Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR.

Jing Lu, Jinju Peng, Qianling Xiong, Zhe Liu, Huifang Lin, Xiaohua Tan, Min Kang, Runyu Yuan, Lilian Zeng, Pingping Zhou, Chumin Liang, Lina Yi, Louis du Plessis, Tie Song, Wenjun Ma, Jiufeng Sun, Oliver G Pybus, Changwen Ke
Author Information
  1. Jing Lu: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China; School of Public Health, Southern Medical University, Guangzhou, China.
  2. Jinju Peng: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China; School of Public Health, Southern Medical University, Guangzhou, China.
  3. Qianling Xiong: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China; School of Public Health, Southern Medical University, Guangzhou, China.
  4. Zhe Liu: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  5. Huifang Lin: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  6. Xiaohua Tan: Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  7. Min Kang: Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  8. Runyu Yuan: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  9. Lilian Zeng: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  10. Pingping Zhou: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  11. Chumin Liang: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  12. Lina Yi: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  13. Louis du Plessis: Department of Zoology, University of Oxford, Oxford, United Kingdom.
  14. Tie Song: Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
  15. Wenjun Ma: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China.
  16. Jiufeng Sun: Guangdong Provincial Institution of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160 Qunxian Rd, Dashi Town, Panyu District, Guangdong Province, Guangzhou 511430, China; Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China. Electronic address: sunjiuf@163.com.
  17. Oliver G Pybus: Department of Zoology, University of Oxford, Oxford, United Kingdom.
  18. Changwen Ke: Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China. Electronic address: kecw1965@aliyun.com.

Abstract

BACKGROUND: Some COVID-19 cases test positive again for SARS-CoV-2 RNA following negative test results and discharge, raising questions about the meaning of virus detection. Better characterization of re-positive cases is urgently needed.
METHODS: Clinical data were obtained through Guangdong's COVID-19 surveillance network. Neutralization antibody titre was determined using microneutralization assays. Potential infectivity of clinical samples was evaluated by cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing.
FINDINGS: Among 619 discharged COVID-19 cases, 87 re-tested as SARS-CoV-2 positive in circumstances of social isolation. All re-positive cases had mild or moderate symptoms at initial diagnosis and were younger on average (median, 28). Re-positive cases (n = 59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n = 218) tested here. No infectious strain could be obtained by culture and no full-length viral genomes could be sequenced from re-positive cases.
INTERPRETATION: Re-positive SARS-CoV-2 cases do not appear to be caused by active reinfection and were identified in ~14% of discharged cases. A robust NAb response and potential virus genome degradation were detected in almost all re-positive cases, suggesting a substantially lower transmission risk, especially through respiratory routes.

Keywords

References

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MeSH Term

Adolescent
Adult
Aged
Antibodies, Neutralizing
Betacoronavirus
COVID-19
Child
Child, Preschool
Coronavirus Infections
Female
Humans
Infant
Male
Middle Aged
Pandemics
Patient Discharge
Pneumonia, Viral
RNA, Viral
Reverse Transcriptase Polymerase Chain Reaction
SARS-CoV-2
Severity of Illness Index
Whole Genome Sequencing
Young Adult

Chemicals

Antibodies, Neutralizing
RNA, Viral

Word Cloud

Created with Highcharts 10.0.0casesCOVID-19SARS-CoV-2re-positivetestRe-positivepositiveRNAviruscharacterizationClinicalobtainedantibodytitreusingdetectedRT-PCRdischargedBACKGROUND:followingnegativeresultsdischargeraisingquestionsmeaningdetectionBetterurgentlyneededMETHODS:dataGuangdong'ssurveillancenetworkNeutralizationdeterminedmicroneutralizationassaysPotentialinfectivityclinicalsamplesevaluatedcellinoculationthreedifferentkitsmultiplexPCRnanoporesequencingFINDINGS:Among61987re-testedcircumstancessocialisolationmildmoderatesymptomsinitialdiagnosisyoungeraveragemedian28n = 59exhibitedsimilarneutralizationantibodiesNAbsdistributionsn = 218testedinfectiousstrainculturefull-lengthviralgenomessequencedINTERPRETATION:appearcausedactivereinfectionidentified~14%robustNAbresponsepotentialgenomedegradationalmostsuggestingsubstantiallylowertransmissionriskespeciallyrespiratoryroutesimmunologicalvirologicalpatientsNeutralizingVirology

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