| disease | Atypical Pneumonia |
| alias | WHO |
Severe Acute Respiratory Syndrome (SARS) is a highly contagious and atypical pneumonia caused by the SARS coronavirus (SARS-CoV), capable of affecting multiple organ systems. The World Health Organization (WHO) designated it as Severe Acute Respiratory Syndrome (SARS). Clinically, it primarily manifests with systemic symptoms such as fever, fatigue, headache, muscle and joint pain, as well as respiratory symptoms including dry cough, chest tightness, and difficulty breathing. Some cases may also present with gastrointestinal symptoms like diarrhea. Key diagnostic features include pulmonary infiltrates on chest X-rays, normal or decreased white blood cell counts in laboratory tests, and ineffectiveness of antibiotic treatment. Severe cases exhibit pronounced respiratory distress and can rapidly progress to Acute Respiratory Distress Syndrome (ARDS). As of August 7, 2003, the global cumulative number of reported cases reached 8,422, with an average case fatality rate of 9.3%.
bubble_chart Epidemiology
SARS is a pestilence disease, and most patients can trace back to epidemiological contact history, meaning there is a possibility or evidence of being pestilence and/or pestilence by others.
If the patient has had contact with a SARS patient within the past two weeks, especially close contact (referring to living together with a SARS patient, caring for a SARS patient, or having been exposed to the secretions of a SARS patient, particularly respiratory secretions); or if the patient is part of a group outbreak following contact with a SARS patient; or if the patient has clear evidence of pestilence to others, especially pestilence to multiple SARS patients, it can be considered that the patient has epidemiological grounds for SARS.
For patients who have visited or resided in areas currently experiencing a SARS outbreak within the past two weeks, the possibility of SARS should be considered.The epidemiological evidence available at the time of the patient's visit is considered forward-looking epidemiological grounds, while further evidence that emerges after the visit is backward-looking epidemiological grounds. When there is no or insufficient epidemiological evidence at the time of the patient's visit, dynamic tracking of backward-looking epidemiological grounds must be conducted.
The available materials on SARS biopsies and autopsies are limited, so the understanding of its pathological changes remains incomplete. Based on current autopsy materials and a small number of bronchial biopsies, SARS primarily affects the lungs and immune organs such as the spleen and lymph nodes. Other organs, including the heart, liver, kidneys, adrenal glands, and brain, may also exhibit varying degrees of damage.
**Lungs**: Generally, they are significantly distended, swollen, and increased in weight. Except in cases of secondary infection, the pleura is usually smooth, dark red, or dark gray-brown. The pleural cavity may or may not contain a small amount of fluid. The cut surface of the lung tissue is mostly uniformly affected, involving all lobes of the lung, resembling the hepatization stage of lobar pneumonia. The color is reddish-brown or dark purple. Secondary infections may lead to abscesses of varying sizes. Thrombi may be observed in pulmonary blood vessels, and some cases may exhibit localized pulmonary infarction. In some cases, hilar lymph node enlargement may be seen.
**Changes in other organs**:
**Heart**: Cardiac hypertrophy is relatively common in SARS patients, typically manifesting as uniform thickening of both ventricles. Myocardial interstitial edema is evident, with scattered lymphocyte and monocyte infiltration. Some cases exhibit vacuolar degeneration of myocardial cells, focal myocarditis, or small focal myocardial necrosis. Severe secondary infections, such as fungal infections, may also involve the heart.
**Liver**: In most cases, the kidneys show significant glomerular congestion and degeneration of renal tubular epithelial cells. In some cases, extensive fibrin thrombi are observed in glomerular capillaries, while others exhibit small focal necrosis in the medulla with lymphocyte and monocyte infiltration. Renal interstitial vessels are dilated and congested. Some cases may show small abscesses due to secondary infection, and vasculitis is occasionally observed.
**Adrenal glands**: Some cases exhibit focal hemorrhage, necrosis, lymphocyte infiltration, vacuolar degeneration of zona fasciculata cells, and/or reduced lipid content in the adrenal cortex and medulla.
Brain: Brain tissue shows varying degrees of edema. In some cases, scattered neuronal degenerative changes can be observed, and in severe cases, even necrosis of brain tissue may be seen. Some nerve fibers may exhibit demyelination.
Bone marrow: In most patients, the number of granulocytic and megakaryocytic system cells in the hematopoietic tissue is relatively reduced, while in some cases, erythroid cells show small focal hyperplasia.
Gastrointestinal tract: Lymphoid tissue in the submucosa of the stomach, small intestine, and colon is reduced, with sparse lymphocytes and interstitial edema. Superficial erosions or ulcers are observed in the stomach in some cases.
