Severe acute respiratory syndrome

What is severe acute respiratory syndrome?¹

Severe acute respiratory syndrome (SARS) is caused by a coronavirus called SARS-CoV.

Severe acute respiratory syndrome coronavirus (SARS-CoV), emerged from China and rapidly spread worldwide.

Bats are likely an important reservoir for SARS-CoV. SARS-like CoVs have been detected in horseshoe bats and civet cats. The main mode of transmission of SARS-CoV is through inhalation of respiratory droplets. Faeco-oral transmission has been recorded.

Fever and respiratory symptoms predominate, and diarrhoea is common.

Strict infection control procedures with respiratory and contact precautions are essential.

It seems that both abnormal immune responses and injury to immune cells may be key factors in the pathogenesis of this disease.²

NB: SARS should not be confused with another zoonosis from the same area, called avian flu.

See also the article on Middle East Respiratory Syndrome Coronavirus.

How common is severe acute respiratory syndrome? (Epidemiology)¹

In a chest hospital in Guangzhou city, a retrospective study of 55 patients hospitalised with atypical pneumonia between 24 January and 18 February 2003, showed a positive culture of SARS-CoV in the nasopharyngeal aspirates of 3 patients, and positive serology to SARS-CoV in 48 patients (87%). The genetic sequence of the virus isolated from patients in Guangdong was found subsequently to be prototypical of the SARS-CoV found in affected areas around the world.

The index case for the major SARS-CoV outbreak in Hong Kong was a 64-year-old male renal physician, who travelled from the Guangdong province on 21 February 2003, to Hong Kong. The renal physician subsequently died of severe pneumonia a few days later. Within a few weeks, catalysed by the speed of international air travel, the infection spread SARS-CoV to 29 countries/regions. Over 8098 people fell ill and 774 died before the epidemic ended in July 2003.

Clinical suspicion¹

SARS is not usually suspected unless the person is known to have come from an area where they have potentially been exposed. The incubation period is usually 2-7 days but may be up to 10 days and 14 days has been reported.

Clinical features^{3 4 5}

Most patients identified with SARS were previously healthy adults aged 25–70 years. A few suspected cases of SARS have been reported among children under 15 years.⁶

• The first stage is a flu-like prodrome with fever reported in 99 to 100%, fatigue, headache, chills in 62% and 73%, aching muscles in 69% and 61%, malaise, anorexia, and sometimes diarrhoea. This phase lasts 3-7 days.

• The second stage affects the lower respiratory tract and begins three days or more after incubation. There is a dry non-productive cough in 69%, dyspnoea and possibly progressive hypoxia. The cough varies from mild to severe and is usually unproductive. Dyspnoea was reported in 42% and 41%.

Examination

• Temperature is usually over 38°C but antipyretics may bring this down. In Toronto, fever was reported in 99% but found in only 85%.

• Moderate respiratory disease is diagnosed with pyrexia and at least one respiratory feature of cough, dyspnoea, breathing difficulties or hypoxia.

• Severe disease is diagnosed with the above plus pneumonia or respiratory distress syndrome.

• Examination of the chest is often remarkably normal.

• Rhinorrhoea was found in only 2%.

Investigations^{3 4 5}

• Pulse oximetry and blood gases should be monitored, as oxygen and even ventilation may be required.

• FBC shows a modest lymphopenia in 54%, 72% and 70%, leukopenia, and thrombocytopenia in 35% and 45%.

• U&E show mild hyponatraemia and hypokalaemia. Hypocalcaemia was found in 60%.

• Enzymes show elevated lactate dehydrogenase in 87%, 62% and 71%, alanine aminotransferase, hepatic transaminase and creatine kinase levels in 32%.

• CXR may be normal at first and it may take a week or more to become abnormal but by 10-14 days all are abnormal:
  

  • However, in Taiwan all CXRs were abnormal at presentation and 69% became worse.

  • Focal interstitial infiltrates can occur early and may progress to a more patchy, general distribution.

  • At first a peripheral opacity near the pleura may be the only abnormality. High-resolution CT (HRCT) of the chest may show infiltration behind the heart.

  • With progression, opacities become more widespread.

  • The lower lung fields are affected first.

  • Calcification, cavitation, pleural effusion or lymphadenopathy do not occur.

  • HRCT may be useful where there is strong suspicion of the disease but CXR appears normal.

