Biomedical subjects
Alan Wu
Publications and source records attributed to Alan Wu.
Clinical significance of hepatic derangement in severe acute respiratory syndrome.
AIM: Elevation of alanine aminotransferase (ALT) level is commonly seen among patients suffering from severe acute respiratory syndrome (SARS). We report the progression and clinical significance of liver derangement in a large cohort of SARS patient. METHODS: Serial assay of serum ALT was followed in patients who fulfilled the WHO criteria of SARS. Those with elevated ALT were compared with those with normal liver functions for clinical outcome. Serology for hepatitis B virus (HBV) infection was checked. Adverse outcomes were defined as oxygen desaturation, need of intensive care unit (ICU) and mechanical ventilation and death. RESULTS: Two hundred and ninety-four patients were included in this study. Seventy (24%) patients had elevated serum ALT on admission and 204 (69%) patients had elevated ALT during the subsequent course of illness. Using peak ALT >5XULN as a cut-off and after adjusting for potential confounding factors, the odds ratio of peak ALT >5X ULN for oxygen desaturation was 3.24 (95%CI 1.23-8.59, P = 0.018), ICU care was 3.70 (95%CI 1.38-9.89, P = 0.009), mechanical ventilation was 6.64 (95%CI 2.22-19.81, P = 0.001) and death was 7.34 (95%CI 2.28-24.89, P = 0.001). Ninety-three percent of the survived patients had ALT levels normalized or were on the improving trend during follow-up. Chronic hepatitis B was not associated with worse clinical outcomes. CONCLUSION: Reactive hepatitis is a common complication of SARS-coronavirus infection. Those patients with severe hepatitis had worse clinical outcome.
Severe acute respiratory syndrome: correlation between clinical outcome and radiologic features.
PURPOSE: To evaluate whether there is a correlation between the clinical outcomes and radiologic features of severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: The clinical, laboratory, and radiologic features of 138 patients with SARS were analyzed. Three radiologists in consensus retrospectively assessed the frontal chest radiographs obtained at presentation and during treatment (n = 2045) for the distribution (each lung was divided into upper, middle, and lower zones) and extent of lung parenchymal abnormality. Clinical end points included intensive care unit (ICU) admission and death. RESULTS: Thirty-six (26.1%) patients required ICU care, and eight (5.8%) died. The patients who required ICU care and/or died had more extensive consolidation on chest radiographs obtained initially (median percentage of consolidation, 3.30%, with interquartile range [IR] of 1.70%-8.78% vs 1.70% [IR, 0%-3.30%]; P < .001) and on day 7 after fever onset (median percentage of consolidation, 15.00% [IR, 6.48%-28.73%] vs 5.00% [IR, 2.50%-7.50%]; P < .001) than did surviving patients who did not require ICU care. Patients with involvement of more than one lung zone on initial and day 7 chest radiographs were more likely to require ICU care and/or die than were those with involvement of one or fewer zones (P < .001). Patients with bilateral pneumonic changes at presentation were more likely to have an adverse outcome than were those with unilateral pneumonia (P < .001). Involvement of more than one lung zone at baseline chest radiography was an independent predictor of ICU admission and/or death (odds ratio, 3.16; 95% confidence interval: 1.07, 9.32; P = .037) after adjustments for other significant factors (ie, patient age, and baseline neutrophil count and lactate dehydrogenase level). CONCLUSION: More extensive airspace disease at presentation is an independent predictor of adverse outcome in patients with SARS.
Seroprevalence of antibody to severe acute respiratory syndrome (SARS)-associated coronavirus among health care workers in SARS and non-SARS medical wards.
The seroprevalence of antibody to severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in cohorts of health care workers (HCWs) with subclinical infection in SARS and non-SARS medical wards was 2.3% (3 of 131 HCWs) and 0% (0 of 192 HCWs), respectively. Rates for clinical SARS-CoV infection among 742 HCWs on these wards were highest among nurses (11.6%) and health care assistants (11.8%), indicating that these occupations are associated with the highest risks for exposure.
