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Biomedical subjects

C M Chu

Publications and source records attributed to C M Chu.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of clinical staging systems in predicting survival of hepatocellular carcinoma patients receiving major or minor hepatectomy.

AIM: To compare the utility of seven commonly used staging systems in the prediction of survival among patients with hepatocellular carcinoma (HCC) undergoing major or minor hepatectomy. METHODS: All patients were classified by the Okuda, the TNM, the CLIP, the BCLC, the CUPI, the JIS and the MELD classifications to estimate the probabilities of survival. Survival curves were calculated using the Kaplan-Meier method and were examined using log-rank testing. The overall predictive power for patient survival with each staging system was evaluated using linear trend chi(2) tests and from the area under the receiver operating characteristic (ROC) curve. RESULTS: In our patient cohort, the log-rank test and the linear trend chi(2) test of the CLIP and JIS systems gave better results than did the other staging systems. The discriminatory ability of the CLIP and JIS staging for death, evaluated by ROC curve areas, was also better. In the subgroups of major hepatectomy patients with a non-cirrhotic liver or minor hepatectomy patients with a cirrhotic liver, the CLIP and JIS systems showed similar better performances in these three tests. The discriminatory ability of the CLIP system was the best in major hepatectomy patients with a non-cirrhotic liver while JIS score discriminated best in minor hepatectomy patients with a cirrhotic liver. CONCLUSION: Among the seven staging systems, the CLIP and JIS systems perform better than do the others. While the CLIP system should be considered to stage major hepatectomy patients, the JIS system could be chosen to stage minor hepatectomy patients.

Carcinoma, Hepatocellular↗
PubMed2006

Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) frequently suffer from infections, but the predisposing risk factors, as well as the exact frequency and nature of such infections, are not fully understood. AIM: To describe the frequency, types and risk factors for infections in a group of Chinese patients in the early stage of SLE in Hong Kong. DESIGN: Retrospective record study. METHODS: We reviewed the case records of 91 Chinese SLE patients, presenting <12 months after SLE diagnosis. Details of major infections (requiring intravenous antimicrobial therapy, or any confirmed mycobacterial infection) and minor infections were reviewed. Clinical and laboratory features, the systemic lupus erythematosus disease activity index (SLEDAI) at presentation and drug treatment were recorded and analysed. RESULTS: There were 48 major infections and 62 minor infections during 260 patient-years of follow-up. A lymphocyte count < or =1.0 x 10(9)/l at presentation was independently associated with an increased risk for major infection: hazard ratio 4.7 (95%CI 1.6-13.7), p = 0.005. SLEDAI, use of corticosteroids and immunosuppressive therapy were all not associated with increased risk of infection. DISCUSSION: Lymphopenia was an important risk factor for major infections in this group of Chinese patients in the early stages of SLE. SLE patients with lymphopenia at presentation should be closely monitored for the development of infective complications.

Adolescent↗
PubMed2006

The general picture of supportive health environments for persons with intellectual disabilities among 121 disability welfare institutions in Taiwan.

BACKGROUND: Little information is available on the provision of supportive health environments for persons with intellectual disabilities (ID) in institutions. The aim of this study was to present an overview of supportive environments for health in institutions in Taiwan. METHODS: A cross-sectional survey was conducted to examine the perceptions of 121 Taiwanese Institutional Directors on their setting's implementation of supportive healthy physical, social, and economic environments. RESULTS: Analyses showed that first-aid kits (97.5%) and medicine cabinets (85.5%) were the most common health facilities in institutions. Seventy-three per cent of institutions had set up specific areas to be used for rehabilitation practice, while only 43.1% thought their rehabilitation equipment/devices adequate for their real needs. Eighty-eight per cent of institutions implemented health promotion plans for people with ID, while 76.6% had appropriated specific health promotion plans. Sixty-three institutions (52.1%) reported employment of skilled nurses to serve people with ID, and these institutions showed statistically significant differences in implementation of each health facility. CONCLUSIONS: The present paper is the first to analyze supportive environments for health in disability institutions in Taiwan. An important focus of future research will be the extension of the present findings to consider the appropriateness of each area of supportive environments for improving the quality of institutional care for people with ID.

Attitude of Health Personnel↗
PubMed2005

Increased incidence of fulminant hepatic failure in previously unrecognized HBsAg carriers with acute hepatitis independent of etiology.

