key: cord-259949-ewcv8m06 authors: Xiao, Shu‐Yuan; Wu, Yingjie; Liu, Huan title: Evolving status of the 2019 novel coronavirus infection: Proposal of conventional serologic assays for disease diagnosis and infection monitoring date: 2020-02-17 journal: J Med Virol DOI: 10.1002/jmv.25702 sha: doc_id: 259949 cord_uid: ewcv8m06 The novel coronavirus (nCoV-2019) outbreak in Wuhan, China has spread rapidly nationwide, with some cases occurring in other parts of the world. Although most patients present with mild febrile illness with patchy pulmonary inflammation, a significant portion develop severe acute respiratory distress syndrome (ARDS), with a current case fatality of 2.3-3%. Diagnosis is based on clinical history and laboratory and chest radiographic findings, but confirmation currently relies on nucleic acid-based assays. The latter are playing an important role in facilitating patient isolation, treatment and assessment of infectious activities. However, due to their limited capacity to handle an epidemic of the current scale and insufficient supply of assay kits, only a portion of suspected cases can be tested, leading to incompleteness and inaccuracy in updating new cases, as well as delayed diagnosis. Furthermore, there has not been enough time to assess specificity and sensitivity. Conventional serological assays, such as enzyme-linked immunoassay (ELISA) for specific IgM and IgG antibodies, should offer a high-throughput alternative, which allows for uniform tests for all suspected patients, and can facilitate more complete identification of infected cases and avoidance of unnecessary cross infection among unselected patients. This article is protected by copyright. All rights reserved. The diagnosis needs to be differentiated from influenza, parainfluenza, adenovirus, respiratory syncytial virus, rhinovirus, SARS coronavirus, mycoplasma, chlamydia, and bacterial pneumonia, as well as noninfectious diseases such as vasculitis. 2, 6 2 | DIAGNOSIS USING THE RNA-BASED ASSAYS Currently, the diagnosis of suspected cases is confirmed by RNA tests with real-time RT-PCR or next-generation sequencing. It had been shown that viral RNA can be detected from the nasal and pharyngeal swab, bronchoalveolar lavage, and blood plasma using RT -PCR targeting the NP gene of the virus. 2, 4, 6 Before the Wuhan citywide shutdown, specimens for confirmatory tests had to be sent to China CDC, with a long turnaround time. Subsequently, several main tertiary care hospitals in Wuhan were authorized to perform the tests. Therefore, in the earlier stages of the outbreak, a very limited number of patients were tested and confirmed for the diagnosis. Since 25 January tests have become increasingly available for clinically suspected patients, with a history of exposure, fever, and positive findings on chest CT. However, since only a limited number of tests can be offered each day due to limited supplies and lab facilities, only a portion of the targeted population received tests. For example, during the month of January 2020, only 1700 specimens were tested (media report by the hospital on WeChat, 1/29/2020), compared with the vast number of clinic patients during that period (between 22 January and 30 January alone, there were over 7000 visits to one of the designated fever clinic). This created a significant backlog, as many patients had to wait for days to receive a confirmation or exclusion of diagnosis. It also led to problems in realtime reporting, causing artificial fluctuation in daily updates of new cases ( Figure 2B ). For example, as shown in Table 1 , using data collected from the National Health Commission's daily updates, 7 on some dates, the change in the number of newly confirmed cases varies drastically. This cannot be explained by realistic changes in the speed of infection spread. Needless to say, the recorded figures of daily confirmed cases are likely underestimated. F I G U R E 1 CT images of patients with novel coronavirus pneumonia. A, Patchy ground-glass-like density change from a 33-year-old woman who developed a mild illness after exposure at work. B, Bilateral diffuse thickening of interlobular septa with network-like densities, bronchiolar thickening, and consolidation of the left lower lobe from an 83-year-old woman. She presented with fever, chills, and sore throat; she had dry cough, chest tightness, and shortness of breath for a week. Her body temperature at presentation was 38.8°C, CBC showed WBC 4.6 × 10 9 /L, neutrophilic differential 65.8%, and lymphocytic differential 19.9% (reduced). (Courtesy of Prof Haibo Xu). CBC, complete blood count; CT, computed tomography; WBC, white blood cells Another concern related to the nucleic acid tests is that there has not been sufficient time to assess their sensitivity and specificity. A fast-performing serologic assay is acutely needed for the current and future outbreaks. The authors would like to thank Dr Haibo Xu for graciously providing the computed tomography images and Dr Jingyi Fan for sharing her personal observations. 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