Abstract
Background: The proportion of recurrences after discharge among patients with coronavirus disease 2019 (COVID-19) was reported to be between 9.1% and 31.0%. Little is known about this issue, however, so we performed a meta-analysis to summarize the demographical, clinical, and laboratorial characteristics of non-recurrence and recurrence groups. Methods: Comprehensive searches were conducted using eight electronic databases. Data regarding the demographic, clinical, and laboratorial characteristics of both recurrence and non-recurrence groups were extracted, and quantitative and qualitative analyses were conducted. Results: Ten studies involving 2071 COVID-19 cases were included in this analysis. The proportion of recurrence cases involving patients with COVID-19 was 17.65% (between 12.38% and 25.16%) while older patients were more likely to experience recurrence (weighted mean difference (WMD)=1.67, range between 0.08 and 3.26). The time from discharge to recurrence was 13.38 d (between 12.08 and 14.69 d). Patients were categorized as having moderate severity (odds ratio (OR)=2.69, range between 1.30 and 5.58), while those with clinical symptoms including cough (OR=5.52, range between 3.18 and 9.60), sputum production (OR=5.10, range between 2.60 and 9.97), headache (OR=3.57, range between 1.36 and 9.35), and dizziness (OR=3.17, range between 1.12 and 8.96) were more likely to be associated with recurrence. Patients presenting with bilateral pulmonary infiltration and decreased leucocyte, platelet, and CD4+ T counts were at risk of COVID-19 recurrence (OR=1.71, range between 1.07 and 2.75; WMD=−1.06, range between −1.55 and −0.57, WMD=−40.39, range between −80.20 and −0.48, and WMD=−55.26, range between −105.92 and −4.60, respectively). Conclusions: The main factors associated with the recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after hospital discharge were older age, moderate severity, bilateral pulmonary infiltration, laboratory findings including decreased leucocytes, platelets, and CD4+ T counts, and clinical symptoms including cough, sputum production, headache, and dizziness. These factors can be considered warning indicators for the recurrence of SARS-CoV-2 and might help the development of specific management strategies.
概要
通过检索筛选到 10 项涉及 2071 例新型冠状病毒肺炎 (COVID-19) 患者出院后复查严重急性呼吸综合征冠状病毒 2 型 (SARS-CoV-2) 核酸检测的研究, 总结其流行病学、 临床症状和辅助检查特征. COVID-19 患者出院后病毒检测复阳病例占比为 17.65%, 而年龄较大的患者更有可能病毒复阳, 临床症状合并咳嗽、咳痰、头晕症状的患者有 SARS-CoV-2 复阳的风险. 此外, 辅助检查结果呈双侧肺浸润且白细胞、 血小板和 CD4+ T 计数降低的患者有 SARS-CoV-2 病毒复阳的风险. 这些因素可以被视为 SARS-CoV-2 复阳的预警指标, 并可能有助于临床制定个体化管理策略.
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References
Ades AE, Lu G, Higgins JPT, 2005. The interpretation of random-effects meta-analysis in decision models. Med Decis Making, 25(6):646–654. https://doi.org/10.1177/0272989x05282643
Ahmad I, Rathore F, 2020. Neurological manifestations and complications of COVID-19: a literature review. J Clin Neurosci, 77:8–12. https://doi.org/10.1016/j.jocn.2020.05.017
Altmann DM, Boyton RJ, 2020. SARS-CoV-2 T cell immunity: specificity, function, durability, and role in protection. Sci Immunol, 5(49):eabd6160. https://doi.org/10.1126/sciimmunol.abd6160
An JH, Liao XJ, Xiao TY, et al., 2020. Clinical characteristics of the recovered COVID-19 patients with re-detectable positive RNA test. Ann Transl Med, 8(17):1–12. https://doi.org/10.21037/atm-20-5602
Bellesi S, Metafuni E, Hohaus S, et al., 2020. Increased CD95 (Fas) and PD-1 expression in peripheral blood T lymphocytes in COVID-19 patients. Br J Haematol, 191(2): 207–211. https://doi.org/10.1111/bjh.17034
Cai JH, Xu J, Lin DJ, et al., 2020. A case series of children with 2019 novel coronavirus infection: clinical and epidemiological features. Clin Infect Dis, 71 (6):1547–1551. https://doi.org/10.1093/cid/ciaa198
Cauchemez S, van Kerkhove MD, Riley S, et al., 2013. Transmission scenarios for Middle East respiratory syndrome coronavirus (MERS-CoV) and how to tell them apart. Euro Surveill, 18(24):20503.
