Abstract
Recent studies have highlighted observations regarding re-tested positivity (RP) of SARS-CoV-2 RNA in discharged COVID-19 patients, however, the immune mechanisms underlying SARS-CoV-2 RNA RP in immunocompetent patients remain elusive. Herein, we describe the case of an immunocompetent COVID-19 patient with moderate symptoms who was twice re-tested as positive for SARS-CoV-2 RNA, and the period between first and third viral RNA positivity was 95 days, longer than previously reported (18–25 days). The chest computed tomography findings, plasma anti-SARS-CoV-2 antibody, neutralizing antibodies (NAbs) titer, and whole blood transcriptic characteristics in the viral RNA RP patient and other COVID-19 patients were analyzed. During the SARS-CoV-2 RNA RP period, new lung lesions were observed. The COVID-19 patient with viral RNA RP had delayed seroconversion of anti-spike/receptor-binding domain (RBD) IgA antibody and NAbs and were accompanied with disappearance of the lung lesions. Further experimental data validated that NAbs titer was significantly associated with anti-RBD IgA and IgG, and anti-spike IgG. The RP patient had lower interferon-, T cells- and B cell-related genes expression than non-RP patients with mild-to-moderate symptoms, and displayed lower cytokines and chemokines gene expression than severe patients. Interestingly, the RP patient had low expression of antigen presentation-related genes and low B cell counts which might have contributed to the delayed anti-RBD specific antibody and low CD8+ cell response. Collectively, delayed antigen presentation-related gene expression was found related to delayed adaptive immune response and contributed to the SARS-CoV-2 RNA RP in this described immunocompetent patient.
Highlights
Recent reports have highlighted the recurrence of SARS-CoV-2 RNA positivity in discharged COVID-19 patients (1) and their risk of being infectious (2)
The re-tested positivity (RP) patient had a new lesion in his lung during the re-detectable RNA positive stage but all the close contact family members of the patient were not infected and were tested negative for SARS-CoV-2 RNA and antibody following a long surveillance; suggesting the previous infected SARS-CoV-2 isolate was not completely cleared during the first discharge
The RP patient could not be excluded for reinfection of novel mutated SARS-CoV-2 isolates because prolonged infection of SARS-CoV-2 could accelerate its mutation in immunocompromised hosts (5)
Summary
Recent reports have highlighted the recurrence of SARS-CoV-2 RNA positivity in discharged COVID-19 patients (1) and their risk of being infectious (2). The causes for recurrent positive detection of SARS-CoV-2 RNA might be low virus load in the respiratory samples of discharged COVID-19 patients and/or low assay-sensitivity of detection methods; leading to false negative results at the time of discharge (3). The “turned positive” phenomenon of SARS-CoV-2 RNA could be indicating prolonged viral shedding rather than “recurrence” (4). SARS-CoV-2 could accelerate its mutation during prolonged infection in immunocompromised COVID-19 patients, the mutation of receptor-binding domain (RBD) region of spike gene could lead to immunologic escape, bring about novel higher infectious virus isolates emergence, leading to recurrence of infection or fatality (5). Infectious virus could be shedded in few SARS-CoV-2 RNA redetectable patients (6). There is great urgency to promptly identify these patients to implement timely therapy and quarantine measures
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