BACKGROUND: Previous studies have shown a high risk of fulminant hepatitis in HBsAg carriers with acute hepatitis. The etiology of acute hepatitis in HBsAg carriers was heterogeneous. This study aimed to correlate the incidence of fulminant hepatitis with the etiology in HBsAg carriers with acute hepatitis. PATIENTS AND METHODS: The incidence of fulminant hepatitis was studied in 334 adults hospitalized for overt acute viral hepatitis. There were 12 patients with acute hepatitis A, 17 with acute hepatitis B, 70 with acute hepatitis C, five with acute hepatitis E, 53 with acute hepatitis non-A-E, and 177 previously unrecognized HBsAg carriers with acute hepatitis (patients who were positive for HBsAg but negative for IgM antibody against hepatitis B core antigen). Of the latter, 64 (36%) had serological evidence of non-B hepatotropic virus superinfection. RESULTS: The incidence of fulminant hepatitis was 3.2% (5/157) in patients with acute hepatitis A, B, C, E or non-A-E, and 20.3% (36/177) in HBsAg carriers with acute hepatitis (p < 0.001). HBsAg carriers were at a 9-fold increased risk of fulminant hepatitis than noncarriers. Among HBsAg carriers with acute hepatitis, the incidence of fulminant hepatitis showed no significant difference between patients with viral superinfection (23% or 15/64) and those without (19% or 21/113). The incidence of fulminant hepatitis in HBsAg carriers with viral superinfection also showed no significant difference between different etiologies of virus superinfection. CONCLUSION: There is a 9-fold increased risk of fulminant hepatitis in HBsAg carriers with acute hepatitis, independent of the underlying etiology.

Adolescent↗
PubMed2005

Duration of RT-PCR positivity in severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a highly infectious respiratory infection with a high mortality. The duration of infectivity is unknown. The RT-PCR positivity for SARS-associated coronavirus (SARS-CoV) was followed in 45 virologically confirmed SARS patients. Serial RT-PCRs for SARS-CoV were performed in the nasopharyngeal aspirate, stool and urine of 45 SARS patients who survived until discharge. All patients had at least one site that was positive for SARS-CoV on presentation. Time to RT-PCR conversion was studied in all patients. There were 15 males (33.3%) and 30 females (66.7%), with a mean+/- SD age of 40.7+/-14.7 yrs. The median (range) time of RT-PCR conversion was 30 days (2-81). On discharge from the hospital, 18 (40%) remained RT-PCR positive in at least one site. For patients with positive RT-PCR on discharge, the median (range) time to RT-PCR conversion after discharge was 13 days (2-60). A significant proportion of severe acute respiratory syndrome patients remained RT-PCR positive for severe acute respiratory syndrome-associated coronavirus for a substantial duration after discharge. The clinical significance is unknown and this finding merits further study. It is prudent to advise patients to adhere to strict personal hygiene on discharge until RT-PCR becomes negative.

Adolescent↗
PubMed2004

Viral replication in the nasopharynx is associated with diarrhea in patients with severe acute respiratory syndrome.

The role of severe acute respiratory syndrome (SARS) coronavirus as an enteric pathogen was investigated in a cohort of 142 patients with SARS who were treated with a standard treatment protocol. Data from daily hematological, biochemical, radiological, and microbiological investigations were prospectively collected, and the correlation of these findings with diarrhea was retrospectively analyzed. Sixty-nine patients (48.6%) developed diarrhea at a mean (+/- standard deviation [SD]) of 7.6+/-2.6 days after the onset of symptoms. The diarrhea was most severe at a mean (+/-SD) of 8.8+/-2.4 days after onset, with a maximum frequency of 24 episodes per day (median, 5 episodes; range, 3-24 episodes). A higher mean virus load in nasopharyngeal specimens obtained on day 10 after the onset of symptoms was significantly associated with the occurrence of diarrhea (3.1 log10 vs. 1.8 log10 copies/mL; P=.01) and mortality (6.2 vs. 1.7 log10 copies/mL; P<.01). However, diarrhea was not associated with mortality. The lung and the gastrointestinal tract may react differently to SARS coronavirus infection. Additional investigation of the role of SARS coronavirus in the pathogenesis of diarrhea in patients with SARS should be conducted.

Adult↗
PubMed2004

Sequential changes of hepatitis C virus antibody profiles during treatment of chronic hepatitis C of genotype 1b: pretreatment antibody response to E2/NS1 correlated sustained response.

