Lancet Infect Dis 2025
Published Online February 10, 2025 https://doi.org/10.1016/S1473-3099(24)00769-2
“SARS-CoV-2 RNA and protein in the blood of individuals with long COVID might also persist inside host cells including monocytes, megakaryocytes, or platelets. High-throughput assays capable of measuring cell associated viral RNA, such as digital transcriptomics in whole blood, might be needed to account for this possibility. Given these gaps, it is imperative to accelerate efforts to further develop and optimise assays for SARS-CoV-2 RNA and protein in accessible matrices, such as whole blood, plasma, stool, and saliva.”
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“Post-acute virus persistence
Early in the pandemic, the common assumption was that SARS-CoV-2 infection would prove to be transient, as is the case with coronaviruses in general. This assumption was challenged by early reports that viral nucleic acid and proteins could be detected in the gut months after infection.86 Subsequently, reports indicated that some people—both immunocompromised87,88,89 and immunocompetent90,91,92,93—could harbor replicating virus for months. Many more studies have since emerged. A proportion of individuals with long COVID have intermittently detectable antigen in plasma for up to a year post-infection,94,95 and a transcriptomic analysis demonstrated upregulation of SARS-CoV-2 RNAs in whole blood of people with long COVID.96 At least one study has noted serologic responses in those with long COVID that are broadly suggestive of chronic antigen stimulation, even when the direct detection of such antigen was limited.97 “
“It is possible for RNA viruses to persist for months to years, as demonstrated with Ebola, Zika, and measles99; there is also precedence for the persistence of feline coronaviruses.100,101 Putative mechanisms include immune evasion (e.g., virus-mediated inhibition of interferons) and/or the avoidance of cell death through selection of less virulent viruses.99 “
https://www.cell.com/cell/fulltext/S0092-8674(24)00886-9
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“The pandemic has laid bare a blind spot in epidemiology and surveillance data systems for infectious diseases. Nearly all surveillance data systems are built on the archaic, and now obsolete, notion that accounting for cases, hospitalization, and death in the acute phase is sufficient to capture the health burden of the infection. This approach does not account for the burden of long-term health loss due to infectious illnesses, which obscures their true toll. Adding to this challenge are the absent, underdeveloped, or siloed health care data systems in much of the world. This calls for the need to redesign surveillance data systems for infectious agents “
https://www.science.org/doi/10.1126/science.adl0867
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“it may be possible that SARS-CoV-2 in a reservoir could have periods of inactivity and resume protein production and/or replication at other times such as when immune control is altered. Such a phenomenon is in line with the fluctuating symptoms reported by many patients with PASC (Long COVID). A study of survivors with post-Ebola syndrome suggests that the activity of persistent viral RNA in reservoir sites can change over time.”
https://www.nature.com/articles/s41590-023-01601-2
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