Chen DB, Xu WX, Lei ZY, et al., 2020. Recurrence of positive SARS-CoV-2 RNA in COVID-19: a case report. Int J Infect Dis, 93:297–299. https://doi.org/10.1016/j.ijid.2020.03.003
Chen J, Xu XP, Hu J, et al., 2020. Clinical course and risk factors for recurrence of positive SARS-CoV-2 RNA: a retrospective cohort study from Wuhan, China. Aging, 12(17):16675–16689. https://doi.org/10.18632/aging.103795
Chen NS, Zhou M, Dong X, et al., 2020. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 395(10223):507–513. https://doi.org/10.1016/s0140-6736(20)30211-7
Cui J, Li F, Shi ZL, 2019. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol, 17(3):181–192. https://doi.org/10.1038/s41579-018-0118-9
Guo LX, Wei D, Zhang XX, et al., 2019. Clinical features predicting mortality risk in patients with viral pneumonia: the MuLBSTA score. Front Microbiol, 10:2752. https://doi.org/10.3389/fmicb.2019.02752
Hoang VT, Dao TL, Gautret P, 2020. Recurrence of positive SARS-CoV-2 in patients recovered from COVID-19. J Med Virol, 92(11):2366–2367. https://doi.org/10.1002/jmv.26056
Hottz ED, Azevedo-Quintanilha IG, Palhinha L, et al., 2020. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood, 136(11):1330–1341. https://doi.org/10.1182/blood.2020007252
Hu RJ, Jiang ZX, Gao HM, et al., 2020. Recurrent positive reverse transcriptase-polymerase chain reaction results for coronavirus disease 2019 in patients discharged from a hospital in China. JAMA Netw Open, 3(5):e2010475. https://doi.org/10.1001/jamanetworkopen.2020.10475
Huang J, Zheng L, Li Z, et al., 2020. Recurrence of SARS-CoV-2 PCR positivity in COVID-19 patients: a single center experience and potential implications. medRxiv, preprint. https://doi.org/10.1101/2020.05.06.20089573
Hui KPY, Cheung MC, Perera RAMP, et al., 2020. Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures. Lancet Respir Med, 8(7):687–695. https://doi.org/10.1016/s2213-2600(20)30193-4
Jaiswal S, Liu XB, Wei QC, et al., 2018. Effect of corticosteroids on atrial fibrillation after catheter ablation: a meta-analysis. J Zhejiang Univ-Sci B (Biomed &Biotechnol), 19(1):57–64. https://doi.org/10.1631/jzus.B1600529
Jiang ML, Li Y, Han ML, et al., 2020. Recurrent PCR positivity after hospital discharge of people with coronavirus disease 2019 (COVID-19). J Infect, 81(1):147–178. https://doi.org/10.1016/j.jinf.2020.03.024
Khose S, Moore JX, Wang HE, 2020. Epidemiology of the 2020 pandemic of COVID-19 in the state of Texas: the first month of community spread. J Community Health, 45(4):696–701. https://doi.org/10.1007/s10900-020-00854-4
Li LQ, Huang SL, 2020. Whether the repositive rate of 14% of discharged patients in guangdong is infectious is not clear. Caixin (in Chinese). http://china.caixin.com/2020-02-25/101520334.html
Li N, Wang X, Lv TF, 2020. Prolonged SARS-CoV-2 RNA shedding: not a rare phenomenon. J Med Virol, 92(11): 2286–2287. https://doi.org/10.1002/jmv.25952
Li Q, Zhang H, Deng SY, et al., 2020. Expression and morphological analysis of peripheral blood lymphocytes subsets in patients with 2019 noval coronavirus. Chongqing Med, online (in Chinese).
Li TS, Lu HZ, Zhang WH, 2020. Clinical observation and management of COVID-19 patients. Emerg Microbes Infect, 9(1):687–690. https://doi.org/10.1080/22221751.2020.1741327
Li YJ, Hu YY, Yu YY, et al., 2020. Positive result of Sars-Cov-2 in faeces and sputum from discharged patient with COVID-19 in Yiwu, China. J Med Virol, 92(10):1938–1947. https://doi.org/10.1002/jmv.25905
Lippi G, Plebani M, Henry BM, 2020. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta, 506:145–148. https://doi.org/10.1016/j.cca.2020.03.022
Liu S, Zhi YX, Ying S, 2020. COVID-19 and asthma: reflection during the pandemic. Clin Rev Allergy Immunol, 59(1):78–88. https://doi.org/10.1007/s12016-020-08797-3
Liu W, Tao ZW, Wang L, et al., 2020. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chin Med J, 133(9): 1032–1038. https://doi.org/10.1097/cm9.0000000000000775
Luo DH, Wan X, Liu JM, et al., 2018. Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range. Stat Methods in Med Res, 27(6): 1785–1805. https://doi.org/10.1177/0962280216669183
Medical Administration and Hospital Authority, 2020. National Health Commission’s COVID-19 Diagnosis and Treatment Protocol (Trial Version 7) (in Chinese). http://www.nhc.gov.cn/yzygj/s7652m/202003/a31191442e29474b98bfed5579d5af95.shtml
National Health Commission of the People’s Republic of China, 2020. Update on COVID-19 as of 24:00, March 17 (in Chinese). http://www.nhc.gov.cn/xcs/yqtb/202003/97b96f03fa3c4e8d8d0bf536271a10c0.shtml
Peters JL, Sutton AJ, Jones DR, et al., 2006. Comparison of two methods to detect publication bias in meta-analysis. JAMA, 295(6):676–680. https://doi.org/10.1001/jama.295.6.676
