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Persistent spike protein may account for long COVID

The presence of persistent spike protein has been detected in patients with long COVID and might account for continued symptoms

The continued presence of spike protein in patients with long COVID may be responsible for their persistent symptoms and serve as a biomarker for the condition according to a small scale study by researchers from Boston, US.

Although many millions of people who have been infected with COVID-19 make a full recovery, for some, symptoms may continue and they develop a wide range of persistent symptoms that fail to resolve over the course of many months. Such patients are diagnosed with long COVID or post-acute sequelae of COVID-19 (PASC).

The World Health Organization have described what it terms ‘post COVID-19 condition’ defined as occurring in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis.

The cause of PASC remains to be determined although many theories have been proposed including tissue persistence of viral antigen, systemic and tissue localised inflammatory responses, reactivation of human herpesviruses (e.g., Epstein-Barr virus), alterations in the gut microbiome, issues related to clotting, and the interplay between SARS-CoV-2-specific and auto-reactive immunity.

Nevertheless, untangling the complex biology involved may be assisted through the identification of biomarkers in those with PASC.

In the present study, the US team analysed plasma samples from patients with PASC and for comparative purposes those who had been infected with COVID-19 but made a full recovery. The researchers measured the levels of three antigens: the S1 subunit of spike, full length spike protein and nucleocapsid (N).

Spike protein levels in PASC

The study included a sample of 37 PASC patients with a median age of 46 years (81% female) and 26 (median age 63, 38% female) without PASC.

For the PASC patients, blood samples were collected two or more times up to 12 months after their initial PCR confirmed COVID-19 infection. Blood samples were collected from individuals who had COVID-19 but not PASC, up to five months post-diagnosis.

The team were able to detect either S1, full length spike protein or N in roughly 65% of PASC patients at any given point in time, several months post-COVID-19. For the 3 antigens however, spike protein was detected in 60% of PASC patients, whereas S1 was detected to a lesser extent and N only in a single patient at different time points. Spike protein was undetectable in those who had fully recovered from COVID-19 although both S1 and N were found.

In cases where PASC patients had blood samples collected a multiple time points, all three antigens could be detected several months after the acute infection, although spike protein was detected most often over time.

Commenting on these results, the authors noted how circulating levels of spike protein in the majority of PASC patients but none of those without PASC was compelling. Given that only two patients with PASC had been hospitalised, these results suggested the continued presence of spike protein was associated with COVID-19 infection per se rather than the severity of infection.

The authors added that detection of spike protein was likely to indicate that PASC is associated with a reservoir of active virus and which persisted in the body.

The authors concluded that spike protein could potentially serve as a biomarker for PASC although further studies with larger patient cohorts were required to confirm these findings.

Swank Z et al. Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae MedRxiv 2022