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Since late February, 2003, WHO has received reports of outbreaks of a severe form of atypical pneumonia in Vietnam, Hong Kong, and Singapore. Hong Kong is the most severely affected city. WHO has referred to this unusual form of severe pneumonia as severe acute respiratory syndrome (SARS).1 The surveillance case definition of SARS is: history of high fever (>38·C); one or more respiratory symptoms, including cough, shortness of breath, and difficulty breathing; and close contact within 10 days before onset of symptoms with a person who has been diagnosed with SARS, history of travel within 10 days before onset before symptoms to an area with reported foci of SARS transmission, or both.1 Household contact and contacts in health-care settings are believed to be important routes of transmission.2, 3 This transmission route could put children at particular risk, but most data available so far have been in adults. We therefore decided to report our experience in treating children with SARS. Between March 13 and 28, 2003, ten children with suspected SARS were admitted to and managed at the Prince of Wales and Princess Margaret Hospitals, Hong Kong. We prospectively followed up the clinical, laboratory, and radiological profiles and treatment outcomes of these children. Microbiological investigations were done to detect common bacterial and viral pathogens associated with community-acquired pneumonia.

the Prince of Wales and Princess Margaret Hospitals, Hong Kong. We prospectively followed up the clinical, laboratory, and radiological profiles and treatment outcomes of these children. Microbiological investigations were done to detect common bacterial and viral pathogens associated with community-acquired pneumonia. We treated all patients with combined corticosteroids, antivirals, and antibacterial agents. Intravenous cefotaxime, oral clarithromycin, and oral ribavirin (40 mg/kg daily, given in two or three doses) were started if a diagnosis of SARS was suspected on admission. Oral prednisolone (0·5 mg/kg daily at Prince of Wales Hospital, and 2·0 mg/kg daily at Princess Margaret Hospital) was added if fever persisted after 48 h. In addition, we treated patients who had moderate symptoms of high fluctuating fever and notable malaise with intravenous ribavirin (20 mg/kg daily, given in three doses) and hydrocortisone (2 mg/kg every 6 h) immediately after admission. For patients who had persistent fever and progressive worsening clinically or radiologically, we used pulse intravenous methylprednisolone (10–20 mg/kg). Ribavirin was administered for 1–2 weeks and corticosteroid dose was tapered over 2–4 weeks.

oses) and hydrocortisone (2 mg/kg every 6 h) immediately after admission. For patients who had persistent fever and progressive worsening clinically or radiologically, we used pulse intravenous methylprednisolone (10–20 mg/kg). Ribavirin was administered for 1–2 weeks and corticosteroid dose was tapered over 2–4 weeks. All children satisfied the WHO case definition for SARS and all had been in close contact with infected adults. The demographic, clinical, and laboratory data are shown in the table . Fever was a consistent symptom in all children, and lasted for a median duration of 6 days (range 3–11). There was no clinically significant drop in haemoglobin concentrations during treatment with ribavirin. In eight patients, corticosteroid was added to the regimen when fever did not subside. Pulse methylprednisolone was given to one young child (patient 2) and four teenagers (patients 6–9). Within 2 days of corticosteroid administration, all but one patient (patient 9) became afebrile. The same four teenagers developed respiratory distress and oxygen desaturation on day 5, 4, 6 and 7, respectively, after the onset of fever. These children were placed under strict isolation for 21 days and became asymptomatic before discharge.Table Clinical features and treatment outcomes among SARS children

