SARS-CoV-2 continued to replicate and mutate in a patient for 218 days | AGÊNCIA FAPESP

SARS-CoV-2 continued to replicate and mutate in a patient for 218 days The case of persistent infection was documented by researchers at the University of São Paulo, involving an immunocompromised patient in his forties. Several mutations were detected by whole-genome sequencing of the virus in samples collected during a seven-month period (image: effelle/Pixabay)

SARS-CoV-2 continued to replicate and mutate in a patient for 218 days

July 07, 2021

By Karina Toledo  |  Agência FAPESP – A case of infection by the novel coronavirus that lasted at least 218 days is reported by researchers affiliated with the University of São Paulo (USP) in Brazil and collaborators in an article awaiting peer review posted to the medRxiv preprint platform.

The case involved a man in his forties who before contracting COVID-19 had undergone aggressive treatment for cancer that severely compromised his immune system. He was infected by SARS-CoV-2 in early September 2020 and continued to test positive for the virus until April 2021.

“All nasopharyngeal secretion samples collected from this patient between the sixth and 218th day after symptom onset tested positive for SARS-CoV-2 by RT-PCR. The virus wasn’t simply present in his organism. It was replicating. Throughout the entire period, there was a risk of transmission to other people,” said Maria Cássia Mendes-Correa, a professor at the university’s Medical School (FM-USP) and first author of the article.

Confirmation that the virus remained infectious in the patient’s organism was obtained by means of in vitro tests conducted as part of a project supported by FAPESP. In a laboratory with a high level of biosafety at the Institute of Tropical Medicine (IMT-USP), samples of nasopharyngeal secretion and saliva collected weekly were incubated with cell lines susceptible to SARS-CoV-2. The cultures were observed for a few days, virus replication was confirmed by RT-PCR, and cell death due to viral action was detected. “This replicative capacity was continuous and persistent for 196 consecutive days,” Mendes-Correa said.

The group also collected blood, urine and anal swabs weekly between January and April 2021. Analysis of the samples showed persistence of the virus for most of the period. Serological testing confirmed that the patient did not produce either immunoglobulins (IgG and IgA), which combat invading pathogens, or neutralizing antibodies that block viral entry into cells.

An evolving virus 

Nasopharyngeal swabs collected 6, 77, 134, 169 and 196 days after symptom onset were submitted to whole-genome sequencing and viral culture. The results showed that the virus had mutated several times during continuous replication for the long period concerned. Some of the mutations were in the spike protein used by the virus to invade human cells.

“Our findings suggest the occurrence of an evolutionary process in the same host that’s normally observed in the community. The phenomenon is disturbing, as it points to the possibility of viral variants that are better adapted to the human organism,” Mendes-Correa said.

The genome sequenced was B1.1.28, which predominated in Brazil throughout 2020. In this case, she explained, it is impossible to know whether the evolution of the virus resulted in a variant of concern because every precaution was taken to prevent transmission to other people. “The patient was in hospital for most of the period, and self-isolated while at home for a short time,” she said.

For Mendes-Correa, cases such as this are rare but health workers should pay close attention to them. “Physicians who treat patients with cancer or autoimmune diseases, for example, should be very careful and watchful. They should keep a close eye on COVID-19 cases in this population, and take care to prevent transmission of the virus to other immunocompromised patients and other health workers,” she said.

A paper published in November 2020 in the New England Journal of Medicine reported the case of a male patient, also in his forties, with an autoimmune blood disease. The virus replicated continuously in his organism for 143 days. “That was the longest documented case of viral persistence until the publication of our study, as far as I know,” Mendes-Correa said.

The article “SARS-CoV-2 shedding, infectivity and evolution in an immunocompromised adult patient” is at:




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