The spectrum of severe acute respiratory syndrome-associated coronavirus infection.
BACKGROUND: Whether subclinical or atypical presentations of severe acute respiratory syndrome (SARS) occur and whether clinical judgment is accurate in detecting SARS are unknown. OBJECTIVES: To describe the spectrum of SARS coronavirus infection in a large outbreak and to compare diagnoses based on clinical judgment with the SARS coronavirus test. DESIGN: Secondary analysis of prospectively collected clinical data and archived serum. SETTING: A SARS screening clinic of a university hospital in the New Territories of Hong Kong. PATIENTS: 1221 patients attending the clinic between 12 March 2003 and 12 May 2003. MEASUREMENTS: SARS coronavirus serology. RESULTS: 145 of 553 (26%) patients had serologic evidence of SARS coronavirus infection. Of 910 patients who were managed without hospitalization, only 6 had serologic evidence of SARS. Five of the six patients had normal chest radiographs, and four had symptoms such as myalgia, chills, coughing, and feeling feverish. With the SARS coronavirus serologic test as the gold standard, the clinical diagnosis of probable SARS at hospitalization had a sensitivity of 0.96 (95% CI, 0.91 to 0.98) and a specificity of 0.96 (CI, 0.92 to 0.97). LIMITATIONS: Follow-up serologic samples were not obtained from almost half of the patients because they declined further testing. Some people living in the community who were infected but who had minor or no symptoms might not have visited the clinic. CONCLUSIONS: There is little evidence of widespread subclinical or mild forms of SARS coronavirus infection. Clinical diagnoses during the outbreak were reasonable and resulted in appropriate triaging.
Retrospective analysis of liver function derangement in severe acute respiratory syndrome.
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Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients.
BACKGROUND: The effect of corticosteroid treatment on the viral load of Severe Acute Respiratory Syndrome (SARS) patients is unknown. OBJECTIVE: To compare the plasma SARS-CoV RNA concentrations in ribavirin-treated patients who received early hydrocortisone therapy with those who received placebo. STUDY DESIGN: Serial plasma SARS-CoV RNA concentrations measured in the setting of a prospective, randomized double-blinded, placebo-controlled trial designed to assess the efficacy of "early" (<7 days of illness) hydrocortisone use in previously healthy SARS patients were analyzed. SARS-CoV RNA was quantified using a one-step real-time RT-PCR assay targeting the nucleocapsid gene. RESULTS: Among 16 non-ICU cases, SARS-CoV RNA was detected in plasma since day 3-4 after fever onset; viral concentration peaked in the first week, which then rapidly declined in the second week of illness. On days 8, 12, 16, and 20, the cumulative proportion of patients with undetectable virus in plasma was 31%, 69%, 92%, and 100%, respectively. Plasma SARS-CoV RNA concentrations in the second and third week of illness were significantly higher in patients who received initial hydrocortisone treatment (n = 9), as compared to those who received placebo (n = 7)(AUC; Mann-Whitney, P = 0.023). The median time for SARS-CoV to become undetectable in plasma was 12 days (11-20 days) versus 8 days (8-15 days), respectively. CONCLUSION: Our findings suggested "early" corticosteroid treatment was associated with a higher subsequent plasma viral load.
Immunofluorescence assay for serologic diagnosis of SARS.
We evaluated an indirect immunofluorescence assay based on virus-infected cells for detecting anti-severe acute respiratory syndrome-associated coronavirus (SARS-CoV) immunoglobulin (Ig) G antibody. All confirmed SARS cases demonstrated seroconversion or fourfold rise in IgG antibody titer; no control was positive. Sensitivity and specificity of this assay were both 100%. Immunofluorescence assay can ascertain the status of SARS-CoV infection.
Human metapneumovirus-associated atypical pneumonia and SARS.
Acute pneumonia developed in a previously healthy man during the outbreak of severe acute respiratory syndrome (SARS) in southern China in March 2003. Antibiotic treatment was ineffective, and he died 8 days after illness onset. Human metapneumovirus was isolated from lung tissue. No other pathogen was found. Other etiologic agents should thus be sought in apparent SARS cases when coronavirus infection cannot be confirmed.
