Persistent circulation of soluble and extracellular vesicle-linked Spike protein in individuals with postacute sequelae of COVID-19

J Med Virol. 2023 Feb;95(2):e28568. doi: 10.1002/jmv.28568.


SARS-CoV-2, the causative agent of COVID-19 disease, has resulted in the death of millions worldwide since the beginning of the pandemic in December 2019. While much progress has been made to understand acute manifestations of SARS-CoV-2 infection, less is known about post-acute sequelae of COVID-19 (PASC). We investigated the levels of both Spike protein (Spike) and viral RNA circulating in patients hospitalized with acute COVID-19 and in patients with and without PASC. We found that Spike and viral RNA were more likely to be present in patients with PASC. Among these patients, 30% were positive for both Spike and viral RNA; whereas, none of the individuals without PASC were positive for both. The levels of Spike and/or viral RNA in the PASC+ve patients were found to be increased or remained the same as in the acute phase; whereas, in the PASC-ve group, these viral components decreased or were totally absent. Additionally, this is the first report to show that part of the circulating Spike is linked to extracellular vesicles without any presence of viral RNA in these vesicles. In conclusion, our findings suggest that Spike and/or viral RNA fragments persist in the recovered COVID-19 patients with PASC up to 1 year or longer after acute SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; Spike; extracellular vesicles; plasma; viral RNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • COVID-19*
  • Disease Progression
  • Extracellular Vesicles*
  • Humans
  • Post-Acute COVID-19 Syndrome
  • RNA, Viral
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus


  • spike protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus
  • RNA, Viral