Department of Immunology, University Hospital Zurich, Zurich, Switzerland.
Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Solna, Sweden.
Allergy. 2022 Aug;77(8):2415-2430. doi: 10.1111/all.15302. Epub 2022 Apr 8.
Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19.
We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls.
Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B-cell compartment after recovery.
Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures.
在 2019 年冠状病毒病（COVID-19）期间出现了几种自身免疫特征，这可能对疾病过程、免疫和自身免疫病理学有影响。在这项研究中，我们进行了纵向筛查以评估其临床相关的系统性自身抗体的患病率、时间轨迹及其与免疫、合并症和 COVID-19 严重程度的关联。
我们对 175 名 COVID-19 患者进行了高度敏感的间接免疫荧光检测，以检测抗核抗体（ANA）和抗中性粒细胞胞浆抗体（ANCA），并对感染后 1 年的多中心队列中的血清蛋白质组学和病毒组学进行了血清学分析，该队列包括 11 名接种者和 41 名未暴露者作为对照。
与健康对照组相比，在 COVID-19 患者急性和恢复期都存在相似的 ANA 患病率和模式。然而，配对分析显示，在急性 COVID-19 期间存在某些 ANA 模式短暂存在的患者亚组。此外，患有严重 COVID-19 的患者在急性疾病期间 ANCA 的患病率较高。这些自身抗体与 COVID-19 患者和接种者中更高的 SARS-CoV-2 特异性抗体滴度定量相关，因此将自身抗体的产生与增加的抗原特异性体液反应联系起来。值得注意的是，在急性 COVID-19 期间，ANA 阳性和 ANA 阴性个体的交叉反应抗体的定性广度相当。在自身抗体阳性的患者中，多参数特征显示急性 COVID-19 期间存在炎症特征，并且在恢复后 B 细胞群发生改变。
高度敏感的间接免疫荧光检测揭示了急性 SARS-CoV-2 感染期间的短暂自身抗体产生，而 COVID-19 患者中自身抗体的存在与增加的抗病毒体液免疫反应和炎症免疫特征相关。
