To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection.

为了更好地了解 SARS-CoV-2 特异性免疫随时间的发展，需要对体液和细胞反应进行详细评估。在这里，我们在诊断后长达 217 天的 431 名 SARS-CoV-2 感染者的代表性人群队列中表征了抗尖峰 (S) IgA 和 IgG，证明 85% 的人发展并维持抗 S 反应。在 64 名参与者的子样本中，我们进一步评估了抗核衣壳 (N) IgG、中和抗体活性以及 T 细胞对膜 (M)、N 和 S 蛋白的反应。与 S 特异性抗体反应相比，抗 N IgG 水平随着时间的推移大幅下降，并且在野生型 SARS-CoV-2 感染的短短几周内，对 Delta 和 Omicron 变体的中和活性很低甚至不存在。大多数参与者都可以检测到病毒特异性 T 细胞，尽管比抗体反应更具可变性。对个体内抗体和 T 细胞反应共同进化的聚类分析确定了以特定免疫模式和临床因素为特征的五种不同轨迹。这些发现证明了对 SARS-CoV-2 的体液和细胞免疫的相关异质性，同时还确定了抗体和 T 细胞反应可能以补偿方式提供保护的一致模式。