33% of genomically supported COVID-19 reinfections missed by clinical assessments
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Although clinical and cycle threshold value assessment can distinguish COVID-19 reinfection from detecting virus from a prior infection, it failed to identify 33% of genomically supported reinfections, according to a recent study.
“When someone who had COVID-19 infection a couple of months ago has a repeat positive COVID-19 PCR test, it can be hard for clinicians to distinguish whether this positive test reflects reinfection with COVID-19 vs. detection of dying or residual low-level virus from the prior infection,” Caitlin Dugdale, MD, a physician in Massachusetts General Hospital’s division of infectious diseases, told Healio. “Understanding whether or not the repeat positive test reflects a COVID-19 ‘reinfection’ is important, as it helps to guide decisions about isolation precautions, as well as whether or not to offer another round of COVID-19 treatment.”
Dugdale added, however, that without sequencing the viral genome from both the initial COVID-19 infection and the subsequent positive test, clinicians cannot say for sure whether the repeat test represents reinfection.
“In this study, we assessed clinicians’ ability to distinguish COVID-19 reinfection from persistent detection from a prior COVID-19 episode using clinical judgement and a marker of the level virus detected (ie, the cycle threshold value), as compared to viral genomic sequencing,” she said.
During the study, all patients at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) 45 days or more after an initial positive test — with both tests between March 14 and Dec. 30, 2020 — were analyzed for potential reinfection. According to the study, inclusion criteria included having two or more positive NAATs collected 45 days or more apart with a cycle threshold (Ct) value of less than 35 at repeat testing.
Researchers then assessed the likelihood of reinfection by viral genomic analysis of all available specimens with a Ct value less than 35, structured Ct trajectory criteria and a case-by-case review by infectious diseases physicians.
Among 1,569 patients with repeat SARS-CoV-2 testing 45 days or more after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Among these patients, viral genomic analysis was successful for 14 (22%). Of these, six had genomically supported reinfection, whereas eight had genomically supported persistent RNA detection.
According to the study, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12 (86%) subjects but missed two (33%) genomically supported reinfections compared with viral genomic analysis.
“Overall, clinical and cycle threshold value assessment is very good at distinguishing COVID-19 reinfection from persistent detection of virus from a prior infection,” Dugdale said. “However, scaling-up genomic analysis for clinical use would improve detection of COVID-19 reinfection with potential implications for isolation guidance and eligibility for COVID-19 treatment.”
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