key: cord-303027-r2jgu2be
authors: Lu, Yen-Ta; Chen, Pei-Jan; Sheu, Chin-Yin; Liu, Ching-Lung
title: Viral load and outcome in SARS infection: The role of personal protective equipment in the emergency department
date: 2006-01-24
journal: J Emerg Med
DOI: 10.1016/j.jemermed.2005.03.011
sha: 
doc_id: 303027
cord_uid: r2jgu2be

This study was conducted to evaluate the effectiveness of personal protective equipment (PPE) against severe acute respiratory syndrome (SARS). Sixteen patients in a SARS cluster, including 4 health care workers (HCWs) and 12 non-HCWs were studied. We compared the initial viral load by nasopharyngeal swabs, clinical progression, and outcome of this cluster. The HCWs had a lower viral load. The non-HCWs had a higher mean C-reactive protein, lower oxygen saturation, and a higher incidence of intubation and death. Secondary household transmission developed in three of the non-HCWs’ families. One month after discharge, non-HCWs had more signs of fibrosis on high resolution computed tomography (HRCT) scan and an impaired pulmonary function test. Although most of the PPE do not confer absolute protection against SARS, it seems that they may lower exposure to the virus, leading to a lower risk of secondary transmission, and be associated with relatively mild disease and a better early outcome.

On March 12, 2003 , the World Health Organization (WHO) issued a worldwide alert for cases of atypical pneumonia with severe respiratory illness that was rap-idly spreading among hospital staffs (1) . The transmission route of the emerging disease was believed to be by inhalation of contaminated aerosols or by oral route through contact with a contaminated environment (2, 3) . Both specific droplet and rigorous universal precautions were thus recommended for healthcare workers (HCWs) taking care of patients with severe acute respiratory syndrome (SARS) (4) . Early in the SARS epidemic, investigators reported that surgical masks were equivalent to N-95 masks in protecting against SARS, but it was later shown that even N-95 masks were not completely protective (3, 5, 6) . This confusion, plus the fact that many HCWs became infected despite wearing masks, contributed to the tremendous fear and chaos in some areas affected by SARS (7, 8) .

From 1 November 2002 to 31 July 2003, a total of 8098 patients were probably infected with SARS, of whom 21% were HCWs (9) . Nosocomial spread was one of the major striking features of SARS outbreaks (10 -12) . Most infected HCWs were young, previously healthy, and immunocompetent. Many had a relatively mild SARS infection, and seemed to be at a lower risk for death (13, 14) . In addition, in Hong-Kong and Singapore, secondary household transmission was less likely to occur in HCWs' families compared with non-HCWs (15, 16) .

The outcome of SARS has been adversely associated with factors such as old age, increased levels of C-reactive protein (CRP) and even hepatitis B carrier (2, 17) . It has also been reported that higher viral loads in nasopharyngeal aspirates (NPS) is a useful prognostic indicator of respiratory failure and mortality (18) . Given that the NPS procedure has not been well standardized, it is quite possible that inconsistency in performing sampling may render inaccurate the comparison between different individuals' results of real-time polymerase chain reaction (PCR) or comparison between a series of the same individual's data.

We designed this study to explore the relationship between personal protective equipment (PPE) used by HCWs and the clinical course, outcome, and viral load in both HCWs and non-HCWs involved in a SARS cluster stemming from exposure to a single index case in our Emergency Department. The cluster was carefully selected because the spread of transmission occurred in a very short time, making the cause-relationship unambiguous. We also used the human 18s-rRNA as an internal control to avoid sampling variation. Although we could not control for a number of other factors that might have affected transmission, we believe it is worth attempting to assess the effect of PPE, including an N-95 mask, on viral load and subsequent outcome of SARS.

