Severe Acute Respiratory Syndrome SARS Lydia Ho Rui

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-Co. V Virus

Discovery of the new virus n Kochs postulates n n 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 n n n A family of large, enveloped, positivesense single stranded RNA virus Irregular shape Characteristic ‘clubshaped’ surface projections (~20 nm)

SARS-Co. V Genome n n 71% of the genome codes for polyproteins Remainder: codes for structural proteins n n S (spike): receptor binding, cell fusion, major antigen E (envelop): envelop-associated protein M (membrane): transmembrane-budding N (nucleocapsid): genome-associated phosphoprotein

SARS-Co. V Genome

SARS-Co. V Life Cycle n n n S-protein binds to receptor initiation of induced endocytosis Translation of viral RNA polymerase Transcription of (+) RNA into genomic and subgenomic m. RNA 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 n 10 days before onset of symptoms n Close contact with probable/suspected SARS patients n Live in / travel to area with transmission of SARS

Transmission of SARS

Transmission of SARS-Co. V n n Highly probable: origination is a crossspecies jump from civet cat to human Human-to-human transmission n Direct contact Spread in droplets shed from respiratory secretions Possible fecal transmission

Infectiousness of SARS n Debatable n n n Most patients are moderately infectious Cases of “superspreaders” reported Factors affecting infectiousness are n n n Viral load of the secretion from index patient Aerosol-generation procedures Distance of the index patient

Methods of Diagnosis

Virus Detection n Virus isolation: inoculate suitable cell culture with patient specimens

Antibody Detection When infected by SARS-Co. V antibodies (e. g. Ig. M and Ig. G) are produced / change in level n Enzyme-linked immunosorbent assay (ELISA)

Antibody Detection n Immunofluorescence assay (IFA): n Sample: patient serum n Method: n n n Fix SARS-Co. V-infected cells on microscope’s slide (patient antibodies already bound to viral antigens) Immunofluorescent-labeled 2º antibodies bind to human Ig. G/Ig. M Significance: positive result after 10 days of onset of illness

Clinical Findings n Clinical history & observation n Chest radiography: important role n 70 -80% patients have abnormal chest radiographs al m r o N t S en i t a p ARS

Method of Cure

Immunomodulatory therapy n Corticosteroid n n Very powerful: affect entire body Anti-inflammatory & immunosuppressive effects n Significance: early improvement of fever, better radiographic infiltrates n Controversy: n n ? Effectiveness Adverse side effects

Antiviral Agents n Ribavirin: nucleoside analog n n n Most frequently administered Have antiviral activity against many DNA & RNA viruses Criticism: n n ? Effectiveness Adverse side effects

Antiviral Agents n Protease inhibitor: n n 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 n n Principle: to break the chain of transmission from infected to healthy person 3 -step protocol of disease confinement n n n Case detection Prompt isolation Contract tracing n n Daily health check Voluntary home isolation

Epidemic Containment n n Creation of emergency operating center Institutional support n n n Efficient quarantine measures Legislation International collaboration—WHO n n n 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%20 cycle%20 of%20 SARS%20 virus. htm Siddell, S, Wege H. , ter Meulen V. The biology of coronaviruses. J. Gen Virol. 1983; 64 (Pt 4): 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 ft. 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/