General Information on SARS

General Medical Information about Atypical Pneumonia and SARS

1. What is Atypical Pneumonia?

'Pneumonia' means infection of the lungs.
Symptoms include fever, cough and breathing difficulties; and signs on clinical examinations and x-ray of the chest.
Depending on the type of infective agents, some presented as 'Atypical pneumonia' or as 'Unusual pneumonia' They can give rise to a wide spectrum of manifestations ranging from mild to serious infections and health consequences.

2. What is SARS?

SARS stands for Severe Acute Respiratory Syndrome. This term describes more aptly the nature of the current condition as a severe acute type of 'Atypically atypical pneumonia'. WHO definition of Suspect Case and Probable case of SARS :

Suspect Case of SARS

In accordance with WHO, symptoms and signs include:
1.          high fever above 38 degree AND
2.          one or more respiratory symptoms (cough, shortness of breath, difficulty breath or hypoxia) AND
3.          Close contact with a person who has been diagnosed with SARS (in the previous 10 days)

In addition to fever and respiratory symptoms, SARS may be associated with other symptoms including: headache, muscular stiffness, loss of appetite, malaise, confusion, rash, and diarrhea.
*	*close contact* means i) having cared for or ii) having lived with, or iii) having had direct contact with respiratory secretions and body fluids of person with SARS.

Probable Case

A suspect case with one of the following:

Radiographic evidence of pneumonia or respiratory distress syndrome
Autopsy findings consistent with respiratory distress syndrome without an identifiable cause

WHO, in its Update 85 dated June 20, 2003, has pointed out that a more precise case definitions is required for longer-term surveillance. WHO welcomes the study conducted by professors of our Medical Faculty published in the British Medical Journal concerning the WHO case definition for suspected and probable SARS. The two papers written by professors of our Faculty of Medicine published in the British Medical Journal (Volume 326, Number 7403, Issue of 21 Jun 2003) are:

· Evaluation of WHO criteria for identifying patients with severe acute respiratory syndrome out of hospital: prospective observational study (http://bmj.com/cgi/content/full/bmj;326/7403/1354)

· Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis (http://bmj.com/cgi/content/full/bmj;326/7403/1358)

3. What are the characteristics Signs and Symptoms of the current SARS outbreak?

Frequency of Symptoms presented include the following :

(From Lancet, May 7, 2003 -
1,425 SARS patients from Hong Kong – Joint publication UK, CUHK, HKU, DH and HA hospitals)

Fever (94.0%)

Influenza-like (72.3%)

Chills (65.4%)

Malaise (64.3%)

Loss of appetite (54.6%)

Myalgia (50.8%)

Cough (50.4%)

Headache (50.1%)

Rigor (43.7%)

Dizziness (30.7%)

Shortness of breath (30.6%)

Sputum production (27.8%)

Night sweat (27.8%)

Diarrhoea (27.0%)

Coryza (24.6%)

Sore throat (23.1%)

Nausea (22.2%)

Vomiting (14.0%)

Abdominal pain (12.6%)

Fever + at least 1 other (87.6%)

Fever + at least 2 other (80.3%)

Fever + at least 3 other (70.7%)

(In the Amoy Garden cases and more recent cases, Diarrhea occurred in higher percentage of up to 60 to 70%, fever may be less obvious in less than 5 %)

The mean incubation period for SARS is estimated to be 6.4 days (95% CI 5.2-7.7 days). The mean time from onset of clinical symptoms to admission to hospital varied between 3 to 5 days, with longer time earlier in the epidemic. Exceptional cases with up to or more than 10 days or more have also been reported.

4. Mode of Transmission of SARS?

The available evidence suggests the mode of transmission is most consistent with droplet spread through respiratory secretions. Contact with contaminated surfaces and other body fluids may also be another route of spread. (The unusual spread in Amoy Garden could be related to special associated environmental hazardous factors - the Main findings and report on the Investigation has been released by the Department of Health on April 17. It was also concluded that Airborne spread is most unlikely). The findings were also subsequently endorsed by the WHO experts on May 16. http://www.info.gov.hk/dh/ap.htm

Although experts are still not sure about the exact mode and peak time of spread, from the accumulated clinical observations, asymptomatic person during the incubation period is basically not infectious.(CDC of USA and WHO also supports such observations May 16). It is likely that the Infectivity of SARS is highest when the affected person develops symptoms i.e. fever and particularly when coughing. Crowded enclosed space together with prolonged exposure to the affected symptomatic patient gives the highest risk of being infected (explaining the higher infection rate of medical and health care personnel). Early diagnosis and treatment is most important therefore, not only for the better results of treatment but also for containment of the spread of the disease.

5. The SARS Virus ?

In the past few weeks, CUHK microbiologists have initially detected a virus metapneumovirus belonging to the Paramyxoviridae family in a number of specimens from the patients. HKU has identified a different virus Coronavirus. Infection by unusual Chlamydia species has been reported from previous mainland studies. Many other laboratories in the WHO collaborative laboratories throughout the world have also identified metapneumovirus and coronavirus at different stages.

WHO has announced on April 16 that a new Coronavirus is now the most definite virus causing the SARS. Complete genetic decoding of the virus has been completed in Canada, USA, HKU, CUHK and mainland China etc in the past few days. Most of the genetic sequences by different centres look very similar with only a few base differences. Evidence of mutation occurring in the coronavirus has been observed by scientists from CUHK and other laboratories. All of these latest findings points to a subgroup of new coronavirus which may have relationship to certain animal source. Civet cat has been suspected as one of the likely animal source of coronavirus from a recent report from HKU and Shenzhen CDC on May 23.