The Mackay Memorial Hospital in Taiwan is a 2000bed teaching hospital that employs approximately 4500 doctors, nurses, allied health professionals, and clerical staff members. Between April 27 and June 16, 2003, a total of 167 patients diagnosed as probable (n ϭ 71) and suspected (n ϭ 96) SARS were treated in the hospital wards and Emergency Department (ED). Since May 12, a total of 41 negative pressure isolation rooms (including four in the ED) were established for these patients. Clearly, it is very difficult to track and clarify every transmission route in facing such variable sources of patients. Therefore, we carefully selected a cluster of victims whose source of infection can be tracked back to a common index patient. On May 4, 2003, a 50-year-old male was sent to the ED of Mackay Memorial Hospital in Taipei. He had had fever for the previous 6 days, and a severe cough with dyspnea for 1 day. He was a cook, and had no travel history or specific contact history for SARS. On arrival in the ED, he was given bronchodilatator therapy by nebulization for his respiratory distress. Two hours later, his chest X-ray study showed multi-focal air space consolidations, and the patient was then immediately isolated. Five hours later, he developed intrac-table hypoxia and respiratory failure, so he was intubated and mechanically ventilated. Twenty-four hours later, he died of SARS in the ED isolation unit.

Sixteen individuals who were directly or secondarily linked to this index patient, including 4 HCWs and 12 non-HCWs (Figure 1 ), subsequently fulfilled the modified WHO SARS case definition (revised 1 May 2003) (19) . All 16 had a positive reverse transcriptase polymerase chain reaction (RT-PCR) nasopharyngeal swab for SARS-CoV or positive serologic antibody tests (except for 3 who died before an antibody test was available).

The clinical course of each patient, including vital signs, the use of O 2 , oxygenation status, and chest X-ray were collected for comparison. Laboratory tests consisted of consecutive hematological examinations, including absolute lymphocyte and platelet counts, and serum biochemistry, including lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and C-reactive protein (CRP). To define the chronological progression, the first day of documented fever Ͼ 38°C was designated as FD 1. O 2 saturation was recorded after admission to the hospital. A nasopharyngeal swab was taken to detect SARS-CoV as soon as patients were admitted to an isolation room.

The nasopharyngeal swab specimens were collected in Trizol reagent and total RNA was extracted according to the manufacturer's instructions (GIBCO/BRL, Grand Island, NY). Primers and probes for SARS Co-V and human 18s rRNA were purchased from Assays-on-Demand™ Gene Expression Products (Applied Biosystems, Foster City, CA). Quantitative RT-PCR was done by using SARS-specific primers and a 5'-nuclease probe as prepared in the Assays-on-Demand™ Gene Expression Products (Applied Biosystems). The 381-bp target fragment of SARS-CoV RNA was transcribed and amplified in an ABI PRISM 7700 sequence detection system (Applied Biosystems). Plasmids supplied by the Center for Disease Control of Taiwan were used with the target sequence to generate a standard curve. To avoid variation in the sampling procedures, quantitative RT-PCR for 18s-rRNA was also done in each sample as an internal control. Individual quantitative RT-PCR for SARS-CoV was normalized to the same level of 18s-rRNA, in this study 10 6 copies/mL. The initial and the normalized data will be compared and presented.

Quantification of mRNA was performed by using a TaqMan one-step RT-PCR Master Mix Reagent kit (Applied Biosystems). Real-time fluorescence measurements were taken and a cycle threshold (CT) value for each sample was calculated by determining the point at which the fluorescence exceeded a threshold limit. A standard curve of the CT values obtained from serial dilutions of the standard was compiled. The coefficient of linear regression and the slope for each standard curve were calculated. The CT values from samples were plotted on the standard curve for calculating the number of genomes.

The follow-up protocol for all surviving patients included an outpatient interview, physical examination, high-resolution computed tomography (HRCT) scan, pulmonary function test (PFT), and a 6-min walk test (6MWT). HRCT, PFT and 6MWT were performed at 1 month after discharge. HRCT and PFT were done again 6 months after discharge.

The HRCT images were all reviewed by one chest physician (C.L.L.) and one radiologist (C.Y.S.). The thorax was divided into upper, middle, and lower lung zones, and the HRCT findings in each zone were recorded. HRCT scores were based on the following scheme: 0 ϭ normal CT; 1 ϭ mild disease (patches of ground-glass opacification); 2 ϭ moderate disease (moderate reticulation, traction bronchiectasis, peribronchovascular thickening); 3 ϭ severe disease (areas of parenchymal consolidations, diffuse areas of peribronchovascular thickening, and traction bronchiectasis) (20) . Examples of HRCT scans with corresponding scores are shown in Figure  2 . The final HRCT score was the mean value of the scores from all three zones. 

