Immunology Laboratory, National Oncology and Radiobiology Institute (INOR), Havana, Cuba.
MEDICC Rev. 2021 Apr;23(2):42. doi: 10.37757/MR2021.V23.N2.4. Epub 2021 Apr 30.
Advanced age and chronic disease comorbidities are indicators of poor prognosis in COVID-19 clinical progression. Fatal outcomes in patients with these characteristics are due to a dysfunctional immune response. Understanding COVID-19's immunopathogenesis helps in designing strategies to prevent and mitigate complications during treatment.
Describe the main immunopathogenic alterations of COVID-19 in patients of advanced age or with chronic non-communicable diseases.
We carried out a bibliographic search of primary references in PubMed, Elsevier, Science Direct and SciELO. A total of 270 articles met our initial search criteria. Duplicate articles or those unrelated to at least one chronic comorbidity, senescence or inflammation and those that studied only patient clinical characteristics, laboratory tests or treatments were excluded. Finally, our selection included 124 articles for analysis: 10 meta-analyses, 24 original research articles, 67 review articles, 9 editorials, 9 comments, 3 books and 2 websites.
Hypertension and diabetes mellitus are the most common comorbidities in COVID-19 patients. Risk of developing severe manifestations of the disease, including death, is increased in senescent and obese patients and those with cardiovascular disease, cancer or chronic obstructive pulmonary disease. Low-grade chronic inflammation is characteristic of all these conditions, reflected in a pro-inflammatory state, endothelial dysfunction, and changes to innate immunity; mainly of the monocyte-macrophage system with changes in polarization, inflammation, cytotoxicity and altered antigenic presentation. In the case of SARS-CoV-2 infection, mechanisms involved in acute inflammation overlap with the patient's pro-inflammatory state, causing immune system dysfunction. SARS-CoV-2 infection amplifies already-existing alterations, causing failures in the immune system's control mechanisms. The resulting cytokine storm causes an uncontrolled systemic inflammatory response marked by high serum levels of inflammatory biomarkers and a pro-inflammatory cytokine profile with decompensation of underlying diseases. In asthma, chronic eosinophilic inflammation protects against infection by producing a reduced interferon-mediated response and a reduced number of ACE2 receptors.
Low-grade chronic inflammation present in advanced age and chronic diseases-but not in bronchial asthma-produces a pro-inflammatory state that triggers a dysregulated immune response, favoring development of severe forms of COVID-19 and increasing lethality.
在 COVID-19 临床进展中，高龄和慢性疾病合并症是预后不良的指标。这些特征患者的死亡结局是由于免疫功能失调所致。了解 COVID-19 的免疫发病机制有助于设计预防和减轻治疗期间并发症的策略。
描述高龄或患有慢性非传染性疾病患者 COVID-19 的主要免疫发病机制改变。
我们在 PubMed、Elsevier、Science Direct 和 SciELO 中对主要参考文献进行了文献检索。共有 270 篇文章符合我们的初始搜索标准。排除了重复文章或与至少一种慢性合并症、衰老或炎症无关的文章，以及仅研究患者临床特征、实验室检查或治疗的文章。最后，我们的选择包括 124 篇文章进行分析：10 篇荟萃分析、24 篇原始研究文章、67 篇综述文章、9 篇社论、9 篇评论、3 本书籍和 2 个网站。
高血压和糖尿病是 COVID-19 患者最常见的合并症。在衰老和肥胖患者以及患有心血管疾病、癌症或慢性阻塞性肺疾病的患者中，发生疾病严重表现（包括死亡）的风险增加。低度慢性炎症是所有这些情况的特征，表现为促炎状态、内皮功能障碍和固有免疫改变；主要是单核细胞-巨噬细胞系统的极化、炎症、细胞毒性和抗原呈递改变。在 SARS-CoV-2 感染的情况下，急性炎症涉及的机制与患者的促炎状态重叠，导致免疫系统功能障碍。SARS-CoV-2 感染放大了已经存在的改变，导致免疫系统控制机制失效。由此产生的细胞因子风暴引起失控的全身炎症反应，特征为炎症生物标志物血清水平升高和促炎细胞因子谱，伴有基础疾病失代偿。在哮喘中，慢性嗜酸性粒细胞炎症通过产生减少的干扰素介导反应和减少的 ACE2 受体数量来保护免受感染。
高龄和慢性疾病中存在的低度慢性炎症会产生促炎状态，触发失调的免疫反应，有利于 COVID-19 严重形式的发展，并增加死亡率。
