The objective of this retrospective pilot study, conducted by US researchers, was to determine the presence of circulating viral antigens and inflammatory markers associated with postacute sequelae of coronavirus disease (PASC). Results showed that circulating SARS-CoV-2 spike (S) protein was present in approximately 60% of vaccinated and unvaccinated patients with PASC, up to 12 months after diagnosis of SARS-CoV-2 infection.
More than two years after the global COVID-19 pandemic, it is clear that infection with SARS-CoV-2 can lead to a new disease called PASC or long COVID. WHO defines long COVID as: “the continuation or development of new symptoms 3 months (12 weeks) after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation”. Despite the extensive research on long COVID, its pathogenesis is still unclear.
About the study
Blood was collected from 63 individuals who had suffered from COVID-19. 37 participants were diagnosed with PASC, and the majority of PASC patients were female (n=30). This confirms the hypothesis that women are more likely than men to suffer from PACS. https://discovermednews.com/women-are-more-likely-than-men-to-suffer-from-long-covid/
For most PASC patients (n=31), blood samples were collected two or more times up to 12 months after diagnosis of SARS-CoV-2 infection (by positive nasopharyngeal swab reverse transcription polymerase chain reaction test). Blood was also collected from individuals who had suffered from COVID-19 but were not diagnosed with PASC up to 5 months after the diagnosis of COVID-19.
To identify biomarkers associated with PASC, the plasma concentrations of viral antigens, including full-length S protein, S1 subunit of the spike protein, and nucleocapsid (N), and a panel of cytokines, including interferon-γ, interleukin 1β (IL-1β), IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, and tumor necrosis factor-α were measured.
The results showed presence of circulating viral antigens in plasma samples from approximately 65% of patients with PASC at some time point up to 12 months after diagnosis of SARS-CoV-2 infection. Of the three antigens measured, the S protein was found most frequently (in 60% of patients), S1 was detected in approximately 20% of PASC patients, whereas N was detected in one patient at multiple time points. Importantly, the S protein was not found in plasma samples of participants who were not diagnosed with PASC after they had suffered from COVID-19.
The analysis of temporal antigen profiles, which was done by collecting blood samples at multiple times, showed that viral antigen was detected more than once in longitudinal samples from 12 patients with PASC. Of these 12 patients, 7 were vaccinated and 5 unvaccinated within 1 month of the time frame.
The plasma concentrations of cytokines, including interferon-γ, interleukin 1β (IL-1β), IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-22, and tumor necrosis factor-α remained within normal ranges.
The researchers also clasiffied reported symptoms of PASC according to the associated organ system, and related those symptoms to the presence of circulating viral antigens. The results showed that circulating viral antigens were found in >70% of patients with cardiovascular, head-eye-ear-nose-throat and musculoskeletal symptoms. Also, the circulating viral antigens were more frequently found in patients with gastrointestinal and neuropsychiatric symptoms.
According to the authors, the findings of circulating SARS-CoV-2 S protein in approximately 60% of patients with PASC up to 12 months after diagnosis, support the proposed pathophysiological model of long COVID as a viral reservoir and an infection-associated chronic disease. https://discovermednews.com/a-pathophysiological-model-of-long-covid-based-on-the-persistence-of-the-sars-cov-2-virus/
On the other hand, they pointed out that S protein alone have different pathological effects causing damage of various cells and organs.
In conclusion, the authors said that many overlapping mechanisms contribute to PASC, and that a detection of S protein alone cannot confirm the presence of active viral reservoirs.
This article was published in Clinical Infectious Diseases.
Journal Reference
Swank Z et al. Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae. CID 2023:76 (1 February) e487. (Open Access) https://doi.org/10.1093/cid/ciac722