COVID-19

Question 1

4 common coronavirus

Answer 1

OC43
HKU1
229E
NL63

*10% of the common cold
(rest are rhinoviruses)

Question 2

COVID-19 structure

Answer 2

Spike glycoprotein
- how virus enters cell

M protein
- virus germination

Hemagglutinin-esterase (HE)
- adsorb cell membrane

RNA and N Protein
- formation of nucleocapsid in RNA genome

E protein
- envelope protein

Question 3

What structures are Abs produced against

Answer 3

• Spike protein
• M protein

Question 4

COVID-19 type of virus

Answer 4

+ strand RNA virus

Question 5

How do variants emerge

Answer 5

The more people infected, greater chance of mutation due to evolutionary advantage

Question 6

Natural selection for mutants

Answer 6

Allow virus to propagate more efficiently - becomes dominant strain of virus

Question 7

Escape mutations

Answer 7

when multiple mutations arise in persistent infection of IC patient

Question 8

Innate response to SARS-CoV2

Answer 8

• TLR7/8 (senses ssRNA by pDCs)
• TLR3 (senses dsRNA intermediates)
• RIG1/MDA5 (senses cytoplasmic RNA)
• inflammasome (activated by viral proteins: ORF3a, ORF8b)

*triggers NF-kB and IRF TFs

Production of:
- cytokines (IL1B, IL6, TNFa, IL8, IL18)
- IFNs (IFNa, IFNB, IFNlamda)

*good at evading innate recognition & IFN production (IFN I or III)

Question 9

IFN levels in Covid-19 patients

Answer 9

IFN I or III - lower in lungs than other resp viruses

Prolonged IFN production in late stage - correlated with worse outcome

Question 10

Characteristics of immune response in severe COVID-19 patients

Answer 10

ARDS

• increased IL-6, IL-8, TNFa, IP10
• conc associated with disease severity
• cytokine storm
• blood borne cytokines from lungs
• high abundance of inflamm macrophages in lungs
• sluggish NFs and monocytes
• partially activated and dysfunctional myeloid cells
• disregulation of IFN response

Question 11

Long Covid

Answer 11

prolonged symptoms following SARS infection that are not explained by alternative diagnosis

Question 12

Symptoms of long covid

Answer 12

• across multiple systems
• shortness of breath
• cognitive dysfunction
• fatigue

Question 13

Features of SARS variants

Location of mutation

Answer 13

different AA mutation locations on their S proteins

*most commonly in S-protein RBD which binds ACE2 receptor

Question 14

Does COVID-19 variants affect CD4/CD8 T cell responses

Answer 14

• variants good at evading B cell/Ab response
• most Ab generated against spike protein, envelope, nucleoprotein

CD4 (93% conserved in variants)
CD8 (97% conserved in variants)
* SARS-CoV-2 T cell specific response remain robust against Omicron

Question 15

How mRNA triggers innate, Ab and T cell immunity

Answer 15

• mRNA molecule released from LNP into cytosol
• sensed by TLR7/8, RIG1
• promotion of IFN secretion to ECM
• creates environment that favours Th1 responses over Th2
• mRNA translated by ribosomes into polypeptides
• processed by proteosome
• peptide presentation onto MHCI
• post-translation modification into membrane anchored or secreted protein
• MHC II peptide presentation on APCS after protein uptake of extracellular proteins or of cell debis containing protein

Question 16

Factors that determine vaccine immunogenicity

Answer 16

• age
• immune competency

Question 17

Adapted vaccines or Updated Boosters

Answer 17

• contain mRNA of original WT strain and mRNA in common between Omicron variant lineages

Question 18

COVID-19 Antivirals

Answer 18

Molnupiravir

• RNA dependent RNA pol inhibitor
• ribonucleoside analogue

Oral Paxlovid (Ritonavir)
- SARS-CoV-2 PI

*ACTIVE immunity

Question 19

mAbs to COVID-19 Spike protein

Answer 19

Regeneron
(casirivimab + imdevimab)

• 2 mAbs to spike protein
• recombinant mAbs that bind to nonoverlapping epitopes of spike protein RBD
  *not effective against Omicron

Bamlanivimab
(bamlanivimab + etesevimab)
- neutralising mAbs
- bind to different, overlapping epitopes of spike protein RBD
*active against Omicron

*PASSIVE immunity