21st Century Pandemics: Influenza and COVID Flashcards
What are Pandemic Ingredients?
- A pandemic virus will have novel antigenicity.
- A pandemic virus will replicate efficiently in human cells.
- A pandemic virus will transmit efficiently between people.
What viral pathogens have pandemic potential?
- Influenza
- SARS-CoV-2
- Nipah
- West Nile Virus
- Dengue
- Zika
How many of us are infected by seasonal influenza?
- 10% every winter
- 500,000 deaths world-wide
What viruses pose a constant threat?
Avian influenza viruses
World War I lasted 4 years from 1914 to 1918 and resulted in 16 million deaths worldwide.
How many people died as a result of the 1918 influenza pandemic?
- 50,000
- 500,000
- 5 million
- 50 million
50 M
The natural reservoir of influenza A viruses is
- Pigs
- Chickens
- Ducks
- Tigers
Ducls
What are aquatic birds natural hosts to?
to 16 atnigenically distinct influenza A viruses.
Describe the structure of influenza virus?
- 8 segmented single stranded negative sense RNA virus
- Important proteins: Haemagglutinin and neuraminidase - spike protein
- Haemaglutinnin - 16 flavours
Why don’t we catch flu from birds?
- Viruses in ducks not well evolved
- To affect humans
- Ducks - water Borne
- Humans - airborne
What ad to happen to influenza virus from birds to humans?
- Mutate to
- Replicate efficiently in human airway
- Change spike protein to transmit airborne in humans
What is ANP32? How is it different in birds?
Protein in the human cell nucleus that is essential host cofactor - supports influenza polymerase activit.
In birds - extra 33 exon
In human - no 33 exon (virus mutates an utilises this cofactor)
What mutation Is responsible for the polymerase adaptation to mammals ?
What is a reasserted virus?
- Human adapted virus and avian virus enter the same cell
- Because the genetic material neatly separated in 8 segments, both viruses share this and make a reasserted virus → pandemic potential
- Also called Antigenic Shift
- Can occur in pigs due to close proximity
What else apart from antigenic shift must occur to give a virus pandemic potential?
The haemagglutinin must also undergo a mutation - fir in human cells and transmissible through air
What do viruses have to overcome in order to successfully infect human? How do some do this?
- Penetrate mucus in airway
- Human viruses - mutate to be able to bind to receptors in epithelium
- Avian viruses can latch on to receptors in LRT
What is the significance of the haemagglutinin protein being pH sensitive?
Virus must release genetic material in endosome
pH of airborne droplets is low
Avian influenza - very sensitive to low pH - cannot be transmitted in airborne droplets
How do we respond to pandemics?
• Non pharmaceutical interventions
- Antiviral drugs
- Vaccines
Several antiviral drugs already exist for influenza, and are licensed for use in the clinic. However unlike HAART for HIV we don’t use them together.
True of false?
True - not licensed
Describe the influenza virus replication cycle.
What important process occurs in the budding out process in the viral replication cycle?
- Neuraminidase - needs to cut itself away from the receptor contains silalic acid
- If pt takes naeuraminidase inhibitor drugs (ralenza or tamiflu) → tethers virus → halts virus spread
What does baloxavir target?
PA endonuclease
The influenza vaccine given to those at greater risk of complications from flu in the UK is
- A live attenuated virus
- A purified fraction containing HA and NA of an inactivated virus
- A purified HA protein expressed in insect cells
- An immunoglobulin fraction from sera of immune patients.
A purified fraction containing HA and NA of an inactivated virus
How is the influenza vaccine strain selected and produced?
What influenza vaccine do we use in the UK?
How could we make a universal vaccine for all flus?
- target conserved stem/stalk domain in HA protein
What part of the haemagglutinin protein do current vaccines target?
500,000 people die each year from seasonal influenza. The number of deaths from COVID worldwide since January 2020 is
- 60 million
- 6 million
- 600,000
- 60,000
6 M
What is a coronavirus? What is the structure?
RNA genomes, single stranded positive sense RNA, very large genomes… 30kb!
Enveloped virions. 100nm
Family of Nidovirales- a nested set of mRNAs from one large genome
Seven coronaviruses have infected humans:
- OC43, 229E, NL-63 and HKU-1 cause 20-30% common colds
- SARS and MERS are zoonotic .
How do SARS and SARS CoV2 enter cells?
Bind to ACE2 - only expressed on 2% of cells in the respiratory tract also on GI tract
The most likely origin of SARS CoV2 is:
- Wild waterfowl
- Horseshoe bats
- Created in a laboratory
- Pangolins
Horseshoe bats
What is the time course of SARS CoV2 infection and COVID19?
A COVID patient in ITU is most likely to benefit from
- Kaletra, a combination of lopinavir and ritonavir usually used to treat HIV
- Hydroxychloroquine, an antimalarial
- Remdesivir a nucleoside analogue
- Dexamethasone, a steroid.
Dexamethasone, a steroid.
Describe the use of dexamethasone in the tx of COVID.
• Cheapandextensively used steroid
RECOVERY trial found Dex was effective in those receiving oxygen or ventilated.
Reduceddeathsinillest cohort by 1/3.
Now standard of care in UK.
What monoclonal antibodies are used in COVID?
Regereneron
Sotrovimab - GSK antibody
Target Spike
What are the use small molecule antivirals in Covid?
Molnupiravir: targets polymerase, nucleoside analgue
Paxlovid: targets protease
What are the covid vaccines?
- Inject mRNA (modified-nucleoside, purified mRNA)
- Used perfusion spike state
- Host makes proteins antigen
Describe the different variants of COVID?
Why is Omicron less well controlled by current vaccines?
- Large number of spike mutations that affect antibody neutralisation
