8.1 Pathophysiology of SARS-CoV-2 Flashcards
Which receptor does COVID-19 use to attach to host cells?
ACE 2
Which receptor does COVID-19 use to fuse with the host cell?
TMPRSS2
How can people have asymptomatic/mild cases of COVID-19
- Early innate immune response
- Detection of PAMPs through PRRs
- Rapid response controls infection
The lungs only have a medium density of ACE2 relative to other tissues in the body; why is the infection mostly in the lungs?
- Because the mode of infection of the virus is respiratory
ACE vs ACE2
ACE: Turns Ang I to Ang II
ACE2: Hydrolyses Ang I, not making Ang II
What is the role of ACE2 in the lung?
To protect the lung from Ang II induced inflammation
What is PANoptosis?
Inflammatory cell death pathway
List two ways in which PANoptosis can damage tissue
- Damages structure of tissue
- Leads to release of DAMPs and inflammatory cytokines from dying cells, possibly triggering cytokine storms
What is a cytokine storm?
A life-threatening condition caused by inflammatory programmed cell death
Which cytokines trigger PANoptosome formation?
- TNF
- IFN gamma
Describe the positive feedback loop of a cytokine storm
- Infection
- Release of cytokines
- Recruitment of cells
- New cells released cytokines (including TNF and IFN gamma)
- PANoptosome fomation
- PANoptosis (more cell death)
- PANoptosis causes further cytokine release (uh oh…)
Severe outcomes of cytokine storm
Systemic inflammation and organ failure
What happens to the alveoli during COVID-induced ARDS?
- Increased fluid in alveoli
- Surfactant breakdown
- Decreased efficiency of gas exchange
ARDS symptoms/signs
- Dyspnoea
- Low O2 sat
- Tahchypnoea
- Rattling sounds when breathing
What happens to ACE2 levels as you age?
It decreases
How can COVID-19 infect multiple organs?
Because the ACE2 inhibitors are expressed in many organs of the lung, often in higher density than the lungs
Risk factors for severe illness in COVID-19
- Age
- Smoking
- Pregnancy
- Male gender
- Chemotherapy
- Childhood cancer
- Diabetes
Symptoms of cytokine storm
- Fever
- Nausea/vomiting
- Confusion
- Chills
Is COVID-19 enveloped or non-enveloped? What does this mean?
- It is enveloped
- This means it has a protein capsid surrounding its RNA
List some organs with high levels of ACE2
- Small intestine
- Testis
- Kidneys
List some organs with medium levels of ACE2
- Lungs
- Liver
- Bladder
List some organs with low levels of ACE2
- Blood
- Brain
Main mechanism of transmission of SARS-CoV2
Close-contact droplet infection
Primary target cells for SARS-CoV2
Epithelium is respiratory and intestinal tract
Why is COVID-19 prone to mutation?
RNA Dependent RNA Polymerase does not have a proofreading mechanism
Variant of interest vs variant of concern
Interest: consistent thorughout community/within clusters
Concern: Increased transmissibility, virulence, or decreased effectiveness of treatment
Order of dominance of COVID variants
- Alpha
- Beta
- Gamma
- Delta
- Omicron
Change in case numbers and mortality of COVID over time
- Case numbers going up
- Mortality going down
Define endemic
Health conditions that occurs at a predictable rate in a particular region
Define outbreak
Unpredicted increase in the number of people presenting a health condition of the occurrence of cases in a new area
Define epidemic
Outbreak that spreads to larger geographic areas
Define pandemic
Epidemic that’s spread over multiple countries or continents
Early infection COVID symptoms
- Cold like symptoms
- Smell/taste disorders
- Lymphopaenia
Pulmonary phase (Stage 2) COVID symptoms
- Respiratory distress
- Coughing/phlegm
- Dyspnoea +/- hypoxia
Hyperinflammation phase COVID symptoms
- ARDS
- Shock
- Cardiac failure
Breathing support for COVID (with increasing severity)
Nothing -> Oxygen -> More O2/BiPAP -> ventilation
Describe the symptoms of COVID-related Kawasaki disease
- Inflammation of blood vessels, particularly in eyes, palms, soles of feet, tongue
List preventative measures for COVID-19
- Vaccination
- Masks
- Social distancing
- Isolation/quarantine
How does an increased number of comorbidities change an individual’s chance of death from COVID?
It increases it
What two medications are used during stage 1 of COVID-19 (viral replication; mild symptoms)?
- Antivirals
- Anti-spike monoclonal antibodies
What two medications are used during stage 2 of COVID-19 (pulmonary phase)?
- Antivirals (remdesivir)
- Corticosteroid (dexamethasone)
What two medications are given during stage 3 of COVID-19 (hyperinflammation phase)?
- Corticosteroid (dexamethasone)
- Anti-Il 6 mAbs, JAK inhibitors
How do monoclonal antibodies limit the virulence of COVID-19?
Bind to spike protein
For whom are monoclonal antibodies indicated in COVID-19?
- Unvaccinated
- Immunocompromised
How can oral antivirals reduce viral replication through amino acid insertion
Insert foreign amino acid into genetic material of virus, nullifying genetic code and preventing replication
How does remdesivir (IV antiviral) inhibit viral replication
Inhibits activity of RdRp
Broadly, how do JAK inhibitors work?
- Prevent activation of signal transducers
- Prevents release of cytokines
Which patients should be considered for long-acting antibody combination against covid-19?
- Immunocompromised
- Allergy; cannot be vaccinated
Risk factors for severe disease in COVID-19
- Age > 55
- Obesity
- Pregnancy
- CKD
- Immunosuppressive disease
- CVD
- Diabetes
In what % of COVID-19 patients does ARDS occur?
5%
What % of patients require ventilation with COVID-19?
20-100%
List some complications of COVID-19
- ARDS
- Persistent fever
- Dehydration
- Hypovolaemia
Cardiac complications of COVID-19
- MI
- Arrhythmia
- Cardiac arrest
Neurological complications of COVID-19
- Delirium
- Nerve inflammation/paarlysis
- Stroke
Liver and GI complications of COVID-19
- Liver dysfunction
- Mesenteric ischaemia
Steroids can be used in treatment of COVID-19. Provide some complications that can arise from this
- Stress ulcers
- Hyperglycaemia
- Fungal pneumonia
How do steroids increase risk of fungal infection
Delay epithelial regeneration
Is long COVID more common in older or younger people?
Older
Risk factors for long COVID
- Women
- Increasing age
- Diabetes
Is there any correlation between disease severity and long COVID occurrence?
No
Complications of long COVID
- Organ damage
- Altered immune status
List a bunch of possible symptoms of long covid
- Fatigue
- Muscular weakness
- Joint pain
- Dyspnoea
- Cough
- Headaches
- Palpitations
