【病毒外文文献】2015 Acute Middle East Respiratory Syndrome Coronavirus_ Temporal Lung Changes Observed on the Chest Radiographs of 55 P

AJR 205 September 2015 W1 tients with MERS CoV infection present with nonspecific clinical symptoms such as fever cough and shortness of breath 3 4 One of the recent studies reported unilat eral and bilateral lung abnormalities ranging from subtle to extensive on chest radiographs in 87 of 47 patients with MERS CoV 5 However the report did not specifically ex amine the type and extent of the pulmonary Acute Middle East Respiratory Syndrome Coronavirus Temporal Lung Changes Observed on the Chest Radiographs of 55 Patients Karuna M Das 1 2 Edward Y Lee 3 4 Suhayla E Al Jawder 5 Mushira A Enani 6 Rajvir Singh 7 Leila Skakni 8 Nizar Al Nakshabandi 1 9 Khalid AlDossari 1 Sven G Larsson 1 Das KM Lee EY Al Jawder SE et al 1 Department of Medical Imaging King Fahad Medical City Riyadh 11525 KSA Address correspondence to K M Das daskmoy 2 Department of Radiology College of Medicine and Health Sciences United Arab Emirates University Al Ain UAE 3 Department of Radiology Boston Children s Hospital and Harvard Medical School Boston MA 4 Department of Medicine Pulmonary Division Boston Children s Hospital and Harvard Medical School Boston MA 5 Department of Pulmonary the final version will appear in the September 2015 issue of the AJR WEB This is a web exclusive article AJR 2015 205 W1 W8 0361 803X 15 2053 W1 American Roentgen Ray Society O utbreaks of acute infection by the Middle East respiratory syn drome coronavirus MERS CoV were recently reported by health authorities in Riyadh Saudi Arabia 1 The first case was identified in September 2012 As of December 17 2014 the number of MERS CoV infected patients had increased to 821 with 355 recorded deaths 2 Most pa Keywords chest radiographic score chest radiographs Middle East respiratory syndrome coronavirus MERS CoV mortality radiographic deterioration pattern DOI 10 2214 AJR 15 14445 Received January 20 2015 accepted after revision March 16 2015 OBJECTIVE The objective of our study was to describe lung changes on serial chest ra diographs from patients infected with the acute Middle East respiratory syndrome corona virus MERS CoV and to compare the chest radiographic findings and final outcomes with those of health care workers HCWs infected with the same virus Chest radiographic scores and comorbidities were also examined as indicators of a fatal outcome to determine their po tential prognostic value MATERIALS AND METHODS Chest radiographs of 33 patients and 22 HCWs in fected with MERS CoV were examined for radiologic features indicative of disease and for evidence of radiographic deterioration and progression Chest radiographic scores were esti mated after dividing each lung into three zones The scores 1 mild to 4 severe for all six zones per chest radiographic examination were summed to provide a cumulative chest radio graphic score range 0 24 Serial radiographs were also examined to assess for radiograph ic deterioration and progression from type 1 mild to type 4 severe disease Multivariate logistic regression analysis Kaplan Meier survival curve analysis and the Mann Whitney U test were used to compare data of deceased patients with those of individuals who recovered to identify prognostic radiographic features RESULTS Ground glass opacity was the most common abnormality 66 followed by consolidation 18 Overall mortality was 35 19 55 Mortality was higher in the patient group 55 18 33 than in the HCW group 5 1 22 The mean chest radiographic score for deceased patients was significantly higher than that for those who recovered 13 2 6 SD vs 5 8 5 6 respectively p 0 001 in addition higher rates of pneumothorax de ceased patients vs patients who recovered 47 vs 0 p 0 001 pleural effusion 63 vs 14 p 0 001 and type 4 radiographic progression 63 vs 6 p 0 001 were seen in the deceased patients compared with those who recovered Univariate and logistic regres sion analyses identified the chest radiographic score as an independent predictor of mortality odds ratio OR 1 38 95 CI 1 07 1 77 p 0 01 The number of comorbidities in the pa tient group n 33 was significantly higher than that in the HCW group n 22 mean num ber of comorbidities 1 90 1 27 vs 0 17 0 65 respectively p 0 001 The Kaplan Meier analysis revealed a median survival time of 15 days 95 CI 4 26 days CONCLUSION Ground glass opacity in a peripheral location was the most common abnormality noted on chest radiographs A higher chest radiographic score coupled with a high number of medical comorbidities was associated with a poor prognosis and higher mor tality in those infected with MERS CoV Younger HCWs with few or no comorbidities had a higher survival rate Das et al Chest Radiography of Middle East Respiratory Syndrome Coronavirus Cardiopulmonary Imaging Original Research Downloaded from www ajronline org by NYU Langone Med Ctr Sch of Med on 06 24 15 from IP address 128 122 253 228 Copyright ARRS For personal use only all