Scientists Discover One of the Longest-Lasting Cases of COVID-19

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An international team, including researchers from HSE University, examined an unusual SARS-CoV-2 sample obtained from an HIV-positive patient. Genetic analysis revealed multiple mutations and showed that the virus had been evolving inside the patient’s body for two years. This finding supports the theory that the virus can persist in individuals for years, gradually accumulate mutations, and eventually spill back into the population. The study's findings have been published in Frontiers in Cellular and Infection Microbiology.

Although COVID-19 typically presents as an acute disease, rare cases of persistent, asymptomatic SARS-CoV-2 infection have been documented, most often in immunocompromised patients. Scientists hypothesise that such cases can give rise to dangerous viral variants, defined by the WHO as variants of concern (VOCs).

A team of researchers from Russia, Italy, Switzerland, the UK, and South Africa—including scientists from HSE University—identified a SARS-CoV-2 sample that had accumulated 89 mutations since diverging from its closest known relative. The sample was collected in 2022, while its nearest sequenced neighbour in the phylogenetic tree, obtained in September 2020 and belonging to the B.1.1 lineage, had largely disappeared by 2022. This indicates that SARS-CoV-2 had been persisting, evolving, and accumulating mutations in a single individual’s body for two years—one of the longest documented cases of COVID-19.  

Galya Klink

'The sample came from an HIV-positive patient in Kaluga who had never received highly active antiretroviral therapy (HAART). We had only one sample from her, and in theory, it could have been assumed that this was an acute infection caused by a previously unknown coronavirus variant. However, our analysis showed that such a large number of mutations could have accumulated through acute infections only over roughly seven years of viral circulation in the population—longer than SARS-CoV-2 has existed. Using phylodynamic analysis, we established that the patient had already been living with COVID-19 for two years by the time the sample was collected,' explains Galya Klink, Senior Research Fellow of the International Laboratory of Statistical and Computational Genomics at the HSE University Faculty of Computer Science.

The scientists also found that the virus had been evolving three to four times faster than typical SARS-CoV-2 strains; of the 89 mutations detected, 33 occurred in the spike protein, including changes characteristic of variants with increased transmissibility and antibody resistance. 

In addition, some of the mutations matched those found in wastewater-derived coronavirus variants. Wastewater analysis is routinely used during periods of rising infections, as it often allows new viral variants to be detected earlier than in the population. The presence of mutations in this sample that are characteristic of wastewater rather than the respiratory tract suggests that the virus may have undergone adaptation to the gastrointestinal tract. 

The researchers emphasise that persistent infections are typical in immunosuppressed patients. This highlights the need for close monitoring of such individuals to identify potentially dangerous viral variants in a timely manner.

'Our patient did not infect anyone during the course of her illness. Over time, the sample accumulated mutations that overlapped with those later seen in the Omicron variant, even though Omicron had not yet emerged or spread at that point. This means that the natural selection acting within a single patient differs from that between individuals,' says Klink. 'At the same time, the mutations we observed in the sample support the theory that new, potentially dangerous coronavirus variants can emerge in individuals with weakened immune systems, and that the virus may circulate through different parts of the host’s body.'