COVID-19 Flashcards
Common animals infected with coronaviruses
Pigs, humans, bats
Coronavirus (crown of spike proteins) structure
+RNA: Same as messenger RNA in our cells
Enveloped: Stolen from previously infected cells (Spike proteins and others on surface)
Cold causing coronaviruses
-Infect upper airways (Coughing, Malaise, Sneezing)
-Low(ish) infectivity
-Low mortality
-4 known
SARS-CoV-1 (SARS Classic) Origin
Bat (intermediate civet cat)
Uses ACE2 to infect cells
SARS-CoV-1(SARS Classic) and SARS-CoV-2 (PANDEMIC CORONAVIRUS)
ACE2
Protein on many cell types
◦ Lung
◦ Cardiac
◦ GI tract
◦ Kidneys
SARS-CoV-1 Symptoms
-Fever
-Malaise
-Difficulty breathing
-GI distress
-Infectious when symptomatic
-Causes lower respiratory tract infections
◦ Pneumonia
◦ Ground glass opacity
SARS meaning
Severe Acute Respiratory Syndrome
SARS-CoV-1 Infection
Causes severe disease often
◦ Not many asymptomatic cases
◦ Most cases needed medical intervention
◦ 30% need ventilation
Fatality rate for SARS-CoV-1 or SARS Classic is
Fatality rate is about 10%
◦ lots of variance depending on age/underlying health
◦ Roughly 50% mortality in > 75 years old
SARS-CoV-1 or SARS Classic Transmission
Spread by respiratory droplets
◦ Fomites?
◦ Fecal transmission?
◦ Poo cloud or “toilet plume” (little evidence, mostly theory)
SARS outbreak
November 2002 cluster of viral pneumonia cases
SARS outbreak started in
Open air markets Guangdong province (Wet markets)
First coronavirus that caused severe disease in people
The SARS Outbreak; identified March 21st coronavirus found by multiple agencies
SARS outbreak containment
Contained by aggressive containment measures
◦ Testing (thermal scanning)
◦ Contact tracing
◦Quarantine
◦ Social distancing
Hasn’t been seen since 2005!
MERS-CoV origin
Bat (intermediate dromedary camels)
MERS-CoV transmission
Lower transmissibility between people
◦ Droplet spread
◦ Fomites
◦ Many cases/outbreaks involve direct contact with camels
MERS stands for
Middle Eastern Respiratory Syndrome
MERS Infection
-Some asymptomatic and mild cases
-Severe cases present with viral pneumonia
◦ Ventilation needed in high percentage
-Roughly 35% mortality rate
◦ Most cases had underlying medical conditions
MERS outbreaks (Very often associated with healthcare spread)
Small cluster outbreaks (2012-2015)
◦ Saudi Arabia
◦Jordan
◦ Korea
◦ UK
SARS-CoV-2 (PANDEMIC CORONAVIRUS) Receptor
Uses ACE2 to gain entry in to host cells, but likely does not entirely rely on it and has an alternative receptor.
Virus amplification
Most rise in viral load
SARS-CoV-2 Infection
-The virus gets in your mouth, eyes, nose
-Symptom onset: Decline in viral load after about 1 week
The Disease caused by SARS-COV-2
COVID-19
How do you become infected with COVID-19?
Droplet spread: “The wetness of our coughs and sneezes”
Symptoms of COVID-19
Typical:
◦ Fever
◦ Dry cough
◦ Malaise
◦ GI upset
◦ Loss of taste or smell
COVID-19 completely asymptomatic usually is simply
Pre-symptomatic
Mild disease COVID-19
Common cold ~ 3 days
Moderate disease COVID-19
Bad flu-like illness
COVID-19 Severe disease
Hospitalization (not all equal)
◦ As little as just needing fluid therapy or Remdesivir therapy
◦Oxygen in a tube
◦ Full oxygen mask
◦Intubation (In dire cases only; mortality is high in these cases)
COVID-19 Higher risk factors
-Age
-Smoking
-Obesity
-Heart disease (Lots of ACE2)
-Pregnancy
-Diabetes (Slightly delays immune response maybe)
COVID-19 Post infection issues
◦ Thrombotic problems
◦ Bacterial infection
◦ Tail phase “Long haulers”
◦ Brain fog
◦Inflammatory skin disease
Can reinfection of COVID-19 occur?
Yes, but probably not right away in most people (3 months)
Reinfection of COVID-19, why?
High levels of neutralizing antibodies
◦ (Also non-neutralizing antibodies)
◦ Plateau after a few months
◦ Memory B cells persist
◦ Plasma cells have perished
◦ T cell activation
◦ To clear infection
◦ Memory T cells persist
RT-PCR tests
Reverse transcriptase PCR (Used to determine if RNA is present)
RT-PCR tests use
Enzyme that compliments RNA in to cDNA
◦ cDNA denotes the original RNA template
◦ Doesn’t exist in cellular life
RT-PCR tests results +
Viral RNA present (Currently infectious?)
RT-PCR tests results -
No viral RNA present (can still become +)
Limits of RT-PCR tests
Viral RNA present
◦ 1 day – 5 weeks
◦ Viral RNA load
Good for clinical diagnosis of symptomatic patient
Antigen tests
Rapid kit-based kits
◦ Nasal swab
◦ Positive band means virus protein binding
Antigen tests good
Could be as little as $1 (they aren’t currently that cheap), Fast results – 15 minutes
Antigen tests Bad
Less sensitivity, Might miss some + cases, (Does it matter?)
When/why to test
When feeling poorly (Rapid antigen or RT-PCR), When traveling or going to an event (Rapid antigen, RT-PCR might be too sensitive)
Viral phase
in first week
Inflammatory phases
After first week
Paxlovid – antiviral drug
Inhibits SARS-CoV-2 protease
◦ Enzyme that cleaves large, non-functional amino acid blob
in to multiple, functional proteins
◦ Given 0-5 days after symptom onset (earlier the better)
Remdesivir – antiviral drug
◦Effects RDRP of SARS-CoV-2
◦ Given early in infection
Monoclonal antibody therapy
Laboratory derived
◦ Uses monoclonal antibody from a lab (or combo of
monoclonal antibodies)
◦ Neutralize virus
◦ Late vs early use? (Early)
◦ Works against variants? (Not as of now)
Dexamethasone (and other corticosteroids) to suppress the immune response
Good: Reduces inflammation, short duration, can reduce mortality by 30% in critical cases
Bad: Broad – suppresses immune system, open for infection of other types
COVID19 Vaccines Measuring efficacy
What are the endpoints?
◦ Any symptomatic disease?
◦ Severe disease (Hospitalization)
◦ Death?
Vaccine Development
When you can use other people’s
money to not risk your own.
(Operation WARP Speed) No steps in vaccine development were skipped.
Real world data
Once you start vaccinating millions, the numbers can
change (no such thing as 100% in real life) Also variants can change the picture. Agencies track data and report (Getting more complicated now)
How many do you need?
Many vaccines are 2 doses or 3 doses
Pfizer
Comirnaty
Moderna
Spikevax
To boost or not to boost?
-Lab experiments show increase in neutralizing antibodies
-no adverse reactions
