Why does viral RNA sometimes persist after recovery from acute infections?

Abstract

DNA viruses often persist in the body of their host, becoming latent and recurring many months or years later. By contrast, most RNA viruses cause acute infections that are cleared from the host as they lack the mechanisms to persist. However, it is becoming clear that viral RNA can persist after clinical recovery and elimination of detectable infectious virus. This persistence can either be asymptomatic or associated with late progressive disease or nonspecific lingering symptoms, such as may be the case following infection with Ebola or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Why does viral RNA sometimes persist after recovery from an acute infection? Where does the RNA come from? And what are the consequences?

Retrospective detection of monkeypox virus in the testes of nonhuman primate survivors

“…The testes are targets of many viral infections, including Zika virus (ZIKV) 44 , EBOV 40,45 , MARV 39 and CCHFV 41 in animal models. Shedding in semen and/or related sexual transmission has also been reported for ZIKV, EBOV, MARV and CCHFV in human patients [46][47][48] . Although direct evidence of transmission of MPXV via semen has not been reported, it has been hypothesized that sexual contact, including skin-to-skin sexual contact, may underlie some of the transmission of monkeypox in the ongoing 2022 outbreak 22,23,49 .…”

Persistent Presence of Spike protein and Viral RNA in the Circulation of Individuals with Post-Acute Sequelae of COVID-19

“…Several theories have been proposed, including that parts of the SARS-CoV-2 genome can be incorporated into the DNA of infected cells and that fragments of the SARS-CoV-2 genome may be transcribed at random, but the evidence for this is disputed 18, 19 . Alternative explanations for SARS-CoV-2 persistence include mechanisms that are used by other RNA viruses to persist in host cells, including evasion of the host immune response, infection of long-lived cells, and/or infection of immune privileged tissues such as the brain, eyes, or testes, or diminished cell-mediated immunity within a patient 2, 20, 21 . Additionally, SARS-CoV-2 may be able to persist due to an insufficient immune response during acute COVID-19 22, 23 .…”

“…This has become known as Post-acute Sequelae of COVID-19 or PASC. Studies to date estimate that 30-50% of people who had COVID-19 still experience at least one post-COVID symptom 4 weeks after infection and 10-30% even after 12 weeks of acute infection 2, 3 . While the definition and scope of PASC remains to be determined, it is currently defined as new or persistent symptoms of COVID-19 beyond 4 weeks of acute infection that cannot be explained by other underlying etiologies 4, 5 .…”

Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: Multilayered cross-talks in the setting of coinfections and comorbidities

“…Detection of viral RNA after SARS-CoV-2 infection has also been reported by multiple groups many months post-recovery from COVID-19 [ 2 , 3 , 96 , 145 – 147 ]. Possibly, there is an immune-escape strategy behind the persistence of undegraded RNA of SARS-CoV-2 like HIV where methylation of viral RNA was found to help avoid immune cell sensing [ 148 , 149 ]. Further studies will show whether SARS-CoV-2 virus pursues such an immune-escape strategy or not.…”