Pancreas: Interstitial vascular congestion is present, with grade I fibrous tissue hyperplasia and lymphocyte infiltration in the stroma in some cases. Exocrine glands are atrophied, zymogen granules are reduced, and some islet cells show degeneration.
Gallbladder: No significant lesions are observed.
Testis: In some cases, spermatogenic cells show degeneration, and spermatogenesis is reduced. Interstitial vascular dilation and hemorrhage may be seen.
Prostate, uterus, ovaries, and fallopian tubes: No significant lesions are observed.
In addition, some cases exhibit small vasculitis lesions, predominantly involving small veins, in the lungs, heart, liver, kidneys, brain, adrenal glands, and striated muscles. These lesions manifest as vascular wall and perivascular edema, swelling and apoptosis of vascular endothelial cells, fibrinoid necrosis of the vascular wall, and infiltration of monocytes and lymphocytes within and around the vascular wall.
bubble_chart Clinical Manifestations
1. Incubation Period
The incubation period for SARS is typically limited to within 2 weeks, generally around 2~10 days.
2. Clinical Symptoms
The onset is acute, and the condition may progress within 2–3 weeks from the onset of illness. There are mainly three categories of symptoms.
(1) Fever and related symptoms
Fever is often the first and main symptom, with body temperature usually above 38°C, often presenting as persistent high fever. It may be accompanied by fear of cold, muscle aches, joint pain, headache, and lack of strength. In the early stages, antipyretics may be effective; during the progression phase, high fever is usually difficult to control with antipyretics. The use of glucocorticoids can interfere with the fever pattern.
(2) Respiratory symptoms
Cough may occur, mostly dry cough with little sputum, and a small number of patients may experience sore throat. Upper respiratory catarrhal symptoms are often absent. Chest tightness may occur, and in severe cases, patients may gradually develop accelerated breathing, shortness of breath, or even respiratory distress. Dyspnea and hypoxemia are more common 6–12 days after the onset of illness.
(3) Other symptoms
Some patients may experience gastrointestinal symptoms such as diarrhea, nausea, and vomiting.
3. Signs
Lung signs in SARS patients are often not obvious. Some patients may exhibit a few moist rales or signs of lung excess changes. Occasionally, localized dullness on percussion or reduced breath sounds may indicate a small amount of pleural effusion.
(3) General Laboratory Tests
1. Peripheral Blood Count
White blood cell count is generally normal or decreased; lymphocyte count is often reduced [if the lymphocyte count is <0.9×109/L, it has significant diagnostic implications; if the lymphocyte count is between (0.9–1.2)×109/L, the diagnostic implication is only suggestive]. Some patients may have thrombocytopenia.
2. T-Lymphocyte Subset Count
CD4+ and CD8+ cell counts often decrease early in the illness, with their ratio being normal or decreased.
(4) Chest Imaging
In the initial stage [first stage], the lungs show varying degrees of patchy or ground-glass opacities, with a few cases showing lung excess changes. The shadows are often multifocal or bilateral and tend to progress during the course of the illness. Some cases progress rapidly, with shadows merging into large patches within a short period.
When lung lesions are in the early stage, the shadows may be small or faint, or their location may overlap with the cardiac shadow and/or major vascular shadows, making them difficult to detect on chest X-rays. Therefore, if the initial chest X-ray is negative, dynamic follow-up within 1–2 days is necessary. If possible, a chest CT scan can be arranged to help detect early subtle lesions or those overlapping with the cardiac shadow and/or major vascular shadows.
Regular chest X-ray imaging follow-up is essential to observe the stirred pulse changes in lung lesions.
(5) Specific Sexually Transmitted Pathogen Testing
1. SARS-CoV Serum-Specific Antibody Testing
Using IFA, SARS-CoV-specific antibodies can be detected in patient serum 10 days after onset (if using ELISA, this occurs 21 days after onset). A seroconversion or a fourfold or greater increase in antibody titer from the progression phase to the convalescence stage has diagnostic significance. The first serum sample should be collected as early as possible.
2. SARS-CoV RNA Testing
Accurate SARS-CoV RNA testing has early diagnostic significance. Using RT-PCR, detection of SARS-CoV RNA in human specimens such as respiratory secretions, blood, or feces—especially if multiple specimens and reagent kits yield positive results—provides strong support for etiological diagnosis, provided contamination and technical issues are ruled out.
3. Other Early Diagnostic Methods
Detection methods such as immunofluorescence antibody tests for SARS-CoV-specific structural proteins in nasopharyngeal or airway exfoliated cells, as well as gene chip technology, still require further research.
