Immunological memory to SARS-CoV-2 in convalescent COVID-19 patients at one-year post-infection

Hou, Hongyan; Zhang, Yandi; Tang, Guoxing; Luo, Ying; Liu, Wei; Cheng, Chang; Jiang, Yuhuan; Xiong, Zhigang; Wu, Shiji; Sun, Ziyong; Xu, Shabei; Fan, Xionglin; Wang, Feng

Background Understanding the complexities of immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to gain insights into the durability of protective immunity against reinfection. Objective To evaluate the immune memory to SARS-CoV-2 in convalescent patients with longer follow-up time. Methods SARS-CoV-2-specific humoral and cellular responses were assessed in convalescent coronavirus disease 2019 (COVID-19) patients at one-year post-infection. Results A total of 78 convalescent COVID-19 patients (26 moderate, 43 severe, and 9 critical) were recruited after one year of recovery. The positive rates of both anti-RBD and anti-N antibodies were 100%, whereas we did not observe a statistical difference in antibody levels among different severity groups. Accordingly, the prevalence of neutralizing antibodies (nAbs) reached 93.59% in convalescent patients. Although nAb titres displayed an increasing trend in convalescent patients with increased severity, the difference failed to achieve statistical significance. Notably, there was a significant correlation between nAb titres and anti-RBD levels. Interestingly, SARS-CoV-2-specific T cells could be robustly maintained in convalescent patients, and the number of them was positively correlated with both nAb titres and anti-RBD levels. Amplified SARS-CoV-2-specific CD4+ T cells mainly produced a single cytokine, accompanying with increased expression of exhaustion markers including PD-1, Tim-3, TIGIT, CTLA-4 and CD39, while the proportion of multifunctional cells was low. Conclusions Robust SARS-CoV-2-specific humoral and cellular responses are maintained in convalescent COVID-19 patients at one-year post-infection. However, the dysfunction of SARS-CoV-2-specific CD4+ T cells supports the notion that vaccination is needed in convalescent patients for preventing reinfection.