Severe acute respiratory syndrome (SARS) is the first major new infectious disease to hit the international community in the XXIth century. The first case, reported on November 16, 2002 in Guangdong resulted in a series of major outbreaks all around the world that affected more than 8000 patients and caused a global mortality rate of 11 %, in at least 33 countries (1).

I) EPIDEMIOLOGIC DATA

• SARS, originated from southern China in November 2002, was transmitted by ONE PATIENT to the Hong-Kong territory in February 2003 and spread rapidly to VIETNAM (Hanoi), to CANADA (Toronto) and several ASIAN COUNTRIES. Therafter SARS through air travels (2) was disseminated to 33 different countries on 5 continents. These successive outbreaks were characterized by periods of exponential growth, stability and finally of progressive decay.
• At the end of the Epidemic, the total number of SARS cases was 8422 with 916 deaths. 87 % of patients and 84 % of all deaths were concentrated in CHINA and HONG-KONG. The number of individuals infected by each case has been estimated to 2.7 (3).
• People of all ages were affected but predominantly females. Children were relatively less affected. Health care workers were at high risk and represented 1/5 of all cases. Risk factors for death included old age and comorbidities, especially diabetes.

II) CHARACTERISTICS OF SARS-CORONAVIRUS

SARS is caused by a novel coronavirus, called the SARS coronavirus (SARS-CoV). The genome of SARS-CoV has been sequenced and it is not related to any of the previously known human or animal coronaviruses. Recently cell receptors for SARS-CoV (L-SIGN and Angiotensin-converting enzyme 2), were described ; they are expressed on type II pneumocytes and endothelial cells (4). It is probable that SARS-CoV was primarly an animal virus that adapted in the recent past to human-human transmission (like influenza viruses) (Table I).

AIRBORNE TRANSMISSION OF SARS

• Modalities of transmission of SARS virus has been largely discussed
    - direct from human to human
    - via animal reservoirs
    - via air contaminated by viruses
• Study of Ignatius YU (Hong-Kong)
    - 187 cases in the "Among Gardens Housing Complex"
    - All patients except for 5 lived in 7 buildings
    - More than 50 % (99) in Building E

TWO MODES OF TRANSMISSION
    - Inner ventilation systems
    - Prevalling wind (NE)

Pathogenesis of SARS is still (year 2004) poorly understood : within the first 10 days, histological studies show an ACUTE PHASE OF DIFFUSE ALVEOLAR DAMAGE with the association of inflammatory infiltrates, oedema and hyaline membrane formation. Desquamation of pneumocytes is prominent. In a second stage of the disease (10th day), pathological alterations are dominated by the development of fibrosis, squamous metaplasia and multinucleated giant cells : it is the CHRONIC PHASE OF DIFFUSE ALVEOLAR DAMAGE responsible for long-term sequelae.

III) CLINICAL AND RADIOLOGICAL FEATURES OF SARS

Onset of the disease
The mean incubation period is 6.4 days (range 2-10). The duration between onset of symptoms and hospitalisation is varying from 3 to 5 days : so this relatively prolonged incubation has allowed asymptomatic air-travellers to spread the disease all around the world.

Clinical symptoms (5, 6)

• Fever is the most frequent initial symptom, followed by cough, myalgia, dyspnea and diarrhea : in other words clinical symptoms are similar to common influenza.
• Common abnormal laboratory findings include elevated CRP levels, leukopenia with lymphopenia, thrombocytopenia and enhanced levels of LDH and creatinine phosphokinase.
• All these non specific clinical and laboratory findings are exacerbated during the second week of the disease.

Radiological findings (7)

• Alveolar consolidation is typical in severe SARS and may be indistinguishable from pneumonia of other aetiologies. In the majority of patients during the early acute phase, ground glass opacities progress rapidly to focal or multifocal or diffuse consolidation. Initially unilateral pneumonia is common, becoming bilateral at maximal lung involvement. Radiological opacities usually peak between 8 and 10 days after onset of illness.
• Different complications are observed (pleural effusion, cavitating consolidation, mediastinal enlarged lymph nodes) but are not typical radiographic features.
• CT scan is useful in patients with normal initial chest-X-ray, who had strong contact history and suspicious symptoms. Indeed, in the special situation, HRCT detects the presence of ground-glass opacities with interlobular septal thickening which allows early treatment and immediate isolation (table II).

(Table 2) RADIOLOGICAL MANIFESTATIONS

Initial Chest X ray may be normal
Primary abnormalities
      air spaces opacities ?
                     CT subpleural consolidation
                      with air bronchogram
                      with ground glass opacities
     predominantly lower lobes
Rapid progression    sometimes overnight  =>  ARDS
No lymphadenopathy or pleural effusion

Biological findings
The virus can be found in nasopharyngeal aspirates, urine and stools of SARS patients. P.C.R allows to detect SARS-CoV in nasopharyngeal aspirates of approximately 80 % of patients with SARS within the first 3 days of illness.
Serological tests are also useful : the best methods are immunofluorescence on infected cells and ELISA but the antibody response only appears after the 10th day after beginning of the disease. (A positive response is given in fewer than 1 % of cases within 10 days of the onset of symptoms but reachs 93 % of cases within 28 days of the onset of symptoms).

Follow-up of SARS :
Outcome and prognosis of patients with SARS have still to be more extensively evaluated. After recovery, many patients complained of general weakness and/or shortness of breath ; PFT identified a mild or moderate restrictive pattern in 10-20 % of patients but most of these lung function alterations will improve over time. In short series of subjects who underwent CT scan, 50 % exhibited some changes consistent with pulmonary fibrosis. However more complete and extensive investigations are necessary to confirm these data.

IV) TREATMENT AND PREVENTION OF SARS

Risk factors and prevention when a SARS patient is admitted in an hospital structure, the major risk is transmission to health care workers, other patients and visitors. Hospital outbreaks of SARS typically occurred within the first week after admission when the disease was not yet identified and before isolation measures were complemented. Nosocomial infection needs a history of close contact with a SARS patient (saliva droplets, direct contact with infected material). In some cases, potential airborne transmission was reported in association with endotracheal intubation or mechanical ventilation of SARS patients admitted in intensive care units.

Management of SARS (8)

• Clearly there is a large spectrum of clinical response even to the same treatment regimen, with GOOD and POOR RESPONDERS.

V) THE FUTURE OF SARS

The future of SARS is clearly linked to modalities of transmission of the virus.
Three have been demonstrated :

1. a direct contamination from human to human,
2. a transmission via air contamined by virus (3) ;
3. lastly a transmission via animal reservoirs.

In Asian countries live animal markets are wide-spread (live poultry, fishes but also various mammals like palm civets (9, 10). Another possible source of contamination is represented by research laboratories that manipulate dangerous infectious pathogens like SARS-CoV.

In conclusion it seems logical to accept a zoonotic origin for SARS. On the contrary it is difficult to make prediction regarding the resurgence of SARS but the 2 greatest risks might derive from unknown or uncontrolled animal reservoirs or from infections transmitted in diagnostic and/or research laboratories. These remarks are also true for other new influenzae viruses : SARS epidemic has served to illustrate the POTENTIAL HEALTHY EFFECTS of more transmissible diseases like pandemic influenza or pandemic (?) avian influenza that represent the nightmare of number of virologists and specialists of infectious diseases.

création: décembre 2006