BACKGROUND: This study aimed to investigate the relation between hepatitis C virus (HCV) antibody profiles and response to therapy of chronic HCV infection of genotype 1b. MATERIALS AND METHODS: Quantitative assays of antibody response to HCV antigens were performed sequentially using immunoblot confirmatory assays in 25 patients with genotype 1b chronic hepatitis C who received a 24-week course of interferon and ribavirin therapy. RESULTS: 12 patients had a sustained response (group A), and 13 did not (group B). Serum titers of HCV RNA were significantly higher in group B than in group A (p = 0.02). Pretreatment antibody reactivity to core, NS3, NS4, and NS5 antigens did not differ significantly between the two groups, but group A had significantly higher titers of anti-E2/NS1 than group B (p = 0.04). Sustained response was noted in none of seven patients with HCV RNA > 10(6) copies/ml, but did occur in 12 of 18 patients with HCV RNA < 10(6) copies/ml (p < 0.01). Among the latter, all seven patients with anti- E2/NS1 had sustained responses, as did five (45%) of 11 without (p = 0.04). Antibody profiles changed little or not at all at the end of treatment or at 6 months after treatment in both groups. CONCLUSION: In chronic hepatitis C of genotype 1b, patients with HCV RNA > 10(6) copies/ml respond poorly to therapy compared to those with HCV RNA < 10(6) copies/ml. Among the latter, the presence of pretreatment anti-E2/NS1 correlated with sustained response. Quantitative assay of antibody response to HCV antigens at the end of treatment had no additional value to predict a sustained response.

Adult↗
PubMed2004

Medical treatment of viral pneumonia including SARS in immunocompetent adult.

Since no randomized controlled trials have been conducted on the treatment of viral pneumonia by antivirals or immunomodulators in immunocompetent adults, a review of such anecdotal experience are needed for the more rational use of such agents. Case reports (single or case series) with details on their treatment and outcome in the English literature can be reviewed for pneumonia caused by human or avian influenza A virus (50 patients), varicella zoster virus (120), adenovirus (29), hantavirus (100) and SARS coronavirus (SARS-CoV) (841). Even with steroid therapy alone, the mortality rate appeared to be lower when compared with conservative treatment for pneumonia caused by human influenza virus (12.5% vs. 42.1%) and hantavirus (13.3% vs. 63.4%). Combination of an effective antiviral, acyclovir, with steroid in the treatment of varicella zoster virus may be associated with a lower mortality than acyclovir alone (0% vs. 10.3%). Combination of interferon alfacon-1 plus steroid, or lopinavir/ritonavir, ribavirin plus steroid were associated with a better outcome than ribavirin plus steroid (0% vs. 2.3% vs. 7.7%, respectively). Combination of lopinavir/ritonavir plus ribavirin significantly reduced the virus load of SARS-CoV in nasopharyngeal, serum, stool and urine specimens taken between day 10 and 15 after symptom onset when compared with the historical control group treated with ribavirin. It appears that the combination of an effective antiviral and steroid was associated with a better outcome. Randomized therapeutic trial should be conducted to ascertain the relative usefulness of antiviral alone or in combination with steroid.

Adolescent↗
PubMed2004

Low-level hepatitis C viremia and humoral immune response to NS4 in chronic hepatitis B virus-hepatitis C virus coinfection.

BACKGROUND: There is a limited amount of published data on the interference of hepatitis B virus (HBV) on hepatitis C virus (HCV). The aim of this study was to investigate the effect of concurrent HBV infection on serum titers of HCV RNA and HCV antibody profiles in chronic HCV infection. METHODS: The clinical and virological profiles (serum titers of HCV RNA, HCV genotypes and antibody profiles) of 25 patients with chronic HBV-HCV coinfection were compared with those of 25 age- and sex-matched patients with HCV infection alone. RESULTS: Among the 25 patients with HBV-HCV coinfection, only 3 were found hepatitis Be antigen (HBeAg) and HBV DNA positive by hybridization assays, and the other 11 were found HBV DNA positive by polymerase chain reaction. Genotype 1b was dominant in both HBV-HCV coinfection and HCV infection alone (64% versus 84%, P > 0.1). Patients with HBV-HCV coinfection had significantly lower alanine aminotransferase (ALAT) levels and inflammatory scores but higher fibrosis scores than those with HCV infection alone. Serum titers of HCV RNA were significantly lower in HBV-HCV coinfection than in HCV infection alone. The frequency and relative intensity of antibody response to core, E2/NS1, NS3, and NS5 showed no significant difference between the two groups, but antibody response to NS4 was diminished significantly in HBV-HCV coinfection. CONCLUSIONS: In HBV-HCV coinfection, serum levels of HBV DNA are usually low or undetectable. Concurrent HBV infection, however, could interfere with HCV replication and suppress antibody response to NS4. The biological significance of selective inhibition of humoral immune response to NS4 in HBV-HCV coinfection should be further studied.

DNA, Viral↗
PubMed2004

Serum LD1 isoenzyme and blood lymphocyte subsets as prognostic indicators for severe acute respiratory syndrome.

