SARS-CoV-2 Flashcards
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?
+ssRNA genome
26-32 kilobases in length - longest known genome in RNA virus
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?
SARS-CoV - outbreak 2002
MERS-CoV - outbreak 2012
SARS-CoV2 - outbreak 2019
What are symptoms of COVID-19?
Fever Cough Sough Sore throat Anosmia Diarrhoea
What is case fatality rate of the following diseases?
SARS-CoV
MERS-CoV
SARS-CoV2
SARS-CoV - 10%
MERS-CoV - 36%
SARS-CoV2 - 2.3%
What is incubation period of covid19?
What is R0 for covid19?
3-7 days - transmission occurs before symptoms occur, which contributes to rapid spread
4 to 6
How does SARS-CoV2 enter cells?
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
How does SARS-CoV2 spread?
Transmission via droplets, contact and fomites
Requires contact with mucus membrane - mouth, eyes, nose, lungs
Where did SARS-CoV2 originate from?
Wuhan China food market
Bats natural reservoir -Rhinolophus affinis
May have intermediate hosts in pangolin/ palm civet
SARS-CoV-2 virus RNA has six major open reading frames (ORFs)
What do they code for?
ORF1 - non-structural proteins nsp1-16
ORF2 - S protein
ORF3 - M protein
ORF4 - N protein
ORF5 - P protein
ORF6 - 8 accessory proteins
What pathogenic effects does SARS-CoV-2 have on host?
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
Myocardial injury is often seen in severe covid disease.
What is the pathogenesis of this?
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
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?
SARS-CoV-2 causes endothelial injury
Cytokine storm
Why does lymphopenia occur?
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
Following covid-19 infection, there is been an association with an inflammatory condition similar to Kawasaki’s
What is this called?
Paediatric inflammatory multisystem syndrome temporally associated with covid-19
PIMS-TS
What is case definition of PIMS-TS?
Fever
Inflammation - raised CRP, lymphopenia
Multi-organ dysfunction
Exclusion of other causes e,g toxic shock, enterovirus
SARS-CoV2 testing may be negative
What are potential treatment options for PIMS-TS?
No evidence yet
IVIG trialled.
IVIG has benefit in Kawasaki disease, so treating blindly can exclude this diagnosis.
What are indications for dexamethasone in covid infection? Evidence comes from RECOVERY trial
What should be used in pregnant patients?
Hospitalised patients
Patient on oxygen
Sats <90%
RR >30
Pregnant - use 40mg prednisolone
What are treatment dose recommendations for steroids in covid infection?
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.
4c Mortality score for COVID-19 predicts mortality.
Low score is 0-3
What is included in scoring?
Age Sex co-morbidities RR SpO2 <92% GCS Urea CRP
What is mechanism of action of remdesevir?
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.
What are indications for remdesevir?
Hospitalised patients
requiring oxygen
What are contra-indications for remdesevir?
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
What is dose of remdesevir?
IV
200mg loading
100mg daily
5 days total
SABTO organ donor
What are the rules regarding covid and organ donation?
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.
What are the seasonal strains of coronavirus?
229E
HKU1
NL63
OC43
What is mechanism of action of sotrovimab?
monoclonal antibody binds to high conserved epitope of spike protein of SARS-CoV-2
preventing entry of virus into cell
2024 treatment guidelines
Non-hospitalised
At risk of progression
What to give?
Paxlovid within 5 days of symptoms
Remdesevir wiithin 7 days of symptoms
2024 treatment guidelines
Hospitalised - requiring oxygen
What to give?
Dexamethasone
Remdesevir
Tociluzimab or Baricitinib