rights reserved W2 AJR 205 September 2015 Das et al abnormalities or their relationship to the fi nal outcome The findings presented herein expand on this previous study and show that a higher chest radiographic score i e more extensive lung abnormalities is associated with a poor prognosis and a higher mortal ity rate in patients infected with MERS CoV At our institutions we observed signs of MERS CoV infection on a number of chest radiographs Chest radiography plays a cru cial role in the early diagnosis of infection and monitoring of disease progression dur ing medical treatment 6 Therefore the aim of the current study was to examine seri al chest radiographs of patients infected with MERS CoV to identify pathologic changes in the lungs that are associated with the fi nal outcome The chest radiographic find ings and final outcomes of patients were compared with those of health care workers HCWs infected with the same virus Materials and Methods Subjects This retrospective study was approved by the in stitutional review board and the requirement for in formed consent was waived Fifty five subjects 39 females and 16 males mean age 46 9 years range 12 85 years were enrolled in the study and 581 mean 10 6 9 8 range 1 47 chest radiographic examinations were obtained The initial chest ra diographic study was obtained 2 5 1 days mean SD range 1 5 days after the onset of symptoms The 55 subjects were divided into two different co horts patients n 33 21 females and 12 males mean age 54 16 years range 12 85 years with epidemiologic links to confirmed MERS CoV cas es and HCWs n 22 18 women and four men mean age 34 7 years range 26 56 years with a history of direct contact with MERS CoV infected patients admitted to the hospital All subjects were diagnosed with MERS CoV infection between April 7 2014 and August 28 2014 All subjects re ceived appropriate supportive care oral ribavirin dose based on the calculated creatinine clearance rate and subcutaneous pegylated interferon 2a 180 g wk for 2 weeks The CT findings of 15 of the 55 subjects were published in an article in the April 2015 issue of the AJR 7 The current study presents a detailed anal ysis of chest radiographic findings of the 55 sub jects Data from the patient and HCW groups were compared MERS CoV was diagnosed according to World Health Organization criteria A confirmed case was defined as a suspected case that was posi tive for MERS CoV by real time reverse transcrip tion polymerase chain reaction RT PCR 6 Chest Radiography and Evaluation All chest radiographs obtained on admission to the department of emergency medicine and subse quent radiographs obtained during the course of treatment were included in the study Throughout the study period routine posteroanterior chest ra diographs were obtained using digital radiogra phy and a lateral view was obtained if requested n 21 Anteroposterior views were obtained at the bedside in ICU patients and in patients who were not able to stand Radiographs were obtained using portable computed radiographic equipment Mobilett Plus Siemens Healthcare and standard techniques 8 Patients in a serious condition un derwent follow up radiography daily while in the hospital Radiographs were obtained every other day during the recovery period A Fig 1 69 year old man with Middle East respiratory syndrome coronavirus Serial chest radiographs show type 4 pattern of progression A Frontal chest radiograph obtained at first presentation shows unilateral peripheral focal consolidation in right upper zone and ground glass opacity in right lower zone chest radiographic score is 2 B Follow up frontal chest radiograph obtained on day 5 shows multifocal bilateral airspace opacities in both lungs indicating disease progression chest radiographic score of 9 5 C Subsequent follow up chest radiograph obtained on day 8 shows moderate left sided pleural effusion indicating further deterioration chest radiographic score is 15 5 Patient died on 8th day after admission CB Fig 2 44 year old man with end stage renal disease who developed Middle East respiratory syndrome coronavirus Frontal chest radiograph obtained at day 6 shows bilateral multifocal patchy airspace disease with predominant perihilar distribution and multiple areas of cavitation chest radiographic score is 13 Fig 3 12 year old boy with preexisting craniopharyngioma who developed Middle East respiratory syndrome coronavirus Frontal chest radiograph obtained on day 6 shows bilateral diffuse hazy pulmonary ground glass opacification and moderate left sided pleural effusion arrow chest radiographic score is 15 Patient died 8 days after initial presentation Downloaded from www ajronline org by NYU Langone Med Ctr Sch of Med on 06 24 15 from IP address 128 122 253 228 Copyright ARRS For personal use only all rights reserved AJR 205 September 2015 W3 Chest Radiography of Middle East Respiratory Syndrome Coronavirus Interpretation of Chest Radiographs Serial frontal chest radiographs obtained at ini tial presentation and