【病毒外文文献】2013 Severity and Outcome Associated With Human Coronavirus OC43 Infections Among Children

The Pediatric Infectious Disease Journal Volume 32 Number 4 April 2013 325 Original StudieS Background Human coronaviruses are known causes of the common cold Subtype OC43 HCoV OC43 is the more prevalent human coronavirus in several parts of the world recent studies have suggested these viruses can cause severe lower respiratory tract illnesses in children Objective We sought to determine the epidemiology clinical characteris tics outcomes and severity of illness associated with HCoV OC43 infec tions in a pediatric population Methods We retrospectively identified patients with positive HCoV OC43 respiratory specimens between december 2009 and december 2010 in a pediatric hospital in Montreal each case was compared with 2 controls tested negative for HCoV OC43 Clinical characteristics underlying con ditions outcomes and disease severity were reviewed for both groups risk factors and independent predictors of disease severity were also assessed Results during the study period 68 patients were identified as infected with HCoV OC43 1 8 of specimens tested 4 2 of all respiratory viruses identified by reverse transcription polymerase chain reaction the majority 77 occurred in november 2010 Chief symptoms of HCoV OC43 infec tion were fever in 78 of cases cough 67 and upper respiratory tract infection symptoms 57 HCoV OC43 infection was not more frequent in children with preexisting conditions Coinfection with other respiratory viruses was associated with lower respiratory tract infections in HCoV OC43 infected cases but did not lead to increased rates of hospitalization admission to intensive care unit or death Conclusions in our population HCoV OC43 infections generally caused upper respiratory tract infection but can be associated with lower respira tory tract infection especially in those coinfected with other respiratory viruses Key Words coronavirus HCoV OC43 severity risk factors children Pediatr Infect Dis J 2013 32 325 329 C oronaviruses were first discovered in the 1960s as the cause of self limited upper respiratory tract infections urtis in humans and a wide variety of diseases in other mammals and in birds the identification of a novel coronavirus as the etiologic agent of severe acute respiratory syndrome in late 2002 led to concerns that these pathogens may potentially cause more severe disease than previously appreciated including involvement of other organ systems 1 there are now 5 coronaviruses recognized as human pathogens HCoV HCoV OC 43 HCoV 299e HCoV HKu1 HCoV nl63 and severe acute respiratory syndrome CoV although the recently discovered HCoV nl63 and HCoV HKu1 are detected in only 5 of symptomatic patients tested for res piratory viral agents 2 HCoV OC43 and HCoV 229e are thought to account for about 15 of urti overall but can contribute to as many as 35 of urti during times of peak viral activity 3 5 a recent study has shown that the majority of children seroconvert to human coronaviruses early in childhood before 2 years of age and that HCoV OC43 appears to be the most prevalent 6 addition ally some studies are suggesting that HCoV may play a role in lower respiratory tract infections lrtis and cause hospitaliza tions HCoV have been detected in respiratory specimens of 14 of children younger than 2 years admitted to hospital with respira tory infections in the netherlands 6 and accounted for 4 4 of all pediatric admissions for respiratory tract infection in Hong Kong 7 in other studies HCoV infections were associated with lower res piratory tract disease requiring supplemental oxygen mechanical ventilation and intensive care unit iCu admission but severe disease appeared to be more frequent in cases coinfected with other respiratory pathogens and among children with comorbidi ties or born prematurely 8 10 HCoV OC43 has also been associated with outbreaks of severe respiratory diseases in children and the elderly 11 13 but several other studies which have included asymp tomatic controls for comparison have questioned whether HCoV plays any role in severe illness and hospitalization 14 17 in our institution after the implementation of a multiplex