Preprint Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection, 2023, Peluso, Swank et al.

Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection
Michael J. Peluso; Zoe N. Swank; Sarah A. Goldberg; Scott Lu; Thomas Dalhuisen; Ella Borberg; Yasmeen Senussi; Michael A. Luna; Celina Chang Song; Alexus Clark; Andhy Zamora; Megan Lew; Badri Viswanathan; Beatrice Huang; Khamal Anglin; Rebecca Hoh; Priscila Y. Hsue; Matthew S. Durstenfeld; Matthew A. Spinelli; David V. Glidden; Timothy J. Henrich; J. Daniel Kelly; Steven G. Deeks; David R. Walt; Jeffrey N. Martin

BACKGROUND: Although RNA viruses like SARS-CoV-2 are generally thought to be transient, the persistence of viral components beyond the acute phase can be driven by a variety of virologic and immunologic factors. Recent studies have suggested that SARS-CoV-2 antigens may persist following COVID-19 but were limited by a lack of comparison to a large number of true negative control samples.

METHODS: Using single molecule array (Simoa) assays for SARS-CoV-2 spike, S1, and nucleocapsid antigen in plasma from 171 pandemic-era individuals in the post-acute phase of SARS-CoV-2 infection and 250 pre-pandemic control samples, we compared prevalence of antigen detection. We used logistic regression models and prevalence ratios (PRs) to assess the relationship between demographic and disease factors and antigen persistence.

RESULTS: Compared to the proportion of antigen positivity in the pre-pandemic controls (2%), detection of any SARS-CoV-2 antigen was more frequent across all post-acute COVID-19 time bins (3-6 months: 12.6%, p<0.001; 6-10 months, 10.7%, p=0.0002; 10-14 months, 7.5%, p=0.017). These differences were driven by spike protein for up to 14 months and nucleocapsid in the first 6 months after infection. The co-occurrence of multiple antigens at a single timepoint was uncommon. Hospitalization for acute COVID-19 (versus not hospitalized) and worse self-reported health during acute COVID-19 among those not hospitalized (versus more benign illness) were associated with higher prevalence of post-acute antigen detection (PR 1.86, p=0.03; PR 3.5, p=0.07, respectively) in the pandemic era.

CONCLUSIONS: Our findings provide strong evidence that SARS-CoV-2 antigens can persist beyond the period of acute illness. The observation that more than 10% of plasma samples for over a year following initial SARS-CoV-2 infection contain detectable viral antigen, which are potentially immunogenic, has significant implications given the sheer number of people infected with SARS-CoV-2 to date. More work will be needed to determine whether these antigens have a causal role in post-acute sequelae of SARS-CoV-2 infection (PASC).

FUNDING: This work was supported by funding from the PolyBio Research Foundation to support the LIINC Clinical Core, as well as support from NIH/NIAID 3R01AI141003-03S1, NIH/NIAID R01AI158013, and NIH/NIAID K23AI134327.

Link | PDF (Preprint: MedRxiv)

 

One wonders how you could do a study like this and not ask the participants if they have LC, which seems like the most important question here.

 

I think the point of the study is to validate the SIMOA assay, which has been, and is currently being tested in multiple studies as well as establishing best use practices for it, rather than doing anything else.

 

Now published as Plasma-based antigen persistence in the post-acute phase of COVID-19 in the Lancet Infectious Diseases.

 

Although not without limitations, our data provide strong evidence that SARS-CoV-2, in some form or location, persists for up to 14 months following acute SARS-CoV-2 infection. This persistence is influenced by the events of acute infection. These findings motivate an urgent research agenda regarding the clinical manifestations of SARS-CoV-2 persistence, specifically whether it is causally related to either post-acute chronic symptoms (eg, fatigue, pain, and cognitive difficulty) or discrete incident complications (eg, cardiovascular events).