during treatment were retro spectively reviewed and a consensus opinion was provided by three radiologists none of whom was aware of the clinical progress of the subjects The radiologists involved in the review process had 8 20 and 40 years experience with chest radiogra phy reporting The radiographs were viewed on a dedicated radiology PACS workstation Centric ity 2 1 2 1 GE Healthcare The radiographs were examined for the presence of ground glass opac ity consolidation cavitation pneumothorax and pleural effusion and findings were recorded using the Fleischner Society nomenclature 9 In addi tion the presence of multiple irregular linear air space opacities was recorded 10 The distribution of disease was rated as central if the abnormality predominantly involved the me dial half of the lung and as peripheral if it predomi nantly involved the lateral half of the lung Lung findings were recorded as unifocal or multifocal depending on whether the lung parenchyma was in volved Each lung was divided into three zones and each zone was evaluated in terms of involvement 8 The development of MERS CoV lesions within each lung zone was assigned a score ranging from 0 normal to 4 complete involvement of one zone a score of 24 indicated complete involvement of all six zones 10 The scores for all six zones per chest radiographic study were summed to yield a cumu lative chest radiographic score ranging from 0 to 24 depending on the involvement of the lung paren chyma The scores were recorded at initial presen tation and at the peak of disease activity The serial frontal chest radiographs obtained during treatment were also reviewed to examine the extent of radiographic deterioration during disease progression Disease progression was clas sified as described by Wong et al 8 with minor modifications to the definitions of type 2 and type 3 disease progression Type 2 disease progression was defined as static radiographic changes with no discernible radiographic peak or change in overall mean lung involvement of less than 25 Type 3 disease progression was defined as fluctuating ra diographic changes with at least two radiograph ic peaks separated by a period of mild remission with remission defined as a level of mean lung pa renchyma involvement that differed from the peak level by more than 25 Type 1 progression i e initial radiographic deterioration followed by im provement and type 4 progression i e progres sive radiographic deterioration were defined as previously described 8 Medical charts were reviewed to obtain in formation regarding comorbidities demographic characteristics symptoms duration of hospital ization admission to the ICU initiation and du ration of mechanical ventilation and death One patient with a prior diagnosis of lung fibrosis was also included in the study although this fact was withheld from the reviewers reviewing the chest radiographs All patients who recovered were con tacted within 1 week and were asked to report any additional symptoms additional medical treat ment rehospitalization and current status Statistical Analyses The 55 subjects were divided into two groups according to final outcome The deceased group included 19 patients who died and the recovered group included 36 patients who recovered The mean percentage lung involvement at initial pre sentation and at the time of peak activity the pat tern of disease progression on chest radiographs types 1 4 and the presence or absence of oth er chest radiographic parameters ground glass patchy nodular or confluent nodular opacities ar eas of consolidation linear airspace opacity cav itation plus pleural effusion and pneumothorax were compared between the two groups The chi square test was used to compare categoric data and the Student t test was used to compare normal ly distributed continuous variables The Mann Whitney U test was used to compare nonnormally distributed continuous variables Kolmogorov Smirnov tests were performed to check normal distribution between the groups for continuous variables Demographic characteristics chest ra diographic scores comorbidities and platelet and absolute lymphocyte counts were also compared between groups A Kaplan Meier survival curve analysis was performed according to the num ber of days on mechanical ventilation Quantita tive variables were expressed as the mean SD or as the median and range and qualitative variables were expressed as the frequency and percentage A Fig 4 32 year old woman with Middle East respiratory syndrome coronavirus Serial radiographs show type 3 radiographic deterioration pattern A Frontal chest radiograph obtained on day 4 after admission to ICU shows right upper and middle zone consolidation along with ground glass opacities in left middle zone chest radiographic score is 7 B Subsequent follow up chest radiograph obtained on day 7 after admission to ICU shows significant improvement but remaining bilateral ill defined ground glass opacities chest radiographic score is 2 C Follow up frontal chest radiograph