1、 Week 1 was characterised by fever,myalgia,and other systemic symptoms that generally improve after a few days.The increasing viral load during this phase suggests that the symptoms are largely related to the effect of viral replication and cytolysis.Lancet 09 May,2003As the disease progressed into
2、week 2 Recurrence of fever,onset of diarrhoea,and oxygen desaturation.Strikingly,nearly half the patients had shifting radiographic shadows.Lancet 09 May,2003Lancet 09 May,2003Seroconversion of IgGThe timing of the IgG seroconversion,which starts on day 10,seems to correlate with falls in viral load
3、,which occurs from between day 10 and 15.Lancet 09 May,2003Viral loads of nasopharyngeal aspirateProgressive decrease in rates of viral shedding from nasopharynx,stool,and urine from day 10 to 21 after onset of symptoms.SARS is associated with Epithelial-cell proliferation and an increase in macroph
4、ages in the lung.The presence of haemophagocytosis supports the contention that cytokine dysregulation may account,at least partly,for the severity of the clinical disease.Lung damage at this phase is related to immunopathological damage as a result of an overexuberant host response,rather than unco
5、ntrolled viral replication.Lancet 16 May,2003 20%of patients in this cohort progressed to the third phase,characterised by ARDS necessitating ventilatory support.Lancet 09 May,2003Lancet 09 May,20031.第一期（第一期（17天）：天）：病毒複製期病毒複製期，抗病毒藥物，抗病毒藥物2.第二期（第二期（714天）：天）：細胞激素風暴期細胞激素風暴期（cytokine storm），肺部發炎、破壞，），肺部
6、發炎、破壞，用類固醇用類固醇3.第三期（第三期（14天天-）：）：肺纖維化肺纖維化（呼吸治療）、（呼吸治療）、繼發細菌真菌感染繼發細菌真菌感染應注意藥物副作用、免疫抑制應注意藥物副作用、免疫抑制感染感染-7發病發病 0714第一期第一期第二期第二期第三期第三期 Prevent transmission:reduce viral shedding Reduce mortality Prevent intubation:improve oxygenation,stop clinical progression to ARDS Shorten hospitalization:rapid recove
7、ry Reduce long-term sequelae Antibacterial treatment Cover typical and atypical pneumonia.Ribavirin Methylprednisolone VentilationAntibacterial treatment Cover typical and atypical pneumonia.Start levofloxacin 500 mg once daily intravenously or orally Or clarithromycin 500 mg twice daily orally plus
8、 coamoxiclav(amoxicillin and clavulanic acid)375 mg three times daily orally if patient 18 years,pregnant,or suspected to have tuberculosisLancet 10 May,2003Ribavirin and methylprednisoloneAdd combination treatment when:Extensive or bilateral chest radiographic involvement Or persistent chest radiog
9、raphic involvement and persistent high fever for 2 days Or clinical,chest radiographic,or laboratory findings suggestive of worsening Or oxygen saturation 95%in room airLancet 10 May,2003Ribavirin regimen for 1014 days Ribavirin 400 mg every 8 h(1200 mg daily)intravenously for at least 3 days(or unt
10、il condition becomes stable)Then ribavirin 1200 mg twice daily(2400 mg daily)orallyLancet 10 May,2003Standard for 21 days Methylprednisolone 1 mg/kg every 8 h(3 mg/kg daily)intravenously for 5 days Then methylprednisolone 1 mg/kg every 12 h(2 mg/kg daily)intravenously for 5 days Then prednisolone 05
11、 mg/kg twice daily(1 mg/kg daily)orally for 5 days Then prednisolone 05 mg/kg daily orally for 3 days Then prednisolone 025 mg/kg daily orally for 3 days Then offLancet 10 May,2003 Give pulsed methylprednisolone if clinical condition,chest radiograph,or oxygen saturation worsens(at least two of thes
12、e),and lymphopenia persists Give as methylprednisolone 500 mg twice daily intravenously for 2 days,then back to standard corticosteroid regimenLancet 10 May,2003Consider non-invasive ventilation or mechanical ventilation if oxygen saturation 6 L per min oxygen or if patient complains of increasing s