afebrile. The same four teenagers developed respiratory distress and oxygen desaturation on day 5, 4, 6 and 7, respectively, after the onset of fever. These children were placed under strict isolation for 21 days and became asymptomatic before discharge.Table Clinical features and treatment outcomes among SARS children Patient number 1 2 3 4 5 6 7 8 9 10 Age (years) 1·5 2·2 5·1 6·2 7·5 13·2 13·3 15·6 15·6 16·4 Sex (M/F) F M F F M F F F F F Clinical features Fever Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Dyspnoea No No No No No Yes Yes Yes Yes No Runny nose Yes Yes No Yes No No Yes Yes Yes No Cough Yes Yes No Yes Yes Yes Yes No Yes Yes Sore throat No No No No No No Yes Yes Yes No Chills/rigors No No No No No Yes Yes Yes Yes Yes Myalgia No No No No No No Yes Yes Yes Yes Headache No No No No No No Yes Yes Yes Yes Other ‥ Febrile convulsion ‥ ‥ Dizziness Nausea Abdominal pain ‥ Nausea ‥ Contact history Community outbreak Grandmother Grandmother Family doctor Parents Health-care worker Community outbreak Mother* Mother* Healthcare worker Laboratory findings Lowest Lymphocyte count (×109/L) 3·0 (day 3) 1·1 (day 3) 1·1 (day 4) 1·1 (day 3) 1·2 (day 4) 0·8 (day 6) 0·7 (day 4) 0·4 (day 6) 0·3 (day 4) 0·7 (day 4) Lowest platelet count (×109/L) 345 216 143 196 131 178 147 136 131 209 Highest serum LDH (U/L)† 376 308 324 273 332 286 676 392 431 208 Highest serum ALT (U/L))‡ 29 35 25 12 38 45 44 95 65 168 Radiological findings Initial chest radiograph Right lower-zone focal Right perihilar Left middle-zone consolidation Left upper-zone consolidation Right upper-zone consolidation Right lower-zone consolidation Left and right lower-zone consolidation Left lower-zone consolidation Left lower-zone consolidation Normal Progressive changes of chest radiograph Increased right lower zone consolidation (day 2) Progress to involve right upper zone (day 8) Increased left middle-zone consolidation (day 5) Increased left upper-zone consolidation (day 4) Increased right upper- zone consolidation (day 5) Increased right lower- zone consolidation (day 5) Increased right and left upper-zone consolidation (day 6) Diffuse confluence left and right lower zones (day 9) Diffuse confluence right and left lower zones (day 11) Normal Findings on CT of thorax None Bilateral multifocal air space consolidations None None None None None None None Consolidation at right basal segments Treatment and outcome Oral ribavirin Prescribed Prescribed Prescribed Prescribed Prescribed Prescribed Not prescribed Not prescribed Not

left lower zones (day 11) Normal Findings on CT of thorax None Bilateral multifocal air space consolidations None None None None None None None Consolidation at right basal segments Treatment and outcome Oral ribavirin Prescribed Prescribed Prescribed Prescribed Prescribed Prescribed Not prescribed Not prescribed Not prescribed Prescribed IV ribavirin Not prescribed Prescribed Not prescribed Not prescribed Not prescribed Prescribed Prescribed Prescribed Prescribed Not Oral prednisolone/IV hydrocortisone Not prescribed Prescribed Prescribed Not prescribed Prescribed Prescribed Not prescribed Prescribed Prescribed Prescribed IV pulse methyl-prednisolone Not prescribed Twice (day 10) Not prescribed Not prescribed Not prescribed Once (day 6) Three times (days 4–6) Once (days 6) Once (day 7) Not Duration of fever (days 4 6 7 3 6 6 5 10 11 4 Ventilatory support Not prescribed Not prescribed Not prescribed Not prescribed Not prescribed Nasal cannula (days 5-9) Nasal cannula (days 4-10) Face mask (days 7-8; 12-15), BiPAP (days 8-12) Face mask (days 7-10; 13-19), IPPV (days 10-13) Not prescribed Maximum oxygen requirement Air Air Air Air Air 2 L/min 3 L/min 50% 50% Air LDH=lactic dehydrogenase. ALT=alanine aminotransferase. IV=intravenous. BiPAP=bi-level positive airway pressure. IPPV=intermittent positive pressure ventilation. * Mother of twin sisters (patients 8 and 9) is health-care assistant. † Normal range 110-230 U/L. ‡ Normal range 1-40 U/L.

