A systematic review on the recurrence of SARS-CoV-2 virus: frequency, risk factors, and possible explanations

References

• Xiao AT, Tong YX, Zhang S. False negative of RT-PCR and prolonged nucleic acid conversion in COVID-19: rather than recurrence. J Med Virol. 2020;92(10):1755–1756.
   PubMed Web of Science ®Google Scholar
• Zhou L, Liu K, Liu HG. [Cause analysis and treatment strategies of “recurrence” with novel coronavirus pneumonia (COVID-19) patients after discharge from hospital]. Zhonghua Jie He He Hu Xi Za Zhi. 2020;43(4):281–284.
   PubMedGoogle Scholar
• Ye G, Pan Z, Pan Y, et al. Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation. J Infect. 2020;80(5):e14–e17.
   PubMed Web of Science ®Google Scholar
• Xing Y, Mo P, Xiao Y, et al. Post-discharge surveillance and positive virus detection in two medical staff recovered from coronavirus disease 2019 (COVID-19), China, January to February 2020. Euro Surveill. 2020;25(10):2000191.
   Google Scholar
• Qu Y-M, Kang E-M, Cong H-Y. Positive result of Sars-Cov-2 in sputum from a cured patient with COVID-19. Travel Med Infect Dis. 2020;34:101619.
   PubMed Web of Science ®Google Scholar
• Lan L, Xu D, Ye G, et al. Positive RT-PCR test results in patients recovered from COVID-19. JAMA. 2020;323(15):1502–1503.
   PubMed Web of Science ®Google Scholar
• Li J, Zhang C, Wu Z, et al. The mechanism and clinical outcome of patients with corona virus disease 2019 whose nucleic acid test has changed from negative to positive, and the therapeutic efficacy of Favipiravir: a structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21(1):488.
   PubMedGoogle Scholar
• World Health Organization. Laboratory testing of 2019 novel coronavirus (2019-nCoV) in suspected human cases: interim guidance, 17 January 2020. 2020.
   Google Scholar
• Xia J, Tong J, Liu M, et al. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. J Med Virol. 2020;92(6):589–594.
   PubMed Web of Science ®Google Scholar
• Zhang W, Du R-H, Li B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect. 2020;9(1):386–389.
   PubMed Web of Science ®Google Scholar
• Elberry MH, Ahmed H. Occult SARS-CoV-2 infection; a possible hypothesis for viral relapse. Med Hypotheses. 2020;144:109980.
   PubMedGoogle Scholar
• Mattiuzzi C, Henry BM, Sanchis-Gomar F, et al. SARS-CoV-2 recurrent RNA positivity after recovering from coronavirus disease 2019 (COVID-19): a meta-analysis. Acta Bio-Medica: Atenei Parmensis. 2020;91(3):e2020014.
   PubMedGoogle Scholar
• Zou Y, Wang BR, Sun L, et al. The issue of recurrently positive patients who recovered from COVID-19 according to the current discharge criteria: investigation of patients from multiple medical institutions in Wuhan, China. J Infect Dis. 2020;222(11):1784–1788.
   PubMed Web of Science ®Google Scholar
• Yuan B, Liu HQ, Yang ZR, et al. Recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients during medical isolation observation. Sci Rep. 2020;10(1):11887.
   PubMed Web of Science ®Google Scholar
• Wu J, Liu X, Liu J, et al. Coronavirus disease 2019 test results after clinical recovery and hospital discharge among patients in China. JAMA Netw Open. 2020;3(5):e209759.
   PubMed Web of Science ®Google Scholar
• Kang YJ. South Korea’s COVID-19 infection status: from the perspective of re-positive test results after viral clearance evidenced by negative test results. Disaster Med Public Health Prep. 2020. DOI:10.1017/dmp.2020.168
   Google Scholar
• Li Y, Hu Y, Yu Y, et al. Positive result of Sars-Cov-2 in faeces and sputum from discharged patient with COVID-19 in Yiwu. J Med Virol. 2020;92(10):1938–1947.
   PubMed Web of Science ®Google Scholar
• Wang X, Xu H, Jiang H, et al. The clinical features and outcomes of discharged coronavirus disease 2019 patients： a prospective cohort study. QJM. 2020;hcaa178.
   Web of Science ®Google Scholar
• Zhu H, Fu L, Jin Y, et al. Clinical features of COVID-19 convalescent patients with re-positive nucleic acid detection. J Clin Lab Anal. 2020;34(7):e23392.
