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      Covert COVID-19 and false-positive dengue serology in Singapore

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          Abstract

          Dengue and coronavirus disease 2019 (COVID-19) are difficult to distinguish because they have shared clinical and laboratory features.1, 2 We describe two patients in Singapore with false-positive results from rapid serological testing for dengue, who were later confirmed to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative virus of COVID-19. The first case is a 57-year-old man with no relevant past medical, travel, or contact history, who presented to a regional hospital on Feb 9, 2020, with 3 days of fever and cough. He had thrombocytopenia (platelet count 140 × 109/mL) and a normal chest radiograph. He was discharged after a negative rapid test for dengue NS1, IgM, and IgG (SD Bioline Dengue Duo Kit; Abbott, South Korea). He returned to a public primary health-care clinic with persistent fever, worsening thrombocytopenia (89 × 109/mL), and new onset lymphopenia (0·43 × 109/mL). A repeat dengue rapid test was positive for dengue IgM and IgG (Dengue Combo; Wells Bio, South Korea). He was referred to hospital for dengue with worsening cough and dyspnoea. A chest radiograph led to testing for SARS-CoV-2 by RT-PCR (in-house laboratory-developed test detecting the N and ORF1ab genes) from a nasopharyngeal swab, which returned positive. The original seropositive sample and additional urine and blood samples tested negative for dengue, chikungunya, and Zika viruses by RT-PCR,3, 4, 5 and a repeat dengue rapid test (SD Bioline) was also negative. Thus, the initial dengue seroconversion result was deemed a false positive. The second case is a 57-year-old woman with no relevant past medical, travel, or contact history, who presented to a regional hospital on Feb 13, 2020, with fever, myalgia, a mild cough of 4 days, and 2 days of diarrhoea. She had thrombocytopenia (92 × 109/mL) and tested positive for dengue IgM (SD Bioline). She was discharged with outpatient follow up for dengue fever. She returned 2 days later with a persistent fever, worsening thrombocytopenia (65 × 109/mL), and new onset lymphopenia (0·94 × 109/mL). Liver function tests were abnormal (aspartate aminotransferase 69 U/L [reference range 10–30 U/L], alanine aminotransferase 67 U/L [reference range <55 U/L], total bilirubin 35·8 μmol/L [reference range 4·7–23·2 μmol/L]). Chest radiography was normal and she was admitted for dengue fever. She remained febrile despite normalisation of her blood counts and developed dyspnoea 3 days after admission. She was found to be positive for SARS-CoV-2 by RT-PCR from a nasopharyngeal swab. A repeat dengue test (SD Bioline) was negative and an earlier blood sample also tested negative for dengue by RT-PCR. 6 The initial dengue IgM result was deemed to be a false positive. Failing to consider COVID-19 because of a positive dengue rapid test result has serious implications not only for the patient but also for public health. Our cases highlight the importance of recognising false-positive dengue serology results (with different commercially available assays) in patients with COVID-19. We emphasise the urgent need for rapid, sensitive, and accessible diagnostic tests for SARS-CoV-2, which need to be highly accurate to protect public health.

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          Most cited references 3

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          Chikungunya virus isolated from a returnee to Japan from Sri Lanka: isolation of two sub-strains with different characteristics.

          A large-scale epidemic of chikungunya (CHIK) fever occurred in several Indian Ocean islands in 2004 and spread to India and Sri Lanka. In December 2006, a returnee to Japan from Sri Lanka developed an acute febrile illness. The patient was confirmed to have CHIK fever after reverse transcription-polymerase chain reaction, and specific IgM and IgG detection. CHIK virus was isolated from the serum specimen collected at the acute stage. The isolated virus developed two different sizes of plaques. Two sub-strains with different genetic and biological characteristics were obtained by plaque purification from one isolate. The entire genome was sequenced and phylogenetic analysis of the E1 genome showed that the sub-strains were of the Central/East African genotype, and were closely related to recent isolates in India. This is the first report of CHIK virus genome sequences isolated from a patient infected in Sri Lanka.
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            Distinguishing Zika and Dengue Viruses through Simple Clinical Assessment, Singapore

            Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case–control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.
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              Preliminary evaluation of Thermo Fisher TaqMan® Triplex q-PCR kit for simultaneous detection of chikungunya, dengue, and Zika viruses in mosquitoes.

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                Author and article information

                Contributors
                Journal
                Lancet Infect Dis
                Lancet Infect Dis
                The Lancet. Infectious Diseases
                Elsevier Ltd.
                1473-3099
                1474-4457
                4 March 2020
                4 March 2020
                Affiliations
                [a ]Department of Medicine, National University Health System, 119228, Singapore
                [b ]Department of Laboratory Medicine, University Medicine Cluster, National University Health System, Singapore
                [c ]Pioneer Polyclinic, National University Polyclinics, National University Health System, Singapore
                [d ]Department of Medicine, Ng Teng Fong General Hospital, Singapore
                [e ]Environmental Health Institute, National Environment Agency, Singapore
                Article
                S1473-3099(20)30158-4
                10.1016/S1473-3099(20)30158-4
                7128937
                32145189
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Article

                Infectious disease & Microbiology

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