MICRO: ‘21st century pandemics: influenza and COVID’ Flashcards
What are three main features of pathogens causing a pandemic?
- will have novel antigenicity
- will replicate efficiently in human cells.
- will transmit efficiently between people
List 4 viruses with pandemic potential.
- Inflenza
- Coronavirus (SARS-COV2)
- Nipah - found in Bangladesh etc
- Insect borne:
- West Nile virus
- Dengue
- Zika
When have influenza viruses caused pandemics?
- 1918 - Spanish
- 1957
- 1968
- 2006 - Swine flu
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 million
The natural reservoir of influenza A viruses is
- Pigs
- Chickens
- Ducks
- Tigers
Ducks - Aquatic birds are natural hosts to 16 antigenically distinct influenza A viruses
What are the characteristics of
8 segmented
single stranded
DNA virus
Haemagglutin (HA) and Neuraminidase (NA)
How must an avian influenza virus mutate to infect humans?
To jump from birds to humans an avian-origin influenza must mutate to:
- Replicate efficiently in the human airway.
- Transmit through the air between people (rather than water)
What is the spike protein in influenza called?
Haemagglutinin
How does an avian influenza gain the capacity to replicate in humans? What is the most common mutation?
- Virus enters and buds into the cytoplasm
- Enters nucelus
- ANP32 proteins in nucelus are essential host cofactors that support influenza polymerase activity
- For ANP32 to help it work the virus must adapt by a single amino acid change in PB2 E627K or PB2 627K (1918)
What further genetic changes are necessary for an avian influenza virus gain capacity to replicate in human cells?
- Reassortment –> antigenic shift (But this is not sufficient on its own )
- + Further HA mutations - must occur for it to replicate in the airway and be transmitted through air
How does pH in the respiratory tract affect influenza entry?
Influenza entry is pH dependent and HA protein is pH sensitive
- pH is acidic in the URT - avian viruses cannot survive here and must mutate to do so
- pH is neutral in the LRT
Summarise the steps of adaptation of avian influenza viruses to humans.
What measures are taken in a pandemic response?
- Non pharmaceutical interventions - face mask, isolation, distancing
- 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 or false:
True - we do not combine influenza drugs together as they are not licensed for this
What is the MOA of NA inhibitors?
NA (AKA sialidase - sialic acid enyzume) is important in budding out to infect a new cell
NAi acts by inhibiting NA so that the virus is tethered to the cell and does not leave
Examples are oseltamivir (Tamiflu) and zanamivir (Relenza)
What is a new anti-influenza drug?
Baloxavir
Targets polymerase called 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.
2 - grown in eggs
NB: live attenuated is used in children
Influenza vaccine production
What are the features of the inactivated influenza vaccine?
- Split or subunit- HA rich
- Given to those at risk
- Short term strain specific immunity mediated by antibody to HA head
What are the features of the live attenuated influenza vaccine?
Cold adapted virus limited to URT
Given to children - do not work in adults as they recognise it and do not get a good response
Broader more cross reactive immunity including cellular response
How effective is the LAIV in children?
Cause a decrease in excess mortality when trialed in primary school children by protecting the vulnerable and elderly at home
What is the major influenza viral antigen? What part do antibodies usually target and what are the implications for a universal influenza vaccine?
Haemagglutinin
Globular head domain parts are where antibodies usually attach but the probelm is that they are variable and so a universal vaccine would be difficult to make. The hope is to target the stem/stalk region.
Making a universal vaccine would let us use only one vaccine for all influenza viruses
What does this show about SARS vs influenza?
SARS - transmitted usually if a person is symptomatic
Influenza - transmitted in asymptomatic and symptomatic
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 million
How many coronaviruses infect humans?
Seven infect humans
OC43, 229E, NL-63 and HKU-1 cause 20-30% common colds
What receptor does SARS and SARS-2 use to enter cells?
Bind to cells via Angiotensin Converting Enzyme 2 (ACE-2)
The most likely origin of SARS CoV2 is:
- Wild waterfowl
- Horseshoe bats
- Created in a laboratory
- Pangolins
Horseshoe bats
- CoV with 96% similarity to SARS CoV2 has been found in pangolins.
- CoV with 99% similarity found in bats in Laos
Describe the course of SARS CoV2 infection.
- Incubation is ~3 days
- If virus load is well controlled, by day 8 they may be virus RNA positive but not infectious
- If not, virus may become disseminated
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 - by tume they reach ITU the virus may stop replicating.
When is dexamethasone use in COVID patients helpful?
If using oxygen AND on ventilation
Severely ill patients only beyond the stage where virus is the biggest problem and rather it is the immune system which is causing problems
Apart from dexamethasone, what other targeted therapies exist for COVID-19?
mAbs - Regeneron, Sotrovimab
Small molecule antivirals -
- Molnupiravir: targets polymerase, nucleoside analgue
- Paxlovid: targets protease
What variants of SARS-CoV2 have arisen?
- Alpha
- Beta
- Gamma
- Delta
- Omicron - 35 new mutations in the spike genes, less well controlled by current vaccines and do not protect from symptomatic disease; but associated with less severe disease
