Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates

Tsui, Ping; Kwok, Man Leung; Yuen, Hon; Lai, Sik To

doi:10.3201/eid0909.030362

Cited by 215 publications

(249 citation statements)

References 5 publications

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“…In adult series, the independent predictors of severe illness are advanced age, high initial absolute neutrophil counts, high initial or peak lactate dehydrogenase levels, and positive RT-PCR results for NPA samples. 7,13,28,29 Our clinical case definition has very good sensitivity (97.8%) and specificity (92.7%) in field testing and served us well during the SARS outbreak. However, early in an outbreak, an epidemiologic clue might not be available to satisfy the requirement in the case definition, even for an actual case.…”

Section: Discussionmentioning

confidence: 99%

Severe Acute Respiratory Syndrome Among Children

Leung¹,

Kwan²,

et al. 2004

Pediatrics

122

152

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ABSTRACT. Objective. To study the epidemiologic, clinical, laboratory, and radiologic features, prognostic indicators, and short-term to medium-term outcomes for children with severe acute respiratory syndrome (SARS) and to validate the performance characteristics of a clinical case definition, calculated with respect to SARSassociated coronavirus (SARS-CoV) seroconversion.Methods. Children <18 years of age, from a singlesite outbreak, who satisfied a clinical case definition for SARS, with subsequent serologic confirmation, were treated according to a standard protocol and prospectively monitored.Results. Forty-four children were included. The median age was 12 years. Forty-two children (95.5%) demonstrated an epidemiologic link. Fever, cough, malaise, coryza, sputum production, headache, myalgia, lymphopenia, and elevated lactate dehydrogenase levels were common presenting features. Radiographic findings were nonspecific, but high-resolution computed tomography of the thorax was an early diagnostic aid. A specific reverse transcription-polymerase chain reaction assay for SARS-CoV yielded positive results for <50% of children. Of 9 children who developed hypoxemia, 8 were treated with methylprednisolone. Of 5 children who received intensive care, 3 required assisted ventilation. All children recovered, and serious adverse events in response to treatment were not observed. The outcomes at 3 to 6 months after disease onset, including exercise tolerance, pulmonary functions, and psychologic status, were favorable. An age of >12 years was associated with methylprednisolone therapy for severe illness. After exclusion of the only infant, an age of >12 years was associated with oxygen requirements. Sore throat, high neutrophil count at presentation, and peak neutrophilia were independent factors predicting severe illness. The clinical case definition demonstrated good sensitivity, specificity, and positive and negative predictive values (97.8%, 92.7%, 88%, and 98.7%, respectively) for diagnostic accuracy.Conclusions. 1 Although the majority were adults, 121 children (6.9%) Ͻ18 years of age were registered, yielding an age-specific attack rate of 8.9 cases per 100 000 persons Ͻ18 years of age and a case fatality rate of 0%. A total of 89 hospitalized children in Hong Kong demonstrated serologic evidence of infection by the SARS-associated coronavirus (SARS-CoV) (e-SARS database, Hospital Authority, Hong Kong Special Administrative Region, data on file).Published articles on pediatric SARS have focused on reporting the demographic, clinical, laboratory, and radiologic characteristics. Definitive virologic data, prognostic indicators, and short-term to medium-term follow-up information were lacking in those preliminary reports. [2][3][4] We prospectively monitored a cohort of 44 children with laboratory confirmation of SARS who were treated at a referral center for pediatric infectious diseases that admitted the largest number of pediatric patients with SARS in Hong Kong. Their epidemiologic links; clinical, laboratory,...

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Section: Discussionmentioning

confidence: 99%

Severe Acute Respiratory Syndrome Among Children

Leung¹,

Kwan²,

et al. 2004

Pediatrics

122

152

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“…Age-related loss of lung repair capacity may also explain the progressive age-related increase in the clinical severity of severe acute respiratory syndrome (SARS) (23,24) and pandemic H1N1 virus infection (25) and the higher mortality reported in older patients with acute respiratory distress syndrome (26). Age also determines the severity of SARS in both mouse and macaque experimental models (27,28), and aged mice were more susceptible to exogenous endotoxin (LPS) in an animal model of sepsis-induced kidney injury (29).…”

Section: Discussionmentioning

confidence: 99%

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Chan

Kuok

Leung

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

184

181

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Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium’s protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.

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“…A number of clinical/laboratory parameters have been shown have a prognostic value. Poor prognostic factors include advanced age [3,23,31,141], chronic hepatitis B treated with lamivudine [31], severe hepatitis [27], high initial LDH [141], high peak LDH [3], high neutrophil count on presentation [3,141], diabetes mellitus or other co-morbid conditions [5,142], low CD4 and CD8 lymphocyte counts at presentation [143] and a high initial SARS-CoV viral load [97,144].…”

Section: Short-term Outcomementioning

confidence: 99%

SARS: clinical presentation, transmission, pathogenesis and treatment options

2006

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SARS (severe acute respiratory syndrome) appeared as the first emerging infectious disease of this century. It is fortunate that the culprit virus can be grown without much difficulty from a commonly used cell line, allowing an unlimited supply of isolates for further molecular studies and leading to the development of sensitive diagnostic assays. How the virus has successfully jumped the species barrier is still a mystery. The superspreading events that occurred within hospital, hotel and high-density housing estate opens a new chapter in the mechanisms and routes of virus transmission. The old practice of quarantine proved to be still useful in controlling the global outbreak. Despite all the available sophisticated tests, alertness with early recognition by healthcare workers and prompt isolation of suspected cases is still the most important step for containing the spread of the infection. Although the rapidly evolving outbreak did not allow the conducting of systematic clinical trails to evaluate treatment options, the accumulated experience on managing SARS patients will improve the clinical outcome should SARS return. Although SARS led to more than 700 deaths worldwide, the lessons learnt have prepared healthcare systems worldwide to face future emerging and re-emerging infections.

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Severe Acute Respiratory Syndrome: Clinical Outcome and Prognostic Correlates

Cited by 215 publications

References 5 publications

Severe Acute Respiratory Syndrome Among Children

Severe Acute Respiratory Syndrome Among Children

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

SARS: clinical presentation, transmission, pathogenesis and treatment options

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