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      De-isolating COVID-19 Suspect Cases: A Continuing Challenge

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          Abstract

          To the Editor—As of 15 February 2020, Singapore had screened a total of 991 suspected cases for coronavirus disease 2019 (COVID-19), of which 72 cases tested positive, 812 cases tested negative, and the remaining 107 had pending results [1]. Besides optimizing sample type to increase yield and ease of collection [2], the challenge in clinical management of suspected cases lies in deciding whether they may be de-isolated or if further isolation and repeat testing are required. No single indicator may be effectively used to decide on de-isolation of a suspected case. In our series of positive cases, samples from 1 suspected case only returned positive on the fifth repeated sample (nasopharyngeal swab), on the seventh day of clinical illness. Current evidence suggests that transmission of COVID-19 may be possible even from asymptomatic contacts [3], and polymerase chain reaction testing may not return positive initially [4]. Our suspected case was kept isolated because of a high index of clinical suspicion, with a clinically compatible illness and history of close contact with a laboratory-proven COVID-19 case. While multiplex respiratory virus panels, in general, may be helpful in the evaluation of other viral acute respiratory infections (ARIs), even the detection of an alternate respiratory pathogen may not definitively exclude COVID-19 infection. Dual infections can occur in 10%–20% of viral ARIs, as has been reported with severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus [5]. In our case series, 1 patient with confirmed COVID-19 by a nasopharyngeal sample also exhibited clinical symptoms compatible with dengue fever. This was laboratory confirmed by dengue NS1 antigen test. (P. L. Lim, personal communication, February 2020). There were 2 notable operational challenges in the de-isolation of suspected cases. With substantial numbers of suspected cases admitted for isolation and the need to hold patients for repeated testing, there was a need to manage isolation room occupancy. However, for patients who needed ongoing inpatient care for other reasons, we also needed to address the risk of inadvertent nosocomial amplification, to reduce the risk of transmission from patients who had tested negative early in their clinical illness. A rigorous framework was required to help clinicians de-isolate COVID-19 patients safely. At the National Centre for Infectious Diseases, we have used the algorithm shown in Figure 1 as our decision-making matrix to decide on the disposition of our patients. Figure 1. National Centre for Infectious Diseases de-isolation criteria for coronavirus disease 2019 suspected cases. Abbreviations: COVID-19, coronavirus disease 2019; nCoV, novel coronavirus; PCR, XXX. As with other respiratory viruses, factors such as sample type (lower respiratory samples being preferable in patients with pneumonia) and specimen collection technique will contribute to the sensitivity and ease of diagnostic testing. We addressed the challenge of delayed positivity in coronavirus testing in relation to illness onset, by repeating testing for patients who are within the first 7 days of respiratory symptoms, and for whom COVID-19 is still suspected despite initial negative tests. Our algorithm incorporates epidemiological and clinical features needed to decide the disposition of suspected cases, while acknowledging that microbiologic testing might be negative early in the course of illness. With emerging data and further understanding of COVID-19, this algorithm may be refined further and its performance assessed prospectively.

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          Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