Laboratory diagnosis of SARS depends upon any one of the following:

• Antibodies to SARS-CoV in specimens obtained during the acute illness or more than 28 days after the onset of the illness.

• Detection of SARS-CoV RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) and confirmed with a second PCR assay, using a second aliquot of the specimen.

• Culture of the virus.

It is important to remember that specimens are a biohazard and appropriate precautions must be observed. A combined paper from the British Thoracic Society, British Infection Society and Health Protection Agency make the following recommendations:⁷

For microbiology:

• Expectorated sputum (if available).

• Urine (20-30 ml).

• Stool.

• EDTA blood (20 ml for PCR).

• Acute serology (20 ml of clotted blood).

• Do not obtain a nasopharyngeal aspirate as this is likely to generate aerosols.

For other tests they recommend:

• CXR.

• Pulse oximetry.

• Blood gases if oxygen saturation <92% on air.

• FBC; urea, creatinine, electrolytes, LFTs, lactate dehydrogenase, creatine kinase and C-reactive protein.

• Other samples for diagnostic testing as appropriate (remember there are much more common causes of community-acquired pneumonia than SARS).

Severe acute respiratory syndrome treatment and management¹

Treatment involves supportive care. There are no specific antiviral treatments or vaccines available.

• Isolation is required. Contacts should be isolated at home. The ill patient in hospital requires stringent barrier procedures.

• Pulmonary function and blood gases should be monitored, as ventilation may be required.

• As it is a viral infection, antibiotics are of no benefit unless there is nosocomial infection.

• If the patient requires ventilation, intravenous co-amoxiclav 1.2 g tds or cefuroxime 1.5 g tds plus erythromycin 500 mg qds or clarithromycin 500 mg bd are recommended. Try to avoid high flow rates of oxygen as this facilitates droplet spread.⁷

• Pulse steroids were used in Taiwan with improvement in 14 of 17.⁴

• Antiviral agents may help. Ribavarin was used in 88% in Canada.³ It caused haemolysis in 76% with a fall in Hb of 2 g/dL in 49% whilst benefit was dubious. Its use is not recommended.⁷

• Interferon beta seems promising and is recommended.⁸

After discharge from hospital:⁷

• Patients should monitor and record their temperature twice daily. If they have an elevated temperature of 38°C or above on two consecutive occasions, they should inform (by telephone) the healthcare facility from which they were discharged.

• Patients should remain at home for seven days after discharge, keeping contact with others at a minimum. This is to reduce the risk of transmission until more is known regarding the potential for continued carriage in convalescent cases.

• Additional home confinement may need to be considered, particularly in patients who are immunosuppressed. Inform the local Health Protection Team regarding the hospital discharge of patients to ensure follow-up in the community.

• Convalescent serology should be obtained at 21 days after the date of onset of the disease.

Prevention of spread

• The relevant agencies for communicable diseases must be notified.

• Contact tracing should be performed. Travel restrictions may be implemented or screening of air travellers for pyrexia. Scanners can detect temperatures above 37.5°C but false positives are common from sunburn, alcohol consumption and other causes.

• Patients in home or hospital should be kept away from others as much as possible until 10 days after the resolution of fever.

• Members of the household should wash their hands frequently with an alcohol-based solution.

• Disposable gloves should be used when handling body fluids.

• The patient should wear a mask or at least cover the mouth when coughing.

• Towels, bedding and eating utensils should not be shared.

Prognosis

The death rate is much higher than with influenza. The case fatality among persons with illness meeting the current WHO case definition for probable and suspected cases of SARS is around 3%.⁶

Risk factors for severe disease were diarrhoea, high peak LDH and CRP, high AST and creatine kinase on admission and also peak values.⁴

Mortality increases with age.⁵ Chronic illness and immune suppression are likely to increase mortality. So does diabetes.³ WHO has declared that if no new cases of SARS are reported in an area for 20 days, infection in that area is said to be contained.

A study from the New Territories of Hong Kong concluded that there is little evidence of widespread subclinical or mild forms of SARS-CoV.⁹ Clinical diagnoses during the outbreak were reasonable and resulted in appropriate triaging.

Severe acute respiratory syndrome prevention

Effective prevention lies in early detection of an outbreak and adequate containment.

There is a lot of evidence that various vaccine strategies against SARS are safe and immunogenic; however, vaccinated animals still display significant disease upon challenge. Current data suggest that intranasal vaccination may be crucial and that new or combination strategies may be required for good protective efficacy against SARS in humans.¹⁰