obtained on day 10 after admission to ICU shows recurrence of bilateral significant airspace disease chest radiographic score is 13 D Follow up frontal chest radiograph obtained on day 19 after admission to ICU shows almost total improvement but bilateral basal ill defined ground glass opacities are still present chest radiographic score is 1 Patient made complete recovery C B D Downloaded from www ajronline org by NYU Langone Med Ctr Sch of Med on 06 24 15 from IP address 128 122 253 228 Copyright ARRS For personal use only all rights reserved W4 AJR 205 September 2015 Das et al Multivariate logistic regression analysis was per formed using significant and important variables identified by univariate analysis A p value two tailed of 0 05 was considered statistically sig nificant All statistical analyses were performed using SPSS software version 21 0 IBM Results Clinical Presentation and Appearance of Abnormalities The 55 patients underwent a total of 581 chest radiographic examinations The in dications for chest radiography were dys pnea or findings indicative of pneumonia on auscultation The chest radiographic find ings were considered abnormal in 46 of 55 83 patients The radiologic findings are summarized in Table 1 The most frequent ly observed type of opacity was ground glass 36 55 66 Fig 1 followed by consolida tion 10 55 18 Both ground glass opac ity and consolidation were noted in 9 of 55 16 patients Consolidations appeared patchy 10 55 18 or confluent 16 55 29 or as rounded nodular areas of opac ity 5 55 9 Air bronchogram was noted in 6 of 55 11 patients Irregular linear air space disease was noted in 5 of 55 9 pa tients and multicentric cavitation was noted in one patient 1 55 2 Fig 2 Distribution of Abnormalities Initial lung involvement Table 1 was noted in the right lower 24 55 44 of cases and left middle 16 55 29 zones The radiographic distribution at the time of peak radiographic deterioration Table 1 was more significant in deceased patients who showed a higher incidence of right lower zone 19 19 100 p 0 001 right middle zone 19 19 100 p 0 001 and left middle zone 18 19 95 p 0 002 involvement Peripheral distribution was a predominant feature 32 55 58 which was followed by central distribution 14 55 25 and combined central and peripheral distribution 8 55 15 Unifocal involve ment 38 55 69 was more common than multifocal involvement 17 55 31 At ini tial presentation the median number of lung zones involved was two range 1 5 zones in patients who died and one range 0 4 zones in patients who recovered Duration of Hospital Stay and Disease Course The duration of the hospital stay from the time of admission ranged from 1 to 34 days mean 12 5 8 6 days Of the 55 subjects examined 30 55 were admitted to the ICU for mechanical ventilation treatment of acute respiratory distress syndrome ARDS or both During the later stage of the disease 17 of 55 31 patients developed pleural ef fusion Fig 3 and 9 of 55 16 developed pneumothorax All nine of the patients who developed pneumothorax were intubated The incidence of pleural effusion 12 19 63 p 0 001 and the incidence of pneumothorax 9 19 47 p 0 001 were higher in the de ceased group than in the recovered group Ta ble 1 The mean number of days from symp tom onset to the day of death or recovery was 12 8 5 for the deceased group and 12 6 8 9 for the recovered group Table 2 Superinfection Of the 30 patients admitted to the ICU nine 9 30 30 developed superinfection bacteria were isolated from multiple naso pharyngeal aspirates None of the patients underwent bronchoscopy or bronchial lavage The culture results were as follows Pseudo monas aeruginosa n 4 44 P aerugino sa and Klebsiella species n 1 11 Steno trophomonas maltophilia and Pseudomonas species n 1 11 P aeruginosa and meth icillin resistant Staphylococcus aureus n 1 11 P aeruginosa and Providencia stu artii n 1 11 and methicillin resistant S aureus n 1 11 Six of the nine patients died and three were treated successfully and made a full recovery TABLE 1 Radiographic Findings in 55 Patients Infected With the Middle East Respiratory Syndrome Coronavirus MERS CoV Radiographic Findings No of Patients p Deceased Group n 19 Recovered Group n 36 Total Lung zones involved at initial presentation Right upper zone 4 21 1 5 13 9 9 16 4 0 5 Right middle zone 6 31 6 8 22 2 14 25 5 0 45 Right lower zone 11 57 9 13 36 1 24 43 6 0 12 Left upper zone 2 10 5 3 8 3 5 9 1 0 79 Left middle zone 8 42 1 8 22 2 16 29 1 0 12 Left lower zone 6 31 6 8 22 2 14 25 5 0 45 Lung zones involved at time of peak radiographic deterioration Right upper zone 11 57 9 12 33 3 24 43 6 0 09 Right middle zone 19 100 16 44 4 35 63 6 0 001 Right lower zone 19 100 21 58 3 40 72 7 0 001 Left upper zone 9 47 4 7 19 4 16 29 1 0 03 Left middle zone 18 94 7 19 52 8 37 67 3 0 002 Left lower zone 15 78 9 20 55 6 35 63 6 0 09 Abnormal findings on chest radiographs Ground glass opacity 16 84 2 20 55 6 36 65 5 0 03 Consolidation 3 15 8 7 19 4 10 18 2 0 74 Patchy consolidation 5 26 3 5 13 9 10