reverse transcriptase polymerase chain reaction rt PCr respira tory virus assay in September 2009 we noted that HCoV OC43 accounted for 4 7 of all respiratory viruses identified in respira tory specimens during a one year period with a peak incidence in the fall months of October and november the objective of this study was to use retrospective data to assess the epidemiology clinical characteristics and severity of HCoV OC43 infections in children and to assess risk factors associated with hospitalization and severe disease in infected children in comparison with non HCoV OC43 infected children presenting to the same institution during the study period METHODS Study Setting the Montreal Children s Hospital is a tertiary care pediatric hospital with a medical and surgical emergency department that serves the island of Montreal and its surroundings On average 200 children are seen daily in the emergency department with a peak during winter months January to March approximately 60 of these children are under 5 years of age and 50 present for a respiratory illness Patients with multiple comorbidities including malignancy renal disease and congenital malformations are also treated at this hospital Study Design this was a retrospective case control study conducted on patients presenting to the Montreal Children s Hospital emergency Copyright 2013 by lippincott Williams IQR interquartile range The Pediatric Infectious Disease Journal Volume 32 Number 4 April 2013 Coronavirus OC43 in Children 2013 Lippincott Williams the mean duration of hospitalization for the HCoV OC43 infected group was 23 6 days and 43 2 days for the controls a lower proportion of HCoV OC43 infected cases par ticularly in those younger than 18 months received antibiotics 30 8 of cases overall versus 50 of controls 25 of the cases younger than 18 months versus 45 of the controls younger than 18 months this difference was statistically significant even after stratifying by age younger than 18 months there were fewer admissions to the iCu among cases com pared with controls and fewer deaths in the HCoV OC43 infected group 7 10 3 patients were admitted to the iCu Only one of these patients required admission for a complication of his viral illness febrile seizure whereas the others were admitted with and not because of HCoV OC43 these patients had diagnoses of aspi ration pneumonia necrotizing enterocolitis peritonitis prematu rity herpetic encephalitis or were postcardiac surgery respectively there was 1 death in our cohort of HCoV OC43 infected patients the patient died from severe respiratory distress due to aspiration pneumonia among the controls 29 21 3 were admitted to the iCu Of those 3 were admitted for severe respiratory illness secondary to a viral infection 1 patient was infected with influenza H1n1 pandemic strain and 2 patients were infected with enterovirus rhinovirus Other reasons for admission to the iCu in this group included aspiration or bacterial pneumonia cardiac surgeries or cardiopulmonary malformations Adjusted Analyses Comparing HCoV OC43 infected Patients and Controls in the multivariate analysis presence of other coinfecting respiratory viruses in the HCoV OC43 infected group appeared to be an independent predictor for the development of lrti Or 2 04 95 Ci 1 08 3 83 the only independent predictor for hospitali zation was presence of underlying comorbidities Or 3 68 95 Ci 1 91 7 10 But even after adjusting for underlying comorbidity and presence of coinfection HCoV OC43 infected cases were less likely than controls to be admitted Or 0 40 95 Ci 0 21 0 76 and Or 0 77 95 Ci 0 42 1 41 respectively table 3 DISCUSSION Human coronaviruses have been associated with respira tory illnesses ranging from the common cold to high morbidity outcomes such as pneumonia and bronchiolitis this study was designed to determine the epidemiology the clinical features the severity of illness and outcomes associated with HCoV OC43 infections the more prevalent of the human coronaviruses in Mon treal in a pediatric population TABLE 2 Infection With Other Respiratory Viruses in HCoV OC43 infected Cases and Controls Viruses Detected by RT PCR HCoV OC43 infected Cases N 68 n Controls N 136 n Adenovirus 