Laboratory diagnosis of SARS.
The virologic test results of 415 patients with severe acute respiratory syndrome (SARS) were examined. The peak detection rate for SARS-associated coronavirus occurred at week 2 after illness onset for respiratory specimens, at weeks 2 to 3 for stool or rectal swab specimens, and at week 4 for urine specimens. The latest stool sample that was positive by reverse transcription-polymerase chain reaction (RT-PCR) was collected on day 75 while the patient was receiving intensive care. Tracheal aspirate and stool samples had a higher diagnostic yield (RT-PCR average positive rate for first 2 weeks: 66.7% and 56.5%, respectively). Pooled throat and nasal swabs, rectal swab, nasal swab, throat swab, and nasopharyngeal aspirate specimens provided a moderate yield (29.7%-40.0%), whereas throat washing and urine specimens showed a lower yield (17.3% and 4.5%). The collection procedures for stool and pooled nasal and throat swab specimens were the least likely to transmit infection, and the combination gave the highest yield for coronavirus detection by RT-PCR. Positive virologic test results in patient groups were associated with mechanical ventilation or death (p < 0.001), suggesting a correlation between viral load and disease severity.
Diagnostic criteria during SARS outbreak in Hong Kong.
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Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis.
OBJECTIVES: To evaluate the haematological findings of patients with severe acute respiratory syndrome (SARS). DESIGN: Analysis of the demographic, clinical, and laboratory characteristics of patients with SARS. SETTING: Prince of Wales Hospital, Hong Kong. Subjects All patients with a diagnosis of SARS between 11 March and 29 March 2003 who had no pre-existing haematological disorders. MAIN OUTCOME MEASURES: Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed to examine factors associated with adverse outcome. RESULTS: 64 male and 93 female patients were included in this study. The most common findings included lymphopenia in 153 (98%) of the 157 patients, neutrophilia in 129 (82%), thrombocytopenia in 87 patients (55%), followed by thrombocytosis in 77 (49%), and isolated prolonged activated partial thromboplastin time in 96 patients (63%). The haemoglobin count dropped by more than 20 g/l from baseline in 95 (61%) patients. Four patients (2.5%) developed disseminated intravascular coagulation. Lymphopenia was shown in haemato-lymphoid organs at postmortem examination. Multivariate analysis showed that advanced age and a high concentration of lactate dehydrogenase at presentation were independent predictors of an adverse outcome. Subsets of peripheral blood lymphocytes were analysed in 31 patients. The counts of CD4 positive and CD8 positive T cells fell early in the course of illness. Low counts of CD4 and CD8 cells at presentation were associated with adverse outcomes. CONCLUSIONS: Abnormal haematological variables were common among patients with SARS. Lymphopenia and the depletion of T lymphocyte subsets may be associated with disease activity.
Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience.
PURPOSE: To report the initial experience regarding thin-section computed tomographic (CT) findings in patients with severe acute respiratory syndrome (SARS) who improved clinically after treatment. MATERIALS AND METHODS: Twenty-four patients (10 men, 14 women; mean age, 39 years; age range, 23-70 years) with confirmed SARS underwent follow-up thin-section CT of the thorax. The scans were obtained on average 36.5 days after hospital admission and were analyzed for parenchymal abnormality (ground-glass opacification, consolidation, or interstitial thickening) and evidence of fibrosis (parenchymal band, traction bronchiectasis, irregular interfaces). Patients were assigned to group 1 (with CT evidence of fibrosis) and group 2 (without CT evidence of fibrosis) for analysis. Patient demographics, length of hospital stay, rate of intensive care unit admission, peak lactate dehydrogenase level, pulsed intravenous methylprednisolone therapy, and peak opacification on chest radiographs were compared between the two groups. RESULTS: Parenchymal abnormality was found in 96% (23 of 24) of patients and ranged from residual ground-glass opacification and interstitial thickening in group 2 (nine of 24, 38%) to fibrosis in group 1 (15 of 24, 62%). Patients in group 1 were older (mean age, 45 vs 30.3 years), had a higher rate of intensive care unit admission (27% [four of 15] vs 11% [one of nine]), more requirement for pulsed intravenous methylprednisolone (87%, [13 of 15] vs 67% [six of nine]), higher peak lactate dehydrogenase level (438.9 vs 355.6 U/L), and higher peak opacification on chest radiographs (estimated area, 14% vs 11%) than patients in group 2. CONCLUSION: Pulmonary fibrosis may develop early in patients with SARS who have been discharged after treatment. Patients who are older and have more severe disease during treatment are more likely to develop thin-section CT findings of fibrosis.
