Respiratory viral infections and COVID Flashcards
What are some respiratory viruses beyond the common cold?
- Rhinoviruses (new subtype C)
- Influenza viruses (Flu); types A, B and C
- Paramyxoviruses
– Respiratory Syncytial Virus (RSV)
– Human Metapneumovirus (hMPV)
– Parainfluenza viruses 1 – 5 (PIV1 – 5) - Adenoviruses
- Coronaviruses
Describe Respiratory Syncytial Virus
Respiratory syncytial virus (RSV) is the most important
cause of pneumonia and bronchiolitis in infants. It is also an important cause of otitis media in children and of pneumonia in the elderly and in patients with chronic cardiopulmonary diseases.
Describe the pathogenesis of RSV
RSV replication occurs initially in epithelial cells of the nasopharynx. Virus may spread into the lower respiratory tract and cause bronchiolitis and pneumonia. Viral antigens can be detected in the upper respiratory tract and in shed epithelial cells. Viremia occurs rarely if at all.
An intact immune system seems to be important in
resolving an infection because patients with impaired cell-mediated immunity may become persistently infected with RSV and shed virus for months.
Why are infants a few months old protected from RSV?
High levels of neutralizing antibody that is maternally transmitted and present during the first several months of life are believed to be critical in protective immunity against lower respiratory tract illness. Severe respiratory syncytial disease begins to occur in infants at 2–4 months of age when maternal antibody levels are falling.
We inherit some protective Ig by placental transfer and can acquire it by breast feeding.
Why are younger infants susceptible to RSV?
Younger infants have lower IgG and IgA secretory antibody responses to RSV than do older infants.
We make protective Ig in response to RSV, but this is a poor response in neonates
Despite repeated reinfection our Ig response (at least against the G protein) declines with age
RSV is reasonably genetically stable, so reinfection implies we have a poor immune memory to it
Describe RSV and Immunity; the role of IgA
- RSV infections are predominantly restricted to
the airways - These are mucosal surfaces and are therefore
protected by innate immunity and IgA - IgA memory is relatively poor and recall is slow
- Sufficient to prevent more severe infections later
in life
RSV and Immunity
Describe the problems of an immature immune system
RSV infections show unbalanced Th1/Th2 responses (biased towards Th2)
– This depresses inflammatory cytokine production,
CD8+ responses and IgG production, meaning
clearance is slow and development of memory is poor
– This enhances IgE production, leading to
allergy/asthma
What are prevention methods for RSV?
There is no vaccine. Previous attempts to protect with a killed vaccine resulted in an increase in severity of symptoms.
Passive immunization with a monoclonal antibody
directed against the fusion protein of RSV can be used for prophylaxis in premature or immunocompromised infants.
Describe Coronavirus
- Large (28-33kb) positive-(single)-stranded RNA viruses
- Coronaviruses are transmitted by the respiratory aerosol
- Varied symptoms - fever, cough, shortness of
breath and breathing difficulties. In more severe
cases, infection can cause pneumonia, severe acute
respiratory syndrome, kidney failure and even
death
Describe the origins of SARS
- A coronavirus; no existing immunity in humans!
- Transmitted by droplets, causes severe respiratory
disease - Transmitted from Civet cats!
- Civets in turn got it from bats!
- SARS originated in China in November 2002 and spread rapidly to other countries
Where did SARS-CoV-2 come from?
- Zoonotic transmission event (in Wuhan market, RaTG13 only 94% identity)
- Accidental escape of a cultured stock from a lab
- Accidental escape of a GMO virus stock from a lab
- Coronaviruses show prolific recombination
- SARS-CoV-2 presents a mosaic genome, to which
at least five sequences have contributed. These are
all from bats: - R. malayanus RmYN02 (China 2019)
- R. pusillus RpYN06 (China 2019)
- R. affinis RaTG13 (China 2013)
- R. malayanus BANAL-52 (North Laos 2020)
- R. pusillus BANAL-103 (North Laos 2020)
Temmam et al. (2022). B - None of these have the furin cleavage site
Where does the furin cleavage site come from?
- Accidental escape of a cultured stock from a lab
- Accidental escape of a GMO virus stock from a lab
Furin cleavage site either comes from adaptation of virus to human cells by prolonged culture, or has been
deliberately engineered
- Either of the hypotheses depends upon working with a virus that predates the COVID pandemic
Describe the Immune responses to SARS-CoV-2
- SARS-CoV-2 is extremely sensitive to IFN in
vitro (omicron especially) - SARS-CoV-2 grows much better in cells that can’t
respond to IFN - SARS-CoV-2 encodes multiple antagonists of the
IFN system - Mild infections generate poor antibody responses; more serious infections generate high titres of neutralising antibody
- We generally report on antibodies against the Spike protein, but antibodies are also raised against NP and M
- Antibody titres drop, but not unusually
- Good T cell responses seen in convalescent patients and vaccinated individuals
- Some evidence that prior infection with other coronaviruses can give some T cell immunity
- Human antibodies target multiple sites on the Spike protein
Describe the Vaccines against SARS-CoV-2
- mRNA (Pfizer-Biontech; Moderna)
- Subunit (Novavax)
- Viral vectors (ChAdOx; Sputnik; J & J)
– All give some neutralising antibodies
– All seem to give good protection
– Not good at limiting spreading
But of course this is against the original Wuhan strain
How is SARS-CoV-2 diagnosed?
A. Antigen and Nucleic Acid Detection
Coronavirus antigens in cells in respiratory secretions may be detected using the ELISA test
Polymerase chain reaction (PCR) assays are useful to detect coronavirus nucleic acid
B. Serology
ELISA, indirect immunofluorescent antibody assays, and hemagglutination tests may be used.
