核心提示

1.尽管CT辐射有不可忽略的致癌风险有关，但到目前为止CT对Coivd-19患者的临床处理的作用仍不清楚。

2.目前尚无针对Covid-19病毒的特别治疗方法或疫苗。应对这种疾病的方法是包括感染源，使用个人防护措施以减少传播的风险；以及对患者的早期隔离和支持治疗。

3. CT阳性检查结果仅提示肺炎，胸部CT阴性不能排除Covid-19。

4. CT扫描将过程的步骤有引起的病毒传播的风险。

5. 如果假CT阳性患者（即2019-nCoV以外原因的肺炎患者）在接近Covid-19患者的病房中住院，存在医院内传播风险。

6. 对于中度/重度病例，可以进行 胸部X线 检查以观察肺部病变的进展或消退。

7.对于CT检查，应始终采用最小化辐射剂量的技术。

8. 避免儿童 CT 检查。

9. 一个病例Coivd-19从 可疑 转变为 临床诊断 后可能并不影响临床处理。

虽然有时间更长的病例, 根据当前的流行病学调查2019新冠肺炎(Covid-19)潜伏期主要为3到10天（中位数：3天）。死亡病例估计 2％ (在武汉/湖北以外的地区较低), 并在老年人和患有慢性潜在疾病的人群中更为常见。根据目前的指南，在非武汉/非湖北地区，建议有密切接触和可疑接触的人有14天的健康观察期。对于那些意外接触，低水平接触可疑或确诊患者的人，应进行接触监测。一旦出现任何症状，特别是发烧，呼吸道症状（例如咳嗽，呼吸急促或腹泻），就应立即就医。疑似病例为具有流行病学风险和临床特征的病例。确诊病例依赖检测出诊2019-nCoV病毒的证据

典型的胸部影像学表现包括两个肺部均出现多个，斑块状，亚节段性或节段性毛玻璃密度影，但非典型性表现越来越普遍。CT目前广泛应用于Covid-19检查。 然而，CT辐射有不可忽略的致癌风险，而且但到目前为止，CT在Coivd-19患者处理护理中的作用仍不清楚。当前没有针对2019-nCoV的有效抗病毒治疗或疫苗。这点与肺结核的情况不同。对于结核病，即使没有结核分枝杆菌涂片或培养物的阳性病原诊断，也可以在进行影像学进行临床诊断后进行抗结核药物治疗。而Coivd-19病例，CT可能显示病毒性肺炎的典型体征，从而有助于临床诊断。但是，一个病例Coivd-19从可疑转变为临床诊断后的病例可能并不影响临床处理。

指南提出Covid-19疑似病例应该隔离，并对于中重度患者提供支持治疗。支持治疗主要基于临床症状/体征的严重程度， 并对于严重和危急情况监测血液和生化参数。可以进行 胸部X线 检查观察中重度患者肺部病变的进展或消退。 胸部X线可能有机会通过双侧或多叶浸润的影像学特征短时间内病情迅速发展来帮助早期识别严重。

目前报道对于最初检查，在大约25％的Covid-19病例中胸部CT可能为阴性（将来检查更轻的病例时，CT阴性率可能会大大提高）。一次胸部CT阴性不能排除Covid-19。  胸部X线 可能会错过一些肺部轻度渗出低度患者。但是在已知这一限制的情况下，胸部X线 阴性也不排除对Covid-19诊断并进一步监视患者。影像学上可见的肺部改变的严重程度一般与疾病本身的严重程度有关。对于这些胸部X线可能漏诊的轻度病例，如果应用CT并发现病灶，临床治疗原创最可能是一样不变； 因为所有可疑患者都隔离观察。如果以后找到了有效的抗病毒治疗，则处理能会有所不同，例如如果证明伦德昔韦对Covid-19有效，则可能基于流行病学的风险因素、临床症状和典型的病毒性肺炎CT表现进行Remdesivir治疗(这是一个假设)。

胸部X线的放射剂量约为0.1 mSv，而标准胸部CT的放射剂量约为 4 mSv。据估计一次CT扫描有0.3-0.7％的致癌风险。对于进行多次CT扫描的患者，风险可能高达> 2.7％。CT扫描的过程程序有一定的将导病毒传播的风险。此外CT检查结果仅能提示肺炎。如果假CT阳性患者（即2019-nCoV以外原因的肺炎患者）在有Covid-19患者的病房中住院，则存在更高的医院传播风险。尽管可以通过更多的预防措施加以改善， 在武汉的一项研究中，41％的患者怀疑与医院相关的2019-nCoV传播。

