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