   PubMed Web of Science ®Google Scholar
• Chen X, Chen Z, Azman AS, et al. Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis. medRxiv. 2020. DOI:10.1101/2020.09.11.20192773
   Google Scholar
• Chen JX, Hu X, Chen J, et al. Clinical course and risk factors for recurrence of positive SARS-CoV-2 RNA: a retrospective cohort study from Wuhan, China. Aging (Albany NY). 2020;12(17):16675–16689.
   PubMedGoogle Scholar
• Chen LZL, Chen ZH, Liu J, et al. Can elevated concentrations of ALT and AST predict the risk of ‘recurrence’ of COVID-19? Epidemiol Infect. 2020;148:e218.
   PubMed Web of Science ®Google Scholar
• Chen SLX, Feng H, Sun HY, et al. Epidemiological and clinical findings of short-term recurrence of severe acute respiratory syndrome coronavirus 2 ribonucleic acid polymerase chain reaction positivity in 1282 discharged coronavirus disease 2019 cases: a multicenter, retrospective, observational study. Open Forum Infect Dis. 2020;7(10):ofaa432.
   PubMed Web of Science ®Google Scholar
• Du H-W, Chen J-N, Pan X-B, et al. Prevalence and outcomes of re-positive nucleic acid tests in discharged COVID-19 patients. Eur J Clin Microbiol Infect Dis. 2020. DOI:10.1007/s10096-020-04024-1
   Google Scholar
• He ST, Li J, Zhou X, et al. Positive RT-PCR test results in 420 patients recovered from COVID-19 in Wuhan: an observational study. Front Pharmacol. 2020;11:549117.
   PubMed Web of Science ®Google Scholar
• Lu JP, Xiong J, Liu Q, et al. Ke, C. Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR. EBioMedicine. 2020;59:102960.
   PubMed Web of Science ®Google Scholar
• Shui T-J, Li C, Liu H-B, et al. Characteristics of recovered COVID-19 patients with recurrent positive RT-PCR findings in Wuhan, China: a retrospective study. BMC Infect Dis. 2020;20(1):749.
   PubMed Web of Science ®Google Scholar
• Zheng JZ, Chen R, Tang F, et al. Incidence, clinical course and risk factor for recurrent PCR positivity in discharged COVID-19 patients in Guangzhou, China: a prospective cohort study. PLoS Negl Trop Dis. 2020;14(8):e0008648.
   PubMed Web of Science ®Google Scholar
• Zheng KI, Wang XB, Jin XH, et al. A case series of recurrent viral RNA positivity in recovered COVID-19 Chinese patients. J Gen Intern Med. 2020;35(7):2205–2206.
   PubMed Web of Science ®Google Scholar
• Yuan J, Kou S, Liang Y, et al. Polymerase chain reaction assays reverted to positive in 25 discharged patients with COVID-19. Clin Infect Dis. 2020;71(16):2230–2232.
   Web of Science ®Google Scholar
• Tian M, Long Y, Hong Y, et al. The treatment and follow-up of “recurrence” with discharged COVID-19 patients: data from Guizhou, China. Environ Microbiol. 2020;22(8):3588–3592.
   PubMed Web of Science ®Google Scholar
• Ravioli S, Ochsner H, Lindner G. Reactivation of COVID-19 pneumonia: a report of two cases. J Infect. 2020;81(2):e72–e73.
   PubMed Web of Science ®Google Scholar
• Peng J, Wang M, Zhang G, et al. Seven discharged patients turning positive again for SARS-CoV-2 on quantitative RT-PCR. Am J Infect Control. 2020;48(6):725–726.
   PubMed Web of Science ®Google Scholar
• Fenner J, Min MS, Liu S, et al. A case of neonatal pemphigus vulgaris with co-existing BP180 autoantibodies. Pediatr Dermatol. 2020;37(1):241–243.
   PubMed Web of Science ®Google Scholar
• Lafaie L, Célarier T, Goethals L, et al. Recurrence or relapse of COVID-19 in older patients: a description of three cases. J Am Geriatr Soc. 2020;68(10):2179–2183.
   PubMed Web of Science ®Google Scholar
• Jiang M, Li Y, Han M, et al. Recurrent PCR positivity after hospital discharge of people with coronavirus disease 2019 (COVID-19). J Infect. 2020;81(1):147–178.
   PubMed Web of Science ®Google Scholar
• Hu R, Jiang Z, Gao H, et al. Recurrent positive reverse transcriptase-polymerase chain reaction results for coronavirus disease 2019 in patients discharged from a hospital in China. JAMA Netw Open. 2020;3(5):e2010475.