CT在某些情况下是有意义的。在诸如武汉/湖北等目前医疗保健比较紧张的地区，使用CT技术检测Covid-19肺炎可能是合理的，对已确诊或临床诊断的Covid-19患者给予优先医疗处理。也许CT可能在决定何时可以使患者脱离隔离中发挥作用。CT也许可以用于某些特定的疑似病例，如果这些病例的病原学检查不止一次呈阴性，并且如果CT显示与病毒性肺炎一致的发现，则可以采取特别的具体措施，例如当地的流行病学情况采取更严格的隔离以便控制潜在的病毒传播者。

总言之，目前尚无针对Covid-19的特别治疗方法或疫苗。应对这种疾病主要是控制感染源，使用个人防护措施以减少传播的风险，以及对患者的早期隔离和支持治疗。 CT在Covid-19患者处理过程中的作用仍不明确。 在Covid-19发病率较低的地区 (非武汉/非湖北)，CT作为诊断工具的应用可能不合理。在所有情况下，我们都需要使患者的辐射暴露尽可能低。特别是儿童应尽可能避免进行CT检查。儿童对放射线诱发癌症的敏感性是成年人的十倍。 超声成像可被视为相关技术的替代方法。如美国的病例报告所证明的那样，胸部X线是成可选择的影像学方法，尤其是用于多次监测（Holshue等，doi：10.1056 / NEJMoa2001191）。对于CT检查，应始终采用低辐射剂量模式和最小化辐射剂量的技术。这些问题没有理想的解决方案，我们应采用最佳收益风险率的方法。

特别说明：武汉/湖北流行病学情况例外

现在加拿大及美国的病例报道用了X 线平片。

德国的一组病例没有用放射学检查

The role of CT for Covid-19 patient’s management remains poorly defined

Running title:  CT for Covid-19 management undefined

Yi-Xiang Wang  ¹, Wei-Hong Liu  ², Mo Yang,  ³, Wei Chen,  ^4,5

1, Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.

Email: yixiang_wang@cuhk.edu.hk

2, Department of Radiology, General hospital of China resources & WISCO, Wuhan, Hubei Province 430080, China. 

Email address: liuwhwygn@sina.com

3, Research Centre, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province 518107, China. 

Email address: yangm1091@126.com

4, Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China 

5, Pingshan District People’s Hospital, Pingshan General Hospital of Southern Medical University, Shenzhen, Guangdong Province 518118, China

 Email address: 1530831809@qq.com

Correspondence to: Dr. Yi-Xiang J Wang. Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China. Email: yixiang_wang@cuhk.edu.hk

In December 2019, the 2019 novel coronavirus (2019-nCoV) was identified in the viral pneumonia cases occurred in Wuhan, Hubei Province, China; In the following month, the 2019-nCoV quickly spreading inside and outside of Hubei Province and even other countries. Respiratory droplet transmission is the main route of transmission, while it can also be transmitted through contact. Based on currently epidemiological survey, the latency period is mostly from 3 to 10 days (median:3 days), though much longer cases have been noted (1-4). 2019-nCoV is also contagious during the latency period. The time span of the patients discharging infective virus is not clear. Covid-19 patients commonly have symptoms of fever, fatigue, dry cough, dyspnoea, chest tightness nasal congestion, runny nose or other upper respiratory symptoms. In the early stage of the disease, the total number of leukocytes decreased or remains normal, with lowered lymphocyte count or increased or normal monocytes. C-reactive protein and D-dimer may increase (1-3). The population is generally susceptible to the virus. The elderly and those with underlying diseases may be more seriously affected after infection (2, 3). From current knowledge of the cases, most patients have a good prognosis, and a small portion of patients can have critical condition (1,2,5). Death cases (estimated to be 2%) are more frequently seen in the elderly and those with chronic underlying diseases (1, 3, 5).

According to current recommendation, in non-Wuhan/non-Hubei areas, persons with close contacts and suspicious exposure are advised to have a 14-day health observation period. Contact surveillance should be carried out for those who had exposed to accidental contact, low-level exposure to suspected or confirmed patients (1, 2, 4). Once they display any symptoms, especially fever, respiratory symptoms such as coughing, shortness of breath, or diarrhoea, they should seek medical attention immediately. Suspected cases are those with epidemiologic risk and with clinical features (1,2). Confirmed cases are diagnosed with pathogenic evidence of (1) positive for the 2019-nCoV by the real-time PCR test for nucleic acid in respiratory or blood samples; or (2) viral gene sequencing shows highly homogeneity to the known 2019-nCoV in respiratory or blood samples.