12 17 6 7 5 1 Rhinovirus enterovirus 6 8 8 30 22 1 Respiratory syncytial virus A B 2 2 9 15 11 0 Parainfluenza 1 3 3 4 4 3 2 2 Influenza A B 0 0 3 2 2 HCoV 229E 0 0 0 0 hMPV 0 0 0 0 Overall 22 32 4 62 45 6 Patients in which a respiratory virus other than HCoV OC43 was detected by RT PCR TABLE 3 Outcomes in HCoV OC43 infected Cases in Comparison to Controls Outcomes HCoV OC43 Infected Controls No Crude OR 95 CI Crude OR 95 CI 18 mo Adjusted OR Adjusted for Comorbidities 95 CI Adjusted OR Adjusted for Coinfections 95 CI LRTI 20 29 4 17 30 4 39 28 7 29 31 2 1 04 0 55 1 97 0 96 0 47 1 97 0 98 0 52 1 88 2 04 1 08 3 83 Hospitalization 25 36 4 20 35 7 81 59 6 49 52 7 0 40 0 22 0 72 0 50 0 25 0 99 0 4 0 21 0 76 0 77 0 42 1 41 Length of hospitalization median days IQR 2 1 5 3 5 2 1 4 6 3 22 7 3 39 Antibiotic use 21 30 8 14 25 0 68 50 0 42 45 2 0 45 0 24 0 83 0 40 0 20 0 84 Admission to ICU 7 10 3 6 10 7 29 21 3 20 21 5 0 42 0 18 1 02 0 44 0 16 1 17 Mortality 1 1 5 1 1 8 4 2 9 0 0 0 49 0 05 4 49 None of the comparisons between cases and controls in terms of LRTI admission to ICU duration of hospitalization and mortality reached statistical significance IQR indicates interquartile range Jean et al The Pediatric Infectious Disease Journal Volume 32 Number 4 April 2013 328 2013 Lippincott Williams 16 183 188 2 lau SK Woo PC Yip CC et al Coronavirus HKu1 and other coronavirus infections in Hong Kong J Clin Microbiol 2006 44 2063 2071 3 Monto aS lim SK the tecumseh study of respiratory illness Vi Fre quency of and relationship between outbreaks of coronavirus infection J Infect Dis 1974 129 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talbot HK Crowe Je Jr edwards KM et al new Vaccine Surveillance network Coronavirus infection and hospitalizations for acute respiratory illness in young children J Med Virol 2009 81 853 856 11 Vabret a Mourez t gouarin S et al an outbreak of coronavirus OC43 res piratory infection in normandy France Clin Infect Dis 2003 36 985 989 12 Patrick dM Petric M Skowronski dM et al an Outbreak of Human Coro navirus OC43 infection and Serological Cross reactivity with SarS Coro navirus Can J Infect Dis Med Microbiol 2006 17 330 336 13 Vabret a dina J gouarin S et al Human non severe acute respiratory syn drome coronavirus infections in hospitalised children in France J Paediatr Child Health 2008 44 176 181 14 dare rK Fry aM Chittaganpitch M et al Human coronavirus infections in rural thailand a comprehensive study using real time reverse transcription polymerase chain reaction assays J Infect Dis 2007 196 1321 1328 15 Kusel MM de Klerk nH Holt Pg et al role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life a birth cohort study Pediatr Infect Dis J 2006 25 680 686 16 Prill MM iwane MK edwards KM et al new Vaccine Surveillance network Human coronavirus in young children hospitalized for acute res piratory illness and asymptomatic controls Pediatr Infect Dis J 2012 31 235 240 17 Singleton rJ Bulkow lr Miernyk K et al Viral respiratory infections in hospitalized and community control children in alaska J Med Virol 2010 82 1282 1290 18 Jacobs B Young nl dick Pt et al Canadian acute respiratory illness and Flu Scale CariFS development of a valid measure for childhood respiratory infections J Clin Epidemiol 2000 53 793 799 The Pediatric Infectious Disease Journal Volume 32 Number 4 April 2013 Coronavirus OC43 in Children 2013 Lippincott Williams 4 637 653 20 Cabe a tK Bellei n Human coronavirus nl 63 infection in a Brazilian patient suspected of H1n1 2009 influenza infection description of a fatal case J Clin Virol 2012 53 82 84 21 gaunt er Hardie a Claas eC et al epidemiology and clinical presen tations of the four human coronaviruses 229e HKu1 nl63 and OC43 detected over 3 years using a novel multiplex real time PCr method J Clin Microbiol 2010 48 2940 2947 22 Kon M Watanabe K tazawa t et al detection of human coronavirus nl63 and OC43 in children with acute respiratory infections in niigata Japan between 2010 and 2011 Jpn J Infect Dis 2012 65 270 272 23 Woo PC Yuen KY lau SK epidemiology of coronavirus associated res piratory tract infections and the role of rapid diagnostic tests a prospective study Hong Kong Med J 2012 18 suppl 2 22 24