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Severe Acute Respiratory
Syndrome (SARS)
Lydia Ho & Rui Yang
BISC 209
Professor Mary Allen
November 16, 02
Initial cases of SARS appeared in South China
February 14, 03
305 cases & 5 deaths from an unknown acute
respiratory syndrome
March 03:
New reports of outbreaks came in from Hong Kong, Singapore
& Vietnam
New syndrome was designated as “severe acute
respiratory syndrome,” or SARS
March 12, 03:
WHO issued global alert about SARS
March 17, 03:
WHO called for global collaborative research on SARS
March 24, 03:
Scientists in CDC and HK announced isolation of
new coronavirus from SARS patients
DNA sequencing shows this virus is distinct from all known
human pathogens
April 20-25, 03:
Outbreaks in Hanoi, Hong Kong, China, Singapore &
Toronto showed signs of peaking
City closed down schools & imposes strict quarantine measures
April 25, 03:
Nearly 3000 SARS cases have been identified in China
By the end of June, 03:
Most countries were removed from the list of areas
with recent local transmission of SARS:
Singapore, Hong Kong, Beijing , Toronto , Taiwan
But the investigation continues…
The Pathogen behind it all…
SARS-CoV Virus
Discovery of the new virus

Kochs postulates
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Discovery of novel coronavirus in patient
Isolation of cell culture
Reproducible symptom in cell culture
Identical isolates produced
Novel coronavirus is the cause of SARS
Coronaviridae

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A family of large,
enveloped, positivesense single
stranded RNA virus
Irregular shape
Characteristic ‘clubshaped’ surface
projections (~20nm)
SARS-CoV Genome
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71% of the genome codes for polyproteins
Remainder: codes for structural proteins
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S (spike): receptor binding, cell fusion, major
antigen
E (envelop): envelop-associated protein
M (membrane): transmembrane-budding
N (nucleocapsid): genome-associated
phosphoprotein
SARS-CoV Genome
SARS-CoV Life Cycle


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S-protein binds to receptor  initiation of
induced endocytosis
Translation of viral RNA polymerase
Transcription of (+) RNA into genomic
and subgenomic mRNA in the cytoplasm
N protein synthesized from free ribosome
S and M protein synthesized in RER
Budding from RER as virion, excretion
from cell via Golgi
SARS Case Definition
Clinical Symptoms
High fever
Clinical History

10 days before onset of symptoms
 Close contact with
probable/suspected SARS patients

Live in / travel to area with
transmission of SARS
Transmission of SARS
Transmission of SARS-CoV


Highly probable: origination is a crossspecies jump from civet cat to human
Human-to-human transmission

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
Direct contact
Spread in droplets shed from respiratory
secretions
Possible fecal transmission
Infectiousness of SARS

Debatable

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Most patients are moderately infectious
Cases of “superspreaders” reported
Factors affecting infectiousness are

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Viral load of the secretion from index patient
Aerosol-generation procedures
Distance of the index patient
Methods of Diagnosis
Virus Detection

Virus isolation: inoculate suitable cell culture
with patient specimens
Antibody Detection
When infected by SARS-CoV  antibodies
(e.g. IgM and IgG) are produced / change
in level

Enzyme-linked immunosorbent assay
(ELISA)
Antibody Detection

Immunofluorescence assay (IFA):

Sample: patient serum

Method:

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
Fix SARS-CoV-infected cells on microscope’s slide (patient
antibodies already bound to viral antigens)
Immunofluorescent-labeled 2º antibodies bind to human
IgG/IgM
Significance: positive result after 10 days of onset of
illness
Clinical Findings

Clinical history & observation
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Chest radiography: important role

70-80% patients have abnormal chest radiographs
Method of Cure
Immunomodulatory therapy

Corticosteroid

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Very powerful: affect entire body
Anti-inflammatory & immunosuppressive effects

Significance: early improvement of fever, better
radiographic infiltrates
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Controversy:


? Effectiveness
Adverse side effects
Antiviral Agents
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Ribavirin: nucleoside analog

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Most frequently administered
Have antiviral activity against
many DNA & RNA viruses
Criticism:


? Effectiveness
Adverse side effects
Antiviral Agents
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Protease inhibitor:
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Lopinavir-ritonavir co-formulation: protease
inhibitor used to treat HIV infection
With ribavirin: block processing of the viral
replicase polyprotein  prevent RNA
replication
Method of Prevention &
Control
Principle of Disease
Confinement

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Principle: to break the chain of transmission
from infected to healthy person
3-step protocol of disease confinement
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Case detection
Prompt isolation
Contract tracing
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Daily health check
Voluntary home isolation
Epidemic Containment
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Creation of emergency operating center
Institutional support
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Efficient quarantine measures
Legislation
International collaboration—WHO
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Travel alerts and restrictions
Coordination for research
Agreement of countries on containment protocol
SARS and Beyond…
The early management of SARS
epidermic may serve as a model for
the containment of future epidermics
and pandemics
References
Cann, A. (January 20, 2004). Severe acute respiratory syndrome (SARS). Retrieved
from: http://www-micro.msb.le.ac.uk/3035/coronaviruses.html
Dept. of Communicable Disease Surveillance and Response, WHO. (2003). Consensus
document on the epidemiology of severe acute respiratory syndrome (SARS).
Kamps, Hoffmann. (October, 2003). SARS Reference. Retrieved from:
www.SARSreference.com
Shanghai Center for Bioinfomatics Technology. (2004). Life cycle of the SARS virus.
Retrieved from:
http://www.scbit.org/english/sars/Life%20cycle%20of%20SARS%20virus.htm
Siddell, S, Wege H., ter Meulen V. The biology of coronaviruses. J. Gen Virol. 1983; 64
(Pt4): 761-776
Thiel, et al. (June 19, 2003). Mechanisms and enzymes involved in SARS coronavirus
genome expression, Journal of general virology. Retrieved from:
http://www.socgenmicrobiol.org.uk/JGVDirect/19424/19424ft.htm
Tsang KW, Ho PL, Ooi GC, Yee WK, et al. A Cluster of Cases of Severe Acute Respiratory
Syndrome in Hong Kong. N Engl J Med 2003, 348:1977-85.
http://SARSReference.com/lit.php?id=12671062
World Health Organization. (2004). Case Definition. Retrieved from:
www.who.int/csr/sars/casedefinition/en/
World Health Organization. (2004). Diagnostic Tests. Retrieved from
www.who.int/csr/sars/diagnostictests/en/