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MI Virology > L15 Coronavirus Infections > Flashcards

L15 Coronavirus Infections Flashcards

1
Q

What is the taxonomy of coronavirus?

A

Order : nidovirales
Family : coronaviridae
Subfamily : coronavirinae
Genera : Alphacoronavirus (mammalian + human)
Betacoronavirus (mammalian + human)
Deltacoronavirus (mammalian + avian)
Gammacoronavirus (avian)

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2
Q

What is the genome made up of in coronavirus?

A

A single stranded, positive-sense RNA virus
- genome can act as a mRNA

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3
Q

What is coronavirus made up of?

A
  • genome : single strand positive-sense RNA virus
  • enveloped vision
  • enveloped proteins
  • internal nucleocapsid
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4
Q

What are the key proteins in COVID?

A

Spike protein
M protein
Nucleoprotein
E protein

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5
Q

What is the role of the spike protein?

A

Binds to the cellular receptor
The major immunogenicity target for the current vaccines

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6
Q

What is the role of the M protein?

A

Important for vision assembly

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7
Q

What is the role of the nucleoprotein?

A

Binds to and protects the RNA genome

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8
Q

what is the role of the E protein?

A

It’s needed for efficient viral release from the cell

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9
Q

What are subgenomic mRNAs needed for?

A

They are needed for replication/assembly stages
- this includes spike protein mRNA

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10
Q

What is the genome translated into and why?

A

Translated into polyprotein which is needed for early stages of replication

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11
Q

Why is RNA replication error prone?

A

RNA polymerase does not proofread or correct errors

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12
Q

What enzyme is involved in RNA replication and transcription?

A

Virally encoded RNA-dependant RNA polymerase

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13
Q

Where does RNA replication take place?

A

In the cytosol and buds into the ER/golgi

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14
Q

How does RNA exit the cell after replication?

A

Exits the cell by exocytosis

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15
Q

How does the Covid virus attatch and enter the cell?

A
  • the spike protein binds to ACE2 on the cell surface
  • transmembrane protease, serine 2 cleaves the spike protein which reveals the fusion domain on the protein
  • the viral and cellular membrane fuse and the nucleocapsid can enter (RNA genome)
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16
Q

Explain the process of viral fusion

A

1) the viruses spike roteins have receptor binding domains which bind to cell receptors
2) the virus fuses with the host cell which allows the RNA to enter the cell
3) the cellular machinery is hijacked to duplicate viral RNA and translate viral RNA into proteins
4) viral particles exit the cell and can infect other cell

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17
Q

Where is ACE2 highly expressed?

A
  • lung type II alveolar cells
  • gastrointestinal tract
  • kidney
  • heart
18
Q

What are the three novel coronaviruses that have emerged since 2003?

A
  • SARS-CoV
  • MERS-CoV
  • SARS-CoV-2
    They are all betacoronviruses and they cause severe respiratory disease
19
Q

What are the symptoms of SARS-CoV?

A

Initial fever which is followed by a few days of a non-productive cough and shortness of breath

Pneumonia develops - fatal in around 10% of cases

20
Q

How is SARS-CoV diagnosed?

A

Infrared thermography is used to detect those with high temperatures at airports

RT-PCR and serological tests eventually became available to test for SARS-CoV

21
Q

What are the symptoms of MERS-CoV?

A

Fever
Cough
Shortness of breath
Pneumonia

22
Q

Outline MERS-CoV

A

Middle East respiratory syndrome-related coronavirus

First case in Jeddah, Saudis, Arabia
Case fatality of 37%
Humans are largely infected from camels
Limited spread between humans as it requires prolonged close contact

23
Q

Outline SARS-CoV

A

Severe acute respiratory syndrome

Appeared in the Guangdong province of southern china in November 2002
8 hotel guests carried the virus to other countries including Vietnam, Singapore and Canada
Incubation period of 2-10 days

24
Q

What are the symptoms of COVID-19?

A

High temperature - hot to touch on chest and back
Continuous cough - more than 3 coughing episodes in 24 hours
A loss or change to your sense of smell or taste

25
Q

What are some risk factor for severe illness and mortality caused by COVID-19?

A
  • age
    -cardiovascular disease
  • diabetes
  • cancer
  • obesity
26
Q

When the body is infected by COVID-19 what do macrophages trigger?

A
  • activated T-cells
  • macrophages
  • neutrophils
    This leads to cytokines being produced which leads to an inflammatory cascade
27
Q

What happens due to an inflammatory cascade?

A

Leads to a bacterial infection and an acute respiratory distress syndrome
-> leads to sepsis
-> leads to multi-organ dysfunction syndrome which causes tissue damage and death

28
Q

What are the stages in Covid-19 infection?

A

1) early infection
2) pulmonary phase
3) hyperinflammatory phase

29
Q

Outline the early infection stage

A
  • viral replication takes place
  • asymptomatic or mild to moderate symptoms
  • detection of virus by RT-PCR
  • antiviral response takes place
30
Q

Outline the pulmonary phase

A
  • viral replication
  • affected lungs : pneumonia
  • shortness of breath
  • chest Rx (opacities)
  • CT (glass opacities)
31
Q

Outline the hyper-inflammatory phase

A
  • pneumonia, sepsis, respiratory failure, acute respiratory distress syndrome
  • cytokine storm
  • host inflammatory response takes place
32
Q

What complications arise from Covid-19?

A

Silent hypoxia
- low pO2 levels with no apparent reason

Acute respiratory distress syndrome preceded by pneumonia
- shortness of breath
- eventual lung failure
- pulmonary scarring

Sepsis
- systematic organ failure

Secondary infections
- intensify septic condition

33
Q

How is Covid-19 diagnosed?

A

Nasopharyngeal swabs
- reverse transcription polymerase chain reaction (RT-PCR)
- all hospital inpatients swabbed on admission
- can have detectable RNA for weeks after symptom onset

34
Q

What are lateral flow tests?

A

Test for Covid-19
- quick (20-30 minutes)
- only 50% reliable
- multiple tests to give confidence in a negative result

35
Q

What did the lab find when looking into positive Covid-19 results?

A

Lymphopenia : low lymphocyte count
- associated with ARDS, intensive care admission and mortality

Raised liver function tests

Inflammatory markers

Abnormalities in coagulation tests

36
Q

List therapies for Covid-19

A

Nirmatrelvir/ritonavir - viral protease inhibitors

Baricitinib - immunosuppressive/anti-inflammatory

37
Q

What therapy can be used to target viral replication?

A

Nirmatrelvir plus ritonavir (antiviral)
- mild Covid-19 setting, no need for oxygen
- increased risk for progression to severe disease

38
Q

What therapy is used to target the inflammatory response?

A

Baricitinib
- more severe disease
- patients usually on oxygen

39
Q

Outline the Moderna vaccine

A
  • modified mRNA vaccine expressive the CoV spike protein
  • liposomal/nanoparticle delivery
40
Q

Outline the Pfizer vaccine

A
  • modified mRNA vaccine expressing the CoV spike protein
  • liposomal/nanoparticle delivery
41
Q

Outline the AstraZeneca vaccine

A
  • replication defective adenovirus vector
  • expresses CoV spike protein
42
Q

Outline the Janssen vaccine

A
  • replication defective adenovirus vector
  • expresses CoV spike protein

MI Virology (4 decks)

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