Characterizing "re-positives" in recovered COVID-19 patients

The novel coronavirus pandemic has been spreading silently or explosively in almost every country of the world, causing almost half a million deaths and nearly 8.5 million reported cases in just six months. While much is known about the virus and the illness by now, far more remains unclear. One such is the prevalence and persistence of antiviral immunity following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (blue) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
Novel Coronavirus SARS-CoV-2 Colorized scanning electron micrograph of an apoptotic cell (blue) heavily infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

Now, a new study published on the preprint server medRxiv* in June 2020 explores the features of re-positive results in patients who were believed to have recovered successfully from COVID-19 infection. The current study used data from the COVID-19 surveillance system in Guangdong between January 23, 2020, and February 26, 2020.

Re-Positive, Not Re-Infection

The researchers found that using official diagnostic criteria, the 619 discharged patients who were screened tested positive for SARS-CoV-2 IN 14% of cases. These cases could not be due to secondary viral infection because discharge policy decrees that all patients on discharge go to specified hotels and are strictly quarantined, to cut the chain of disease transmission.

Clinical Characteristics

Secondly, they found that while all the patients who tested positive a second time had only mild to moderate symptoms in the first episode, and were also significantly younger compared to the mean age of COVID-19 patients. The median time from onset to discharge was also lower than that of COVID-19 patients in general, at 19 days vs. 24 days.

All cases had tested negative for both nasopharyngeal and anal swabs twice in succession before being discharged, which limits the possibility that they were discharged before the infection resolved. The median time from the earliest symptom to the time of discharge after two successive negative PCR tests is 19 times, which agrees with the median time of 20 days reported in other studies as the time when SARS-CoV-2 can be detected. The conclusion is that testing re-positive for COVID-19 is chiefly confined to young patients who never had severe illness.

Normal Neutralizing Antibody Titers

The next point is whether these patients are truly infectious, as this would endanger attempts to contain the virus. The results of the microneutralization assay show that in almost 100% of cases, the serum contained specific neutralizing antibodies to the virus at titers similar to that seen in recovered patients and those in hospital. Thus, this seems to rule out the possibility that the neutralizing ability of these patients is relatively low.

Live virus isolation was carried out on samples from these patients, and the cycle time was found to be higher compared with the previous values obtained by the researchers from acutely infected patients. However, the value of this finding is diminished by the known insensitivity of this method.

No Live Virus Isolates

The researchers also carried out multiplex PCR with high-throughput sequencing on the samples, but with widely varying results depending on the kit used, and also whether RT-PCR or multiplex PCR was used. This led to the conclusion that the viral RNA in re-positive cases were possibly highly degraded, yielding a single virus sequence covering about a fifth of the genome from 23 samples that were positive by RT-PCR. This inevitably allays the fear of continuing infectivity from re-positive cases.

Limitations and Applications

However, the study is limited by the lack of consecutive samples and the absence of pairing of acute-phase samples with re-positive samples for the same patients. However, the study throws some light on the characteristics of re-positive tests for SARS-CoV-2. It appears that these patients continue to have a high titer of neutralizing antibodies, but that live infective viral particles are significantly absent, reducing the risk of transmission.

The researchers suggest, “The additional educations related to SARS-CoV-2 re-positive should be performed to calm down the public panic and help allocate the limited medical resources.”

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Lu, J. et al. (2020). Clinical, Immunological and Virological Characterization Of COVID-19 Patients That Test Re-Positive For SARS-Cov-2 by RT-PCR. medRxiv preprint doi: https://doi.org/10.1101/2020.06.15.20131748
Dr. Liji Thomas

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Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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