Severe Acute Respiratory Syndrome SARS

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Severe Acute Respiratory Syndrome (SARS)

• Lydia Ho Rui Yang
• BISC 209
• Professor Mary Allen

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• November 16, 02
• Initial cases of SARS appeared in South China

February 14, 03 305 cases 5 deaths from an
unknown acute respiratory syndrome
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• March 03
• New reports of outbreaks came in from Hong Kong,
  Singapore Vietnam

New syndrome was designated as severe acute
respiratory syndrome, or SARS
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March 12, 03 WHO issued global alert about
SARS
March 17, 03 WHO called for global
collaborative research on SARS
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• 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
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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

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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
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The Pathogen behind it all
SARS-CoV Virus
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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

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Coronaviridae

• A family of large, enveloped, positive-sense
  single stranded RNA virus
• Irregular shape
• Characteristic club-shaped surface projections
  (20nm)

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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

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SARS-CoV Genome
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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

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SARS Case Definition
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Clinical Symptoms
High fever
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Clinical History

• 10 days before onset of symptoms
• Close contact with probable/suspected SARS
  patients
• Live in / travel to area with transmission of
  SARS

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Transmission of SARS
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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

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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

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Methods of Diagnosis
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Virus Detection

• Virus isolation inoculate suitable cell culture
  with patient specimens

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Antibody Detection

• When infected by SARS-CoV ? antibodies (e.g. IgM
  and IgG) are produced / change in level
• Enzyme-linked immunosorbent assay (ELISA)

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Antibody Detection

• Immunofluorescence assay (IFA)
• Sample patient serum
• Method
• Fix SARS-CoV-infected cells on microscopes 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

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Clinical Findings

• Clinical history observation
• Chest radiography important role
• 70-80 patients have abnormal chest radiographs

SARS patient
Normal
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Method of Cure
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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

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Antiviral Agents

• Ribavirin nucleoside analog
• Most frequently administered
• Have antiviral activity against many DNA RNA
  viruses
• Criticism
• ? Effectiveness
• Adverse side effects

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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

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Method of Prevention Control
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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

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Epidemic Containment

• Creation of emergency operating center
• Institutional support
• Efficient quarantine measures
• Legislation
• International collaborationWHO
• Travel alerts and restrictions
• Coordination for research
• Agreement of countries on containment protocol

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SARS and Beyond

• The early management of SARS epidermic may
  serve as a model for the containment of future
  epidermics and pandemics

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References

• Cann, A. (January 20, 2004). Severe acute
  respiratory syndrome (SARS). Retrieved from
  http//www-micro.msb.le.ac.uk/3035/coronaviruses.h
  tml
• 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/Life20cyc
  le20of20SARS20virus.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, 3481977-85.
  http//SARSReference.com/lit.php?id12671062
• World Health Organization. (2004). Case
  Definition. Retrieved from www.who.int/csr/sars/c
  asedefinition/en/
• World Health Organization. (2004). Diagnostic
  Tests. Retrieved from www.who.int/csr/sars/diagnos
  tictests/en/