About Severe acute respiratory syndrome (SARS)
The severe acute respiratory syndrome (SARS) is an infectious disease of the lungs (acute pneumonia) caused by a coronavirus, the SARS-CoV, appeared for the first time in China November 2002, which caused an epidemic fromMay 2003in 29 countries, infected more than 8,000 people and killed at least 774. The disease manifested itself until May 2004.
Responsible agent of SARS
The identification of the virus was fairly rapid (a few months compared to several years for HIV in the 1980s), 11 laboratories having been mobilized by the WHO. The virus responsible for severe acute respiratory syndrome, SARS-CoV, belongs to the Coronaviridae family, in the genus Coronavirus.
The rapid identification of this virus can (among other things) be explained by the fact that this virus has been classified as level 3+, which does not exist in the classification of biological hazards : the virus is either level 3, or level 4. The reason for this choice lies in the fact that only a few laboratories in the world are sophisticated enough to work with level 4 viruses in complete safety. If these laboratories had been the only ones looking for the classification of the virus, surely no antiviral would have been found so quickly. This is why the WHO has decided to classify this virus level 3+, so that as many research teams as possible can work on it. It could have been very dangerous,
Coronaviruses are single-stranded RNA enveloped viruses of positive polarity. In electron microscopy, the viral particles present surface protuberances giving them a "crown" appearance (corona, in Latin) which was used for the name of these viruses. Classification as a coronavirus results from serological reaction tests and genomic sequence analyzes. The Coronaviridae family is divided into three groups: group 1 (canine coronavirus, enteric feline coronavirus FECV and feline infectious peritonitis FIPV, porcine transmissible gastroenteritis virus and porcine respiratory virus), and group 2 (bovine coronavirus, murine hepatitis virus, rat silodacryonitis virus and human coronavirus OC43) include viruses infecting mammals. Group 3 consists of viruses known to be exclusively avian (avian infectious bronchitis virus, turkey coronavirus).
Diagnosis of SARS
The diagnosis of SARS-CoV infection is based on physical examination, radiological signs, and travel to a country where the virus has been detected.
The initial signs of infection are not specific and this diagnosis remains a diagnosis of exclusion. The most common symptom of Severe Acute Respiratory Syndrome is fever above 38 ° C onset quite suddenly after an incubation period of two to ten days. However, this fever may be absent at the onset of the disease or in patients with another pathology affecting the febrile reactions. Fever can be associated with chills, myalgia, general malaise, and headache. The initial symptomatology mainly resembles a picture of atypical pneumonia. A productive cough, dysphagiapainful, nausea and vomiting are rarer. Diarrhoea was a frequent symptom in an epidemiological focus reported in Hong Kong but appears rare in the other groups that have been described. Pulmonary auscultation may find inspiratory rales at the base level, but there is usually no sibilance.
Numerous atypical pictures have been described: afebrile patients, patients with diarrhea but without pulmonary signs, etc. These atypical forms constitute a threat for patients, hospital staff and relatives. The WHO has therefore precisely defined the criteria for a probable case of severe acute respiratory syndrome: a fever above 38 ° C associated with signs of low respiratory impairment (cough, dyspnea, respiratory discomfort, etc.) occurring in a person in from a country or area where active transmission of SARS-CoV has been described or in a person working (or having worked) in a laboratory handling (or having handled) SARS-CoV (regardless of its location geographical).
Biologically, many haematological abnormalities have been reported during the course of the disease. A lymphopenia was present in 98% of patients with the lowest levels observed during the second week of evolution and standardization during the third week. However, in 30% of cases, lymphopenia persisted into the fifth week of progression. In the initial stages of the disease, CD4 and CD8 levels could be lowered. According to some studies, low CD4 and CD8 levels are a factor of poor prognosis. A leukopenia transient was reported in 64% of patients during the first week of illness. However, in 61% of patients, leukocytosiswas found during the second and third weeks of evolution. A neutrophilia is observed in 82% of cases, probably related to treatment with corticosteroids. Relative self-limiting thrombocytopenia was found in 55% of patients. No serious bleeding was observed. The remainder of the biological assessment shows an increase in LDH, ASAT and ALAT and creatine kinase. Elevated LDH and transaminase levels may be secondary to ribavirin treatment. However, in some studies, high LDH levels are reported to be a factor of poor prognosis. Finally, D-dimers can be elevated and TCA prolonged in a large number of patients.
Radiological imaging plays an important role in the initial diagnosis of severe acute respiratory syndrome and then in monitoring the effectiveness of treatment. The most typical images include a predominant peripheral localization, unilateral and focal alveolar opacities progressing under treatment to unilateral multifocal or bilateral involvement. There is no excavation, lymphadenopathy, or pleural effusion. The chest CT scan is a complementary examination that usually helps to identify signs of severe pneumonia.
Currently, the diagnosis of severe acute respiratory syndrome can only be made after ruling out other causes of pneumonia by direct methods of testing for the causative agents of pneumonia. In retrospect, the serological diagnosis may possibly make it possible to reconsider certain difficult cases. In 2004, various virological diagnostic methods for SARS had been validated by the WHO. Since then, pharmaceutical companies have developed other tests or have refined the sensitivity and specificity of existing tests, but in the absence of an epidemic resurgence, these tests have not been validated for infection with SARS-CoV. The diagnostic tools that are described here are those that had been validated by the WHO.
Virological diagnosis is based on the detection of the SARS-CoV virus from nasal, pharyngeal swabs, sputum, endotracheal aspirations, blood, stools or urine by RT-PCR or viral culture. The excretion of the SARS-CoV virus is quite low at the onset of the disease, it is maximum around 10 days after the onset of clinical signs. The virus is then found in respiratory secretions and in the stool. A study on the clinical utility of different diagnostic tests showed that SARS-CoV RNA was detected by RT-PCR in nasopharyngeal secretions in only 32% of patients in the initial phase and in 68% of cases. 14 days after the onset of clinical signs (Peiris, Lancet 2003). Quantitative analysis showed that the viral load peaks 10 days after the onset of clinical signs. The viral RNA is detected in the stools of 98% of the patients later in the disease (to the 14th day) and in the urine after the 15th day. RT-PCR tests currently remain relatively insensitive and it is strongly recommended to increase the number of examinations of nasopharyngeal samples to improve the predictive value of the test. A negative RT-PCR test does not exclude the diagnosis of SARS: the samples may have been taken at a time when the viral load was too low to be detected by available laboratory tests.
The presence of the virus can be demonstrated by inoculating cell cultures (Vero cells) from stool samples, blood or respiratory secretions. Once the virus is isolated, other tests (eg immunofluorescence) must be used to identify SARS-CoV. Isolation of SARS-CoV in cell culture should be performed at a minimum in a laboratory of safety level BSL3. Negative cell culture results do not exclude the diagnosis of severe acute respiratory syndrome, for the same reasons as in negative RT-PCR cases.
Serological diagnosis can help to reconsider cases of unidentified lung disease. An ELISA test can reliably detect a mixture of IgG and IgM in serum of infected patients to the 21st day after the onset of clinical signs. Several immunofluorescence tests requiring the use of cells infected with SARS-CoV fixed on slides can detect patient antibodies (IgG, IgM or both). These tests are positive around the 10th day after onset of disease, quantitative results can be reported using serial dilutions of patient sera. A neutralization test has been developed which evaluates and quantifies the neutralization capacity of patient sera. This test requires working in a BSL3 containment level laboratory.