For quantitative RT-PCR, the viral RNA loads were expressed as mean Ϯ SEM, whereas all other data were expressed as mean Ϯ SD. Categorical variables were analyzed by Fisher's exact test and continuous variables by Student's t test. Differences between the quantitative RT-PCR values for SARS-CoV in nasopharyngeal swab and HRCT scores in HCWs and non-HCWs were tested for significance using the Mann-Whitney U test. We considered a p of Ͻ 0.05 to be significant. We used SPSS 10.0 software (SPSS Inc., Chicago, IL) for all analyses.

The 16 patients in this cluster had a mean age 42.9 Ϯ 17.9 years (range 20 to 91). The HCWs were younger than non-HCWs (28.0 Ϯ 1.4 vs. 47.8 Ϯ 18.2 years, respectively, p ϭ 0.051). The majority of patients (10 of 16) were female. Only 1 patient (patient 15) had a history of smoking and chronic obstructive pulmonary disease (COPD). All patients presented with fever as the initial specific manifestation of SARS. All but one (patient 15 with COPD) had several days of high fever before developing respiratory symptoms. The mean incubation period between exposure to the index patient and onset of fever (Ͼ 38°C) was 5.5 Ϯ 0.6 days in HCWs and 6.2 Ϯ 1.8 days in non-HCWs. Patients sought medical treatment at a mean of FD 2.3 Ϯ 2.5 days in HCWs and FD 4.0 Ϯ 3.0 days in non-HCWs. The infected HCWs had all been wearing PPE, including an N-95 mask, gloves, gown, and head covering when working in the ED (Figure 3 ). Patients 12 and 13, who cared for the index patient in isolation and assisted with the intubation, wore an additional gown and eye protection when in the isolation unit. The procedures were double-checked (including N-95 mask with fittesting) by their colleagues according to WHO recommendations. The non-HCWs, apparently exposed to the index patient in the ED, had no specific protective equipment, except that some wore surgical, cloth, or paper masks.

Nasopharyngeal swabs were taken at a mean of FD 6.0 Ϯ 1.8 days, when the patients were in a negative isolation room or had been started on our SARS treatment protocol. A total of 18 samples were obtained from 11 patients for quantitative RT-PCR. Initial RT-PCR data showed that HCWs had a significantly lower viral load than the non-HCWs (24.36 Ϯ 15.84 vs. 4346 Ϯ 3246 copies/mL, respectively, p Ͻ 0.0001) (Figure 4) . HCWs also had a significantly lower level human 18s-rRNA than the non-HCWs (80.97 Ϯ 35.2 vs. 5945 Ϯ 1674 copies/L, respectively, p Ͻ 0.001), indicating that mucosal shedding was more extensive in non-HCW ( Figure 5 ). Figure 6 shows that non-HCWs had a significantly higher viral load in their NPS after normalization than the HCWs (463.8 Ϯ 450.2 vs. 9349 Ϯ 7687 copies of RNA/mL, respectively). Although non-HCWs still had a higher viral load after normalization, the difference between (Table 1) .

Non-HCWs had significantly higher CRP values (11.0 Ϯ 6.1 vs. 3.5 Ϯ 4.0 mg/dL, respectively, p ϭ 0.038) and lower O 2 saturation (peak pO 2 /FiO 2 ratio, 167.6 Ϯ 91.9 vs, 274.5 Ϯ 58.6, respectively, p ϭ 0.049), than HCWs ( Table 2 ). Four of the 12 non-HCWs required intubation and 3 died, compared with none of the 4 HCWs (p ϭ 0.516, p ϭ 0.529, respectively). There were no differences in lymphocyte or platelet counts, LDH, CK, AST, or ALT between the HCWs and non-HCWs. The FD on which abnormal laboratory findings occurred also did not differ significantly between the two groups.

Secondary household transmission occurred in 3 of 7 non-HCWs' families compared with none of the HCW families (3/7 vs. 0/4, p ϭ 0.505).