II. Clinical Stages
(1) Early Stage
Generally occurs within the first 1-7 days of illness onset. The onset is acute, with fever as the primary symptom, typically with a body temperature >38°C. More than half of the patients experience symptoms such as headache, joint and muscle pain, and lack of strength. Some patients may exhibit dry cough, chest pain, diarrhea, and other symptoms; however, upper respiratory catarrhal symptoms are rare, and lung signs are mostly indistinct. A few patients may present with mild moist rales. Lung shadows on chest X-rays can appear as early as the second day of illness onset, with an average appearance on day 4. Over 95% of patients show positive changes within 7 days of the disease course.
(2) Progressive Stage
Most commonly occurs between days 8–14 of the disease course, though some patients may experience it for longer. During this stage, fever and systemic infection symptoms persist, and lung lesions progressively worsen, manifesting as chest tightness, shortness of breath, and difficulty breathing, especially after physical activity. Chest X-rays reveal rapid progression of lung shadows, often involving multiple lobes. A small number of patients (10–15%) may develop ARDS, which can be life-threatening.
(3) Stage of Convalescence
After the progressive stage, body temperature gradually decreases, clinical symptoms alleviate, and lung lesions begin to resolve. Most patients recover sufficiently to meet discharge criteria after approximately 2 weeks, although the absorption of lung shadows may take longer. A minority of severe cases may experience lingering restrictive ventilatory dysfunction and reduced lung diffusion capacity for an extended period, but most gradually recover within 2-3 months after discharge.
Combining the above epidemiological history, clinical symptoms and signs, general laboratory tests, and changes in chest X-ray imaging, along with a positive SARS pathogen test, and excluding other diseases with similar manifestations, a diagnosis of SARS can be made.
The presence of clinical symptoms and changes in lung X-ray imaging are the basic conditions for diagnosing SARS.
Clear supporting evidence in epidemiology and the ability to exclude other diseases are the most important supporting bases for making a clinical diagnosis.
For those without traceable forward epidemiological evidence, attention should be paid to dynamic follow-up of backward epidemiological evidence.
Dynamic observation of disease progression (symptoms, oxygenation status, lung X-ray imaging), the effectiveness of antibacterial treatment, and SARS pathogen indicators is of great significance for diagnosis.
Reasonable and prompt arrangement of initial treatment and relevant tests should be made to strive for a clear diagnosis as soon as possible.
1. Clinical Diagnosis
For those with SARS epidemiological evidence, symptoms, changes in lung X-ray imaging, and the ability to exclude other diseases, a clinical diagnosis of SARS can be made.
On the basis of clinical diagnosis, if the SARS-CoV RNA test is positive in secretions, or SARS-CoV antibodies seroconvert or antibody titers increase fourfold or more, a definitive diagnosis can be made.
2. Suspected Cases
For those lacking clear epidemiological evidence but with other SARS supporting evidence, they can be considered suspected cases and require further epidemiological follow-up and pathogen testing for verification.
For those with epidemiological evidence and clinical symptoms but no changes in lung X-ray imaging, they should also be considered suspected cases. For such cases, dynamic review of chest X-rays or chest CT is needed. Once lung lesions appear, a clinical diagnosis can be made after excluding other diseases.
3. Medical Isolation Observation Cases
For those with a history of contact with SARS patients or suspected SARS patients within the past two weeks but no clinical manifestations, medical isolation observation should be conducted for two weeks starting from the date of last contact.
Suggestions for Triage Categories and Corresponding Management
In clinical reasoning, the diagnosis of SARS can be divided into five levels, with patients categorized into five groups and marked accordingly.
1. Not SARS: SARS diagnosis can be excluded, and the patient enters the normal diagnostic process.
2. Unlikely SARS: Not resembling SARS but cannot be absolutely excluded. Arrange for medical isolation observation. Home isolation observation and follow-up can be adopted.
3. Suspected SARS: Comprehensive judgment shows many similarities with SARS but cannot yet make a clinical diagnosis. Hospital observation is required, and the patient should be admitted to a single observation room.
4. Clinical Diagnosis (probable case): Basically confirmed as SARS but without pathogen evidence. Admit to a designated SARS hospital, but to avoid cross-infection of the few non-SARS cases, place in a single room.
5. Definitive Diagnosis (diagnosed case): Based on clinical diagnosis with supporting pathogen evidence. Admit to a designated SARS hospital and can be placed in a multi-person ward.
6. Diagnostic Criteria for Severe SARS
Any one of the following three items can be used to diagnose severe SARS.
1. Dyspnea, with a respiratory rate ≥30 breaths/min at rest in adults, accompanied by one of the following:
(1) Chest X-ray shows multi-lobe lesions or the total lesion area occupies more than one-third of the total lung area on the frontal chest X-ray;
(2) Disease progression, with lesion area increasing by more than 50% within 48 hours and occupying more than one-fourth of the total lung area on the frontal chest X-ray;
2. Significant hypoxemia is present, with an oxygenation index below 300mmHg (1mmHg=0.133kPa);
3. The occurrence of shock or multiple organ dysfunction syndrome (MODS). Identifying critically ill SARS patients and intervening promptly is crucial for controlling the condition.