Severe acute respiratory syndrome: radiographic appearances and pattern of progression in 138 patients.
PURPOSE: To retrospectively evaluate the radiographic appearances and pattern of progression of severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: Chest radiographs obtained at clinical presentation and during treatment in 138 patients with confirmed SARS (66 men, 72 women; mean age, 39 years; age range, 20-83 years) were assessed. Radiographic appearances of pulmonary parenchymal abnormality, distribution, and extent of involvement on initial chest radiographs were documented. Recognizable patterns of radiographic progression were determined by comparing the overall mean percentage of lung involvement for each patient on serial radiographs. RESULTS: Initial chest radiographs were abnormal in 108 of 138 (78.3%) patients and showed air-space opacity. Lower lung zone (70 of 108, 64.8%) and right lung (82 of 108, 75.9%) were more commonly involved. In most patients, peripheral lung involvement was more common (81 of 108, 75.0%). Unifocal involvement (59 of 108, 54.6%) was more common than multifocal or bilateral involvement. No cavitation, lymphadenopathy, or pleural effusion was demonstrated. Four patterns of radiographic progression were recognized: type 1 (initial radiographic deterioration to peak level followed by radiographic improvement) in 97 of 138 patients (70.3%), type 2 (fluctuating radiographic changes) in 24 patients (17.4%), type 3 (static radiographic appearance) in 10 patients (7.3%), and type 4 (progressive radiographic deterioration) in seven patients (5.1%). Initial focal air-space opacity in 44 of 59 patients (74.6%) progressed to unilateral multifocal or bilateral involvement during treatment. CONCLUSION: Predominant peripheral location; common progression pattern from unilateral focal air-space opacity to unilateral multifocal or bilateral involvement during treatment; and lack of cavitation, lymphadenopathy, and pleural effusion are the more distinctive radiographic findings of SARS.
Thin-section CT of severe acute respiratory syndrome: evaluation of 73 patients exposed to or with the disease.
PURPOSE: To retrospectively analyze the thin-section computed tomographic (CT) features in patients with severe acute respiratory syndrome (SARS) at the authors' institution. MATERIALS AND METHODS: From March 11, 2003, to April 2, 2003, 74 patients with symptoms and signs suggestive of SARS underwent CT of the thorax; all underwent thin-section CT except for one patient who underwent conventional CT. Group 1 (n = 23) patients had symptoms of SARS in keeping with criteria from the Centers for Disease Control and Prevention and a positive chest radiograph. Group 2 (n = 17) patients had a high clinical suspicion of SARS but a normal radiograph. Group 3 (n = 34) patients had minor symptoms and a normal chest radiograph. The thin-section CT images were analyzed for ground-glass opacification or consolidation, lesion size in each lung segment, peripheral or central location, interstitial thickening, and other abnormalities. RESULTS: Thin-section CT scans were abnormal only for patients in groups 1 and 2. The patient with only conventional CT scans was in group 3; scans for group 3 patients were normal. Affected segments were predominantly in the lower lobes (91 of 149 affected segments). Common findings included ground-glass opacification, sometimes with consolidation, and interlobular septal and intralobular interstitial thickening. The size of each lesion and the total number of segments involved were smaller in group 2 patients. A majority of patients in group 1 (14 of 23) had mixed central and peripheral lesions. In group 2, however, peripheral lesions were more common (10 of 17). In both groups, a purely central lesion was uncommon (one of 23 in group 1 and two of 17 in group 2). CONCLUSION: Common thin-section CT features of SARS are ground-glass opacification and lower lobe and peripheral distribution.
