Study finds virus markers can linger for over a year

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A recent study posted medRxiv Preprint* server, researchers pursued evidence of whether the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen, the spike (S) protein of which is highly immunogenic, persists beyond the acute phase of coronavirus disease 2019 (COVID-19).

Study: plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection.  Image credit: Created with assistance from DALL·E 3Study: Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection. Image credit: Created with assistance from DALL·E 3

*Important Notice: medRxiv Preliminary scientific reports are published that are not peer-reviewed and, therefore, should not be considered conclusive, guidelines for clinical practice/health-related behavior, or established information.


Infections caused by most ribonucleic acid (RNA) viruses are transient. Thus, the researchers hypothesized that COVID-19, caused by SARS-CoV-2, an RNA virus, is not a persistent infection; However, the evidence points to a different reality.

Studies have shown that SARS-CoV-2 antigens, particularly spike subunits 1 and 2 (S1 and S2) and nucleocapsid (NC), can persist after COVID-19. Studies also indicate that several virologic and immunological factors operate behind the persistence of SARS-CoV-2 antigens beyond the acute phase of illness.

However, the results of this study are limited given the need for a large sample set of negative control samples.

About the study

In the current study, researchers created two cohorts consisting of pre-pandemic (prior to 2019) and pandemic era participants to test their plasma samples for the presence of S, S1 and NC antigens using single molecule array (SMA) assays.

Pre-epidemic plasma samples were randomly collected from participants in the Study of Protease Era Consequences (SCOPE) study conducted in 2001 at the University of California, San Francisco (UCSF). HIV). For each HIV-infected participant, four uninfected participants matched for age and race/ethnicity provided samples for the current analysis.

They collected pooled plasma samples from participants in the Long-Term Effects of Infection with Novel Coronavirus (LIINC) study completed at UCSF, who had the most study visits in the 1.25 years following the COVID-19 pandemic.

Further, researchers administered questionnaires to both groups to collect data on sociodemographic, economic and clinical characteristics. In the pandemic-era group, they specifically looked at self-reported symptom experience and perceptions of overall health on a scale of zero to 100 during the first three weeks of the acute phase of COVID-19, and whether there were any Covid-19-related hospitalizations. . In addition, they monitored SARS-CoV-2 vaccination and any additional SARS-CoV-2 infections since the index infection.

S, S1 and NC assays were performed separately using antibodies specific for S1, S2 and NC conjugated to carboxylated magnetic beads. The team calculated mean enzyme (AEB) values ​​above the limit of detection (LOD) as background AEB and reported them separately. Further, they used a four-parameter logistic regression and prevalence ratios (PRs) to illustrate the association of demographic and clinical factors with antigen persistence across both study groups.

In statistical analyses, assays evaluating epidemiologic samples observed the presence of antigen at 3, 6, to 10 months, and 11 to 14 months after the onset of Covid-19 symptoms. They defined the presence or absence of each antigen in the three assays and at least one antigen against the three antigens.


Epidemic- and pre-epidemic groups were similar in characteristics; However, they were variable in proportion to women. The former has 50% women, with an average age of 46 years, while the latter has only 22% women. Study follow-up for epidemic-era participants continued long after the index infection, between 0.9 and 15.4 months.

SARS-CoV-2 antigens, S, S1, and NC were present in three, three, and two samples, respectively, out of a total of 250 pre-epidemic samples. The presence of at least one antigen in all 250 plasma samples suggests a tendency for false positives.

The presence of any SARS-CoV-2 antigen was relatively more frequent at all epidemic-era time points, driven by NC in the first six, and S index up to 14 months of SARS-CoV-2 infection. Notably, a single antigen was identified in most epidemic-era cases (59/61, 96.7%).

Detection of multiple antigens at a single time was uncommon. Accordingly, all three antigens could not be detected simultaneously; However, two antigens (one for each of S1 and N) were detected simultaneously. In samples with detectable antigen, mean S, S1, and N concentrations were 27.7 pg/mL, 31.2 pg/mL, and 23.6 pg/mL, respectively.

Among vaccinated individuals, in five instances (three for S1 and one each for S and N) antigen was detected within three weeks of receiving the vaccine dose.

Evidence of an association between age, gender, race/ethnicity, body mass index (BMI), or HIV status was lacking among other determinants of antigen positivity among epidemic-era participants. However, the effect of severity on the acute phase of illness was stronger.

Thus, participants who required hospitalization for acute COVID-19 were twice as likely to have antigen detection (PR=1.86, p=0.03), compared to those who were not hospitalized for COVID-19 but had severe illness. It was three times more. antigen detection compared to less severe acute illness (PR=3.5, p=0.07).


Studies have confirmed a link between antigens of SARS-CoV-2 and post-acute sequelae of SARS-CoV-2 (PASC). Accordingly, even in this study, researchers detected potentially immunogenic viral antigens in 10% of plasma samples from Covid-19 patients up to 14 months after SARS-CoV-2 infection during the pandemic period, providing strong evidence that SARS-CoV-2 is a unique RNA virus.

Millions of people have been infected with SARS-CoV-2, and its S is a highly immunogenic antigen, with significant implications for this phenomenon. First and foremost, this implies that, unlike most other RNA viruses, SARS-CoV-2 infection is not transient in all cases and can develop in immunocompromised individuals.

However, unlike previous studies, which examined the persistence of SARS-CoV-2 antigens in patients receiving clinical care at PASC clinics, researchers in this study used samples from individuals in the post-acute phase of COVID-19, regardless of the severity of their symptoms. Furthermore, they conducted a direct comparison of SARS-CoV-2 antigen persistence in the post-acute phase between pre-epidemic (control) and epidemic samples, which alleviated all concerns of obtaining false positive results.

Further work is warranted to assess whether persistence of SARS-CoV-2 antigens is a driver of PASC or a trivial consequence of prior infection. Furthermore, larger sample size studies are needed to determine whether antigen persistence is causally related to symptoms.

*Important Notice: medRxiv Preliminary scientific reports are published that are not peer-reviewed and, therefore, should not be considered conclusive, guidelines for clinical practice/health-related behavior, or established information.

Journal Reference:

  • Preliminary Scientific Report. Plasma-Based Antigen Persistence in the Post-Acute Phase of SARS-CoV-2 Infection, Michael J. Peluso, Joe N. Swank, Sarah A. Goldberg, Scott Lu, Thomas Dalhuisen, Ella Borberg, Yasmin Senusi, Michael A. Luna, Selina Chang Song, Alexa Clark, Andhi Zamora, Megan Liu, Badri Viswanathan, Beatrice Huang, Khamal Anglin, Rebecca Ho, Priscilla Y. Hisu, Matthew S. Durstenfeld, Matthew A. Spinelli, David V. Glidden, Timothy J. Heinrich, JD Kelly, Steven G. Deeks, David R. Walt, Jeffrey N. Martin, medRxiv 2023.10.24.23297114; doi:,

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