High-risk factors for SARS mortality
1. Age over 50;
2. Severe underlying diseases of the heart, kidneys, liver, or respiratory system, or other serious conditions such as malignant tumors, diabetes, severe malnutrition, or cerebrovascular diseases;
3. Recent major surgical procedures;
4. Progressive decline in total peripheral blood lymphocyte count;
5. Persistently high blood glucose levels despite aggressive treatment.
bubble_chart Treatment Measures
Based on the above epidemiological history, clinical symptoms and signs, general laboratory tests, and changes in chest X-ray imaging, combined with a positive SARS pathogen test and the exclusion of other diseases with similar manifestations, a diagnosis of SARS can be made.
The presence of clinical symptoms and changes in lung X-ray imaging are the basic conditions for diagnosing SARS.
Clear supporting evidence in epidemiology and the ability to exclude other diseases are the most important supporting bases for making a clinical diagnosis.
For those who cannot be traced with forward epidemiological evidence, attention should be paid to dynamic follow-up of backward epidemiological evidence.
Dynamic observation of disease progression (symptoms, oxygenation status, lung X-ray imaging), the effectiveness of antibacterial treatment, and SARS pathogen indicators is of great significance for diagnosis.
Reasonable and prompt arrangements for initial treatment and relevant tests should be made to strive for a rapid and clear diagnosis.
1. Clinical Diagnosis
For those with SARS epidemiological evidence, symptoms, changes in lung X-ray imaging, and the ability to exclude other diseases, a clinical diagnosis of SARS can be made.
On the basis of a clinical diagnosis, if the SARS-CoV RNA test is positive in secretions or the SARS-CoV antibody seroconverts or the antibody titer increases by fourfold or more, a definitive diagnosis can be made.
2. Suspected Cases
For those lacking clear epidemiological evidence but with other SARS supporting evidence, they can be considered suspected cases and require further epidemiological follow-up and pathogen testing for verification.
For those with epidemiological evidence and clinical symptoms but no changes in lung X-ray imaging, they should also be considered suspected cases. For such cases, dynamic review of chest X-rays or chest CT is needed. Once lung lesions appear, a clinical diagnosis can be made after excluding other diseases.
3. Medical Isolation Observation Cases
For those who have had contact with SARS patients or suspected SARS patients within the past two weeks but show no clinical manifestations, medical isolation observation should be conducted for two weeks starting from the date of last contact.
Suggestions for Triage Categories and Corresponding Management Approaches
In clinical reasoning, the diagnosis of SARS can be divided into five levels, with patients categorized into five groups and given corresponding labels.
1. Not SARS: SARS diagnosis can be excluded, and the patient enters the normal treatment process.
2. Unlikely SARS: Not resembling SARS but cannot be absolutely excluded. Arrange for medical isolation observation. Home isolation observation and follow-up can be adopted.
3. Suspected SARS: Comprehensive judgment shows significant alignment with SARS but a clinical diagnosis cannot yet be made. Hospital observation is required, and the patient should be admitted to a single observation room.
4. Clinical Diagnosis (probable case): Essentially confirmed as a SARS case but lacks pathogen evidence. Admit to a designated SARS hospital, but to avoid cross-infection of the few non-SARS cases, place in a single room.
5. Definitive Diagnosis (diagnosed case): Based on clinical diagnosis with supporting pathogen evidence. Admit to a designated SARS hospital and can be placed in a multi-person ward.
6. Diagnostic Criteria for Severe SARS
Any one of the following three items can be used to diagnose severe SARS.
1. Dyspnea, with a respiratory rate ≥30 breaths/min at rest in adults, accompanied by one of the following conditions.
(1) Chest X-ray shows multi-lobe lesions or the total lesion area occupies more than one-third of the total lung area on the frontal chest X-ray;
(2) Disease progression, with lesion area increasing by more than 50% within 48 hours and occupying more than one-fourth of the total lung area on the frontal chest X-ray;
2. Significant hypoxemia occurs, with an oxygenation index below 300mmHg (1mmHg=0.133kPa);
3. The occurrence of shock or multiple organ dysfunction syndrome (MODS). Identifying critically ill SARS patients and intervening promptly is crucial for controlling the condition.
High-risk factors for SARS mortality
1. Age over 50;
2. Presence of severe underlying diseases in the heart, kidneys, liver, or respiratory system, or other serious conditions such as malignant tumors, diabetes, severe malnutrition, or cerebrovascular diseases;
3. Recent major surgical procedures;
4. Progressive decline in total peripheral blood lymphocyte count;
5. Persistently high blood glucose levels despite aggressive treatment.
