16 - Coronaviruses Flashcards
Four genera of coronaviruses
- alphacoronavirus
- betacoronavirus
- deltacoronavirus
- gammacoronavirus
Important coronaviruses & their genera
- Porcine epidemic diarrhea virus (alpha)
- Severe acute respiratory syndrome CoV (SARS-CoV) (beta)
- Middle East respiratory syndrome CoV (MERS-CoV) (beta)
- SARS-CoV-2 (beta)
Subgenus of betacoronaviruses, animal reservoir, routes of human infection
Sarbecoviruses
Bats (rhinolocus or horseshoe bats) ~ 100 spp
2 routes:
- direct contact w bats
- contact w mammalian species infected w virus (e.g. civet cats, camel)
Coronavirus genome?
Enveloped positive-strand RNA viruses
30-32 kb
Outbreak, symptoms and risk group of SARS
2003 in Guangdong China
Symptoms: headache, fever, dry cough, sore throat, shortness of breath
Risk group: >60 years old, other conditions
Transmission, intermediate host of SARS. Status?
Person to person
Droplets from sneezing, touching contaminated surfaces
Civet cats intermediate hosts
Last case in late 2003, extinct in humans
infected, fatality rate of SARS
> 8000 infected
774 deaths
9.5% fatatlity
MERS-CoV outbreak, what is it? Symptoms? Fatality rate? R0?
2012, still circulating
Respiratory disease in middle east
Symptoms: fever, cough, breathing difficulties, vomiting
34% fatality rate
R0 = 2-5
Similarities and differences between SARS and MERS
Both originated in bats
SARS = bats to civet cats to humans
MERS = bats to camels to humans
Zoonotic diseases transmitted by bats
- rabies
- histoplasmosis
- marburg hemorrhagic fever
- Nipah
- SARS
- Ebola
What is the bat virome
19 families of mammalian viruses identified in analysis of 40 bat species in China
Large majority were coronaviruses
What makes bats dangerous hosts
They harbor viruses with few clinical signs of disease
Describe the 1918 H1N1 PANDEMIC
Spanish flu
500 x 10^6 infected
~50 million deaths worldwide
Affected young adults
Life expectancy declined by 10 years in US
Origins of Spanish Flu
Likely not Spain
During WW1. media censored news about flu. Except in Spain, where cases (infection, dead) were reported and publicized
Origin(s) unclear: US? Britain? China?
H1N1 deaths in Canada
30,000-50,000
Spanish flu response difference in Philadelphia vs St Louis
Philly: Did not take action for 2 weeks after first case, had a city-wide parade. Numbers were high
St Louis: closed theatres, schools, banned public gatherings two days after first case. Numbers were low
What is ProMED
Program for Monitoring Emerging Diseases
Largest publicly available system providing global reporting on infectious disease outbreaks (measles, dengue, zika, FMD, COVID)
Where do we speculate COVID-19 originated
Wuhan, China in a market selling wild animals or a lab escape from Wuhan Institute of Virology (CoV research)
What are raccoon dogs
Relative of foxes, susceptible to SARS CoV 2
Intermediate host for CoV 19
COVID-19 virus
Severe Acute Respiratory Syndrome Coronavirus 2
COVID-19 symptoms
- fever or chills
- cough
- difficulty breathing
- fatigue
- body aches
- headache
- loss of taste or smell
- sore throat
- congestion
What is PCC?
Post-COVID conditions (long-covid)
Occurring in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from onset, with symptoms lasting at least 2 months and not explained by alternative diagnosis
Long covid more common in? Management?
Individuals that had severe covid
Higher risk if unvaccinated & infected
Supportive care
Current covid deaths? In Canada?
7 million
58,560
How are changing COVID-19 viruses affecting reporting
Omicron variants less severe than previous delta variants
Fewer COVID cases being reported
“Living with COVID” disregards immune comp, long covid
Human to animal transmission of COVID-19
Reverse zoonosis
Not many cases
Dogs, cats, non-human primates, mink, deer
Slide 48
Reverse zoonosis
Danger of reverse zoonosis
Likelihood of virus changing when adapting to new host = novel SARS CoV 2 variants in humans
What is ACE-2
Receptor for SARS-CoV-2
Angiotensin 1 converting enzyme
For virus to enter cell, interaction btw spike protein and ACE2 on outside of cell membrane
How did we identify large numbers of animals that could be infected with SARS-CoV-2
If they have ACE-2 similar to humans
Identical sequences (non-human primates) or high sequence homology (caribou, WTD)
SARS CoV 2 prevalence in white tailed deer
~36% of deer in Ohio were positive
Sequence changes were accelerated when virus in WTD
What is incubation period? Varies with…
Time of infection to first clinical symptoms
Varies with pathogen (influenza=days, rabies=months) and can vary with dose
= preclinical phase
What is the latent period? Infectious period?
Latent = time of infection to onset of infectiousness
Infectious = time the individual can transit to others (contagious)
What is a type A disease?
Infectiousness comes before symptoms
Difficult to control; shedding pathogen with no symptoms
Slide 56
What is a type B disease?
Onset of infectiousness occurs at the time or onset of symptoms or later
Easier to contain than type A
Slide 57, 58
What is ‘excess mortality’
Number of deaths from all causes above and beyond what we would have expected to see under ‘normal’ conditions
Deaths from COVID not reported (poor testing, existing medical conditions that worsened)
EM = reported deaths - expected deaths
Estimates of excess mortality due to COVID
18.2 million in one study
14.83 million in another
Slide 63
Typical vaccine development timeline (7)
- Preclinical trials
- Phase 1 clinical trials (demonstrate vaccine does no harm)
- Phase 2 clinical trials (assess safety & immune response)
- Phase 3 clinical trials (efficacy of vaccine, larger cohort)
- Regulatory approval process (send to federal gov)
- Scaling up vaccine manufacturing
- Post-licensure vaccine safety monitoring
Why was COVID vaccine development/approval so fast?
- newer technologies (RNA vaccines)
- governmental funding (guaranteed purchase, bankrolling companies, invested in building manufacturing capacity)
- bureaucratic changes
Three forms of “traditional vaccines”
- Live-attenuated vaccine: weakened form of virus, strong long-lasting immune response
- Inactivated vaccine: killed virus (heat, chemicals). e.g. rabies
- Subunit recombinant vaccines: protein subunit.
Why don’t mRNA vaccines affect or interact with our DNA
- mRNA never enters nucleus of cell (where DNA is kept)
- cell breaks down and gets rid of mRNA soon after creating protein
% vaccinated in high income vs low income countries
High income: 73%
Low income: 32%
What is the SARS-CoV-2 mutation rate
Average ~2 mutations per month
Slower than influenza and HIV
One of the first SARS-CoV-2 mutations
Aspartic acid originally at position 614 of spike protein (interacts w ACE-2): Jan 2020
Feb 2020: Glycine at position 614 of spike protein
D614 -> G614
mutation = D614G
Slide 73, 74
Dominant strain in early pandemic
Delta variant, now seeing more omicron
One health approaches to future viromics research
- categorizing sequences is important, but not super functional
- reverse genetic approaches
- identify viruses that could initiate another pandemic
- deal with human-wildlife interface to slow new zoonotic diseases
Future of COVID-19
- WHO downgrades pandemic (public emergency -> global threat)
- long covid
- new variants
- reverse zoonoses
- live with covid phase