prescribed Prescribed IV ribavirin Not prescribed Prescribed Not prescribed Not prescribed Not prescribed Prescribed Prescribed Prescribed Prescribed Not Oral prednisolone/IV hydrocortisone Not prescribed Prescribed Prescribed Not prescribed Prescribed Prescribed Not prescribed Prescribed Prescribed Prescribed IV pulse methyl-prednisolone Not prescribed Twice (day 10) Not prescribed Not prescribed Not prescribed Once (day 6) Three times (days 4–6) Once (days 6) Once (day 7) Not Duration of fever (days 4 6 7 3 6 6 5 10 11 4 Ventilatory support Not prescribed Not prescribed Not prescribed Not prescribed Not prescribed Nasal cannula (days 5-9) Nasal cannula (days 4-10) Face mask (days 7-8; 12-15), BiPAP (days 8-12) Face mask (days 7-10; 13-19), IPPV (days 10-13) Not prescribed Maximum oxygen requirement Air Air Air Air Air 2 L/min 3 L/min 50% 50% Air LDH=lactic dehydrogenase. ALT=alanine aminotransferase. IV=intravenous. BiPAP=bi-level positive airway pressure. IPPV=intermittent positive pressure ventilation. * Mother of twin sisters (patients 8 and 9) is health-care assistant. † Normal range 110-230 U/L. ‡ Normal range 1-40 U/L. Nine children had abnormal chest radiographs on presentation. The primary abnormality was air-space opacification. Of the five children aged 12 years or younger (patients 1–5), four presented with focal segmental consolidation. Patient 2 had ill-defined patchy consolidation, but CT of the thorax showed multifocal air-space consolidation. All these patients had mild progressive consolidative change on serial chest radiographs but complete resolution was achieved within 14 days. The typical radiographic changes in one patient are shown in the figure . Three of the five teenagers (patients 7–9) presented with bilateral lower-lobe opacification at presentation, which progressed rapidly within days. Despite clinical improvement, these consolidative changes persisted into the 2nd week of the illness. Patient 10 showed no abnormality on chest radiography at presentation, but high-resolution CT confirmed focal consolidation in the right lower lobe. In CT of the thorax in patients 2 and 6, the characteristic features of peripheral and alveolar opacities simulated the radiological appearances of bronchiolitis obliterans organising pneumonia. Four teenagers required supplemental oxygen, one required bi-level positive airway pressure and intermittent positive-pressure ventilation. Respiratory distress developed 4–7 days after presentation.Figure 1 Serial chest radiographs of patient 5, who presented with fever and cough A=ill-defined air-space consolidation in periphery of right upper lobe and abutting horizontal fissure. B=Increased consolidation in right upper zone on day 5.

ssure ventilation. Respiratory distress developed 4–7 days after presentation.Figure 1 Serial chest radiographs of patient 5, who presented with fever and cough A=ill-defined air-space consolidation in periphery of right upper lobe and abutting horizontal fissure. B=Increased consolidation in right upper zone on day 5. Lymphopenia (0·3–3·0 · 109/L) was reported in all patients, but the teenagers were generally more severely affected than the younger children. Lymphopenia mostly occurred between days 3 and 7, after the onset of fever. No bacteria, fungi, mycoplasma, chlamydia, or common respiratory viruses were detected by the laboratory investigations. Coronavirus was isolated by viral culture from the nasopharyngeal aspirates of patients 2 and 3. Reverse-transcriptase PCR targeting the novel coronavirus present in the nasopharyngeal aspirate samples was positive in four of six children tested (patients 1, 7, 9, and 10).

ere detected by the laboratory investigations. Coronavirus was isolated by viral culture from the nasopharyngeal aspirates of patients 2 and 3. Reverse-transcriptase PCR targeting the novel coronavirus present in the nasopharyngeal aspirate samples was positive in four of six children tested (patients 1, 7, 9, and 10). We noted two distinct patterns of clinical presentation among the children we studied. Teenage patients presented with symptoms of malaise, myalgia, chill, and rigor similar to those of adults,2, 3 whereas the younger children presented mainly with cough and runny nose, and none had chills, rigor, or myalgia. The clinical course was much milder and shorter among younger patients, and radiological changes were milder and generally resolved more quickly than in the teenagers. All paediatric patients had clinically important lymphopenia,3 but it was more severe among the teenage children. However, since young children normally have higher lymphocyte counts than adults, the interpretation of results must take into account the patients' ages.4 Furthermore, lymphopenia frequently resolves when the disease is improving.

ad clinically important lymphopenia,3 but it was more severe among the teenage children. However, since young children normally have higher lymphocyte counts than adults, the interpretation of results must take into account the patients' ages.4 Furthermore, lymphopenia frequently resolves when the disease is improving. We adopted a treatment regimen of ribavirin and steroids similar to that used in adult SARS patients.2, 3 Ribavirin is a broad-spectrum antiviral agent and has been used for treatment of severe respiratory syncytial virus infection in children.5 Among our patients, short-term use of high-dose ribavirin was well tolerated and had no major short-term adverse effects such as severe haemolytic anaemia. In addition, high-dose corticosteroid was used in combination with the antiviral agent because severe immune-mediated damage of lung tissue was reported in postmortem examination of SARS patients.3 Eight of the ten children had been attending school at the time of presentation. There was no evidence that they had spread the infection to their classmates. This finding is in sharp contrast to the experience reported among adults that SARS carries a very high infectivity rate.2,3 At the time of our study, 22 adults had died in Hong Kong.3 During the study period, around 30 children were suspected as having SARS in Hong Kong. So far, no child has died. Our preliminary findings suggest that young children develop a milder form of the disease with a less-aggressive clinical course than do teenagers and adults.