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

EBioMedicine. 2020 Sep:59:102960. doi: 10.1016/j.ebiom.2020.102960. Epub 2020 Aug 24.

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: COVID-19; Neutralizing antibody; Re-positive; SARS-CoV-2; Virology.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Betacoronavirus / genetics*
  • Betacoronavirus / isolation & purification
  • COVID-19
  • Child
  • Child, Preschool
  • Coronavirus Infections / diagnosis*
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Pandemics
  • Patient Discharge
  • Pneumonia, Viral / diagnosis*
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • RNA, Viral / chemistry
  • RNA, Viral / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • SARS-CoV-2
  • Severity of Illness Index
  • Whole Genome Sequencing
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • RNA, Viral