   PubMed Web of Science ®Google Scholar
• Chen Y, Bai W, Liu B, et al. Re-evaluation of retested nucleic acid-positive cases in recovered COVID-19 patients: report from a designated transfer hospital in Chongqing, China. J Infect Public Health. 2020;13(7):932–934.
   PubMed Web of Science ®Google Scholar
• Batisse D, Benech N, Botelho-Nevers E, et al. Clinical recurrences of COVID-19 symptoms after recovery: viral relapse, reinfection or inflammatory rebound? J Infect. 2020;81:816–846.
   PubMed Web of Science ®Google Scholar
• Zhang B, Liu S, Dong Y, et al. Positive rectal swabs in young patients recovered from coronavirus disease 2019 (COVID-19). J Infect. 2020;81(2):e49–e52.
   PubMed Web of Science ®Google Scholar
• Bongiovanni M, Basile F. Re-infection by COVID-19: a real threat for the future management of pandemia? Infect Dis (Lond). 2020;52(8):581–582.
   PubMed Web of Science ®Google Scholar
• Tomassini S, Kotecha D, Bird PW, et al. Setting the criteria for SARS-CoV-2 reinfection – six possible cases. J Infect. 2020. DOI:10.1016/j.jinf.2020.08.011
   PubMed Web of Science ®Google Scholar
• Gidari A, Nofri M, Saccarelli L, et al. Is recurrence possible in coronavirus disease 2019 (COVID-19)? Case series and systematic review of literature. Eur J Clin Microbiol Infect Dis. 2021;40(1):1–12.
   PubMed Web of Science ®Google Scholar
• Gupta V, Bhoyar RC, Jain A, et al. Asymptomatic reinfection in two healthcare workers from India with genetically distinct SARS-CoV-2. Clin Infect Dis. 2020. DOI:10.1093/cid/ciaa1451
   Google Scholar
• Song KH, Kim DM, Lee H, et al. Dynamics of viral load and anti-SARS-CoV-2 antibodies in patients with positive RT-PCR results after recovery from COVID-19. Kor J Intern Med. 2020. DOI:10.3904/kjim.2020.325
   Web of Science ®Google Scholar
• Zhou X, Zhou J, Zhao J. Recurrent pneumonia in a patient with new coronavirus infection after discharge from hospital for insufficient antibody production: a case report. BMC Infect Dis. 2020;20(1):500.
   PubMed Web of Science ®Google Scholar
• Yoo SY, Lee Y, Lee GH, et al. Reactivation of SARS-CoV-2 after recovery. Pediatr Int. 2020;62(7):879–881.
   PubMed Web of Science ®Google Scholar
• Wang P. Recurrent presence of SARS-CoV-2 RNA in a 33-year-old man. J Med Virol. 2020;93(2):592–594.
   PubMed Web of Science ®Google Scholar
• Loconsole D, Passerini F, Palmieri VO, et al. Recurrence of COVID-19 after recovery: a case report from Italy. Infection. 2020;48(6):965–963.
   PubMed Web of Science ®Google Scholar
• Liu F, Cai ZB, Huang JS, et al. Positive SARS-CoV-2 RNA recurs repeatedly in a case recovered from COVID-19: dynamic results from 108 days of follow-up. Pathog Dis. 2020;78(4):ftaa031.
   PubMed Web of Science ®Google Scholar
• Györfi AH, Kopp M, May M, et al. Glucocorticoid-induced relapse of COVID-19 in a patient with sarcoidosis. Ann Rheumat Dis. 2020. DOI:10.1136/annrheumdis-2020-218258
   Google Scholar
• Dou C, Xie X, Peng Z, et al. A case presentation for positive SARS-CoV-2 RNA recurrence in a patient with a history of type 2 diabetes that had recovered from severe COVID-19. Diabetes Res Clin Pract. 2020;166:108300.
   PubMed Web of Science ®Google Scholar
• Chen D, Xu W, Lei Z, et al. Recurrence of positive SARS-CoV-2 RNA in COVID-19: a case report. Int J Infect Dis. 2020;93:297–299.
   PubMed Web of Science ®Google Scholar
• Bentivegna E, Sentimentale A, Luciani M, et al. New IgM seroconversion and positive RT-PCR test after exposure to the virus in recovered COVID-19 patient. J Med Virol. 2020;93(1):97–98.
