Montes-Cobos Elena, Bastos Victoria C, Monteiro Clarice, de Freitas João C R, Fernandes Heiny D P, Constancio Clarice S, Rodrigues Danielle A S, Gama Andreza M D S, Vidal Vinicius M, Alves Leticia S, Zalcberg-Renault Laura, de Lira Guilherme S, Ota Victor A, Caloba Carolina, Conde Luciana, Leitão Isabela C, Tanuri Amilcar, Ferreira Orlando D C, Pereira Renata M, Vale André M, Castiñeiras Terezinha M, Kaiserlian Dominique, Echevarria-Lima Juliana, Bozza Marcelo T
Laboratório de Inflamação e Imunidade, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Departamento de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
iScience. 2023 Jun 28;26(7):107219. doi: 10.1016/j.isci.2023.107219. eCollection 2023 Jul 21.
The vast spectrum of clinical features of COVID-19 keeps challenging scientists and clinicians. Low resistance to infection might result in long-term viral persistence, but the underlying mechanisms remain unclear. Here, we studied the immune response of immunocompetent COVID-19 patients with prolonged SARS-CoV-2 infection by immunophenotyping, cytokine and serological analysis. Despite viral loads and symptoms comparable to regular mildly symptomatic patients, long-term carriers displayed weaker systemic IFN-I responses and fewer circulating pDCs and NK cells at disease onset. Type 1 cytokines remained low, while type-3 cytokines were in turn enhanced. Of interest, we observed no defects in antigen-specific cytotoxic T cell responses, and circulating antibodies displayed higher affinity against different variants of SARS-CoV-2 Spike protein in these patients. The identification of distinct immune responses in long-term carriers adds up to our understanding of essential host protective mechanisms to ensure tissue damage control despite prolonged viral infection.
新冠病毒病（COVID-19）广泛的临床特征持续挑战着科学家和临床医生。对感染的低抵抗力可能导致病毒长期持续存在，但其潜在机制仍不清楚。在此，我们通过免疫表型分析、细胞因子和血清学分析，研究了免疫功能正常但感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）时间延长的COVID-19患者的免疫反应。尽管病毒载量和症状与普通轻症患者相当，但长期携带者在疾病发作时全身I型干扰素（IFN-I）反应较弱，循环浆细胞样树突状细胞（pDC）和自然杀伤（NK）细胞较少。1型细胞因子水平仍然较低，而3型细胞因子则相应升高。有趣的是，我们观察到这些患者的抗原特异性细胞毒性T细胞反应没有缺陷，并且循环抗体对SARS-CoV-2刺突蛋白的不同变体显示出更高的亲和力。长期携带者中独特免疫反应的识别，进一步加深了我们对基本宿主保护机制的理解，以确保尽管病毒感染持续时间延长，但仍能控制组织损伤。
