The immune memory to common cold coronaviruses (CCCs) influences SARS-CoV-2 infection outcome, and understanding its effect is crucial for pan-coronavirus vaccine development. We performed a longitudinal analysis of pre-COVID19-pandemic samples from 2016–2019 in young adults and assessed CCC-specific CD4+ T cell and antibody responses. Notably, CCC responses were commonly detected with comparable frequencies as with other common antigens and were sustained over time. CCC-specific CD4+ T cell responses were associated with low HLA-DR+CD38+ signals, and their magnitude did not correlate with yearly CCC infection prevalence. Similarly, CCC-specific and spike RBD-specific IgG responses were stable in time. Finally, high CCC-specific CD4+ T cell reactivity, but not antibody titers, was associated with pre-existing SARS-CoV-2 immunity. These results provide a valuable reference for understanding the immune response to endemic coronaviruses and suggest that steady and sustained CCC responses are likely from a stable pool of memory CD4+ T cells due to repeated earlier exposures and possibly occasional reinfections.

对普通感冒冠状病毒 (CCC) 的免疫记忆会影响 SARS-CoV-2 感染结果，了解其作用对于泛冠状病毒疫苗的开发至关重要。我们对 2016-2019 年 COVID19 大流行前的年轻人样本进行了纵向分析，并评估了 CCC 特异性 CD4+ T 细胞和抗体反应。值得注意的是，CCC 反应通常以与其他常见抗原相当的频率被检测到，并且随着时间的推移而持续。CCC 特异性 CD4+ T 细胞反应与低 HLA-DR+CD38+ 信号相关，并且它们的大小与年度 CCC 感染流行率无关。同样，CCC 特异性和尖峰 RBD 特异性 IgG 反应及时稳定。最后，高 CCC 特异性 CD4+ T 细胞反应性与预先存在的 SARS-CoV-2 免疫力相关，但与抗体滴度无关。