13、hortness of breathLancet 10 May,2003 RibavirinGuanosine analogueinhibits replication of many RNA and DNA virusesRibavirin Ribavirin activitiesRSVInfluenza A and B,HSV-1 and HSV-2Parainfluenza Aerosol therapy:-not employedmay help spreading of virus RSV bronchiolitis and pneumonia in hospitalized chi
14、ldren:aerosol+/-IVIG Chronic hepatitis C:oral ribavirin+IFN Lassa fever+elevated AST or high-titer viremia:IV or oral ribavirin(within 6 days of illness)Viral hemoorhagic fever with renal syndrome Hantavirus pulmonary syndrome Post-exposure prophylaxis in contacts of Lassa fever and other viral hemo
15、rragic fever 3 hypotheses:decrease intracellular pools of guanosine triphosphate,suppress synthesis of viral nucleic acidsynthesis of RNA with abnormal 5 cap structures leads to inefficicent translation of viral transcriptsdirect suppressive effect on viral polymerase activities Contraindications:ch
16、ronic anemia and Hb 10g/dlCrCl 30ml/minhypersensitivity to the drug Precautions:predisposition goutrenal and hepatic impairment(dosage reduction)Contraindications:chronic anemia and Hb 10g/dlCrCl 2gm/dl：49%Hemolysis：76%Bradycardia：14%Sore throat：4%Aminotransferase：40%18%病人因副作用而停止用藥。Teratogenicity:co
17、ntraceptive cover 6 months after cessation females&males約在發病7天後（進入細胞激素風暴期），才開始使用。一種劑量使用五天後，才開始減少劑量。Methylprednisolone 效果比Decadron好。香港中文大學醫學院，40位SARS病患甲組：使用康復者血清 20位 無人死亡乙組：沒有使用康復者血清 20位 3人死亡香港中文大學沈祖堯醫師發病兩週內使用恢復期血清療法：住院及發燒時間縮短死亡率降低限制：需由康復者捐出需選擇合適血型有病毒血症之問題適應症：病情發展快，有生命危險之人有潛在疾病之老年人孕婦The significance
18、of neuramidase in SARS is this:There is NO KNOWN neuramidase in any known coronavirus.Neuramidase is found in influenza viruses.SARS appears possibly to be an influenza orthomyxovirus-coronavirus hybrid.Neuramidase cleaves sialic acid inside cells and mediates viral attachment to the respiratory epi
19、thelium of the host and consequent infection of susceptible cells.If this is,in fact,neuramidase,this would be the first known appearance of neuramidase in any coronavirus and would further suggest that SARS is an orthomyxovirus-coronavirus hybrid.Interestingly,the hemagglutinin-esterase in SARS sho
20、ws some relationship to a Type C Influenza as well-but SARS IS a coronavirus.a very weird coronavirus.but still a coronavirus.If SARS coronavirus is a naturally occurring coronavirus,efforts should be directed toward discovery of other orthymyxovirus-coronavirus hybrid-like viruses.There may be suff
21、icient evidence developed in time to reveal that SARS is not a true coronavirus nor a true orthomyxovirus and so become an entirely new species of virus all together.Oseltamivir phosphate(Tamiflu)Action:inhibition of influenza virus neuraminidase with possible alteration of virus particle aggregatio
22、n and release.廣東鍾南山醫師Tamiflu 75mg 每天一顆口服，給工作人員使用，可降低染病率，若染病，症狀亦較輕微。138 位病人 SARS 病人 Positive response:退燒超過四天X光片infiltration 減少25%不再需要氧氣lRibavirin and low dose steroid:31(18%)有陽性反應lHigh dose steroid therapy/pulse therapy:95為有陽性反應lTotal response rate:126(95%)死亡率：75:28.6%68%死亡病人有一個或一個長期疾病。死亡病例：發病到入院 7 日
23、存活病例：發病到入院 5 日Pamela Youde Nethersole Eastern Hospital,Hong Kong31位SARS病患，其中1位只用抗生素便痊癒，17位接受標準治療處方即有明顯改善，另外13位在增加類固醇劑量後也得到改善。有4位病人需要non-invasive ventilation，無人接受氣管插管。Lancet 2003:361:161517效用或優點副作用免疫球蛋白M協調及加強免疫系統發燒干擾素原至血癌，可殺病毒出現感冒病徵如發燒，或影響肝、腎病人Kaletra原用作抑制HIV病毒，他可抑制病毒中的蛋白酶，使病毒複製時難以完全成長。肚子，臉部脂肪會有轉移，導致容貌改變。Thalidomide治關節藥物，防止免疫系統反噬曾導致嬰兒沒有四肢15 May,200318 May,200320 May,2003非典科學研究的進展步伐是驚人的，短短幾個月，科學家不僅發現了非典病毒，測定了病毒的基因組序列，開發出防治非典用的猴子動物模型，而且開始尋早抑制劑等藥物，雖然具體時間誰也不敢打包票，但長遠來說，人們會找到非典藥物和疫苗。