   PubMed Web of Science ®Google Scholar
• Du W, Yu J, Liu X, et al. Persistence of SARS-CoV-2 virus RNA in feces: a case series of children. J Infect Public Health. 2020;13(7):926–931.
   PubMed Web of Science ®Google Scholar
• Alonso FOM, Sabino BD, Guimarães MAAM, et al. Recurrence of SARS-CoV-2 infection with a more severe case after mild COVID-19, reversion of RT-qPCR for positive and late antibody response: Case report. J Med Virol. 2021;93(2):655–656.
   PubMed Web of Science ®Google Scholar
• Duggan NM, Ludy SM, Shannon BC, et al. A case report of possible novel coronavirus 2019 reinfection. Am J Emerg Med. 2020;39:256.e1-256.e3.
   PubMed Web of Science ®Google Scholar
• Wu S, Gao D, Zhang Y, et al. Follicular lymphoma with paraneoplastic pemphigus as the first symptom: a case report and review of the literature. Int J Clin Exp Pathol. 2020;13(7):1915–1923.
   PubMed Web of Science ®Google Scholar
• Geling T, Huaizheng G, Ying C, et al. Recurrent positive nucleic acid detection in a recovered COVID-19 patient: a case report and literature review. Respir Med Case Rep. 2020;31:101152.
   PubMed Web of Science ®Google Scholar
• He FL, Lei Q, Fan M, et al. Successful recovery of recurrence of positive SARS-CoV-2 RNA in COVID-19 patient with systemic lupus erythematosus: a case report and review. Clin Rheumatol. 2020;39(9):2803–2810.
   PubMed Web of Science ®Google Scholar
• van Beek N, Schumacher N, Rose C, et al. [Modern diagnostics of autoimmune bullous diseases]. Pathologe. 2020;41(4):317–325.
   PubMed Web of Science ®Google Scholar
• Liu F, Cai ZB, Huang JS, et al. Repeated COVID-19 relapse during post-discharge surveillance with viral shedding lasting for 67 days in a recovered patient infected with SARS-CoV-2. J Microbiol Immunol Infect. 2020. DOI:10.1016/j.jmii.2020.07.017
   Google Scholar
• Mardani M, Nadji SA, Sarhangipor KA, et al. COVID-19 infection recurrence presenting with meningoencephalitis. New Microbes New Infect. 2020;37:100732.
   PubMed Web of Science ®Google Scholar
• AlFehaidi A, Ahmad SA, Hamed E. SARS-CoV-2 re-infection: a case report from Qatar. J Infect. 2020. DOI:10.1016/j.jinf.2020.10.019
   Google Scholar
• Bongiovanni M. COVID-19 re-infection in an healthcare worker. J Med Virol. 2020. DOI:10.1002/jmv.26565
   PubMed Web of Science ®Google Scholar
• Colson P, Finaud M, Levy N, et al. Evidence of SARS-CoV-2 re-infection with a different genotype. J Infect. 2020. DOI:10.1016/j.jinf.2020.11.011
   Google Scholar
• Coppola A, Annunziata A, Carannante N, et al. Late reactivation of SARS-CoV-2: a case report. Front Med (Lausanne). 2020;7:531.
   PubMed Web of Science ®Google Scholar
• Goldman JD, Wang K, Roltgen K, et al. Reinfection with SARS-CoV-2 and failure of humoral immunity: a case report. medRxiv. 2020. DOI:10.1101/2020.09.22.20192443
   Google Scholar
• Lancman G, Mascarenhas J, Bar-Natan M. Severe COVID-19 virus reactivation following treatment for B cell acute lymphoblastic leukemia. J Hematol Oncol. 2020;13(1):131.
   PubMed Web of Science ®Google Scholar
• Ma BMH, Chan IFN, Tam GCW, et al. Case of “relapsing” COVID-19 in a kidney transplant recipient. Nephrology (Carlton, Vic). 2020;25(12):933–936.
   PubMed Web of Science ®Google Scholar
• Nachmias V, Fusman R, Mann S, et al. The first case of documented Covid-19 reinfection in Israel. IDCases. 2020;22:e00970.
   PubMed Web of Science ®Google Scholar
• Patrocínio de Jesus RS, Aliyeva R, Lopes E, et al. Reactivation of SARS-CoV-2 after asymptomatic infection while on high-dose corticosteroids. SN Compr Clin Med. 2020;2(11):2402–2404.
   Google Scholar
• Tillett RL, Sevinsky JR, Hartley PD, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis. 2021;21(1):52–58.
