Former COVID-19 Patients Could Test Positive Again; Here's Why

Healthcare staff interpreting test outcomes have been perplexed by a curious phenomenon. Experts discovered that patients who had recovered from COVID-19 would sometimes test positive for RT-PCR test weeks or months later.

These patients did not contract COVID-19 disease a second time, as has occurred in other cases. No live viruses were isolated from their samples and positive findings were impossible to be caused by latent RNAs, which have a short lifespan.

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NEW DELHI, INDIA - MAY 02: A medical worker in PPE observes patients who have been infected by Covid-19 inside a makeshift covid care facility in a sports stadium at the Commonwealth Games Village in New Delhi on May 02, 2021 in New Delhi, India. With cases crossing 400,000 a day and with more than 3500 deaths recorded in the last 24 hours, India's Covid-19 crisis is intensifying and shows no signs of easing pressure on the country. A new wave of the pandemic has totally overwhelmed the country's healthcare services and has caused crematoriums to operate day and night as the number of victims continues to spiral out of control.

The SARS-CoV-2 RNA can be reverse-transcribed and inserted into the genome of the infected cell, according to researchers from the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology (MIT). These genome segments would then be "read" into RNAs, which could be detected using a PCR test.

"SARS-CoV-2 is not a retrovirus, which means it doesn't need reverse transcription for its replication," says Whitehead Institute postdoc and first author Liguo Zhang said in a statement posted in Whitehouse Institue's website.

"However, non-retroviral RNA virus sequences have been detected in the genomes of many vertebrate species, including humans," Zhang added on the same statement.

How Experts Detected The Cells

To detect genomic SARS-CoV-2 sequences incorporated into the genome of infected cells, the researchers infected human cells with the novel coronavirus in the lab. They used three separate ways to detect genomic SARS-CoV-2 sequences integrated into the genome of infected cells.

The study, titled "Reverse-Transcribed Sars-Cov-2 Rna Can Integrate Into the Genome of Cultured Human Cells and Can Be Expressed in Patient-Derived Tissues," looked at published datasets of RNA transcripts from various types of samples, including COVID-19 patients' samples. They measured the percentage of genes in these patients' cells transcribed with viral sequences extracted from integrated viral copies.

Last year, Zhang and his colleagues shared the preliminary findings of a research titled "Sars-Cov-2 RNA Reverse-Transcribed and Integrated Into the Human Genome." The said research, published in bioRxiv, suggested SARS-CoV-2 could have other means of completing such a mission after all.

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SARS-CoV-2 Could Insert Itself Into the Human Genome

While the amount ranged from sample to sample, it appears that a significant portion of viral transcripts transcribed from viral genetic material was inserted into the genome in some cases.

Only a small percentage of human cells likely undergo viral integration. The frequency of SARS-CoV-2 integration in humans is still uncertain.

"The fraction of cells which have the integrating with could be very small," said another researcher Rudolf Jaenisch, the professor of biology at MIT, per DT Next. "But even if it's rare, there are more than 140 million people who have been infected already, right?"

LINE1 Integration Responsible For This Footprint

The team discovered "a very simple footprint" for LINE1 integration-a typical segment of DNA that can travel from one area of the genome to another-while searching for clues to the process by which they got there.

"There's a very clear footprint for LINE1 integration," fellow researcher Whitehead Institute biologist Rudolf Jaenisch said per Science Alert.

According to Jaenisch, the viral sequence's junction with cellular DNA may result in a 20-base-pair duplication.

However, experts conducted this research on laboratory-infected cell cultures rather than live human hosts raises questions.

Other scholars were skeptical of this study, partly because it was made public as a preprint before going through the peer-review process. They also pointed out that the virus-human sequences may actually be products of the procedure used to detect them.

There's also the issue of what it does - while the fragments can't create new viral particles, it's unclear whether they're biologically active in other ways, for good or ill.