In a 38-year-old man who showed mild symptoms of COVID-19 for 20 days, the novel coronavirus was still detected in his organism and mutated for 232 days. If he hadn’t had continuous medical attention, maintained social distancing and worn a mask, he could have spread the virus in those seven months.
The atypical case of SARS-CoV-2 infection was part of a study of 38 Brazilian patients monitored weekly between April and November 2020 by researchers from the Pasteur-USP Scientific Platform, a partnership between France̵
7;s Pasteur Institute and the university by Sao Paulo (USP) and the Oswaldo Cruz Foundation (Fiocruz) in Brazil. Patients were followed up two or three consecutive times by RT-qPCR until testing negative.
The study was supported by FAPESP. An article reporting his findings will be published in the journal frontiers in medicine.
It serves as a warning about the risk of limiting quarantine for COVID-19 patients to seven, 10 or even 14 days after they test positive, as originally mandated by protocols to combat the disease. It also reinforces the importance of vaccinations, social distancing and wearing masks.
Of the 38 cases we tracked, two men and one woman were atypical in the sense that the virus was continuously detected in their organism for more than 70 days. Based on this result, we can say that about 8% of people infected with SARS-CoV-2 can potentially transmit the virus for more than two months without necessarily showing symptoms in the final stages of infection.
Marielton dos Passos Cunha, first author of the article
The study was conducted when he was a postdoctoral fellow at the Pasteur-USP Scientific Platform.
“We wanted to know whether a period of 14 days was really long enough for the virus to become undetectable. We concluded that this was not the case. It can take a month for a patient to test negative, and in some cases in our enrolled study, patients remained positive for 71 to 232 days,” said Paola Minoprio, one of the platform’s coordinators and principal investigator of the study.
This isn’t the first indication that the virus can remain active longer than expected, even in patients with mild symptoms. In early 2021, researchers from the Institute of Tropical Medicine (IMT-USP) at the University of São Paulo in Brazil analyzed 29 samples of nasopharyngeal secretions from patients who tested positive for COVID-19. The material was collected at a public primary health care center on the 10th day after the onset of symptoms and inoculated into cells grown in the laboratory. In 25% of the cases, the viruses present in the samples were able to infect the cells and multiply in vitro. So, in theory, other people could become infected if they come into contact with saliva droplets, which 25% of these patients expelled at the time the sample was taken (more at: https://agencia.FAPESP.br/35303/).
The risk appears to be even greater for people with compromised immune systems. In a paper published in June 2021, researchers at the same university’s School of Medicine (FM-USP) described a case of infection that lasted at least 218 days.
The patient was approximately 40 years old and had been undergoing aggressive cancer treatment before contracting COVID-19 (more at: https://agencia.FAPESP.br/36281 /).
An article published in the New England Journal of Medicine reported in early December 2020 the case of an immunocompromised 45-year-old male with an autoimmune blood disorder in which the virus continued to replicate for 143 days. And an article published in cell outlined a case study in late December of a leukemia patient in whom the virus continued to replicate for at least 70 days despite having no symptoms of COVID-19.
Despite this, the Brazilian Ministry of Health this week reduced the recommended length of self-isolation from ten to seven days for patients with mild or moderate symptoms and to five days for people without symptoms if they test negative. In late 2021, the U.S. Centers for Disease Control and Prevention (CDC) reduced its recommendation for asymptomatic patients from 10 to 5 days, provided they continue to wear a mask and have tested negative for COVID-19.
intrahost mutations
In the study led by Minoprio, the difference between women and men in terms of duration of viral activity was not significant (22 days and 33 days on average, respectively). In the three atypical cases, the virus remained detectable for 71 days in the woman and 81 days in one of the two men. None of them had comorbidities and all had mild symptoms of COVID-19.
The other atypical man remained positive for coronavirus for 232 days (April-November 2020), after which he tested negative three times by RT-qPCR. He has had HIV, the virus that causes AIDS, since 2018 but has no detectable viral load thanks to antiretroviral therapy.
“The fact that he is seropositive for HIV does not mean he is more susceptible to other infections as he has been undergoing therapy since his diagnosis. His ability to respond to infection by any other pathogen is comparable to that of any other person, and in fact he was responding to the coronavirus when he was infected. He’s not immunocompromised [like cancer patients, people with autoimmune diseases or transplantees, for example]’ said Minoprios.
According to the researchers, his HIV-positive status does not explain the long duration of his coronavirus infection. Many patients co-infected with HIV and SARS-CoV-2 would need to be compared to an appropriate control group to determine whether genetic or immunological characteristics in the host could be associated with such prolonged viral shedding.
The patient underwent weekly tests that demonstrated the persistence of the infection, and samples of the virus were sequenced regularly to show that there was no reinfection and that the virus not only continued to replicate but also mutated.
The virus’ strategies to evade the immune system during infection were mapped, showing that when more neutralizing antibodies were present, viral load dropped and that the virus was able to bypass the body’s defenses to rebuild the load . The cycle repeated itself, forcing more antibodies to be produced until the viral load was reduced again.
“It’s important to follow patients like this because we can learn more about how the virus mutates and what mutations can lead to variants that are of concern,” Cunha said.
The patient in the study was infected with lineage B.1.1.28, which migrated to Brazil in early 2020. The researchers did not discover any mutations in the virus isolated from the patient that could justify classifying it as a transmissible or resistant immune system.
The Pasteur-USP Scientific Platform is continuing to investigate these and other cases. The 38 patients analyzed in the Minoprio-led study are part of a bank of blood and nasopharyngeal secretion samples collected from 721 people who were showing symptoms related to this coronavirus.
“Fresh data will come from these samples, and we may be able to provide more tangible explanations for these atypical cases,” Cunha said.
“These cases are further evidence that mask-wearing and social distancing are the best tools to combat the pandemic. If a person is not tested again 14 days after testing positive, they may still be shedding active virus and may infect others, contributing to community transmission,” Minoprio said. “Keeping track of infected people is crucial so that we can learn more about mutations, novel variants and the transmissibility of SARS-CoV-2.”