1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
2Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Am J Trop Med Hyg. 2020 Dec;103(6):2412-2418. doi: 10.4269/ajtmh.20-1110. Epub 2020 Oct 27.
The severity of COVID-19 ranges from mild to critical diseases. However, limited data have been published on the detailed kinetics of viral load and host immune response throughout the disease course depending on disease severity. In this study, we comprehensively analyzed viral load, antibody responses to SARS-CoV-2, and cytokines/chemokines during the disease course, and identified the factors related to severity. Nasopharyngeal (NP) and plasma specimens were obtained from 31 patients with COVID-19 during hospitalization. Viral RNA in NP specimens was quantified by reverse transcription-PCR. Anti-SARS-CoV-2 antibodies and cytokines/chemokines in plasma specimens were analyzed by ELISA and cytometric bead array. The viral load in patients with COVID-19 peaked at the early stage of the disease and continuously decreased. Severe and critical cases showed higher viral load and prolonged viral shedding than asymptomatic and mild cases. Whereas plasma IgG was gradually increased and maintained during hospitalization, plasma IgM peaked at 3 weeks after symptom onset and dissipated. The antibody response in severe and critical cases was slightly delayed but stronger than those in others. High levels of interferon (IFN)-α, IFN-γ-induced protein-10, monokine induced by IFN-γ, and interleukin-6 at 5-10 days from symptom onset were associated with the severity of COVID-19. Our data indicate that high viral load in the respiratory tract and excessive production of cytokines and chemokines between 1 and 2 weeks from the symptom onset were significantly associated with the severity of COVID-19.
COVID-19 的严重程度从轻症到重症不等。然而，根据疾病严重程度，关于病毒载量和宿主免疫反应在整个病程中的详细动力学的数据有限。在这项研究中，我们全面分析了疾病过程中的病毒载量、对 SARS-CoV-2 的抗体反应和细胞因子/趋化因子，并确定了与严重程度相关的因素。我们从 31 名住院 COVID-19 患者中获得了鼻咽（NP）和血浆标本。通过逆转录-PCR 定量 NP 标本中的病毒 RNA。通过 ELISA 和流式细胞术珠阵列分析血浆标本中的抗 SARS-CoV-2 抗体和细胞因子/趋化因子。COVID-19 患者的病毒载量在疾病早期达到峰值，并持续下降。严重和危重症患者的病毒载量较高，病毒脱落时间较长。而住院期间血浆 IgG 逐渐增加并保持稳定，血浆 IgM 在症状出现后 3 周达到峰值并消散。严重和危重症患者的抗体反应稍延迟但更强。症状出现后 5-10 天 IFN-α、IFN-γ 诱导蛋白 10、IFN-γ 诱导的单核细胞因子和白细胞介素-6 的高水平与 COVID-19 的严重程度相关。我们的数据表明，呼吸道中的高病毒载量和症状出现后 1-2 周内细胞因子和趋化因子的过度产生与 COVID-19 的严重程度显著相关。
