On 27 May 2020, WHO published updated interim guidance on the clinical management of COVID-19,1,2 and provided updated recommendations on the criteria for discharging patients from isolation. The updated criteria reflect recent findings that patients whose symptoms have resolved may still test positive for the COVID-19 virus (SARS-CoV-2) by RT-PCR for many weeks. Despite this positive test result, these patients are not likely to be infectious and therefore are unlikely to be able to transmit the virus to another person.
This scientific brief provides the rationale for the changes made to the clinical management of COVID-19 guidance, based on recent scientific evidence. WHO will update these criteria as more information becomes available. For more information about clinical care of COVID-19 patients, see WHO’s full guidance.1
Initial recommendation (published on 12 January 2020)
WHO’s first technical package of guidance for the clinical management of the novel coronavirus, now known as COVID-19, was published in early January 2020, shortly after a cluster of atypical pneumonia cases was first reported in Wuhan, People’s Republic of China,3 and included recommendations on when a patient with COVID-19 is no longer considered infectious.
The initial recommendation to confirm clearance of the virus, and thus allow discharge from isolation, required a patient to be clinically recovered and to have two negative RT-PCR results on sequential samples taken at least 24 hours apart.4 This recommendation was based on our knowledge and experience with similar coronaviruses, including those that cause SARS and MERS.5
New recommendation (published on 27 May 2020 as part of more comprehensive clinical care guidance1)
Within the Clinical Management of COVID-19 interim guidance published on 27 May 2020,1 WHO updated the criteria for discharge from isolation as part of the clinical care pathway of a COVID-19 patient. These criteria apply to all COVID-19 cases regardless of isolation location or disease severity.
Criteria for discharging patients from isolation (i.e., discontinuing transmission-based precautions) without requiring retesting:
- For symptomatic patients: 10 days after symptom onset, plus at least 3 additional days without symptoms (including without fever  and without respiratory symptoms)
- For asymptomatic cases: 10 days after positive test for SARS-CoV-2
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伊法斯夫拉腾以英国独立党(U.K. Independence Party)为例，它的官方平台力主脱欧，但是面向选民的宣传中又强调移民对经济与文化的影响，她说这是一种混合了务实与民粹的论调。
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*Countries may choose to continue to use testing as part of the release criteria. If so, the initial recommendation of two negative PCR tests at least 24 hours apart can be used.
What is the reason for the change?
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- Long periods of isolation for individuals with prolonged viral RNA detection after resolution of symptoms, affecting individual well-being, society ,and access to healthcare.13
- Prolonged viral shedding around the limit of detection, having negative results followed by positive results, which unnecessarily challenges trust in the laboratory system.23-28
These challenges and newly available data on the risk of viral transmission over the course of the COVID-19 illness provided the framework for updating WHO’s position on the timing of discharging recovered patients from isolation in and outside health care facilities. WHO continuously reviews scientific literature on COVID-19 through its Science Division and its COVID-19 technical teams. All aspects of clinical management of COVID-19 patients and laboratory testing strategies are discussed within WHO and with Member States and WHO’s global expert networks of public health professionals, clinicians, and academics around the world. These expert networks and the Strategic and Technical Advisory Group for Infectious Hazards (STAG-IH)7 considered the challenges and reviewed the available data in the decision process to change the initial recommendation.
The GDP of Southwest China's Chongqing Municipality grew by 10.7 percent in 2016, hitting 1.76 trillion yuan. Southwest China's Guizhou province and Tibet autonomous region posted 10.5 percent and 10 percent growth respectively.
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China’s exports and imports suffered larger-than-expected drops in the first month of this year in both renminbi- and dollar-denominated terms.
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WHO encourages the scientific community to compile additional evidence to further improve isolation discharge criteria and establish the conditions under which isolation can be abbreviated or where the possible risks of the current discharge criteria require further adaptation. Better understanding of transmission risk among individuals with different clinical presentations or comorbidities and in different settings will aid further refinement of these criteria. For situations that might still require a laboratory-based approach, we encourage the further optimization of such a laboratory algorithm. WHO encourages countries to continue testing patients, if they have the capacity to do so, for systematic data collection that will enhance understanding and better guide decisions about infection prevention and control measures, especially among patients with prolonged illness or those who are immunocompromised.
