Severe acute respiratory syndrome (SARS) is caused by a coronavirus called SARS-CoV. The disease may have started in pigs or ducks in rural south China and mutated to affect humans.
It seems that both abnormal immune responses and injury to immune cells may be key factors in the pathogenesis of this new disease.
NB: SARS should not be confused with another zoonosis from the same area, called avian flu.
SARS was first recognised in March 2003 but probably had its origins in the Guangdong Province of China in November 2002.
Between March and July 2003, over 8,000 probable cases of SARS were reported from around 30 countries. The 2002-2003 SARS outbreak affected mostly China, Hong Kong, Singapore and Taiwan. Canada had a significant outbreak around Toronto. Since April 2005, SARS seems to have been contained worldwide.
- Most cases of SARS appear to have been transmitted from close contact with infected patients. In May 2003, the World Health Organization (WHO) reported that only 16 of more than 7,800 people infected with the virus had contracted it on aeroplanes. After airlines began screening passengers for symptoms, especially fever, no further cases from air travel were reported.
- There is no difference in susceptibility to infection with regard to age, sex or race.
- Where percentages are given below they will be based mainly on papers giving experience of:
- Figures from all centres tend to be fairly similar.
- Another paper from Toronto also looked at those who required admission to the intensive care unit.
- Middle East respiratory syndrome (MERS) is a respiratory disease with high mortality caused by a novel single-stranded, positive-sense RNA betacoronavirus (MERS-CoV).
- Dromedary camels are hosts for MERS-CoV and are implicated in direct or indirect transmission to humans. The exact mode of transmission is unknown.
- The virus was first isolated from a patient who died from a severe respiratory illness in June 2012, in Jeddah, Saudi Arabia.
- Although most cases of MERS have occurred in Saudi Arabia and the United Arab Emirates, cases have been reported in Europe, the USA and Asia in people who travelled from the Middle East or their contacts. Since May 2015, the Republic of Korea has been investigating an outbreak of MERS.
- Compared to SARS, MERS-CoV appears to kill more people (40% versus 10%), more quickly, and is more severe in those with pre-existing medical conditions.
- Clinical features of MERS range from asymptomatic or mild disease to acute respiratory distress syndrome and multiorgan failure resulting in death, especially in individuals with underlying comorbidities.
- No specific drug treatment exists and infection prevention and control measures are crucial to prevent spread in healthcare facilities.
- MERS-CoV continues to be an endemic, relatively low-level public health threat. However, it could mutate to have increased interhuman transmissibility and so potentially lead to a pandemic.
- SARS is not usually suspected unless the person is known to have come from an area where they have been exposed.
- The most common mode of transmission is droplet spread.
- Healthcare workers and the families or carers of those who have been infected are at greatest risk:
- In the Toronto study:
- 77% (111/144) were exposed within a hospital setting.
- 164 healthcare workers were quarantined, closing 73 ICU beds.
- 16 workers (10%) developed SARS.
- Of 196 patients, 38(19%) became critically ill, of whom 7 (18%) were healthcare workers.
- In Hong Kong half of 138 patients were healthcare workers.
- Close contact permits spread. Close contact means kissing, embracing, sharing eating or drinking utensils, conversation less than a metre apart or physical examination of the person. It does not include walking past someone or sitting across a waiting room or office for a brief period.
- Faeco-oral spread from diarrhoea may be possible.
- Visiting an infected or suspected area, including an airport, within the preceding 10 days raises suspicion.
- Incubation period is usually 2-7 days but may be up to 10 days and 14 days has been reported.
- 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%.
- 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%.
- 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:
- Expectorated sputum (if available).
- Urine (20-30 ml).
- 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:
- 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).
- 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. In the Taiwan study, 31% required ventilationalthough a study from Canada suggested up to 20%. A different Canadian study supported this with 38/196 becoming critically ill, of whom 29 required ventilation. This represents 76% of the critically ill and 15% overall.
- 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.
- Pulse steroids were used in Taiwan with improvement in 14 of 17.
- Antiviral agents may help. Ribavarin was used in 88% in Canada. 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.
- Interferon beta seems promising and is recommended.
After discharge from hospital:
- 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.
The death rate is much higher than with influenza. Between November 2002 and July 2003 there were 8,098 cases reported worldwide, of whom 774 died (9.6%) and 7,324 recovered.
Outcome of SARS
|Country||Number of cases||Number of deaths||Mortality rate %|
These figures suggest that, despite the need for high technology, the death rate appears lowest in China. Figures for various clinical parameters from Taiwan, Canada and Hong Kong were remarkably similar[2, 3, 4]. However, government statistics from China are greeted with a degree of scepticism. Risk factors for severe disease were diarrhoea, high peak LDH and CRP, high AST and creatine kinase on admission and also peak values.
Mortality increases with age. Chronic illness and immune suppression are likely to increase mortality. So does diabetes. 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. Clinical diagnoses during the outbreak were reasonable and resulted in appropriate triaging.
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.
Further reading and references
Severe Acute Respiratory Syndrome (SARS); World Health Organization, October 2004
Gu J, Korteweg C; Pathology and pathogenesis of severe acute respiratory syndrome. Am J Pathol. 2007 Apr170(4):1136-47.
Booth CM, Matukas LM, Tomlinson GA, et al; Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. 2003 Jun 4289(21):2801-9. Epub 2003 May 6.
Jang TN, Yeh DY, Shen SH, et al; Severe acute respiratory syndrome in Taiwan: analysis of epidemiological characteristics in 29 cases. J Infect. 2004 Jan48(1):23-31.
Lee N, Hui D, Wu A, et al; A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003 May 15348(20):1986-94. Epub 2003 Apr 7.
Fowler RA, Lapinsky SE, Hallett D, et al; Critically ill patients with severe acute respiratory syndrome. JAMA. 2003 Jul 16290(3):367-73.
Coronavirus infections; World Health Organization (WHO)
Middle East Respiratory Syndrome (MERS); Centers for Disease Control and Prevention.
Zumla A, Hui DS, Perlman S; Middle East respiratory syndrome. Lancet. 2015 Jun 3. pii: S0140-6736(15)60454-8. doi: 10.1016/S0140-6736(15)60454-8.
Banik GR, Khandaker G, Rashid H; Middle East Respiratory Syndrome Coronavirus "MERS-CoV": Current Knowledge Gaps. Paediatr Respir Rev. 2015 Apr 18. pii: S1526-0542(15)00031-7. doi: 10.1016/j.prrv.2015.04.002.
Hospital Management of adults with Severe Acute Respiratory Syndrome (SARS) if SARS re-emerges; British Thoracic Society (2004)
Lapinsky SE, Hawryluck L; ICU management of severe acute respiratory syndrome. Intensive Care Med. 2003 Jun29(6):870-5. Epub 2003 May 9.
Cinatl J, Morgenstern B, Bauer G, et al; Treatment of SARS with human interferons. Lancet. 2003 Jul 26362(9380):293-4.
Rainer TH, Chan PK, Ip M, et al; The spectrum of severe acute respiratory syndrome-associated coronavirus infection. Ann Intern Med. 2004 Apr 20140(8):614-9.
Roper RL, Rehm KE; SARS vaccines: where are we? Expert Rev Vaccines. 2009 Jul8(7):887-98.