Severe Acute Respiratory Syndrome (SARS) Presented by Parth Dave & Kuan-Mei Lin December 2, 2005

Outbreaks In November 2002, highly contagious and severe atypical pneumonia were observed in the Guangdong Province of southern China The virus was spread to Hong Kong in February 2003 by a doctor who died 10 days after admission into local hospital  a mysterious death Similar outbreaks occurred at different local communities subsequently The virus was identified by Hong Kong, the U.S. and Germany in March kw04/images/sars-cdc.gif

Outbreaks The considered “hot zones” were Vietnam, Hong Kong, Singapore and Toronto and China Younger victims In Hong Kong, a group of younger people killed by Sars causes concern More countries report cases, including India and South Africa. In China, the situation is described as "very grave" by officials Worldwide, 8,450 cases have been reported, caused 810 deaths in 33 countries

Investigation Similar to:  Influenza virus found in birds from outbreak in Hong Kong in 1997  Chlaymydia like organisms from atypical pneumonia patients in Guangdong outbreak  Paramyxovirus – similar particles ALL RULED OUT  WHO announced new Coronavirus never before seen in humans termed SARS (Severe Acute Respiratory Syndrome) or SARS – HCoVs Techniques used – cell culture isolates, electron microscopy, PCR, microarray, Immunofluorescent antibody test from inoculated cynomolgus macaques monkeys

Coronavirus classification Order Nidovirales Family Coronaviridae Genus Coronavirus Non-segmented (+) ssRNA virus There are 4 major groups within coronavirus:  group 1- HCoV-229E (6 species)  group 2- HCoV-OC43 (7 species)  group 3- Avian CoV (1 specie)  SARS- CoV (1 specie)- responsible for SARS epidemiology in

Coronavirus Viral protein structure:  Pleomorophic and enveloped particles  Characteristic long projected surface protein (spike) about 20 nm long The first coronavirus was isolated from chickens in 1937 Viral genome structure:  The non-segmented RNA genome has 5’ cap and 3’ poly A tail  Genome size ranging from 27 to 32 kb contains 6 ORFs  Monocistronic mRNA  The virions is about 100 to 140 nm in diameter /sars.jpg

Genome organization Characteristic gene order of Typical coronaviruses and SARS: 5’-- Replicase (Rep)-- Spike (S)-- Envelope (E)-- Membrane (M)-- Nucleocapsid (N) –3’ Rota. P. et. al

Replication Viral entry Binds by using spike proteins. Enters either by membrane fusion or reseptor mediated endocytosis (clathrin pits) Viral replication (+) ssRNA used to create (-) ssRNA in cytoplasm Has its own RNA poly (-) strand forms replication complex attached to membrane Complex produces new genomic RNAs and subgenomic mRNAs. mRNAs code for N, M & S Ribonucleoprotiens form from N + genomic RNA Ribonucleoprotiens attach to S & M proteins at membrane This complex comes detached into lumen (immature virion) Mature as they progress through periphery of Golgi apparatus and becoming denser and more icosohedral. Buds off

SARS natural host Masked palm civets (Paguma larvata) 6 species were found by PCR to harbor the SARS virus initially SARS-like CoV with > 99 % nucleotide homology with human SARS-CoV was identified 10,000 civets killed, as well as other animals suspected of harboring SARS Evidences suggested palm civets are not SARS reservoir No widespread infection in wild or farmed civets Civets have no immunity agaisnt SARS-CoV Indian_Civet.jpg Paguma_larvata.jpg

SARS natural hosts SARS may have originated in wild horseshoe bats in China Indications: 92% similar to the human SARS virus from three species of bats found at the Zoology at the Chinese Academy of Sciences, Beijing Infected bats shows little or no symptoms Direct human infection is not likely to occur The differences in genes is in the genes which able the binding of virus particle and host cell Possibly the virus can jump to intermediate animal such as the civet and adapt in such a way that it is able to infect humans Horseshoe bats are considered SARS natural reservoir host galleries.news24.com/.../images/11.jpg zmmu.msu.ru/bats/rusbats/ pictures/rhboch.jpg

Transmission  SARS-CoV is predominantly spread in droplets shed from respiratory secretions of patients direct or indirect contacts  Less likely by oral-fecal transmission fecal or airborne transmission Viral load is peaked at around 10 days and days in stool  It is believed that only the symptomatic patients can spread the SARS virus in a moderate rather than explosive way Toronto case-woman went home to Toronto from Hong Kong, she died 9 days later after symptoms 5 of 6 family members showed SARS symptoms  Superspreaders: Infectivity of a large population by major viral shedding by patients due to high concentration of virus Singapore epidemic idsc.tokyo-eiken.go.jp/ SARS/fig1.gif

Symptoms images/center/sars_flu.jpg Clinical course:  short incubation period (6 days)  time period from exposure to onset of symptoms ranging from 2 to 16 days  intensive care usually required about 10 days after onset of symptoms There are generally 3 phases:  week 1: cold like symptoms,fever, myalgia, chill and a sore throat  week 2, recurrence of fever. Onset of diarrhea, and oxygen desaturation  only 20% of patients reach this phase, requires ventilatory support  The fatality rate is about 10% upon infection Sudden onset of high fever (>38°C) & dry cough Chills and shivering & muscle aches Breathing difficulties 3-7 days from onset of symptoms

Antiviral drugs/Vaccines Currently, no specific antiviral drugs available for SARS-CoV Vaccines are under development :  In China, a second-phase human trials of a SARS vaccine- using inactivated SARS-CoV might have safty concerns  The first U.S. SARS vaccine trial at NIH by using recombinant plasmid for S protein expression  Development of transgenic tomato and tobacco expressing SARS-CoV S protein  An experimental attenuated Vesicular Stomatitis Virus (VSV)-based vaccine

Control measures image.guardian.co.uk/.../ 2003/12/29/sars.jpg Close contacts of a probable or suspect case of SARS are at high risk of becoming a case, and should be isolated in the community during their potential incubation period Travelers from areas with recent local transmission of SARS should be given advice about whom to contact, and what to do if they develop a fever within their potential incubation period Health departments should assign staff to undertake contact tracing and daily review of contacts in the community. Ideally, this should be in conjunction with a 24-hour SARS hotline The recovered patients will be quarantined at home for at least 14 days after discharged from hospital Wearing N95 mask was one of the main public preventive measures against SARS

Questions and Comments

References Association of Southeast Asia nations. Copyright 2003 ASEAN Secretariat. Cann, Alan. Leicester - Coronavirus & SARS. June 10, Russell Kightley Media: Scientific Illustration Virus Pictures: Coronavirus life cycle /SARS virus replication Black, Richard. BBC News - Bats a 'likely source' of Sars. Sept 29, Jiang, S., He, Y., and Liu, S SARS vaccine development. Vol. 11 (7). Pogrebnyak, N., Golovkin, M., Andrianov, V., Spitsin, S., Smirnov, Y., Egolf, R., and Koprowski, H Severe acute respiratory Syndrom (SARS) S protein production in plants: Development of recombinant vaccine. PNAS. 102: Kamps, Bernd. Hoffman Christian SARS Reference. Chan, Henry. Tsui, Stephen. Sung, Joseph. Coronavirus in severe acute respiratory syndrome. Trend in Molecular Medicine. Vol 9 No. 8 August 2003