L10 Immunity to Covid-19 Flashcards
is covid-19 double or single stranded? DNA or RNA?
single stranded RNA virus
which part of the virus structure is responsible for variants of this virus
the spike glycoprotein
name the domain of the spike protein where the most changes are seen in variants of SARS-CoV2
the RBD domain, receptor binding domain which binds to ACE2.
where does omicron have a higher affinity for replication within the respiratory system?
omicron has been shown to replicate 70 times faster in cultured bronchi tissue. much less efficient at replicating in the lung epithelia.
which variant(s) of SARS-CoV2 has shown higher levels of replication in the lower respiratory tract?
delta has higher levels in LRT than Omicron
average incubation period for omicron
3-5 days
when is an individual most infectious after infection with omicron?
1-2 days before the onset of symptoms
How do variants emerge?
The more people that are infected, the greater the chance of mutations arising. These mutations/variants give the virus an evolutionary advantage.
explain natural selection for mutants of the virus
natural selection for mutants allows the virus to propagate more efficiently and become the predominant strain of the virus.
Which animal did Covid-19 originate in?
bats, COVID-19 most similar (96%) to Bat coronavirus RaTG13
describe how covid is transmitted from person to person
spread via respiratory droplets which can be either inhaled or deposited on muscosal surfaces.
respiratory droplets released via talking and coughing.
why do children and adolescents have a lower susceptibility to infection than adults?
this is because kids and teens have underlying protection as they were likely infected with coronaviruses as an infant, more recently than adults
when does virus shedding most commonly occur?
most often before symptom onset or a diagnosis
peak infectiousness from covid?
2 days prior to onset of symptoms
which age group is associated with higher viral loads?
over age 60 years
What are the risk factors for severe disease (COVID-19 infection)?
Age (life-threatening disease increases sharply over age 65)
Male patients more likely to suffer severe Covid-19 infection
Diabetes
Hypertension
Obesity
COPD
Chronic Kidney Disease
common symptoms (omicron and severe infections)
omicron: cough, stuffy/runny nose, fatigue, sore throat, headache, fever.
severe cases: pneumonia with fever, dry cough, dyspnea, pulmonary infiltrates.
which variant is loss of smell/taste associated with?
Delta
name the protein which helps the virus gain access to the host cell
Transmembrane protease serine-2 (TMPRSS2) is critical for the fusion of the virus with the host cell membrane and its subsequent entry into the cell
which part of the respiratory tract is TMPRSS2 present most?
in the LRT, not as common in URT.
omicron does not bind very well to TMPRSS2 hence, less pathogenicity.
name another protease which also is involved in covid-19 infections
FURIN. can cleave a unique amino acid sequence (PRRA) located between S1 and S2 domains of the spike protein.
define hypoxemia
lower levels of oxygen in the blood than normal
what part of the virus does TLR7/TLR8 recognise?
ssRNA
what part of the virus does TLR3 recognise?
any dsRNA intermediates.
what activates the inflammasome?
viral proteins ORF3a and ORF8b
What results from triggering NF-κβ and IRF transcription factors? Which cytokines and interferons?
Cytokine release: IL-1β, IL-6, TNF-α, IL-8, IL-18
Interferons: IFNα, IFNβ, Type III IFN
Is there lower or higher production of interferons in the lungs in Covid compared to other respiratory viruses?
There is lower IFN production in the early stages of the Covid infection than other respiratory infections. This is a way that Covid evades the innate immune system.
is late stage disease and prolonged IFN production associated with better or worse outcomes?
worse outcomes, possibly due to chemokine and inflammatory cell infiltration of the lung
severe covid infection is associated with impaired response of which component of the immune system?
the interferon response.
at what stage of disease must recombinant interferons be administered?
must admin early in disease as late admin can actually worsen condition.
What is the function of interferons in relation to viruses?
IFNs trigger anti-viral responses in neighbouring cells
Do covid antibodies decay over time?
Yes, this makes reinfection possible.
How long have long-life plasma B cells (LLPCs) been shown to survive in the bone marrow?