A major outbreak of severe acute respiratory syndrome in Hong Kong.
BACKGROUND: There has been an outbreak of the severe acute respiratory syndrome (SARS) worldwide. We report the clinical, laboratory, and radiologic features of 138 cases of suspected SARS during a hospital outbreak in Hong Kong. METHODS: From March 11 to 25, 2003, all patients with suspected SARS after exposure to an index patient or ward were admitted to the isolation wards of the Prince of Wales Hospital. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed. RESULTS: There were 66 male patients and 72 female patients in this cohort, 69 of whom were health care workers. The most common symptoms included fever (in 100 percent of the patients); chills, rigors, or both (73.2 percent); and myalgia (60.9 percent). Cough and headache were also reported in more than 50 percent of the patients. Other common findings were lymphopenia (in 69.6 percent), thrombocytopenia (44.8 percent), and elevated lactate dehydrogenase and creatine kinase levels (71.0 percent and 32.1 percent, respectively). Peripheral air-space consolidation was commonly observed on thoracic computed tomographic scanning. A total of 32 patients (23.2 percent) were admitted to the intensive care unit; 5 patients died, all of whom had coexisting conditions. In a multivariate analysis, the independent predictors of an adverse outcome were advanced age (odds ratio per decade of life, 1.80; 95 percent confidence interval, 1.16 to 2.81; P=0.009), a high peak lactate dehydrogenase level (odds ratio per 100 U per liter, 2.09; 95 percent confidence interval, 1.28 to 3.42; P=0.003), and an absolute neutrophil count that exceeded the upper limit of the normal range on presentation (odds ratio, 1.60; 95 percent confidence interval, 1.03 to 2.50; P=0.04). CONCLUSIONS: SARS is a serious respiratory illness that led to significant morbidity and mortality in our cohort.
Quantitative analysis and prognostic implication of SARS coronavirus RNA in the plasma and serum of patients with severe acute respiratory syndrome.
BACKGROUND: The availability of an early diagnostic tool for severe acute respiratory syndrome (SARS) would have major public health implications. We investigated whether the SARS coronavirus (SARS-CoV) can be detected in serum and plasma samples during the early stages of SARS and studied the potential prognostic implications of such an approach. METHODS: We developed two real-time quantitative reverse transcription-PCR (RT-PCR) assays, one for the polymerase and the other for the nucleocapsid region of the virus genome, for measuring the concentration of SARS-CoV RNA in serum/plasma samples from SARS patients. Plasma samples were obtained from 12 confirmed SARS patients on the day of hospital admission, as well as on days 7 and 14 after fever onset. Serum samples were also obtained from 23 confirmed SARS patients on the day of hospital admission, 11 of whom subsequently required intensive care. Viral RNA was extracted from the plasma/serum samples. The extracted RNA was subjected to analysis by the RT-PCR assays. RESULTS: The RT-PCR system for the polymerase region detected SARS-CoV RNA in 50% of plasma and 78% of serum samples from SARS patients during the first week of illness. The detection rates for plasma dropped to 25% at day 14 after fever onset. The median serum SARS-CoV concentrations in patients who required and did not require intensive care unit admission during the course of hospitalization were 5800 and 140 copies/mL, respectively (Mann-Whitney test, P <0.005). These data were confirmed by the RT-PCR system for the nucleocapsid region, which showed an even higher detection rate of 87%. The correlation between the results obtained by the two RT-PCR systems was high (Pearson correlation analysis, r = 0.998; P <0.001). CONCLUSION: Plasma/serum SARS-CoV quantification represents a potentially useful early diagnostic and prognostic tool for SARS.
Imaging of severe acute respiratory syndrome in Hong Kong.
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