Roles of TNF-alpha gene polymorphisms in the occurrence and progress of SARS-Cov infection: a case-control study.

BACKGROUND: Host genetic factors may play a role in the occurrence and progress of SARS-Cov infection. This study was to investigate the relationship between tumor necrosis factor (TNF)-alpha gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis. METHODS: The association between genetic polymorphisms of TNF-alpha gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-alpha gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. PCR sequencing based typing (PCR-SBT) method was used to determine the polymorphisms of TNF-alpha gene in locus of the promoter region and univariate logistic analysis was conducted in analyzing the collected data. RESULTS: Compared to TT genotype, the CT genotype at the -204 locus was found associated with a protective effect on SARS with OR(95%CI) of 0.95(0.90-0.99). Also, TT genotype, CT and CC were found associated with a risk effect on femoral head necrosis with ORs(95%CI) of 5.33(1.39-20.45) and 5.67(2.74-11.71), respectively and the glucocorticoid adjusted OR of CT was 5.25(95%CI 1.18-23.46) and the combined (CT and CC) genotype OR was 6.0 (95%CI 1.60-22.55) at -1031 site of TNF-alpha gene. At the same time, the -863 AC genotype was manifested as another risk effect associated with femoral head necrosis with OR(95%CI) of 6.42(1.53-26.88) and the adjusted OR was 8.40(95%CI 1.76-40.02) in cured SARS patients compared to CC genotype. CONCLUSION: SNPs of TNF-alpha gene of promoter region may not associate with SARS-CoV infection. And these SNPs may not affect interstitial lung fibrosis in cured SARS patients. However, the -1031CT/CC and -863 AC genotypes may be risk factors of femoral head necrosis in discharged SARS patients.

[Factors of avascular necrosis of femoral head and osteoporosis in SARS patients' convalescence].

OBJECTIVE: To explore the factors affecting the pathogenesis of avascular necrosis of femoral head and osteoporosis of SARS patients during convalescent stage. METHODS: The clinical data of 40 SARS patients, 12 males and 28 females, aged 29 +/- 9, hospitalized from April to June 2003, were reviewed, targeted on the use of glucocorticoids. Three months after the discharge ELISA and indirect immunofluorescent antibody (IFA) assay were used to detect the serum IgG. Magnetic resonance imaging (MRI) was used to detect the damage of the head of femur and quantitative ultrasound (QUS) was used to detect osteoporosis at the left heel. RESULTS: The average total dosage of methylprednisolone was (4949 +/- 2959) mg, and the average course of treatment was (24 +/- 5) days (16 to 30 days). Twenty-three patients underwent ictus therapy of corticosteroids for (8 +/- 4) days. The extenuation time of corticosteroid' dosage was (33 +/- 26) mg/d. Of the 40 patients, 36 were IgG positive with an average A value of (0.91 +/- 0.24) and 4 patients were IgG negative. Twelve patients (30%) were with type I avascular necrosis of femoral head, including 3 cases with unilateral left--necrosis and 9 cases of bilateral necrosis. The other 28 patients were without necrosis. Two patients were suffering from osteoporosis and 30 patients were with bone density decrement. The average Z values of the parameter BUA and VOS were (-1.26 +/- 0. 53) and (-0.53 +/- 0.30) respectively. The corresponding T values of the parameter BUA and VOS were (-1.49 +/- 0.59) and (-0.65 +/- 0.05) respectively. The influencing factors of femoral necrosis included the degree of healing activity, the dosage summation of corticosteroids, and length of ictus therapy. The influencing factors of bone density included age, dosage summation, and length of ictus therapy. The influencing factors of the bone fabric and flexibility included the use and length of ictus therapy. Statistics showed that serum IgG was not related with avascular necrosis of femoral head and osteoporosis. CONCLUSIONS: The incidence rates of avascular necrosis of femoral head and of osteoporosis were higher in convalescent SARS patients than in general population. The influencing factors of femoral necrosis included the degree of healing activity, the dosage summation of corticosteroids, and length of ictus therapy. The influencing factors of bone density included age, dosage summation, and length of ictus therapy. The influencing factors of the bone fabric and flexibility included the use and length of ictus therapy. Statistics showed that serum IgG was not related with avascular necrosis of femoral head and osteoporosis. SARS virus may not affect the pathogenesis of avascular necrosis of femoral head and osteoporosis.

[Analysis of relation between the usage of corticosteroid in treatment and arthralgia as a sequela of SARS patients].

OBJECTIVE: To analyze relation between the use of corticosteroids in the treatment for severe acute respiratory syndrome (SARS) patients and arthralgia as a sequela. METHODS: Clinical date of 30 SARS patients without other diseases in whom corticosteroid was used were reviewed including total dosage, duration of use, the highest dosage and its duration, and speed of reduction in dosage. The information about arthralgia was investigated one month after discharge of SARS patients from the hospital. RESULTS: The average total dosage of methylprednisolone was (4 244.16+/-2 292.30) mg, and the duration of use of the treatment was (25.36+/-5.88) days (ranging from 12 to 35 days). The maximum dosage was (321.33+/-174.03) mg/d, and the duration of its use was (7.73+/-4.08) days. The speed of reduction of dosage of corticosteroids was (21.33+/-10.18) mg/d. There were 26 of 30 patients (86.67 percent) experienced arthralgia symptom during convalescence. In 3.6 percent of patients arthralgia occurred within one month after SARS, 53.85 percent of the patients experienced low-grade arthralgia. By unifactor analysis, the total dosage and its duration of use, the highest dosage and its duration, speed of reduction of dosage of corticosteroids were correlated with the degree of arthralgia, respectively. The duration of arthralgia was correlated with the total dosage, the duration of high dosage, and high dosage. Age was not correlated with either the degree or the persisting time of arthralgia. The degree of arthralgia was only correlated with the total dosage, and the duration of arthralgia was correlated with administration time of glucocorticosteroids by multifactor analysis. CONCLUSION: There is a dosage- effect relation between the degree of arthralgia and the total dosage of corticosteroid, and a time-effect relation between the duration of arthralgia and length of the use of corticosteroids.

Advances in clinical diagnosis and treatment of severe acute respiratory syndrome.

It has been proved that severe acute respiratory syndrome (SARS) is caused by SARS-associated coronavirus, a novel coronavirus. SARS originated in Guangdong Province, the People's Republic of China at the end of 2002. At present, it has spread to more than 33 countries or regions all over the world and affected 8 360 people and killed 764 by May 31,2003. Identification of the SARS causative agent and development of a diagnostic test are important. Detecting disease in its early stage, understanding its pathways of transmission and implementing specific prevention measures for the disease are dependent upon swift progress. Due to the efforts of the WHO-led network of laboratories testing for SARS, tests for the novel coronavirus have been developed with unprecedented speed. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses. WHO established the definitions of suspected and confirmed and probable cases. But the laboratory tests and definitions are limited. Until now, the primary measures included isolation, ribavirin and corticosteroid therapy, mechanical ventilation, etc. Other therapies such as convalescent plasma are being explored. It is necessary to find more effective therapy. There still are many problems to be solved in the course of conquering SARS.