   PubMed Web of Science ®Google Scholar
• To KK-W, Hung IF-N, Ip JD, et al. COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing. Clin Infect Dis. 2020. DOI:10.1093/cid/ciaa1275
   Google Scholar
• Liu BS, Zhang Y, Li W, et al. Recovered COVID-19 patients with recurrent viral RNA exhibit lower levels of anti-RBD antibodies. Cell Mol Immunol. 2020;17(10):1098–1100.
   PubMed Web of Science ®Google Scholar
• Kaur N, Gupta I, Singh H, et al. Epidemiological and clinical characteristics of 6635 COVID-19 patients: a pooled analysis. SN Compr Clin Med. 2020. DOI:10.1007/s42399-020-00393-y
   Google Scholar
• Ota M. Will we see protection or reinfection in COVID-19? Nat Rev Immunol. 2020;20(6):351.
   PubMedGoogle Scholar
• Ling Y, Xu S-B, Lin Y-X, et al. Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin Med J. 2020;133(9):1039–1043.
   PubMed Web of Science ®Google Scholar
• Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. 2020;323(15):1488–1494.
   PubMed Web of Science ®Google Scholar
• Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020;395(10229):1054–1062.
   PubMed Web of Science ®Google Scholar
• Zou L, Ruan F, Huang M, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020;382(12):1177–1179.
   PubMed Web of Science ®Google Scholar
• Carver C, Jones N. Comparative accuracy of oropharyngeal and nasopharyngeal swabs for diagnosis of COVID-19 - CEBM [Internet]. CEBM 2020 [cited 20 Nov 2020]. Available from: https://www.cebm.net/covid-19/comparative-accuracy-of-oropharyngeal-and-nasopharyngeal-swabs-for-diagnosis-of-covid-19/
   Google Scholar
• Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. Jama. 2020;323(18):1843–1844.
   PubMed Web of Science ®Google Scholar
• Zhang J-f, Yan K, Ye H-h, et al. SARS-CoV-2 turned positive in a discharged patient with COVID-19 arouses concern regarding the present standards for discharge. Int J Infect Dis. 2020;97:212–214.
   PubMed Web of Science ®Google Scholar
• Yilla M, Harcourt BH, Hickman CJ, et al. SARS-coronavirus replication in human peripheral monocytes/macrophages. Virus Res. 2005;107(1):93–101.
   PubMed Web of Science ®Google Scholar
• Li L, Wo J, Shao J, et al. SARS-coronavirus replicates in mononuclear cells of peripheral blood (PBMCs) from SARS patients. J Clin Virol. 2003;28(3):239–244.
   PubMed Web of Science ®Google Scholar
• Wang H, Mao Y, Ju L, et al. Detection and monitoring of SARS coronavirus in the plasma and peripheral blood lymphocytes of patients with severe acute respiratory syndrome. Clin Chem. 2004;50(7):1237–1240.
   PubMed Web of Science ®Google Scholar
• Ravi D, Prabhu SS, Rao R, et al. Comparison of immunofluorescence and desmoglein enzyme-linked immunosorbent assay in the diagnosis of pemphigus: a prospective, cross-sectional study in a tertiary care hospital. Indian J Dermatol. 2017;62(2):171–177.
   PubMed Web of Science ®Google Scholar
• Hong Kong man was reinfected with Covid: study 2020. Available from: https://news.rthk.hk/rthk/en/component/k2/1545589-20200824.htm.
   Google Scholar
• Joseph A. Scientists are reporting several cases of Covid-19 reinfection — but the implications are complicated; 2020. Available from: https://www.statnews.com/2020/08/28/covid-19-reinfection-implications/
   Google Scholar
• Tillett R, Sevinsky J, Hartley P, et al. Genomic evidence for a case of reinfection with SARS-CoV-2: THELANCETID-D-20-05376; 2020. Available from: https://ssrn.com/abstract=3681489
   Google Scholar
• Tirado SMC, Yoon K-J. Antibody-dependent enhancement of virus infection and disease. Viral Immunol. 2003;16(1):69–86.
   PubMed Web of Science ®Google Scholar
• Galanti M, Shaman J. Direct observation of repeated infections with endemic coronaviruses. J Infect Dis. 2020. DOI:10.1093/infdis/jiaa392
   PubMedGoogle Scholar
• Robbiani DF, Gaebler C, Muecksch F, et al. Convergent antibody responses to SARS-CoV-2 infection in convalescent individuals. Nature 2020;584:437–442.
   Google Scholar