Current understanding of transmission risk
Infection with the virus causing COVID-19 (SARS-CoV-2) is confirmed by the presence of viral RNA detected by molecular testing, usually RT-PCR. Detection of viral RNA does not necessarily mean that a person is infectious and able to transmit the virus to another person. Factors that determine transmission risk include whether a virus is still replication-competent, whether the patient has symptoms, such as a cough, which can spread infectious droplets, and the behavior and environmental factors associated with the infected individual. Usually 5-10 days after infection with SARS-CoV-2, the infected individual starts to gradually produce neutralizing antibodies. Binding of these neutralizing antibodies to the virus is expected to reduce the risk of virus transmission.10,11,29,35
SARS-CoV-2 RNA has been detected in patients 1-3 days before symptom onset, and viral load in the upper respiratory tract peaks within the first week of infection, followed by a gradual decline over time.10,12,15,19,21,22,36-39 In the feces and lower respiratory tract, this viral load seems to peak in the second week of illness.19 Viral RNA has been detected in upper respiratory tract (URT) and lower respiratory tract (LRT) and feces, regardless of severity of disease.19 There seems to be a trend in longer detection of viral RNA in more severely ill patients.10,14,15,18,19,41-43 Studies of viral RNA detection in immunocompromised patients are limited, but one study suggested prolonged detection of viral RNA in renal transplant patients.33 Some studies analyzed the risk of transmission related to symptom of onset, and the estimated risk of transmission was highest at or around the time of symptom onset and in the first 5 days of illness.13,15
The ability of the virus to replicate in cultured cells serves as a surrogate marker of infectivity but requires special laboratory capabilities and may not be as sensitive as PCR.10,20 Animal models can aid understanding of transmission risk. In a study by Sia, et al., hamsters infected with SARS-CoV-2 were housed with healthy hamsters on either day 1 or day 6 after infection. Transmission to healthy hamsters occurred in the day 1 group, but not in those exposed 6 days after inoculation. In this model, the timing of transmission correlated with the detection of virus using cell culture, but not with detection of viral RNA in donor nasal washes.31
Studies using viral culture of patient samples to assess the presence of infectious SARS-CoV-2 are limited.8-10,21,29,30,34 Viable virus has been isolated from an asymptomatic case.9 A study of 9 COVID-19 patients with mild to moderate disease found no SARS-CoV-2 virus able to be cultured from respiratory samples after day 8 of symptom onset.10 Three studies of patients with undisclosed or variable degree of illness showed an inability to culture virus after days 7-9 of symptom onset.8,29,30 Patients who were RT-PCR positive on retesting after an initial negative RT-PCR on discharge from isolation were also studied, and none of these patients yielded positive viral cultures.29 One possible outlier is a case report of a patient with mild COVID-19 who remained PCR-positive for 63 days after symptom onset. In this patient, viral cultures were positive from upper respiratory tract specimens only on the day of symptom onset, but were culture-positive from sputum samples until day 18.22 It is unclear whether this posed a transmission risk as the patient had no respiratory symptoms. In a hospital-based study of 129 patients severely or critically ill with COVID-19, 23 patients yielded at least one positive viral culture. This study included 30 patients who were immunocompromised. The median duration of viral shedding as measured by culture was 8 days post onset, the interquartile range was 5-11, and the range was 0-20 days.11 The probability of detecting virus in culture dropped below 5% after 15.2 days after of symptoms. In this study, patients testing positive by viral culture were still experiencing symptoms at the time of sample collection.11 This and other studies have described the correlation between reduced infectivity with the decrease in viral loads10,11,29,34 and a rise in neutralizing antibodies.10,11,29 Although viral RNA can be detected by PCR even after the resolution of symptoms, the amount of detected viral RNA is substantially reduced over time and generally below the threshold where replication competent virus can be isolated. Therefore, the combination of time after onset of symptoms and the clearance of symptoms seems to be a generally safe approach based on current data.
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在纽约市许多公寓楼的大门背后，充斥着居民们不协调的抱怨声。从我的“房地产答疑”(Ask Real Estate)专栏所收到的抱怨信中，我们可以一窥居民们是如何应对生活在拥挤、昂贵的住房中的种种不顺心的。比方说，有个合作公寓的股东被邻居家的老鼠窝吓坏了；有一对父母被禁止将婴儿车推进楼内的电梯；有个租户厨房里的橱柜从墙壁上掉了下来。
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These modifications to the criteria for discharge from isolation (in a health facility or elsewhere) balance the understanding of infectious risk and the practicality of requiring repeated negative PCR testing, especially in settings of intense transmission or limited testing supplies. Although the risk of transmission after symptom resolution is likely to be minimal based on what is currently known, it cannot be completely ruled out. However, there is no zero-risk approach, and strict reliance on PCR confirmation of viral RNA clearance creates other risks (e.g. straining resources and limiting access to health care for new patients with acute disease). In patients with severe disease who are symptomatic for prolonged periods of time, a laboratory-based approach might also aid decision-making on the need for prolonged isolation. Such a laboratory-based approach can include measuring viral load and neutralizing antibody (or proven equivalent antibody) levels.10,11,29 More research is needed to further validate such an approach.