BACKGROUND: The pathophysiology of severe acute respiratory syndrome (SARS) is at present poorly understood, but advanced age and serum total lactate dehydrogenase (LD) activity >300 U L(-1) have been associated with adverse clinical outcomes. Blood leucocytes and lymphocyte subsets were reported to decrease, respectively, in 47% and up to 100% of 38 patients in Beijing. However, their prognostic implications have not been thoroughly investigated. OBJECTIVE: To investigate serum total LD, LD isoenzymes, and other parameters including blood lymphocyte subsets as prognostic indicators in SARS patients for adverse clinical outcomes in terms of admission to intensive care unit (ICU) and death. DESIGN: Retrospective analysis. SUBJECTS AND METHODS: A total of 109 patients with a clinical diagnosis of SARS according to the modified World Health Organization case definition of SARS were recruited from two major acute hospitals in Hong Kong. They were either involved in the initial outbreak of SARS, or cases from the community outbreak of Amoy Gardens between 10 March and 5 May 2003. The clinical diagnosis was subsequently confirmed by serological test and/or molecular analysis. Serum total LD and LD isoenzyme activities, complete blood picture with total leucocyte count and differential counts, absolute counts of CD3+, CD4+, CD8+, natural killer cells and B lymphocytes were measured daily upon admission. Receiver operating characteristic curve analysis was used to determine and compare different cut-offs for various biochemical and immunological parameters at peak serum total LD concentration in predicting adverse clinical outcomes. RESULTS: Of a total of 109 patients, 41 were admitted to ICU and 42 died. Of 42 fatal patients, 24 died in ICU and 18 died in general medical wards. Age was found to be an independent prognostic indicator for death with an area under curve (AUC) of 0.96 [95% confidence interval (CI) = 0.90-0.99] but not for admission to ICU [AUC = 0.61 (CI = 0.51-0.70)]. Whilst serum total LD could only achieve AUC of 0.68 (CI = 0.59-0.77) for predicting death, LD1 isoenzyme was found to be the best biochemical prognostic indicator with AUC of 0.84 (CI = 0.75-0.90), sensitivity of 62% (CI = 46-76%), specificity of 93% (CI = 83-98%) at cut-off activity of > or =80 U L(-1). CD3+, CD4+, CD8+ and natural killer cell counts were promising immunological prognostic indicators for predicting admission to ICU with AUC of 0.94 (CI = 0.86-0.98), 0.91 (CI = 0.81-0.96), 0.93 (CI = 0.85-0.98), and 0.87 (CI = 0.76-0.94), respectively. CONCLUSIONS: Apart from age, serum LD1 activity was the best prognostic indicator for predicting death in patients with SARS compared with serum total LD activity, haemoglobin concentration, leucocyte and lymphocyte counts. Its release could possibly be from blood erythrocytes and body tissues other than the myocardium. Blood CD3+, CD4+, CD8+ and natural killer cell counts were found to be good prognostic indicators for predicting admission to ICU in patients with SARS compared with age, leucocyte count and LD isoenzymes. The suppressed CD3+, CD4+, CD8+, and natural killer cell counts were also implicated in the pathophysiology of SARS. Patients with increased serum LD1 should be closely monitored to ensure prompt management, and preparation for admission to ICU could be planned ahead for patients with suppressed lymphocyte subsets.

Adult↗
PubMed2004

Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings.

BACKGROUND: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. METHODS: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. RESULTS: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 micro g/ml and 50 micro g/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls-both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)-but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. CONCLUSIONS: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.

Adult↗
PubMed2004

Readmission rates and life threatening events in COPD survivors treated with non-invasive ventilation for acute hypercapnic respiratory failure.

BACKGROUND: Non-invasive ventilation (NIV) has been shown to reduce intubation and in-hospital mortality in patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure (AHRF). However, little information exists on the outcomes following discharge. A study was undertaken to examine the rates of readmission, recurrent AHRF, and death following discharge and the risk factors associated with them. METHODS: A cohort of COPD patients with AHRF who survived after treatment with NIV in a respiratory high dependency unit was prospectively followed from July 2001 to October 2002. The times to readmission, first recurrent AHRF, and death were recorded and analysed against potential risk factors collected during the index admission. RESULTS: One hundred and ten patients (87 men) of mean (SD) age 73.2 (7.6) years survived AHRF after NIV during the study period. One year after discharge 79.9% had been readmitted, 63.3% had another life threatening event, and 49.1% had died. Survivors spent a median of 12% of the subsequent year in hospital. The number of days in hospital in the previous year (p = 0.016) and a low Katz score (p = 0.018) predicted early readmission; home oxygen use (p = 0.002), APACHE II score (p = 0.006), and a lower body mass index (p = 0.041) predicted early recurrent AHRF or death; the MRC dyspnoea score (p<0.001) predicted early death. CONCLUSIONS: COPD patients with AHRF who survive following treatment with NIV have a high risk of readmission and life threatening events. Further studies are urgently needed to devise strategies to reduce readmission and life threatening events in this group of patients.