Possibilities of co-infection by more than one organism/virus cannot be totally ruled out at this stage. Coordinated collaborative research (under the expert laboratories of the WHO specialist group) will continue to help us to further understand the cause, transmission, epidemiology and unusual clinical behavior of the candidate virus.

Recent reports from the WHO collaborative centres have found that the Coronavirus can survive on contaminated surfaces for up to 24 hours. Also in urine and faeces at room temperature for at least 1-2 days and longer (up to 4 days) in stool from diarrhea patients. Under experimental environment with culture medium, the survival can be further prolonged. The susceptibility to75% alcohol, hypochlorite solution and other known disinfectant has also been clearly proven.

6. Diagnostic Tests for the Virus?

3 main groups of Diagnostic tests for Coronavirus including 1) rapid Molecular Genetic tests (PCR tests) from patient's nasal aspirates, oral secretions, urine or stools and 2) Serological tests for antibodies against the virus are under intensive investigation both locally and internationally at the moment. 3) A third test involves direct Virus culture from patients secretions, throat swabs.

The serological tests for antibodies using immunofluorescence or ELISA tests may take one to 3 weeks after onset of symptoms to be reliably positive. This is currently the most reliable diagnostic test.

Many new improved rapid PCR molecular tests for the earlier detection and confirmation of the diagnosis are evolving or are under trials through the WHO collaborative centres. Early reports on the tests for Coronavirus are appearing in a number of centers. Currently the PCR tests still have significant false negative results. Detail definitive scientific documentation on the sensitivity and specificity of the tests or potential new tests are still pending.

Virus culture has now been used regularly in the major centres in Hong Kong for all suspected cases. It will take 4 to 5 days to have early results and about 7 to 8 days for definitive results.

On June 23, 2003, researchers of our Medical Faculty have successfully developed a new blood test for SARS which can accurately identify SARS patients from day 1 of hospital admission. This is a major breakthrough in substantially reducing the possibility of cross infections in hospitals, preventing outbreaks in the community in future and allowing future quantitative monitoring of the clinical progress and prognostication of the SARS patients if it ever comes back again. Please read the press release “Accurate Day 1 blood testing for SARS”.

7. What are the current treatments and the expected outcome?

Accumulated clinical experience in Hong Kong showed that Combination of an anti-viral drug and corticosteroid as first line treatment plus other intensive supportive treatment has resulted in about 80 to 85% good response in patients who were treated soon after the onset of symptoms.

There is some recent discussion on whether the antiviral agent ribavirin is useful in the clinical treatment of SARS or not. The USA CDC has some initial tissue culture showing poor inhibitory action of the drug on cultured coronavirus. However, HKU microbiologist has demonstrated in vivo the dose related effectiveness of ribavirin in the treatment of mouse liver infected with coronavirus. The local clinical experience also show 80 to 85 % good response in cases presented early from their extensive clinical experiences.

In a joint Press Release on May 10, Professor Yuen kowk yung (HKU) and Professor Joseph Sung (CUHK) and Dr. EK Yeoh (Secretary for Health, Welfare and Food) summarized the research and clinical experiences from all local hospital. The SARS clinical course can be divided into three phases

1) viral replicative phase,

2) immune hyperactive phase,

3) lung destructive phase.

For good response patients, they do not enter the phase 3.

The timing and dosage of giving the antiviral agent, steroids and other medications has been readjusted according to the observation and experience. Importance of convalescent rehabilitation for the lung function has been emphasized for the severe cases after discharge.

More scientific data and properly controlled clinical randomized studies are gradually emerging which are necessary to further address the issue in an evidence based approach.

For the most severely affected patients with poorer response to the regular first line treatment, serum from convalescent patients and plasmapheresis has been used with many favorable responses from PWH experience.

Other alternative treatment methods with other antiviral agents, immunoglobulin or cytotoxic agents are under studies for the poor responding patients in different hospitals in Hong Kong and the rest of the world. Possibility of adding adjuvant Traditional Chinese Medicine for selected patients has just been started in some hospital by special arrangement and consultation with experts from Guangdong.

The 4 most important factors related to the fatal cases were: Old Age, Co-morbid chronic illness, Delay in presentation for treatment and Severity of the pneumonia. The mean death rate has been readjusted to 15% on May 8 by WHO as better follow up and understanding of SARS is progressing. The death rate is most significantly affected by the old age with the highest mortality occurring in patients above 60 years old.

There is some recent controversy in the calculation of death rate – The currently used calculation is consistent with WHO (WHO is also actively reviewing their definition). Please see the note from Department of Health’s for clarification http://www.info.gov.hk/gia/general/200304/26/0426132.htm

Recently, there seems to be a noticeable increasing in the ratio of elderly affected with SARS with less obvious systemic fever. The percentage of old aged patients above age 65 in Hong Kong has rise to 19% at May 20 summary statistics from Department of Health HKSAR.

Recent reports have found that patients recovering from SARS can still have coronavirus in the body secretion including urine and stools. It is thus strongly recommended that the discharged patient should follow closely the instructions and precautions as advised by the WHO. Up till now, no true documented cases of any cross infection from the discharged patient has been reported locally.

8. Are there differences between SARS in the children and the adults?

· From a recently published paper in Lancet (April 29) by CUHK Medical Faculty and doctors from PWH and PMH http://image.thelancet.com/extras/03let4127web.pdf

SARS seems to have a less aggressive clinical course in younger children of less than 12 years old with :

o Less severe pneumonia

o Milder symptoms

o Better and more rapid response to treatment

o Less requirement for oxygen therapy and

o Quicker recovery

Updated on June 24, 2003, CUHK Campus (SARS) Task Force