Up to 11 months
What is associated with somatic mutation in VH genes in germinal centres?
This mutation is associated with the production of non-neutralising antibodies.
Which components of the COVID-19 virus is the antibody response tailored to?
The Spike protein and nucleocapsid proteins
Describe the T cell response to Spike proteins in Omicron variant of COVID-19
Spike protein mutations in Omicron are still recognised by T cells due to the presence of conserved peptides on the Spike (glyco)protein
what is acute respiratory distress syndrome?
ARDS is characterised by difficulty breathing and low blood oxygen levels due to fluid build-up in the lungs.
the fluid build-up prevents proper transfer of oxygen from the air into the the body and removing carbon dioxide.
Disease severity and death is associated with drastically increased serum levels of which inflammatory mediators?
IL-6, IL-8, TNFα, IP10
Which immune cells appear ‘sluggish’ in severe Covid-19?
Neutrophils and monocytes
Which cell type has an opposite to normal function in severe Covid?
Monocytes are shown to be pro-inflammatory
treatment for ARDS
extra oxygen via breathing machine, needs quick onset (within a few days) due to potential risk of scarring and permanent reduced function in alveoli.
Laboratory tests to indicate severe Covid-19 infection
- Elevated C-reactive protein (CRP) - produced in liver in response to infection
- Elevated D-dimer: fibrin degradation product present in blood after a clot
- Elevated neutrophils: of an immature phenotype
- Decreased levels of T and B lymphocytes
Examples of monoclonal antibodies to reduce ‘Cytokine Storm’
IL-6 inhibitor Siltuximab, or IL-6 receptor inhibitor Tocilizumab.
Adverse effects of dexamethasone (glucocorticoid)
It is potent so it has many side effects. It can inhibit host response to pathogens, leading to immunosuppression
Effects of glucocorticoids on NF-κβ activation
Activation of NF-κβ by cytokines is blocked by glucocorticoids.
Glucocorticoid-receptor complexes bind to the p65 subunit of NF-κβ. This prevents NF-κβ activation of inflammatory genes.
antivirals for covid-19, indications, risk reduction, what stage of disease
emergency use in mild/moderate cases, 50% risk reduction for hospitalization and death, 5 days after symptoms
Example of passive immunisation
Inject monoclonal antibodies into patient, protection wears off
How do DNA and RNA vaccines work? List the advantages and disadvantages
Use DNA/RNA molecules to teach the immune system how to target key viral proteins.
Adv: easy and quick to design
Disadv: never been done before, none in use currently
What is the basis for Moderna and Pfizer vaccines?
mRNA from Spike gene
How do live attenuated vaccines work? What are the adv & disadv
Weakened version of virus
Adv: stimulates robust immune response without causing serious disease
Disadv: may not be suitable for immunocompromised
Example: MMR vaccine
How does an inactivated vaccine work? List the adv & disadv
Inactivated vaccine uses the whole virus but it is killed first by chemicals or heat.
Adv: safe
Disadv: not as effective as a live virus
Example: Polio, Sinovax (Chinese Covid-19 vaccine)
subunit vaccine how it works, adv and disadv
Uses a piece of virus surface to focus immune system on a single target
Adv: focuses on single target, cannot cause infection
Disadv: may not induce strong response
Example: Hepatitis B, pertussis, HPV
viral vector vaccine how it works, adv, disadv
Uses harmless virus to deliver viral genes to induce immunity
Adv: stronger response
Disadv: careful selection of safe virus, immune response to vector can reduce efficacy
Example: Astrazeneca, Janssen
What are the two different Spike protein conformations?
- Pre-fusion: ‘standing up’ conformation (Moderna mRNA, Pfizer, J&J)
- Post-fusion: flat, ‘lying down’ conformation
(Spike changes when it fuses with ACE receptor)
nucleotide modification in mRNA vaccines
replacing uridine with pseudouridine, prevents mRNA degradation.
Which method of vaccine delivery may be preferred to intramuscular?
Intranasal delivery