          To the Editor: The novel coronavirus (2019-nCoV) from Wuhan is currently causing concern in the medical community as the virus is spreading around the world. 1 Since identification of the virus in late December 2019, the number of cases from China that have been imported into other countries is on the rise, and the epidemiologic picture is changing on a daily basis. We are reporting a case of 2019-nCoV infection acquired outside Asia in which transmission appears to have occurred during the incubation period in the index patient. A 33-year-old otherwise healthy German businessman (Patient 1) became ill with a sore throat, chills, and myalgias on January 24, 2020. The following day, a fever of 39.1°C (102.4°F) developed, along with a productive cough. By the evening of the next day, he started feeling better and went back to work on January 27. Before the onset of symptoms, he had attended meetings with a Chinese business partner at his company near Munich on January 20 and 21. The business partner, a Shanghai resident, had visited Germany between January 19 and 22. During her stay, she had been well with no signs or symptoms of infection but had become ill on her flight back to China, where she tested positive for 2019-nCoV on January 26 (index patient in Figure 1) (see Supplementary Appendix, available at NEJM.org, for details on the timeline of symptom development leading to hospitalization). On January 27, she informed the company about her illness. Contact tracing was started, and the above-mentioned colleague was sent to the Division of Infectious Diseases and Tropical Medicine in Munich for further assessment. At presentation, he was afebrile and well. He reported no previous or chronic illnesses and had no history of foreign travel within 14 days before the onset of symptoms. Two nasopharyngeal swabs and one sputum sample were obtained and were found to be positive for 2019-nCoV on quantitative reverse-transcriptase–polymerase-chain-reaction (qRT-PCR) assay. 2 Follow-up qRT-PCR assay revealed a high viral load of 108 copies per milliliter in his sputum during the following days, with the last available result on January 29. On January 28, three additional employees at the company tested positive for 2019-nCoV (Patients 2 through 4 in Figure 1). Of these patients, only Patient 2 had contact with the index patient; the other two patients had contact only with Patient 1. In accordance with the health authorities, all the patients with confirmed 2019-nCoV infection were admitted to a Munich infectious diseases unit for clinical monitoring and isolation. So far, none of the four confirmed patients show signs of severe clinical illness. This case of 2019-nCoV infection was diagnosed in Germany and transmitted outside Asia. However, it is notable that the infection appears to have been transmitted during the incubation period of the index patient, in whom the illness was brief and nonspecific. 3 The fact that asymptomatic persons are potential sources of 2019-nCoV infection may warrant a reassessment of transmission dynamics of the current outbreak. In this context, the detection of 2019-nCoV and a high sputum viral load in a convalescent patient (Patient 1) arouse concern about prolonged shedding of 2019-nCoV after recovery. Yet, the viability of 2019-nCoV detected on qRT-PCR in this patient remains to be proved by means of viral culture. Despite these concerns, all four patients who were seen in Munich have had mild cases and were hospitalized primarily for public health purposes. Since hospital capacities are limited — in particular, given the concurrent peak of the influenza season in the northern hemisphere — research is needed to determine whether such patients can be treated with appropriate guidance and oversight outside the hospital.
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            Chest CT for Typical 2019-nCoV Pneumonia: Relationship to Negative RT-PCR Testing

            Some patients with positive chest CT findings may present with negative results of real time reverse-transcription–polymerase chain- reaction (RT-PCR) for 2019 novel coronavirus (2019-nCoV). In this report, we present chest CT findings from five patients with 2019-nCoV infection who had initial negative RT-PCR results. All five patients had typical imaging findings, including ground-glass opacity (GGO) (5 patients) and/or mixed GGO and mixed consolidation (2 patients). After isolation for presumed 2019-nCoV pneumonia, all patients were eventually confirmed with 2019-nCoV infection by repeated swab tests. A combination of repeated swab tests and CT scanning may be helpful when for individuals with high clinical suspicion of nCoV infection but negative RT-PCR screening
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              Consistent Detection of 2019 Novel Coronavirus in Saliva

              Abstract The 2019 novel coronavirus (2019-nCoV) was detected in the self-collected saliva of 91.7% (11/12) of patients. Serial saliva viral load monitoring generally showed a declining trend. Live virus was detected in saliva by viral culture. Saliva is a promising noninvasive specimen for diagnosis, monitoring, and infection control in patients with 2019-nCoV infection.
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                Author and article information

                Journal
                Clinical Infectious Diseases
                Oxford University Press (OUP)
                1058-4838
                1537-6591
                February 26 2020
                February 26 2020
                Affiliations
                [1 ]National Centre for Infectious Diseases
                [2 ]Department of Infectious Diseases, Tan Tock Seng Hospital
                Article
                10.1093/cid/ciaa179
                489ff5d8-d36b-4c1c-9b85-b9782dff1706
                © 2020

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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