Nucleocapsid Antigenemia in Patients Receiving Anti-CD20 Therapy With Protracted COVID-19

Wilber, Eli; Piantadosi, Anne; Babiker, Ahmed; McLendon, Kaleb; O’Sick, William; Fitts, Eric; Webster, Andrew; Verkerke, Hans; Kim, James S; Phadke, Varun K; Rouphael, Nadine; Titanji, Boghuma K; Blake, William T; Howard‐Anderson, Jessica; Roback, John D.; Lam, Wilbur A.; Damhorst, Gregory L.

doi:10.1093/ofid/ofac419

Cited by 3 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This patient received tacrolimus and mycophenolate‐mofetil due to kidney transplantation and showed a delayed NCP clearance. Such impaired viral clearance in an immunocompromised patient is consistent with previous reports on protracted mucosal shedding of infectious virus 13 and prolonged systemic antigenemia under immunosuppression 14 …”

Section: Discussionsupporting

confidence: 92%

“…11 Our study is the first to show that prolonged antigenemia in ICU patients is associated with lower S1-but not Such impaired viral clearance in an immunocompromised patient is consistent with previous reports on protracted mucosal shedding of infectious virus 13 and prolonged systemic antigenemia under immunosuppression. 14 As a potential limitation, our study was conducted early in the course of the pandemic, so that the representation of viral variants is limited.…”

Section: Antibody Responses In Ncp-positive Icu Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Impaired systemic nucleocapsid antigen clearance in severe COVID‐19

Bauer

Mack

Hefter

et al. 2023

Journal of Medical Virology

View full text Add to dashboard Cite

The circulating nucleocapsid (NCP) antigen of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is detectable in coronavirus disease‐2019 (COVID‐19) patients. To better understand the biology of disease severity, we investigated NCP clearance kinetics in hospitalized COVID‐19 patients. Serum NCP was quantified using a commercial NCP‐specific enzyme‐linked immunoassay in hospitalized COVID‐19 patients (n = 63) during their hospital stay. Results were correlated to COVID‐19 disease severity, inflammation parameters, antibody response, and results of SARS‐CoV‐2 PCR from nasopharyngeal swabs. We demonstrate that NCP antigen levels in serum remained elevated in 21/45 (46.7%) samples from patients in intensive care units (ICU) after >8 days postdiagnosis. The proportion of ICU patients with detectable antigenemia declined only gradually from 84.6% to 25.0% over several weeks. This was in contrast to complete NCP clearance in all non‐ICU patients after 8 days, and also in contrast to mucosal clearance of the virus as measured by PCR. Antigen clearance was associated with higher IgG against S1 but not NCP. Clearance of NCP antigenemia is delayed in >40% of severely ill COVID‐19 patients. Thus, NCP antigenemia detected after 8 days post COVID‐19 diagnosis is a characteristic of patients requiring intensive care. Prospective trials should further investigate NCP antigen clearance kinetics as a mechanistic biomarker.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Antibody Responses In Ncp-positive Icu Patientsmentioning

confidence: 99%

Impaired systemic nucleocapsid antigen clearance in severe COVID‐19

Bauer

Mack

Hefter

et al. 2023

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…Our requirement for ultraspin to concentrate virus in NPSs and minimize the cytotoxic effects of transport media, degradational, and dilutional effects likely also limited our ability to detect all viable virus present in fresh specimens. Furthermore, cases have been reported in which active virus in the lower respiratory tract is evident but no viral RNA is present in the NPS, highlighting the potential for discordance between the nasopharynx and other sites of infection [ 8 , 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in immunocompromised patients who may develop protracted SARS-CoV-2 infection, this biomarker may be even more sensitive and specific for a period of weeks to months after acute COVID-19. Although our study was not designed to specifically evaluate protracted infection, antigenemia in 3 individuals with culture-positive NPSs after more than 10 days in the subgroup with immune compromise ( Supplementary Figure 8 and Table 1 ) adds to emerging literature supporting antigenemia as an adjunct diagnostic tool in these scenarios [ 8 ]. Finally, when considering the possibility of discordance between the nasopharynx and lower respiratory tract—for example, in an NPS RT-PCR-negative patient for whom clinical suspicion for active SARS-CoV-2 remains—antigenemia may be an important indicator.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of SARS-CoV-2 nucleocapsid protein in blood plasma, or antigenemia, is highly prevalent in individuals with acute COVID-19 and has been observed in individuals with prolonged viral replication [ 8–10 ]. Observations of high prevalence of nucleocapsid protein antigenemia during acute COVID-19 has compelled interest in its potential as a biomarker of active infection, but this has not been directly investigated in the Omicron era.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Investigation of Blood Plasma Viral Nucleocapsid Antigen as a Marker of Active Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Infection

Damhorst

Schoof

Nguyen

et al. 2023

Open Forum Infectious Diseases

Self Cite

View full text Add to dashboard Cite

Background Nasopharyngeal qualitative RT-PCR is the gold standard for diagnosis of SARS-CoV-2 infection, but not practical or sufficient in every clinical scenario due to its inability to distinguish active from resolved infection. Alternative or adjunct testing may be needed to guide isolation precautions and treatment in hospitalized patients. Methods We performed a single-center, retrospective analysis of residual clinical specimens and medical record data to examine blood plasma nucleocapsid antigen as a candidate biomarker of active SARS-CoV-2. Adult patients admitted to the hospital or presenting to the emergency department with SARS-CoV-2 RNA detected by RT-PCR from a nasopharyngeal swab specimen were included. Both nasopharyngeal swab and a paired whole blood sample were required to be available for analysis. Findings 54 patients were included. 8 patients had positive nasopharyngeal swab virus cultures of which 7 (87·5%) had concurrent antigenemia. 19 (79·2%) of 24 patients with detectable sub-genomic RNA and 20 (80·0%) of 25 patients with N2 RT-PCR Ct ≤ 33 had antigenemia. Interpretation Most individuals with active SARS-CoV-2 infection are likely to have concurrent antigenemia, but there may be some individuals with active infection in whom antigenemia is not detectable. The potential for high sensitivity and convenience of a blood test prompts interest in further investigation as a screening tool to reduce reliance on nasopharyngeal swab sampling and as an adjunct diagnostic test to aide in clinical decision making during the period following acute COVID-19.

show abstract