MICR5832 L19: SARS Cov-2 and Covid-19 12/14/25

What is this?

- (+) ssRNA viruses that infect mammals and birds

-Respiratory tract infection in humans/birds

-Four species endemic to humans cause common cold

Coronaviruses

What 4 species of human coronaviruses cause common cold?

-HKU1

-OC43

-229E

-NL63

How did SARS spread to humans?

From bats via civets

How did MERS spread to humans?

From bats via camels

What structures are found in SARS Cov-2?

1) Nucleocapsid

2) Spike Glycoprotein (S)

3) Membrane protein (M)

4) Envelope (E)

5) RNA

6) Hemagglutinin esterase-dimer

True or False: SARS Cov-2 RNA is protected by the nucleocapsid

True

What do the Covid ORFs mostly code for?

-Structural proteins and replication machinery

-RdRp, proteases, helicase, spike, accessory proteins

What nucleotide sequences is the phylogenetic tree of coronaviruses based on?

RNA-dependent RNA polymerases

What are some trends with alpha viruses?

Mainly seasonal variants

What are some trends with beta viruses?

Severe viruses (MERS, SARS, Covid-19)

What are some trends with delta/gamma viruses?

Mostly in nonhuman animals

What is the Incubation period for Covid?

4-5 days

What are common symptoms of mild Covid-19?

-Cough, myalgia, headache

-Sore throat, smell or taste abnormalities, diarrhea

-Coryza, nasal congestion, sneezing

What variants are associated with these mild Covid symptoms?

-Coryza, nasal congestion, sneezing

Delta and Omicron

When do severe symptoms of Covid-19 begin?

5-8 days after initial symptom onset

What are symptoms of severe Covid-19?

-Respiratory failure, shortness of breath

-Cardiovascular, thromboembolic, neurological, inflammatory complications

What are risk factors for severe Covid?

-Age, immunosuppression, diabetes

-Cardiovascular, respiratory, kidney disease

-Obesity, smoking, sedentary

-Pregnant, male, unvaccinated

Describe the pathogenesis of Covid-19

1) Spike proteins attach to ACE-2 receptor in Respiratory Tract

2) Proteolytic cleavage

3) Virion is endocytosed into host cells

4) Buds off into new virions

What causes the viraemia associated with Covid infection?

-Proinflammatory cytokines

-Microangiopathic vasculopathy

-Specific antibody development

What Covid treatment mechanisms interfere with viral replication?

-Remdesivir/Molnupiravir

-Paxlovid

What does this Covid treatment do?

-Remdesivir/Molnupiravir

-Inhibits RNA synthesis

-Interferes w/ Covid replication

What does this Covid treatment do?

-Paxlovid

-Inhibits viral protease

-Interferes with viral replication

What Covid treatment mechanisms interfere with the inflammatory response?

-Baricitinib

-Tocilizumab

What does this Covid treatment do?

-Baricitinib

-JAK antibody

-Interferes with inflammatory response

What does this Covid treatment do?

-Tocilizumab

-Anti IL-6

-Prevents inflammation/respiratory failure

What antiviral is this?

-Paxlovid (Nirmatrelvir/Ritonavir)

-Oral antiviral, 5 days

-Mild disease, risk of progression

-Significant contradindications/interactions

What antiviral is this?

-Oral antiviral, 5 days

-Mild disease, risk of progression

-Significant contradindications/interactions

Paxlovid

What antiviral is this?

-Molnupiravir

-Oral antiviral

-Fewer complications than Paxlovid

-Limited effectiveness

What antiviral is this?

-Oral antiviral

-Fewer complications than Paxlovid

-Limited effectiveness

Molnupavir

What antiviral is this?

-Remdesivir

-Intravenous antiviral, 5-10 days

-Severe disease or pregnancy

What antiviral is this?

-Intravenous antiviral, 5-10 days

-Severe disease or pregnancy

Remdesivir

What antiviral is this?

-Budesonide

-Inhaled steroids

-Mild disease with risk of progression

What antiviral is this?

-Inhaled steroids

-Mild disease with risk of progression

Budesonide

What antiviral is this?

-Dexamethasone

-Intravenous steroids

-Severe disease or requiring oxygen

What antiviral is this?

-Intravenous steroids

-Severe disease or requiring oxygen

Dexamethasone

What antiviral is this?

-Tocilizumab/baritinib

-Monoclonal antibodies + JAK inhibitor

-Severe disease

-Reduces inflammatory response

What antiviral is this?

-Monoclonal antibodies + JAK inhibitor

-Severe disease

-Reduces inflammatory response

Tocilizumab/baritinib

What antiviral is this?

-Sotrovimab

-Evusheld (Tixagevimab/cilgavimab)

-Monoclonal antibodies

-Not recommended anymore for Covid

What antiviral is this?

-Monoclonal antibodies

-Not recommended anymore for Covid

-Sotrovimab

-Evusheld

What monoclonal antibodies were previously used for Omicron (no longer recommended)?

Evusheld (Tixagevimab/Cilgavimab)

How do monoclonal antibodies treat Covid?

-Target spike protein

-Prevent binding to ACE-2 Receptor

List the antibody response to Covid-19 in order of appearance

1) Covid19 RNA + antigen

2) IgM

3) IgA

4) IgG

Which antibodies persist the longest after responding to Covid19?