Recently, CT has been advocated and widely applied in Covid-19 clinical management, including for child subjects (5-9). Typical chest imaging manifestations include multiple, patchy, sub-segmental or segmental ground glass density shadows in both lungs (1). However, hereby we hope to reiterate that while CT radiation is associated with nonnegligible oncogenic risk (10, 11), till now the role of CT for Coivd-19 patients care remain poorly defined. Currently there is no effective anti-viral treatment or vaccine for 2019-nCoV (1). This is different to the cases of pulmonary tuberculosis. For tuberculosis, after a clinical diagnosis aided with imaging is made, anti-tuberculosis treatment can be initiated even without positive pathogenic diagnosis of Mycobacterium tuberculosis smear or culture. For cases of Coivd-19, CT may show signs typical of viral pneumonia, and such help the clinical diagnose. However, a shift from a suspected case to a clinically diagnosed Coivd-19 case may not impact the clinical management.

Covid-19 suspected case should be isolated, and supportive treatments offered. Covid-10 patients are classifications into (a) asymptomatic infection (b) acute upper respiratory tract infection (c) mild pneumonia, (d) severe pneumonia, and (e) critical cases (1,2). The supportive treatments are primarily based on the severity of clinical symptoms/signs. For severe and critical cases, hematological and biochemical parameters analysis are monitored. CXR (chest X-ray) can be performed to watch the progression or regression of pulmonary lesions (12). There may be a chance that CXR can help early identification of critical cases, with imaging features of bilateral or multi-lobe infiltration, or rapid progression of conditions during a very short period (1).  

For the initial disease detection, it should be noted that in about 25% cases of Covid-19, chest CT can be negative (5). A one-time negative chest CT does not rule out Covid-19. CXR is likely to miss some patients with less substantial ground grass opacities. However, with this limitation known, a negative CXR also does not rule out the diagnosis of Covid-19 and the patient will be further monitored. The severity of lung changes visible on imaging is mostly related to the severity of the disease itself (5). For these CXR missed milder cases, if CT is applied and lesions are detected, the clinical treatment management would remain the same; as all suspected patients should be isolated and monitored. The management might be different if an effective anti-viral treatment is found, such as if Remdesivir is proven to be effective for Covid-19, then likely a clinical diagnosis based on epidemiological rick factor, clinical symptoms and typical CT manifestation of viral pneumonia may warrant Remdesivir administration (12).

While a CXR delivers a radiation dosage of around 0.1 mSv, a standard chest CT may deliver around 4 mSv. It was estimated that one CT scan may be associated an oncogenic risk of 0.3-0.7%. For patients had multiple CT scans, the risk can be as high as 2.7%-12% (13, 14). Moreover, CT scan would incur procedure-induced virus transmission. Also, CT findings can only suggest pneumonia.If false CT positive patients i.e., pneumonia patients ofcauses other than2019-nCoV, arehospitalized in wards close to Covid-19 patients, there is an additional high risk of hospital-based transmission.  In one study in Wuhan, hospital-related transmission of 2019-nCoV was suspected in 41% of patients (3); though this can be improved with more precautions.

CT may be useful for some scenarios. Using CT to detect Covid-19 pneumonia may be justified in areas such as Wuhan/Hubei, where the healthcare is currently stretched, and management priority are given to confirmed or clinically diagnosed Covid-19 patients. According to the current guideline, the body temperature returned to normal for more than 3 days; respiratory symptoms improved significantly; inflammation of the lungs showed obvious signs of absorption; and respiratory nucleic acid was negative for two consecutive times (one-day sampling time interval at least); and the patient can be released from isolation (1,2). Upon further studies, we would expect CT may play a role for deciding when patient can be discharged from isolation. We also expect that CT may be applied in some selected suspected cases where pathogenic tests have been negative more than once, and if CT would show findings consistent with viral pneumonia, specific measures can be taken, such as even more stricter isolation according to region-specific guidelines.