Radzikowska U, Ding M, Tan G, et al., 2020. Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors. Allergy, 75(11):2829–2845. https://doi.org/10.1111/all.14429
Remy KE, Mazer M, Striker DA, et al., 2020. Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections. JCI Insight, 5(17):e140329. https://doi.org/10.1172/jci.insight.140329
Rothan HA, Byrareddy SN, 2020. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun, 109:102433. https://doi.org/10.1016/j.jaut.2020.102433
Song JW, Zhang C, Fan X, et al., 2020. Immunological and inflammatory profiles in mild and severe cases of COVID-19. Nat Commun, 11(1):3410. https://doi.org/10.1038/s41467-020-17240-2
Stang A, 2010. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 25(9):603–605. https://doi.org/10.1007/s10654-010-9491-z
Wong J, Koh WC, Momin RN, et al., 2020. Probable causes and risk factors for positive SARS-CoV-2 test in recovered patients: evidence from Brunei Darussalam. J Med Virol, 92(11):2847–2851. https://doi.org/10.1002/jmv.26199
Wu ZY, McGoogan JM, 2020. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA, 323(13):1239–1342. https://doi.org/10.1001/jama.2020.2648
Xiao AT, Tong YX, Zhang S, 2020. False negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: rather than recurrence. J Med Virol, 92(10):1755–1756. https://doi.org/10.1002/jmv.25855
Xu YG, Lu YQ, 2019. Systematic review and meta-analysis of the efficacy and safety of immunosuppressive pulse therapy in the treatment of paraquat poisoning. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(7):588–597. https://doi.org/10.1631/jzus.B1800640
Yang Y, Yang MH, Shen CG, et al., 2020. Laboratory diagnosis and monitoring the viral shedding of SARS-CoV-2 infections. Innovation, 1(3):100061. j.xinn.2020.100061
Ye GM, Pan ZY, Pan YB, et al., 2020. Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation. J Infect, 80(5):e14–e17. https://doi.org/10.1016/j.jinf.2020.03.001
Yuan J, Zou RR, Zeng LJ, et al., 2020. The correlation between viral clearance and biochemical outcomes of 94 COVID-19 infected discharged patients. Inflamm Res, 69(6):599–606. https://doi.org/10.1007/s00011-020-01342-0
Zhang BC, Zhou XY, Qiu YR, et al., 2020. Clinical characteristics of 82 cases of death from COVID-19. PLoS ONE, 15(7):e0235458. https://doi.org/10.1371/journal.pone.0235458
Zhao WP, Wang Y, Tang YF, et al., 2020. Characteristics of children with reactivation of SARS-CoV-2 infection after hospital discharge. Clin Pediatr, 59(9–10):929–932. https://doi.org/10.1177/0009922820928057
Zhou L, Liu K, Liu HG, 2020. Cause analysis and treatment strategies of “recurrence” with novel coronavirus pneumonia (COVID-19) patients after discharge from hospital. Chin J Tuberc Respir Dis, 43(4):281–284 (in Chinese). https://doi.org/10.3760/cmaj.cn112147-20200229-00219
Zhuo L, Wei FF, Zhou JQ, et al., 2020. Factors influencing the outcome of 34 patients with COVID-19. J Pract Med, 36(14):1861–1865 (in Chinese).
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Zhi CHEN, Meng-qi YAO, and Qiu-xian ZHENG designed the analysis. Meng-qi YAO, Qiu-xian ZHENG, and Jia XU finished the analysis and prepared the manuscript. Jing-wen DENG, Tian-tian GE, Hai-bo ZHOU, and Feng-tian WU prepared the figures and tables. Xin-yu GU, Qin YANG, Yan-li REN, and Gang WANG prepared the tables and edited this manuscript. Zhi CHEN supervised the study. All authors reviewed and approved the final version of the manuscript.
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Meng-qi YAO, Qiu-xian ZHENG, Jia XU, Jing-wen DENG, Tian-tian GE, Hai-bo ZHOU, Feng-tian WU, Xin-yu GU, Qin YANG, Yan-li REN, Gang WANG, and Zhi CHEN declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Table S1 Search strategy of the recurrence cases with COVID-19 Fig. S1 Forest plots of meta-analysis on the proportion of the asymptomatic individuals among the COVID-19 infections
Fig. S2 Forest plots of meta-analysis on clinical characteristics and laboratory findings of the recurrence cases among the COVID-19 infections
Fig. S3 Funnel plot assessing publication bias in studies reporting proportion of recurrence cases among the COVID-19 patients
Project supported by the National Science and Technology Major Project of China (Nos. 2018ZX10302206 and 2017ZX10202203) and the Zhejiang University Academic Award for Outstanding Doctoral Candidates (No. 2020052), China
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Yao, Mq., Zheng, Qx., Xu, J. et al. Factors associated with a SARS-CoV-2 recurrence after hospital discharge among patients with COVID-19: systematic review and meta-analysis. J. Zhejiang Univ. Sci. B 21, 940–947 (2020). https://doi.org/10.1631/jzus.B2000304
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DOI: https://doi.org/10.1631/jzus.B2000304