IgA and IgG

List the Variants of Concern (VOC) in order of appearance

1) Alpha

2) Delta (most documented)

3) Omicron

Why are Variants of Concern (VOCs) so dangerous?

-Replication advantage

-Immune evasion

-Severity of disease

What is an underrated source of epidemiological knowledge on pandemics?

-Wastewater surveillance

-Tracks feces and strains of VOCs

Describe the difference between droplets and aerosols

Droplets: Airborne from coughs and sneezes >5 microns

Aerosols: Unaffected by gravity, suspended in air longer <5 microns

How long are infected individuals infectious?

-2 days before symptoms

-7 to 10 days after

True or False: Infected individuals are most infectious around symptom onset, possibly later for Omicron

True

What is the primary route of Covid19 transmission?

Direct person-to-person through close contact

What are some other non-major routes of transmission?

-Indirect contact via contaminated surfaces

-Long distance aerosols due to poor ventilation

-Superspreaders

What vaccine is this?

-Pfizer Comirnaty

-mRNA encoding spike protein

-Low risk of myocarditis, mainly younger males

-Main vaccine in Australia

-Later generations for Omicron BA.4/5 or XBB

What vaccine is this?

-mRNA encoding spike protein

-Low risk of myocarditis, mainly younger males

-Main vaccine in Australia

-Later generations for Omicron BA.4/5 or XBB

Pfizer Comirnaty

What vaccine is this?

-Moderna Spikevax

-mRNA encoding spike protein

-Associated with very low risk of myocarditis

What vaccine is this?

-mRNA encoding spike protein

-Associated with very low risk of myocarditis

Moderna Spikevax

What vaccine is this?

AstraZeneca Vaxzevria

-Non-replicating adenovirus vector encoding spike protein

-Thrombosis and GuillainBarre syndrome

-No longer available in Australia

What vaccine is this?

-Non-replicating adenovirus vector encoding spike protein

-Thrombosis and GuillainBarre syndrome

-No longer available in Australia

AstraZeneca Vaxzevria

What vaccine is this?

-Novavax Nuvaxovid

-Adjuvanted recombinant spike protein

-Possible associated with myocarditis

-No longer available in Australia

What vaccine is this?

-Adjuvanted recombinant spike protein

-Possible associated with myocarditis

-No longer available in Australia

Novavax Nuvaxovid

True or False: Trials showed reduced infectiousness in vaccinated individuals

True

True or False: The vaccines were less effective against symptomatic infections with VOCs like Alpha and Delta

True

Who would you recommend annual booster vaccines for?

>65yo

>18yo if immunocompromised

What Covid diagnostic test is this?

Nucleid Acid Testing (NAT) and PCR

-Gold standard, highest sensitivity and specificity

-Nose & throat swabs, respiratory tract specimens

-High throughput testing equipment very expensive

-POCT low throughput tests also available

What Covid diagnostic test is this?

-Gold standard, highest sensitivity and specificity

-Nose & throat swabs, respiratory tract specimens

-High throughput testing equipment very expensive

-POCT low throughput tests also available

Nucleid Acid Testing (NAT) and PCR

What diagnostic test has the highest sensitivity and specificity?

Nucleic Acid Testing (NAT) and PCR

What Covid diagnostic test is this?

-Rapid Antigen Tests (RAT)

-Nose & throat swabs

-No extra equipment needed

-Rapid, simple, and suitable for POCT

-Within 5 days of symptom onset

What Covid diagnostic test is this?

-Nose & throat swabs

-No extra equipment needed

-Rapid, simple, and suitable for POCT

-Within 5 days of symptom onset

Rapid Antigen Tests (RAT)

True or False: Rapid Antigen Tests (RATs) have higher sensitivity and specificity than NAT

False

True or False: Rapid Antigen Tests (RATs) have a different sensitivity depending on nose/throat/both

True

What Covid diagnostic test is this?

-Culture

-High specificity

-Lower sensitivity than NAT

-Slow results, limited clinical utility

What Covid diagnostic test is this?

-High specificity

-Lower sensitivity than NAT

-Slow results, limited clinical utility

Culture

What Covid diagnostic test is this?

-Whole Genome Sequencing (WGS)

-Assign a lineage

-Mostly direct from specimen

What Covid diagnostic test is this?

-Assign a lineage

-Mostly direct from specimen

Whole Genome Sequencing (WGS)

What Covid diagnostic test is this?

-Antibody Detection

-Retrospective diagnosis

-Nucleocapsid antibodies then spike antibodies

-Antibodies mainly target spike protein

How long do you have to wait after infection for the antibody response to be detectable?

1-3 weeks after infection

True or False: Nucleocapsid antibodies persist longer than spike antibodies

False

True or False: Spike antibodies develop after nucleocapsid antibodies or vaccination

True

How could you determine the vaccine response in an immunocompromised patient?

Spike antibodies

True or False: Serology can be detectable during the incubation period, even if the patient is not be infectious

True

When is the NAAT diagnostic window?

-After infection and symptoms onset

-Until symptoms relief

When will you get a false negative NAAT?

-Before symptoms onset

-After symptoms relief

When will you start to see a positive NAAT?

-After symptoms onset

-Until symptoms relief