Three patients, all non-HCWs, died with SARS. All surviving patients were able to return to normal daily activities after discharge. All of these patients had a normal body mass index (Table 3) . However, 4 of the 9 surviving non-HCWs (4/9, 44%) noted dyspnea on exertion at the 1-month follow-up visit. Some survivors had an uncomplicated skin rash or mild hair loss. Symptoms of post-traumatic stress disorder and minor depression were also seen in 2 of the non-HCW survivors at the initial outpatient follow up. However, these symptoms gradually improved, and all survivors had normal psychosocial daily activity at the 6-month telephone follow-up. Twelve surviving patients completed the follow-up protocol. On the 1-month HCRT, parenchymal abnormalities were found in 8 of 8 non-HCWs and 3 of 4 HCWs. The abnormalities included areas of ground-glass opacification or reticulation of varying size, interlobular septal or intralobular interstitial thickening, traction bronchiectasis with distortion of the architecture, or crazy-paving with consolidations. The middle lung zone was predominantly involved (Figure 2 ). There were signs interpreted as consistent with pulmonary fibrosis (parenchymal bands, irregular interfaces, and traction bronchiectasis) and peribronchovascular interstitial thickening in 6 of 8 non-HCWs and 2 of 4 HCW patients. Patient 10 had had a pneumomediastinum during his hospitalization, but this had spontaneously resolved by the 1-month follow-up. There were no masses, nodules, emphysema, cavitation, or calcification seen. The mean HRCT score Results are presented as un-normalized row data and normalized data (copies of RNA/mL). in non-HCWs was higher than that of HCWs (1.46 Ϯ 1.02 vs. 0.67 Ϯ 0.72, respectively, p ϭ 0.198) ( Table 3) . At the 6-month follow-up, most patients had significant resolution of their HRCT abnormalities. The previously seen signs of pulmonary fibrosis had substantially resolved, leaving only mild residual linear or reticular opacifications in 4 of 8 non-HCWs and 1 of 4 HCWs. The HRCT score decreased in both groups, but it was still higher in the non-HCWs (0.75 Ϯ 0.53 vs. 0.25 Ϯ 0.17, respectively, p ϭ 0.058). At the 1-month follow-up, 1 of 4 HCWs and 4 of 8 non-HCWs had a restrictive ventilatory defect (vital capacity Ͻ 80% predicted). None of the HCWs had evidence of impaired diffusion (D LCO Ͻ 80% of predicted), but 5 of 8 non-HCWs did. The non-HCWs had a lower mean D LCO than HCWs (13.4 Ϯ 5.7 vs. 19.3 Ϯ 2.3 mL/min/mmHg, respectively, p ϭ 0.031) ( Table  3 ). The functional vital capacity and total lung capacity were mildly decreased in both HCWs (84.5 Ϯ 10.3% and 82.3 Ϯ 14.6%, respectively, of predicted) and non-HCWs (75.6 Ϯ 18.8% and 76.3 Ϯ 15.7%, respectively, of predicted), whereas residual volume was markedly reduced (69.3 Ϯ 33.4% of predicted in HCWs and 76.0 Ϯ 19.7% in non-HCWs). D LCO corrected for lung volume (D LCO /V A ) was normal (105.3 Ϯ 12.7% of predicted in HCWs and 99.0 Ϯ 25.3% in non-HCWs). These findings suggest that parenchymal lung damage led to a restrictive lung defect and impaired diffusion capacity. At the 6-month follow-up, lung function was normal in all HCWs and most of the non-HCWs. Among the latter, however, one person had a restrictive defect and two had diffusion impairment.

At the 1-month follow-up, all survivors were able to perform the 6MWT. However, the non-HCWs walked a shorter distance (648.3 Ϯ 64.2 m) and had a lower SpO 2 (93.8 Ϯ 3.1%) at the end of the test than did HCWs (677.5 Ϯ 51.7 m and 96.5 Ϯ 3.0%), although the differences were not statistically significant (Table 3 ).

