SARS-CoV-2 protein detectable in COVID-19 patients up to 14 months after illness
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Key takeaways:
- Of plasma samples taken after COVID-19 infection, 7.5% to 12.6% contained detectable viral antigens.
- Researchers also found evidence of SARS-CoV-2 spike RNA in patients’ guts up to 2 years after infection.
DENVER — SARS-CoV-2 antigens persist in patients with COVID-19 for months to years after infection, according to data presented at the Conference on Retroviruses and Opportunistic Infections.
“At the University of California, San Francisco, we have been studying what happens in the aftermath of COVID-19 since the earliest days of the pandemic,” Michael J. Peluso, MD, MPhil, MHS, DTM&H, assistant professor of medicine in the division of HIV, infectious diseases, and global medicine at the University of California, San Francsico, told Healio.
“We all assumed that SARS-CoV-2 would prove to be a transient pathogen, in contrast to viruses like HIV or herpesviruses, which are known to persist,” he said.
According to Peluso, there have been a number of studies that have challenged this framework over the last year, but they had “major limitations,” such as small sample sizes, immunocompromised participants, inconsistencies in terms of vaccines and reinfections and very few actually had true negative controls.
“This study was meant to address several of these issues,” he said.
Peluso and colleagues assessed viral persistence using single molecule array assays for SARS-CoV-2 spike, S1, and nucleocapsid antigen in plasma collected from 171 patients after infection, as well as from 250 pre-pandemic control samples. The researchers used an RNAscope to assess SARS-CoV-2 spike RNA in rectal tissue in five patients between 90 and 676 days post-COVID-19 infection without reinfection.
Overall, the study revealed that compared with the proportion of antigen positivity in pre-pandemic control (2%), detection of any SARS-CoV-2 antigen in patient plasma was more frequent across all post-acute COVID-19 time periods assessed during the study: 12.6% at 3 to 6 months (P < .001), 10.7% at 6 to 10 months (P = .0002) and 7.5% at 10 to 14 months (P = .017).
Peluso said these data provide the “strongest evidence yet” that antigen persists beyond initial infection and that this is “unlikely to be just false-positive noise.”
Among samples taken from patients’ guts up to 2 years post-COVID, the researchers found evidence of SARS-CoV-2 spike RNA in four of the five patients, primarily in the connective tissue layer, where immune cells traffic.
They also found evidence of double-stranded RNA, which should be present only if the virus is undergoing active replication, according to Peluso. He said this suggests that the genetic material “may not just be inert and may actually reflect an active reservoir of SARS-CoV-2.”
Based on these data, Peluso concluded that SARS-CoV-2 persists in at least some people for months to years after COVID-19 infection, which “goes against our framework for coronaviruses as transient pathogens.”
“What we don't know yet is whether this persistent antigen is responsible for symptoms (of long COVID) or medical events (like heart attacks) that occur in the weeks, months and years after a person has COVID,” he said.
“We believe the evidence is compelling enough to serve as the basis for a major research initiative aimed at understanding the biological impact and clinical significance of this finding — a big portion of which will need to be clinical trials intervening on antigen persistence to see whether we can alter the biology and clinical outcomes in people with these findings,” Peluso said.
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Peluso MJ, et al. Abstract 138. Presented at: Conference on Retroviruses and Opportunistic Infections; March 3-6, 2024; Denver.
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