In conclusion, currently there is no specific treatment or vaccine for Covid-19. The approach to this disease is to control the source of infection; use of personal protection precaution to reduce the risk of transmission; and early isolation and supportive treatments for affected patients. The role of CT in Covid-19 patient’s management course remains undefined and its application as a diagnostic tool may be unjustified among areas with low Covid-19 prevalence (low pre-CT test probability). In all cases, we need to keep patients’ exposure to radiation as low as possible. Particularly, children should avoid CT examination as much as possible. Children are ten times more sensitive than adults to the induction of cancer by radiation (10), and ultrasound imaging can be considered as an alternative to techniques associated with radiation (15, 16). CXR can be the choice for imaging, particularly for serial monitoring, as demonstrated in the case report from USA (12). For CT examinations, low radiation dose mode and techniques to minimise the radiation dosage should always be applied (13, 17).

Footnote

All authors declare no conflict of interests

1. Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, for the Zhongnan Hospital of Wuhan University Novel Coronavirus Management and Research Team, Evidence-Based Medicine Chapter of China International Exchange and Promotive Association for Medical and Health Care (CPAM). A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020 Feb 6;7(1):4. doi: 10.1186/s40779-020-0233-6. [Epub ahead of print]

2.  Zhao D, Jiang Y, Jin R, et al. China National Clinical Research Center for Respiratory Diseases; National Center for Children’s Health, Beijing, China; Group of Respirology, Chinese Pediatric Society, Chinese Medical Association; Chinese Medical Doctor Association Committee on Respirology Pediatrics; China Medicine Education Association Committee on Pediatrics; Chinese Research Hospital Association Committee on Pediatrics; Chinese Non-government Medical Institutions Association Committee on Pediatrics; China Association of Traditional Chinese Medicine, Committee on Children’s Health and Medicine Research; China News of Drug Information Association, Committee on Children’s Safety Medication; Global Pediatric Pulmonology Alliance. Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement. World J Pediatr. 2020 Feb 7. doi: 10.1007/s12519-020-00343-7. [Epub ahead of print]

3. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585. [Epub ahead of print]

4. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance. Published January 28, 2020. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected

5. Guan WJ, Ni ZY, Hu Y, on behalf of China Medical Treatment Expert Group for 2019-nCoV. Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv preprint doi: https://doi.org/10.1101/2020.02.06.20020974. 2020 Feb 9.

6. Chung M, Bernheim A, Mei X, Zhang N, Huang M, Zeng X, et al. CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV). Radiology. 2020 Feb 4:200230. doi: 10.1148/radiol.2020200230.

7. Chinese Society of Radiology. Radiological Diagnosis of New Coronavirus Infected Pneumonitis: Expert Recommendation from the Chinese Society of Radiology (First edition) Chin J Radiol, 2020,54(00): E001-E001. DOI: 10.3760/cma.j.issn.1005-1201.2020.0001 Published 2020-02-08

8. Pan Y, Guan H, Zhou S, Wang Y, Li Q, Zhu T, et al. Initial CT findings and temporal changes in patients with the novel coronavirus pneumonia (2019-nCoV): a study of 63 patients in Wuhan, China. European Radiology. First Online: 13 February 2020

9. Ma HJ, Shao JB, Wang JR, et al. high resolution CT of  New Coronavirus Infected Pneumonitis  in children. Chin J Radiol (In press)

10. Hall EJ. Lessons we have learned from our children: cancer risks from diagnostic radiology. Pediatr Radiol. 2002;32:700-6.

11. Hong JY, Han K, Jung JH, Kim JS. Association of exposure to diagnostic low-dose ionizing radiation with risk of cancer among youths in South Korea. JAMA Netw Open 2019;2:e1910584.

12.  Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al.  Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Jan 31. doi: 10.1056/NEJMoa2001191. [Epub ahead of print]

13. Kalra MK, Maher MM, Rizzo S, Kanarek D, Shepard JA. Radiation exposure from chest CT: issues and strategies. J Korean Med Sci. 2004;19:159-66.

14. <https://www.health.harvard.edu/cancer/radiation-risk-from-medical-imaging > Accessed February 12, 2020

15. Liang HY, Liang XW, Chen ZY, et al. Ultrasound in neonatal lung disease. Quant Imaging Med Surg. 2018;8:535-546.

16. Reali F, Sferrazza Papa GF, Fracasso P, Di Marco F, Mandelli M,et al. Can lung ultrasound replace chest radiography for the diagnosis of pneumonia in hospitalized children? Respiration 2014;88:112-5. 

17. Jin S, Zhang B, Zhang L, Li S, Li S, Li P. Lung nodules assessment in ultra-low-dose CT with iterative reconstruction compared to conventional dose CT. Quant Imaging Med Surg. 2018;8:480-490.