We have described a better clinical outcome after SARS in 4 HCWs compared with 12 non-HCWs; despite all having been involved in a cluster related to one index patient, with 13 apparently directly infected by that patient and 3 others by secondary transmission. In several previous reports on SARS, HCWs were less likely to die than non-HCWs (9, 13, 21) . Possible reasons for this may be that they were often younger than non-HCWs, sought treatment earlier, and were less likely to have coexisting illnesses (especially diabetes mellitus and heart disease) (11, 13, 14, 17) . It has also been postulated that HCWs may have had lower exposure to the virus and thus a lower viral load, possibly due to the use of PPE (13, 14, 22) . The initial exposure to the virus and viral load seem to correlate with disease severity. We speculate that the PPE worn by our HCWs, in particular the N-95 masks, may have minimized their exposure to the virus, resulting in lower viral loads, a relatively mild disease course, and a better outcome. It is likely that a lower exposure to the virus may also reduce the risk of secondary household transmission. Patient 10, who went to Japan after unknowingly having been exposed to the index patient, traveled in the company of other doctors for several days after he developed a fever. However, no one in contact with him, either among his traveling companions or Japanese, became infected, despite the understandable fear in Japan when the patient was diagnosed with SARS on his return to Taiwan (23) . None of the other three HCWs transmitted the disease to coworkers or family members despite contact with others during the incubation period. It should be noted that all 3 were isolated immediately after they developed fever, which presumably also decreased the risk of spread, because the patients with SARS were apparently contagious only with the onset of fever. This contrasts with the non-HCWs, who had not worn N-95 masks, had a higher vial load by quantitative RT-PCR, and 3 of whom transmitted SARS to family members. Although immediate reporting of symptoms with early diagnosis and immediate isolation is key to controlling the spread of SARS, use of a high quality mask may minimize initial exposure and thus reduce secondary household transmission.

It has been reported that genetic polymorphism in the human leukocyte antigen system (HLA-B* 4601) correlates with the risk and severity of SARS infection (24) . HLA-B* 4601/B46 is seen in 13.2% to 15.4% of people of southern Chinese origin, 2.8% in those from northern China, and is seldom present in European populations (25) . In our cluster, 4 of 9 non-HCWs and 1 of 4 HCWs had this particular allele. There is, however, no single laboratory study that has been definitively shown to define accurately the prognosis in SARS. In some studies, an increased LDH and an elevated neutrophil count at the time of admission, as well as low CD4 and CD8 lymphocyte counts, were associated with a poor prognosis (2, 11, 13) . In our series, CRP, an acute-phase protein synthesized by the liver after stimulus by various cytokines produced in response infection or inflammation, was markedly higher in non-HCWs than in HCWs. It has been correlated clinically with an increased risk of organ dysfunction and poor prognosis in a heterogeneous population of critically ill patients (26) . In our series, the greatest hematologic and laboratory abnormalities and oxygen desaturation occurred during the second week after fever onset (FD 7 to FD 14). According to a report from Hong Kong, the second week was a critical period of SARS when patients either clinically improved or worsened and developed respiratory distress syndrome necessitating ventilatory support. In a subset of their series, these authors found that the second week marked the peak and subsequent fall in viral load, concurrent with the appearance of antibodies (17) .

The quantitative RT-PCR analysis of nasopharyngeal swabs reveals interesting features of SARS-CoV infection. Other investigators have reported a relatively higher concentration of viral RNA in the sputum than in the serum, urine, and stool. Its presence in the latter suggests that viral replication occurs elsewhere in addition to the respiratory tract. However, the shedding of virus from the respiratory mucosa would seem to be the primary route of transmission (17, 27) . Such a conclusion is also supported by our observation that the amount of the virus was positively associated with the extent of mucosal shedding. Using human 18s-RNA as internal control in some samples, we found that sampling variation and mucosal shedding may significantly affect the virus numbers. Nevertheless, our findings support the contention that crude viral load on nasopharyngeal swab correlated with disease severity and outcome.

It has been reported that some patients discharged after SARS have some degree of respiratory impairment, possibly related to residual lung defects, muscle weakness, or systemic effects of the viral illness (28) . Chest CT scan reportedly showed changes consistent with pulmonary fibrosis in 62% of 24 survivors of SARS at 5 weeks after discharge (28) . For the majority of patients for whom data are available, the CT abnormalities interpreted as fibrosis had included a patchy ground-glass appearance that was not extensive and that might not have a significant impact on lung function (28 -30) . In our case series, abnormalities on HRCT scan were more common in non-HCWs than HCWs, even 6 months after discharge. The findings were predominantly groundglass opacification rather than parenchymal bands and are therefore more suggestive of potentially reversible fibrosing alveolitis rather than pulmonary fibrosis. Pathophysiologically, the possibility of acute reversible lung damage suggests that SARS infection might cause some degree of chronic viral pneumonitis in addition to acute disease (personal communication).

