key: cord-0911902-pen037ms authors: Liu, Fang; Cai, Zhao-bin; Huang, Jin-song; Yu, Wen-yan; Niu, Hai-ying; Zhang, Yan; Sui, Dong-ming; Wang, Fei; Xue, Li-zhi; Xu, Ai-fang title: Positive SARS-CoV-2 RNA recurs repeatedly in a case recovered from COVID-19: dynamic results from 108 days of follow-up date: 2020-06-27 journal: Pathog Dis DOI: 10.1093/femspd/ftaa031 sha: b11c98033203c688d1ae17216041586f64aa4d4c doc_id: 911902 cord_uid: pen037ms The evidence of long-term clinical dynamic on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA re-positive case are less. We performed a 108 days follow-up on dynamic clinical presentations in a case, who hospitalized three times due to the positive recurrence of SARS-CoV-2 RNA after discharge, to understand the prognosis of the 2019-Coronavirus disease (COVID-19). In this case, positive SARS-CoV-2 recurred even after apparent recovery (normal CT imaging, no clinical symptoms, negative SARS-CoV-2 on stool sample and negative serum IgM test) from COVID-19, viral shedding duration lasted for 65 days, the time from symptom onset to disappearance was up to 95 days. Erythrocyte-associated indicators, liver function and serum lipid metabolism presented abnormal throughout during the observation period. Awareness of atypical presentations such as this one is important to prompt the improvement of the management of COVID-19. Potential infectivity of the recovered patients has been aroused great concern in many countries as the recurrence of positive SARS-CoV-2 during post-discharge surveillance (China Daily Website 2020; Yao et al. 2020; Lan et al. 2020) . Nowadays, the virus is spreading rapidly around the world. There will be more and more discharged patients in the future with medical rescuing. However, the infectivity of such cases remains unknown, and the evidence of long-term clinical dynamic on SARS-CoV-2 RNA re-positive cases are less. The present report describes 3.5-months presentations of the virus, clinical symptom, laboratory finding and CT image in a case who was admitted to hospital three times due to SARS-CoV-2 RNA recurred positive after discharge. At our institution, Xixi Hospital (a designated infectious disease hospital of Zhejiang province, China), the negative pressure isolation ward was reserved for confirmed cases of Republic of China 2020). The patient was isolated in a single-occupancy room of the community hospital for the next two weeks, and evaluated with the results of SARS-CoV-2 RNA on days 7 and 14 after discharge, to determine whether he could be released from quarantine. All Healthcare workers in our hospital and the community hospital underwent two nasopharyngeal swabs for the RT-PCR of SARS CoV-2 RNA, which were performed seven days apart. Each healthcare worker will be released from isolation after fulfilled the criteria of both SARS CoV-2 RNA detection presented negative. This study was approved by the Institutional Review Board of Xixi Hospital. No hospital staff was infected during the observation period. The case was a 35 years old man with an exposure history of Hubei province in China. He presented high fever (39℃), cough, sore throat and fatigue, and was admitted to hospital as positive detection of SARS-CoV-2 RNA on 30 January 2020. He denied other underlining diseases. The severity of disease was mild. Time kinetics of CT presentation, clinical symptom (cough or sputum) and virus are described in Fig. 1 . The day of symptom onset was defined as day 1. On day 2, CT images showed patchy ground-glass opacities and patchy hyperdense areas in the lower lunge zone. During the first hospitalized period, lopinavir (LPV) combined with interferon α2b atomization inhalation (IAI) and arbidol hydrochloride granules (AHG) was used for more than fourteen days, methylprednisolone (MPD) was added to the combined therapy for four days after the radiographic lesions progressed (days 3 and 5), the nasopharyngeal swab tests During the third hospitalization, the case was treated on admission with combined therapy (IAI+AHG) throughout, had a mild symptom of white productive cough which improved continuously since the day 53 and completely disappeared on day 56. But, there was a sore throat following with fever on day 53, which receded significantly after antibiotics using. The test of respiratory tract samples revealed negative on days 54 (nasopharyngeal swab) and 56 (sputum), respectively. Chest radiography was repeated on day 54 and showed Of this mild case, the functionality of lungs, kidney and heart was substantially normal during the follow-up period. High CRP levels and low lymphocyte counts appeared during the initial period of COVID-19, but all returned to normal for 15 days of treatment. Similar findings were also observed in other mild COVID-19 infected patients (Chen et al. 2020 ). The levels of ALT were much higher than that of AST, indicates that acute liver damage occurred on this patient at the early stage of COVID-19. This might be directly caused by the viral infection of liver cells (Zhang, Shi and Wang 2020) . The levels of ALT and AST both decreased to normal on the heels of the first negative SARS-CoV-2 RNA occurrence, which proves the possibility of viral exposure in the liver. However, the repetitive abnormal level of GGT, an index of liver dysfunction (Whitfield 2001) , implicates that liver impairment has not yet recovered completely and liver dysfunction sustained during the follow-up period. The obvious abnormal lipid metabolism may result from prolonged liver dysfunction (Speliotes et al. 2018) . Liver damage in mild cases of COVID-19 is often transient and can return to normal without any special treatment (Zhang, Shi and Wang 2020) . But, in this case, dyslipidemia and liver dysfunction lasted more than two months. Some studies have reported that the abnormalities of lipid metabolism and liver dysfunction associate with the severity of COVID-19 (Ren et al. 2020; Cai et al. 2020) . Given the case of this study presented a mild clinical symptom and a slight lesion of chest CT, it could be one of the underlining causes of the lingering characteristic of COVID-19. How different underlying liver conditions influence the relapse of COVID-19 needs to be meticulously evaluated in large-scale clinical trials. Of this case, the time from symptom onset to disappearance was at least 95 days and the duration of viral shedding after COVID-19 onset lasted for 65 days which is longer than that of 37 days (Zhou et al. 2020) . These issues present great difficulties and challenges for the screen of COVID-19 and for the prevention and control of this epidemic. Our study has limitations; the inherent shortcomings due to a retrospective observational case study, the absence of RT-PCR detection of SARS-CoV-2 RNA on broncho-alveolar lavage fluid and the lack of pathological examination on liver and lung tissues make it difficult to reach a firm conclusion. All above limitations require further study; nonetheless, our primary results provided new and important insights for this topic. COVID-19: Abnormal liver function tests Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China Recovered patient re-hospitalized after positive test Positive RT-PCR Test Results in Patients Recovered From COVID-19 The role of red blood cells in enhancing or preventing HIV infection and other diseases National Health Commission of the People's Republic of China. 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LF, CZB and HJS conceived, designed, and organized the study, interpreted the results, and drafted the manuscript. XAF helped supervise the study. The other authors contributed to collect the data on site. The authors declare that they have no competing interests.