Low Innate Immunity and Lagged Adaptive Immune Response in the Re-Tested Viral RNA Positivity of a COVID-19 Patient

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.

Immunity against Delta and Omicron variants elicited by homologous inactivated vaccine booster in kidney transplant recipients

“…SARS-CoV-2 spike-specific antibodies, especially NAbs, are crucial biomarkers for protective humoral immunity against COVID-19 ( 27 ). Our previous study indicated that 5% (2/40) of KTRs developed NAbs after two doses of the inactivated vaccine ( 14 ).…”

Ad5‐nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants

“… 15 Of note, unvaccinated OIPs had lower antibody levels against Omicron variants and had a risk of re‐infection with SARS‐CoV‐2 variants. 13 , 19 Therefore, unvaccinated OIPs need to be further vaccinated to provide better protective immunity against emergent SARS‐CoV‐2 variants. 19 …”

“… 22 Finally, the coordinated protection of conserved T cells immunity and the early induced humoral immune response contribute to rapid virus clearance and recovery of pre‐vaccinated OIPs. 13 , 23 …”

“…The OIPs were classified as symptomless or having mild or moderate symptoms based on previous guidelines. 13 …”

Different B cell activation patterns in asymptomatic and symptomatic COVID-19 patients

“…In the humoral immune response, B cells are essential for presenting antigens to other immune cells, producing pathogen-specific antibodies, and secreting proinflammatory cytokines. Low B cell counts of some subsets such as memory B cells and expression of B cells related genes such as heavy chain and light V chain genes are observed in severe COVID-19 patients (3; 4; 5).…”