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
 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

 A family of large,
enveloped, positive-
sense single
stranded RNA virus
 Irregular shape
 Characteristic ‘club-
shaped’ surface
projections (~20nm)
SARS-CoV Genome
 71% of the genome codes for polyproteins
 Remainder: codes for structural proteins
 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
 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 cross-
species jump from civet cat to human

 Human-to-human transmission
 Direct contact
 Spread in droplets shed from respiratory
secretions
 Possible fecal transmission
 Infectiousness of SARS
 Debatable
 Most patients are moderately infectious
 Cases of “superspreaders” reported
 Factors affecting infectiousness are
 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:
 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

 Chest radiography: important role

 70-80% patients have abnormal chest radiographs
Method of Cure
 Immunomodulatory therapy
 Corticosteroid
 Very powerful: affect entire body
 Anti-inflammatory & immunosuppressive effects

 Significance: early improvement of fever, better

radiographic infiltrates

 Controversy:
 ? Effectiveness
 Adverse side effects
 Antiviral Agents
 Ribavirin: nucleoside analog
 Most frequently administered

 Have antiviral activity against

many DNA & RNA viruses

 Criticism:
 ? Effectiveness
 Adverse side effects
 Antiviral Agents
 Protease inhibitor:
 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
 Principle: to break the chain of transmission
from infected to healthy person

 3-step protocol of disease confinement

 Case detection
 Prompt isolation
 Contract tracing
 Daily health check
 Voluntary home isolation
Epidemic Containment
 Creation of emergency operating center
 Institutional support
 Efficient quarantine measures
 Legislation
 International collaboration—WHO
 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
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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
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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/