WHO will update these criteria as more information becomes available. For more information about clinical care of COVID-19 patients, see WHO’s full guidance.1
 Countries can choose to continue to use a laboratory testing algorithm as part of the release criteria in (a subset of) infected individuals if their risk assessment gives reason to do so.
 Without the use of any antipyretics.
 Some patients may experience symptoms (such as post viral cough) beyond the period of infectivity. Further research is needed. For more information about clinical care of COVID-19 patients, see our Clinical Management Guidance.1
 An asymptomatic case is an individual who has a laboratory confirmed positive test and who has no symptoms during the complete course of infection.
- World Health Organization. Clinical management of COVID-19 (Interim Guidance) Potus v Korus, published 27 May 2020.
- World Health Organization. Coronavirus disease (COVID-19) Situation Report – 129. 28 May 2020. Available at: Steven Spielberg directs Meryl Streep and Tom Hanks in The Post, a thrilling drama about the unlikely partnership between The Washington Post's Katharine Graham (Streep), the first female publisher of a major American newspaper, and editor Ben Bradlee (Hanks), as they race to catch up with The New York Times to expose a massive cover-up of government secrets that spanned three decades and four U.S. Presidents. The two must overcome their differences as they risk their careers - and their very freedom - to help bring long-buried truths to light.
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- ProMED International Society for Infectious Disease. 30 December 2019. (绿色装修评价标准实施 助推良心地板企业更上层楼 )
- World Health Organization. Laboratory testing of human suspected cases of novel coronavirus (nCOV) infection (Interim Guidance) (2015年风头最劲的品牌：在新款切诺基的拉动下，Jeep在2014年的销量惊人地拉高了44%，而斯巴鲁的销量则静悄悄地提高了21%，现已成为美国第十大最受欢迎的汽车品牌。 10 January 2020)
- World Health Organization. Technical guidance laboratory Middle East Respiratory syndrome coronavirus (MERS-CoV) (她还表示，从较长期来看，另一个让她担心的“R”是“重置”(reset)，她解释称，全球各地的货币和财政政策在回归正常之前还有很长的路要走。她补充称：“最终的重置是那些在全球各地都有必要实施的结构性改革。”)
- World Health Organization. Global surveillance for COVID-19 caused by human infection with COVID-19 virus. (Interim Guidance) (One might expect that online programmes would appeal proportionately more to women than full-time programmes due to their flexibility. How-ever, data from the 2016 rankings show that women account for 30 per cent of enrolled students compared with 35 per cent for full-time programmes.
Last year was the hottest on earth since record-keeping began in 1880, scientists reported on Friday, underscoring warnings about the risks of runaway greenhouse gas emissions and undermining claims by climate change contrarians that global warming had somehow stopped., 20 April 2020)
- World Health Organization. Strategic and Technical Advisory Group for Infectious Hazards (STAG IH) (加快改善生态环境特别是空气质量，是人民群众的迫切愿望，是可持续发展的内在要求。必须科学施策、标本兼治、铁腕治理，努力向人民群众交出合格答卷。)
- Bullard J, Dusk K, Funk D, et al. Predicting infectious SARS-CoV-2 from diagnostic samples, Clin Infect Dis. 2020 doi: 10.1093/cid/ciaa638.
- We learned that we could see a source of ripples in space-time.
Cross-cultural Instrumental performance (Yanni, USA, and Chang Jing)
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“This could be just the beginning,” said Michael Na, a strategist in Seoul with Nomura.?“They have so many options to punish Korean businesses.”
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- Yuan J, Kou S, Liang Y, et al. PCR Assays Turned Positive in 25 Discharged COVID-19 Patients. Clin Infect Dis. 2020 doi: 10.1093/cid/ciaa398.
- Tang X, Zhao S, He D, et al. Positive RT-PCR tests among discharged COVID-19 patients in Shenzhen, China. Infect Control Hosp Epidemiol. 2020 doi: 10.1017/ice.2020.134.
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本文作者为卡内基国际和平基金会(Carnegie Endowment)高级研究员、世界银行(World Bank)中国业务局前局长，译者/何黎
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麻省理工学院（MIT）最近发表了一份白皮书。虽然该报告的题目听起来不免有些不吉利——《你是否已为供应链人才危机做好准备？》（Are You Prepared for the Supply Chain Talent Crisis?），却一语中的。这项研究表明，供应链经理需要掌握先进的技术技能，同时还得具备“高度的外交手腕”，精通总体业务战略，能娴熟地解决各类问题，要能在混沌状态中求生存。
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- Xu K, Chen Y, Yuan J, et al. Factors associated with prolonged viral RNA shedding in patients with COVID-19. Clin Infect Dis. 2020 doi: 10.1093/cid/ciaa351.
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