Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Operative Solutions, Carlos Slim Foundation, Mexico City, Mexico.
Front Immunol. 2022 Aug 15;13:943563. doi: 10.3389/fimmu.2022.943563. eCollection 2022.
Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response.
We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response.
At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8 T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months.
A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.
到目前为止，大多数研究都是针对 2019 年冠状病毒病（COVID-19）的长期体液反应进行的，这些研究仅评估了针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）IgG 的血清滴度，而没有评估基线抗病毒临床和免疫特征，这是本研究的目的，可能是导致广泛和持续抗体反应的关键因素。
我们纳入了 103 例 COVID-19 患者。当患者就诊时（基线），抽取血液样本通过流式细胞术进行淋巴细胞免疫表型分析。患者在基线后 15 天进行评估，然后每月评估一次，直到第三个月，随后在招募后 6 个月进行最后一次随访。我们在所有时间点评估抗 SARS-CoV-2 IgG，并且在随访期间还评估了细胞因子、趋化因子、抗细胞（AC）抗体和中性粒细胞细胞外陷阱的血清水平。本研究的主要结局是存在持续的免疫体液反应，定义为至少两次连续测量中 SARS-CoV-2 IgG 滴度>4.99 个任意单位/mL。我们使用广义线性模型来评估与该结局相关的特征，并评估细胞因子和趋化因子随时间变化对持续体液免疫反应发展的影响。
基线时，与持续免疫体液反应相关的特征是危重症疾病的诊断、淋巴细胞绝对数、血清 IP-10、IL-4、IL-2、调节性 T 细胞、CD8 T 细胞和阳性 AC 抗体。危重症和 AC 抗体阳性与 3 个月后的持续体液免疫反应相关，而危重症和血清 IL-13 是 6 个月后的解释变量。
持续的免疫体液反应与 COVID-19 的危重症密切相关，其特征是存在 AC 抗体、T 细胞群的定量异常以及急性感染期间和整个时间内的血清细胞因子和趋化因子。
