SARS-CoV-2 Flashcards

1
Q

Belongs to coronaviridae, which are enveloped viruses. Specifically beta-coronavirus

Alpha/ beta coronaviruses infect mammals. Gamma/ sigma infect birds, but can occasionally infect mammals.

What is nuclear material of covid?

How long is genome?

A

+ssRNA genome

26-32 kilobases in length - longest known genome in RNA virus

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2
Q

There are 7 known coronaviruses which cause disease in humans. There are many other species which do not cause disease.

229E, HKU1,NL63, OC43 all cause common cold symptoms

Which species cause severe disease?

A

SARS-CoV - outbreak 2002

MERS-CoV - outbreak 2012

SARS-CoV2 - outbreak 2019

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3
Q

What are symptoms of COVID-19?

A
Fever
Cough
Sough
Sore throat
Anosmia
Diarrhoea
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4
Q

What is case fatality rate of the following diseases?

SARS-CoV

MERS-CoV

SARS-CoV2

A

SARS-CoV - 10%

MERS-CoV - 36%

SARS-CoV2 - 2.3%

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5
Q

What is incubation period of covid19?

What is R0 for covid19?

A

3-7 days - transmission occurs before symptoms occur, which contributes to rapid spread

4 to 6

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6
Q

How does SARS-CoV2 enter cells?

A

Similar to other coronaviruses

S protein spike binds to ACE2 receptor of host cell.

ACE2 present in alvelolar epithelial cells, and enterocytes of small intestine

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7
Q

How does SARS-CoV2 spread?

A

Transmission via droplets, contact and fomites

Requires contact with mucus membrane - mouth, eyes, nose, lungs

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8
Q

Where did SARS-CoV2 originate from?

A

Wuhan China food market

Bats natural reservoir -Rhinolophus affinis

May have intermediate hosts in pangolin/ palm civet

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9
Q

SARS-CoV-2 virus RNA has six major open reading frames (ORFs)

What do they code for?

A

ORF1 - non-structural proteins nsp1-16

ORF2 - S protein

ORF3 - M protein

ORF4 - N protein

ORF5 - P protein

ORF6 - 8 accessory proteins

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10
Q

What pathogenic effects does SARS-CoV-2 have on host?

A

Binds to ACE2 and invades pneumocyte - causes cell lysis leading to ARDS

Down-regulation of ACE2 - causes dysregulation of host inflammatory response causing damage, inflammation, thrombosis

Cytokine storm - stimulates massive production of cytokines, which leads to inflammation in lungs

Complement activation - activate via Mannose-binding lectin pathway. Leading to lysis alveolar cells

Lymphopenia - reduced circulating lymphocytes, and lymphocytes have impaired function

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11
Q

Myocardial injury is often seen in severe covid disease.

What is the pathogenesis of this?

A

Direct damage - ACE2 receptors on cardiomyocytes can cause direct damage

Down-regulation of ACE2 - leads to production of reactive oxygen species, which can damage myocytes

Cytokine storm

Oxygen supply-demand mismatch

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12
Q

SARS-CoV-2 is associated with VTE - 20% of patients develop this issue. Many infected patients have raised D-dimer

What is pathogenesis of this?

A

SARS-CoV-2 causes endothelial injury

Cytokine storm

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13
Q

Why does lymphopenia occur?

A

Lymphopenia - reduced circulating lymphocytes, and lymphocytes have impaired function.

Possible explanations:
- cytokine storm causing lymphocyte death via IL-6

  • exhaustion of lymphocytes
  • lymphocytes directly infected by virus causing apoptosis
  • virus down-regulating T-cell genes which normally cause proliferation
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14
Q

Following covid-19 infection, there is been an association with an inflammatory condition similar to Kawasaki’s

What is this called?

A

Paediatric inflammatory multisystem syndrome temporally associated with covid-19

PIMS-TS

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15
Q

What is case definition of PIMS-TS?

A

Fever

Inflammation - raised CRP, lymphopenia

Multi-organ dysfunction

Exclusion of other causes e,g toxic shock, enterovirus

SARS-CoV2 testing may be negative

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16
Q

What are potential treatment options for PIMS-TS?

A

No evidence yet

IVIG trialled.

IVIG has benefit in Kawasaki disease, so treating blindly can exclude this diagnosis.

17
Q

What are indications for dexamethasone in covid infection? Evidence comes from RECOVERY trial

What should be used in pregnant patients?

A

Hospitalised patients
Patient on oxygen
Sats <90%
RR >30

Pregnant - use 40mg prednisolone

18
Q

What are treatment dose recommendations for steroids in covid infection?

A

For dexamethasone:
6 mg once a day orally/ IV for 7 to 10 days

For hydrocortisone:
50 mg every 8 hours intravenously.
This may be continued for up to 28 days for
patients with septic shock.

Treatment should stop if the person is discharged from
hospital before the 10 day course is completed.

19
Q

4c Mortality score for COVID-19 predicts mortality.

Low score is 0-3

What is included in scoring?

A
Age
Sex
co-morbidities
RR
SpO2 <92%
GCS
Urea
CRP
20
Q

What is mechanism of action of remdesevir?

A

Remdesivir is an adenosine nucleotide prodrug that is metabolised intracellularly to form the pharmacologically active substrate remdesivir triphosphate. Remdesivir triphosphate inhibits SARS-CoV-2 RNA polymerase which perturbs viral replication.

21
Q

What are indications for remdesevir?

A

Hospitalised patients

requiring oxygen

22
Q

What are contra-indications for remdesevir?

A

if presenting >10 days after symptom onset

ALT >5 ULN

eGFR <30

weight >40kg

relative contra-indication - low 4C mortality score - likely to recover without treatment

relative contra-indication - high 4C mortality score - futile

relative contra-indication - pregnancy. Can give if benefits outweigh risks

23
Q

What is dose of remdesevir?

A

IV

200mg loading

100mg daily

5 days total

24
Q

SABTO organ donor

What are the rules regarding covid and organ donation?

A

If covid pos, and felt to have contributed to death, they are not considered for organ donation

If covid pos, but not contributed to death, then non-lung organs can be donated.

25
Q

What are the seasonal strains of coronavirus?

A

229E

HKU1

NL63

OC43

26
Q

What is mechanism of action of sotrovimab?

A

monoclonal antibody binds to high conserved epitope of spike protein of SARS-CoV-2

preventing entry of virus into cell

27
Q

2024 treatment guidelines

Non-hospitalised
At risk of progression

What to give?

A

Paxlovid within 5 days of symptoms

Remdesevir wiithin 7 days of symptoms

28
Q

2024 treatment guidelines

Hospitalised - requiring oxygen

What to give?

A

Dexamethasone
Remdesevir
Tociluzimab or Baricitinib