Acute Disease↗
PubMed2004

Home mechanical ventilation in Hong Kong.

Home mechanical ventilation (HMV) is increasingly used to treat chronic respiratory failure. This present study was aimed to examine the trend, the disease categories treated and the outcomes of HMV use in Hong Kong. In the year 2002, all adult respiratory units in Hong Kong were invited to report to a multicentre retrospective survey of HMV use. A total of 249 patients (156 males, mean age 62.7 +/- 13.8 yrs) were treated since 1980, with 197 (79%) continuing with HMV at the time of the survey. Cumulative number of HMV grew as a cubic function of time since 1980. Currently, there are 2.9 users per 100,000 population. The predominant mode of HMV was noninvasive ventilation by bilevel pressure support ventilators (n=236). Chronic obstructive pulmonary disease accounted for 48.6% of all cases. The overall 3-yr HMV continuation rate was 66.2%. Death was the main reason for discontinuation. A rapidly rising trend of home mechanical ventilation use is observed in Hong Kong. In contrast to other series, chronic obstructive pulmonary disease was the major group treated and bilevel pressure support ventilation was the predominant mode chosen. Most patients tolerate home mechanical ventilation reasonably well, with approximately two-thirds continuing with its use at 36 months.

Female↗
PubMed2004

Spontaneous pneumomediastinum in patients with severe acute respiratory syndrome.

Spontaneous pneumomediastinum (SP) unrelated to assisted ventilation is a newly recognised complication of severe acute respiratory syndrome (SARS). The objective of the present study was to examine the incidence, risk factors and the outcomes of SP in a cohort of SARS victims from a community outbreak. Data were retrieved from a prospectively collected database of virologically confirmed SARS patients. One hundred and twelve cases were analysable, with 13 patients developing SP (11.6%) at a mean +/- SD of 19.6 +/- 4.6 days from symptom onset. Peak lactate dehydrogenase level was associated with the development of SP. SP was associated with increased intubation and a trend towards death. Drainage was required in five cases. For patients who survived, the SP and/or the associated pneumothoraces took a median of 28 days (interquartile range: 15-45 days) to resolve completely. In conclusion, spontaneous pneumomediastinum appeared to be a frequent complication of severe acute respiratory syndrome. Further research is needed to investigate its pathogenesis.

Adult↗
PubMed2004

Viral loads in clinical specimens and SARS manifestations.

A retrospective viral load study was performed on clinical specimens from 154 patients with laboratory-confirmed severe acute respiratory syndrome (SARS); the specimens were prospectively collected during patients' illness. Viral load in nasopharyngeal aspirates (n = 142) from day 10 to day 15 after onset of symptoms was associated with oxygen desaturation, mechanical ventilation, diarrhea, hepatic dysfunction, and death. Serum viral load (n = 53) was associated with oxygen desaturation, mechanical ventilation, and death. Stool viral load (n = 94) was associated with diarrhea, and urine viral load (n = 111) was associated with abnormal urinalysis results. Viral replications at different sites are important in the pathogenesis of clinical and laboratory abnormalities of SARS.

Adult↗
PubMed2003

Genomic characterisation of the severe acute respiratory syndrome coronavirus of Amoy Gardens outbreak in Hong Kong.

Severe acute respiratory syndrome (SARS) is a global health concern. In Hong Kong, two major outbreaks, one hospital based and the other in the Amoy Gardens apartments, were identified. The frequency of diarrhoea, admission to intensive care, and mortality differed significantly between the two outbreaks. We did genomic sequencing for viral isolates from five Amoy Gardens patients. The virus sequence was identical in four of these five patients. The sequence data from one hospital case and the four identical community cases had only three nucleotide differences. Alterations in the SARS coronavirus genome are unlikely to have caused the distinctive clinical features of the Amoy Gardens patients, and these results highlight the importance of non-viral genomic factors in this outbreak.

Base Sequence↗
PubMed2003

Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study.

BACKGROUND: We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS). METHODS: We followed up 75 patients for 3 weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods. FINDINGS: Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days. INTERPRETATION: The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage.

Administration, Oral↗