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Active Presence of Spike Protein Correlated With Long COVID

An active viral reservoir of COVID-19 spike protein was detected in 65% of patients with post-acute sequelae of COVID-19.

There have been many studies examining why some people experience “long COVID” and others don’t, but the diagnosis and treatment of post-acute sequelae of COVID-19 (PASC) continues to challenge healthcare providers.

One study, published in medRxiv, sought to identify the PASC biomarkers to improve long COVID diagnosis. The team of investigators, from Brigham and Women’s Hospital and the Massachusetts General Hospital, found that excess SARS-CoV-2 spike protein in the plasma indicated long COVID.

The investigators analyzed plasma samples collected from 63 individuals previously infected with COVID-19, 37 of whom were diagnosed with PASC. Blood samples were collected at least 2 times no more than 12 months after a positive COVID-19 RT-PCR or antibody test. As a control, blood samples were also collected from 26 persons who contracted from COVID-19 but had a full recovery, with no PASC diagnosis.

The investigators utilized ultra-sensitive single molecule array assays to measure the concentration of COVID-19 antigens. They detected either the S1 subunit of spike, full length spike, or nucleocapsid (N) in 65% of the plasma from PASC patients. Of all 3 antigens measured, spike was detected most often, in 60% of patients. Notably, no spike could be detected in the fully recovered COVID-19 patients.

Of the 37 long COVID patients, 30 were women, confirming previous research findings that women are disproportionately affected by PASC. Among the 26 patients not diagnosed with PASC, 10 were admitted to the intensive care unit (ICU), and 7 were intubated.

The presence of SARS-CoV-2 spike antigen in the majority of PASC patients suggests long COVID may be due to the active presence of a SARS-CoV-2 viral reservoir. The investigators noted that their sample size was small, but it is significant that spike was detected at various points in time at 2-12 months after COVID-19 infection.