Six percent to 20% of SARS survivors have had impaired diffusion or a restrictive ventilatory defect at 6 to 8 weeks post-discharge (28) . Some of the restrictive defect might be attributable to skeletal muscle weakness rather than parenchymal lung damage alone. Such muscle weakness might be due to several factors, including the use of high-dose steroids, prolonged bed rest leading to physical deconditioning, or residual systemic effect of the acute disease (2, 28) . Whatever the cause, the outcome in our small series indicates that the lung function abnormality caused by SARS may improve spontaneously. We found improvement in radiologic, functional, and psychological abnormalities over time. At almost half a year after SARS, the survivors had normal lung function (including normal cardiopulmonary exercise test, data not shown), normal psychosocial behavior, and only minimal residual radiologic abnormalities.

A major limitation of this study is that we were not able to control for other factors besides PPE that might have affected transmission of the virus from the index case. These may have included ventilation in the ER, proximity of the subjects to the index case, duration of exposure, and perhaps other unknown elements involved in transmission. HCWs may have been more aware of and had better hygiene practices than the non-HCWs. However, the exact extent of the spread of infectious viral-laden droplets when the patient coughed is difficult to determine. RT-PCR for SARS-CoV was positive in samples taken from the floor, a desk, and a bed-rail in the ED (personal communication). Because both HCWs and non-HCWs moved around in the ED, we cannot be certain exactly when and where their exposures actually occurred. This is one reason we selected this one cluster of infection, because it is highly likely that all patients who were present in the ED when the index patient was there were infected at that time. Another limitation is that the numbers in this series are very small, making statistical analysis very uncertain. However, the HCWs did have a lower mean viral load, even though several had very close contact with the index patient, particularly during intubation, when one would expect an extremely high risk of exposure to a heavy viral load.

In conclusion, although PPE, including the N-95 mask, does not confer 100% protection against SARS infection, it seems that it may lessen the initial degree of exposure to the virus with a subsequently lower viral load in the upper respiratory tract. This may result in a milder disease clinically, less chance of secondary transmission, and a faster recovery. 

World Health Organization. WHO issues global alert about cases of atypical pneumonia: cases of severe respiratory illness may spread to hospital staff

Clinical manifestations, laboratory findings, and treatment outcomes of SARS patients

World Health Organization. Consensus document on the epidemiology of severe acute respiratory syndrome (SARS)

World Health Organization. Hospital infection control guidance for severe acute respiratory syndrome (SARS)

Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS)

Centers for Diseases Control and Prevention. Cluster of severe acute respiratory syndrome cases among protected health-care workers-Toronto, Canada

The immediate psychological and occupational impact of the 2003 SARS outbreak in a teaching hospital

The psychosocial impact of the SARS outbreak among children in Taiwan

World Health Organization. Summary of probable SARS cases with onset of illness from 1

Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada

A major outbreak of severe acute respiratory syndrome in Hong Kong

SARS transmission and hospital containment

Severe acute respiratory syndrome: clinical outcome and prognostic correlates

Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS)

Probable secondary infections in households of SARS patients in Hong Kong

Secondary household transmission of SARS

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

Viral loads in clinical specimens and SARS manifestations

World Health Organization. Case definitions for surveillance of severe acute respiratory syndrome (SARS)

Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky-Pudlak syndrome, due to mutation in HPS-1

Clinical and laboratory features of severe acute respiratory syndrome vis-à-vis onset of fever

SARS transmission among hospital workers in Hong Kong

Contact tracing of a laboratory confirmed SARS case in Japan

Association of HLA class I with severe acute respiratory syndrome coronavirus infection

Allele and haplotype frequencies for HLA and complement loci in various ethnic groups

C-reactive protein levels correlate with mortality and organ failure in critically ill patients

Identification of a novel coronavirus in patients with severe acute respiratory syndrome

SARS: prognosis, outcome and sequelae

Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge

High-resolution CT findings in patients with severe acute respiratory syndrome: a pattern-based approach

Acknowledgments-The study was partly supported by the Taiwan National Science Council (NSC92-2751-B-195-001-Y) and National SARS Research Program (SCLI01). We thank Dr. Marie Lin for genetic analysis, and Dr. Mary Jeanne Buttrey for review and revision of the manuscript.