Role of Nucleocapsid Protein Antigen Detection for Safe End of Isolation of SARS-CoV-2 Infected Patients with Long Persistence of Viral RNA in Respiratory Samples

Abstract

Background. In SARS-CoV-2 infection, viral RNA may persist in respiratory samples for several weeks after the resolution of symptoms. Criteria to assess the end of infectivity are not unequivocally defined. In some countries, time from diagnosis is the unique criterion used, in addition to symptom cessation. This study evaluates the role of the Lumipulse® Antigen Assay (LAA) for the safe end of isolation of patients ≥21 days after the diagnosis of infection. Methods. A total of 671 nasopharyngeal swabs from patients diagnosed with infection at least 21 days before were assessed by RT-PCR and LAA, and the role of LAA in predicting the absence of infectivity was evaluated by virus cell culture. Results. Viable virus was present in 10/138 cultured samples. Eight out of ten infective patients suffered from a concomitant disease, predisposing them to long-term shedding of infective virus. In particular, infectious virus was isolated from 10/20 RT-PCR+/LAA+ cultured samples, whereas no viable virus was found in all 118 RT-PCR+/LAA– cultured swabs. LLA and RT-PCR agreed in 484/671 (72.1%) samples, with 100% and 26.7% concordance in RT-PCR negative and positive samples, respectively. Conclusions. Viable virus can be found ≥21 days after diagnosis in immunocompromised or severely ill patients. LAA better than RT-PCR predicts non-infectivity of patients and can be safely used to end isolation in cases with long persistence of viral RNA in the respiratory tract.

SARS-CoV-2 Antigen Test Results to Infer Active or Non-Active Virus Replication Status in COVID-19 Patients

“…Previous studies’ findings supported us to adopt SARS-CoV-2 sgRNA RT-PCR as the reference method for our antigen tests’ assessment [ 6 , 15 , 16 , 17 ]. One study [ 15 ] using respiratory tract samples obtained from COVID-19 patients within 7 days of symptom onset showed the correlation between the SARS-CoV-2 antigen (using the Becton Dickinson BD Veritor System for Rapid Detection of SARS-CoV-2 test) and SARS-CoV-2 culture (using a VeroE6TMPRSS2 cell line-based high-sensitive culture test) positivity.…”

Performance and application evaluation of SARS‐CoV‐2 antigen assay

“…This study showed that SARS‐CoV‐2 could not be cultured from specimens yielding RT‐PCR positive and SARS‐CoV‐2 antigen assay negative results, and the data suggested that patients with RT‐PCR‐proven COVID‐19 testing negative by SARS‐CoV‐2 antigen assay are unlikely to be infectious 34 . Other studies have also confirmed that there is a certain relationship between the amount of SARS‐CoV‐2 antigen and the infection status and virus shedding 51–55 . However, this specific connection needs to be explored continuously.…”

“… 34 Other studies have also confirmed that there is a certain relationship between the amount of SARS‐CoV‐2 antigen and the infection status and virus shedding. 51 , 52 , 53 , 54 , 55 However, this specific connection needs to be explored continuously.…”