Table_1_Low Innate Immunity and Lagged Adaptive Immune Response in the Re-Tested Viral RNA Positivity of a COVID-19 Patient.doc

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.

近期研究凸显了关于出院后COVID-19患者SARS-CoV-2 RNA复检阳性（RP）的观察结果，然而，SARS-CoV-2 RNA复检阳性在免疫健全患者中的免疫机制仍然难以捉摸。本研究详细描述了一位具有中度症状的免疫健全COVID-19患者，其SARS-CoV-2 RNA复检阳性出现两次，首次与第三次病毒RNA阳性之间的时间为95天，长于先前报道的18至25天。分析了复检阳性患者及其他COVID-19患者的胸部计算机断层扫描结果、血浆抗SARS-CoV-2抗体、中和抗体（NAbs）滴度以及全血转录特性。在SARS-CoV-2 RNA复检阳性期间，观察到新的肺部病变。具有病毒RNA复检阳性的COVID-19患者表现出抗刺突/受体结合域（RBD）IgA抗体和NAbs的血清转化延迟，并伴有肺部病变的消失。进一步的实验数据验证了NAbs滴度与抗RBD IgA和IgG、抗刺突IgG的显著相关性。复检阳性患者相较于非复检阳性且症状为轻度至中度的患者，具有较低的干扰素-、T细胞和B细胞相关基因表达，且较重症患者表现出较低的细胞因子和趋化因子基因表达。有趣的是，复检阳性患者的抗原呈递相关基因表达较低，B细胞计数也较低，这或许导致了抗RBD特异性抗体和低CD8+细胞反应的延迟。总体而言，延迟的抗原呈递相关基因表达被发现与延迟的适应性免疫反应相关，并导致了所述免疫健全患者中SARS-CoV-2 RNA复检阳性现象。