An immunocompromised man endured ongoing acute Covid-19 for more than 750 days, with researchers warning that while this record might be easy to dismiss as something that occurs only in vulnerable people, persistent infections have implications for everyone.
During his infection, reports ScienceAlert, the man experienced persistent respiratory symptoms and was admitted to hospital five times, according to the study team.
In their paper in The Lancet, they said that despite its duration, his condition differed from long Covid in that it wasn’t a case of symptoms lingering once the virus had cleared out, but the viral phase of SARS-CoV-2 that continued for more than two years.
“Long-term infections allow the virus to explore ways to infect cells more efficiently, and (this study) adds to the evidence that more transmissible variants have emerged from such infections,” said Harvard University epidemiologist William Hanage.
“Effectively treating such cases is hence a priority for both the health of the individual and the community."
Boston University bioinformatician Joseline Velasquez-Reyes and colleagues’ genetic analysis of viral samples collected from the patient between March 2021 and July 2022 revealed what the virus was up to during its extended invasion.
Its mutation rate within the patient, who has advanced HIV-1, ended up similar to that usually seen across a community. What’s more, some of these mutations were awfully familiar. Spike mutations matched positions of those seen in the omicron variant of SARS-CoV-2, for example.
Within just one person, the same types of mutations that led to the emergence of the faster-multiplying Omicron variant were on their way to being repeated. This backs the theory that Omicron-like changes developed from selection pressures the virus experiences inside our bodies, the researchers said.
The patient is believed to have contracted SARS-CoV-2 in mid-May 2020. During this time, he was not receiving antiretroviral therapy, nor able to access the necessary medical care, despite suffering from respiratory symptoms, headaches, body aches and weakness.
The 41-year-old had an immune helper T-cell count of just 35 cells per microlitre of blood, explaining how the virus managed to persist for so long. The healthy range is 500 to 1 500 cells per microlitre.
Luckily, in this case at least, the stubborn invader was not highly infectious.
“The inferred absence of onward infections might indicate a loss of transmissibility during adaptation to a single host,” theorised Velasquez-Reyes and team.
Still, there’s no guarantee other infections that establish long-term camps inside us will follow the same evolutionary path, which is why experts are wary and calling for continued close monitoring of Covid and adequate access to healthcare for everyone.
“Clearing these infections should be a priority for healthcare systems," the researchers concluded.
Study details
Characterisation of a persistent SARS-CoV-2 infection lasting more than 750 days in a person living with HIV: a genomic analysis
Joseline Velasquez-Reyes, Beau Schaeffer, Scott Curry et al.
Published in The Lancet in September 2025
Summary
Background
People who are immunocompromised can develop persistent SARS-CoV-2 infections. Several viral mutations accumulated during the course of such persistent infections have also been observed in prominent variants of concern (VOCs). Here, we characterise persistent infection and viral evolution of SARS-CoV-2 lasting more than 750 days in a person with advanced HIV-1 infection.
Methods
Between March, 2021, and July, 2022, eight clinical specimens were collected from a person living with HIV, neither receiving antiretroviral therapy nor virally suppressed, and presumed to have been initially infected with SARS-CoV-2 in mid-May, 2020. Viral RNA was extracted from each swab and an amplicon-based sequencing approach was used for genomic analysis of SARS-CoV-2. Variable sites were characterised at the consensus and subconsensus levels, and phylogenetic tools were applied to analyse viral evolution. Publicly available SARS-CoV-2 sequences from GenBank were leveraged to contextualise our sequenced samples and identify any potential evidence of transmission.
Findings
Genomes formed a monophyletic cluster in the B.1 lineage. 68 consensus and 67 subconsensus single nucleotide variants were observed over the course of infection. The intrahost clock rate remained similar to that of the interhost rate in contemporaneous community sequences (6·74 × 10–4 [95% credible interval 5·05 × 10–4 to 8·54 × 10–4] substitutions per site per year vs 6·11 × 10–4 [5·54 × 10–5 to 6·66 × 10–4]). Mutations grouped into two distinct subpopulations present throughout infection. 10 non-synonymous mutations in the spike protein gene were at positions in common with those defining the omicron lineage (BA.1 or BA.2), of which nine were present before November, 2021. Nine of 18 substitutions present throughout infection were rare in online databases, suggesting a lack of long transmission chains descending from this individual.
Interpretation
Convergent SARS-CoV-2 evolution, both in and outside the spike protein, observed in this study suggests parallels with the evolutionary process leading to emergence of the omicron VOC. The inferred absence of onward infections might indicate a loss of transmissibility during adaptation to a single host. Our results underscore the importance of appropriate treatment to cure persistent SARS-CoV-2 infections and monitoring them to understand how mutations contribute to viral adaptation.
ScienceAlert article – Man's COVID Infection Lasted 2 Years, Setting a New Record (Open access)
See more from MedicalBrief archives:
Ongoing challenge to understand – and treat – long Covid
Man tests positive for trio of monkeypox, HIV and Covid-19 on one day
HIV patients: Low CD4 cell count may increase COVID-19 mortality threefold
COVID-19 outcomes and immune function in people with HIV — NY cohort study
‘Most transmissable’ Omicron variant re-infects within weeks