterized by ATN, followed by glomerulosclerosis in some clients.

-Severe COVID-19 can cause AKI (acute kidney injury = sudden decrease in kidney function).

• Kidney damage may include ATN (acute tubular necrosis = damage to kidney tubules) and, in some patients, glomerulosclerosis (scarring of the kidney's filtering structures).

Simplified summary of pathophysiology of covid-19

COVID-19 weakens early immune defences, allowing the virus to multiply. The immune system may then overreact, causing excessive inflammation (cytokine storm), blood vessel damage, increased clotting, and potentially severe organ damage affecting the lungs (ARDS), heart, brain, and kidneys (AKI).

What primarily determines the progression and severity of COVID-19?

The host response (how the body's immune system reacts), rather than just viral virulence (how harmful the virus is). An excessive immune response can cause severe inflammation, blood clots, and organ damage.

What is the incubation period for covid-19 and How many cases are asymptomatic?

Approx. 6 days from exposure to symptoms onset

about 25%

What are the clinical manifestations of COVID-19, and who is at risk for severe disease?

• Most infected individuals have only mild symptoms.

• Older adults and those with underlying medical conditions (CV disease, diabetes, cancer) are at risk for severe disease and death.

• Many organ systems affected!

• Most common symptoms: Fever, cough, shortness of breath, myalgias, fatigue, loss of smell and taste.

• Additional symptoms result from neurologic, cardiac, endocrine, hepatic and renal injury.

What are the major complications and primary causes of mortality in severe COVID-19?

• Thrombotic issues linked to increased risk for stroke and venous thromboembolism.

• Respiratory failure and septic shock are primary causes of mortality

What is the recovery period for COVID-19, and what is long COVID?

• Most recover within 3 to 4 weeks after infection.

• But, nearly 1/3 of affected persons have persistent symptoms lasting for many weeks, even months.

  • Prolonged syndrome called post-acute COVID-19 or “long COVID”.

How does SARS-CoV-2 enter host cells

Receptor-binding portion of spike protein binds with high affinity to ACE2 receptors on cells.

ACE2 receptors are highly expressed in the (3)

lungs, brain, and fat

ACE2 receptors are expressed to a lesser extent in the(4)

heart, kidneys, pancreas, and intestines

What are the clinical manifestations of acute COVID-19 across different organ systems?

• Eyes: Irritation, photophobia (light sensitivity).

• Ears: Hearing loss, vertigo (dizziness).

• Brain: Stroke, encephalitis, loss of smell/taste, confusion, memory loss, brain fog, anxiety, depression.

• Heart: Heart failure, palpitations, chest pain, shortness of breath.

• Liver: Elevated liver enzymes.

• Pancreas: Abdominal pain, hyperglycemia (high blood sugar).

• Kidneys: Acute renal failure.

• Gastrointestinal tract: Nausea, anorexia (loss of appetite), diarrhea, abdominal pain.

• Vasculature: Thrombosis (blood clots) affecting multiple organs.

Covid 19 in children

• most have no or very mild symptoms during acute sars cov 2 infection

• but many develop serious illness occuring says to few weeks after initial infection

What is MIS-C, and when does it occur?

• multisystem inflammatory syndrome in children (MIS-C).

• SARS-CoV-2 can trigger an overwhelming immune response, resulting in hyperinflammation.

What are the manifestations and complications of MIS-C?

• Hyperinflammation results in:

  • Cardiac, pulmonary, renal, GI, and neurological injury.

  • Thrombotic complications.

  • Shock.

*approx 60% require intensive care and 15% require mechanical ventilation

• Distinct rash on palms and soles of feet.

• School-aged children primarily affected.

• Exposure to COVID-19 within the last 4 weeks.

• Elevated inflammatory markers on bloodwork.

• Lethargy is a big indicator, not your typical cough or congestion.

What is long COVID, including its causes, symptoms, and follow-up care?

• Definition: Continuation of COVID-19 symptoms or complications after 3–4 weeks; can occur even after mild illness or hospital discharge.

• Causes: Persistent inflammation, immune dysregulation (abnormal immune response), microvascular injury (small blood vessel damage), possible viral persistence, comorbidities, and recurrent infections.

• Most common symptoms: Fatigue and dyspnea (shortness of breath due to reduced lung diffusion capacity in some patients).

• Neurological symptoms: Brain fog, poor memory/concentration, and behavioural changes.

• Other symptoms: Muscle weakness, joint pain, anxiety, hair loss, and sleep disturbances.

• Complications: Increased thromboembolic risk (blood clots) and reduced quality of life; physical, cognitive, and psychiatric problems after critical illness can worsen symptoms.

• Screening: Assess respiratory, psychiatric, and thromboembolic complications at 4–6 weeks and again at 12 weeks after discharge, as outlined in your lecture.

Who should be tested for COVID-19, and what are the two types of viral tests?

• Testing for those with symptoms, known exposures, or required testing for community/employment purposes.

• Two types of viral tests:

  • Polymerase chain reaction (PCR): Detects viral genetic material (RNA); highly sensitive.

  • Rapid antigen test: Detects viral proteins; provides faster results but is less sensitive than PCR.

What are the common laboratory and diagnostic findings in COVID-19? (3)

• Decreased lymphocytes in blood.

• Elevated levels of inflammatory cytokines and D-dimer.

• Bilateral lung infiltrates on CT.

How do mRNA COVID-19 vaccines work, and what are examples?

• Several vaccines developed globally to prevent SARS-CoV-2 infection.

• mRNA vaccines: Moderna and Pfizer/BioNTech.

• Carry mRNA containing the genetic instructions for the viral spike protein.

• Use host cells' own translation machinery to make harmless pieces of viral spike protein that trigger an immune response.

How do viral vector COVID-19 vaccines work, and why are boosters recommended?

• Viral vector vaccines: AstraZeneca and Janssen (Johnson & Johnson).

• Use a modified virus (vector) to deliver genetic material coding for the spike protein into host cells.

• This triggers an immune response against SARS-CoV-2.

• Duration of immunity varies; booster immunizations are recommended.

• Vaccine effectiveness must be reassessed as new variants emerge.

What are monoclonal antibodies (MABs), and how are they used to treat COVID-19?

• MABs: Identical laboratory-produced antibodies derived from a single B-cell clone.

• Naming: Many monoclonal antibody medications end in -mab.

• Specificity: Target one specific antigen or receptor, allowing targeted treatment.

• Compared to polyclonal antibodies: Polyclonal antibodies are a mixture of different antibodies.

• COVID-19: Certain MABs were used early in infection in high-risk patients to block the spike protein from binding to ACE2 receptors, reducing progression to severe disease.

• Limitation: Many older COVID-19 MABs are no longer effective against newer variants.

Summary: MABs = Identical, targeted antibodies → Block viral entry → Help prevent severe COVID-19.

What is ARDS? (acute respiratory distress syndrome)

Form of acute lung inflammation and diffuse alveolocapillary injury

What causes ARDS?

direct pulmonary injury or from severe systemic inflammation

What are the key clinical manifestations of Acute Respiratory Distress Syndrome (ARDS)?

• Acute onset: Symptoms develop rapidly.

• Bilateral infiltrates on chest X-ray: Fluid accumulation in both lungs (pulmonary edema).

• Persistent hypoxemia: Low oxygen levels in the blood despite supplemental oxygen.

How common is ARDS, and what is its mortality rate?

• Affects approximately 10% of ICU patients.

• Occurs in approximately 23% of patients requiring mechanical ventilation.

• Mortality: Approximately 30–40%, despite advances in treatment.

• COVID-19: Has contributed to a dramatic increase in ARDS cases worldwide.

What causes Pediatric Acute Respiratory Distress Syndrome (PARDS), and what is its pathophysiology?

• PARDS: Acute Respiratory Distress Syndrome occurring in children.

• Causes: COVID-19 and pneumonia can cause direct lung injury.

• Inflammatory response: Causes alveolocapillary injury (damage to the barrier between alveoli and blood capillaries).

• Consequences:

  • Fluid leaks into alveoli → Pulmonary edema.

  • Coagulation → Formation of small blood clots.

  • Surfactant degradation → Alveoli collapse more easily.

  • Fibrosis → Lung tissue becomes scarred and stiff.

What are the clinical manifestations and complications of PARDS?

• Acute onset: Develops rapidly.

• Severe hypoxemia: Dangerously low blood oxygen levels.

• Pulmonary edema: Fluid accumulation in the lungs.

• Pulmonary infiltrates: Abnormal opacities visible on chest imaging.

• Decreased pulmonary compliance: Lungs become stiff and difficult to expand.

• Progressive respiratory distress: Breathing becomes increasingly difficult.

• Management: Most children with severe PARDS require mechanical ventilation.

• Mortality: Approximately 24% according to your lecture slide.