By contrast, the proportions of spike\specific CD4+ T cells, but not CD8+ T cells, in COVID\19 patients after recovery were persistently higher than those in healthy controls

By contrast, the proportions of spike\specific CD4+ T cells, but not CD8+ T cells, in COVID\19 patients after recovery were persistently higher than those in healthy controls. T cells are sufficient to Tebuconazole protect patients from reinfection. Keywords: COVID\19, neutralising antibody, Tebuconazole SARS\CoV\2, T cells We followed up COVID\19 patients discharged from the hospital up to 7?months post infection. We found that the neutralizing antibody responses are declining while T\cell immunities are sustained in COVID\19 patients during the follow\up. Introduction The coronavirus disease 2019 (COVID\19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS\CoV\2), has led to over 190 million cases and more than 4.1?million deaths to date. Therefore, there is an urgent need to develop an effective vaccine that can be used to immunise the global population to halt the transmission of the virus. There is considerable interest in understanding the nature of the immune response to SARS\CoV\2 in patients who have recovered from COVID\19 to shed light on the requirements and likelihood of achieving durable protection from SARS\CoV\2 infection. The immune system comprises several components that work together to develop protective immunity. Adaptive immune responses, which comprise both humoral and T\cell responses specific to SARS\CoV\2, are important for protection against viral infections. Neutralising antibodies against SARS\CoV\2, especially the surface spike protein that mediates viral entry, have been identified in acute and convalescent COVID\19 patients. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 These neutralising antibodies are currently under Tebuconazole development as promising therapeutic options. 10 , 11 Most COVID\19 vaccines that induce the production of neutralising antibodies also target the spike protein of SARS\CoV\2. 12 However, a concern has been raised regarding the longevity of the antibody response to the spike protein in convalescent COVID\19 Tebuconazole patients. Although recent studies have shown that neutralising antibodies last for at least 3?months, some earlier studies have also shown that the level of SARS\CoV\2 IgG declines over time and may become undetectable in a substantial proportion of patients. 5 , 13 , 14 , 15 Helping B cells generate neutralising antibody responses and maintain durable antibody responses is a major function of CD4+ T cells. In addition, recent studies have suggested that T\cell response could be induced by SARS\CoV\2 in the absence of humoral immune responses. 16 Therefore, the balance between humoral and cellular immune responses might be important for protection from COVID\19 and avoidance of vaccine\enhanced disease. 8 , 17 Consequently, several COVID\19 vaccines have been designed to elicit robust CD4+ or CD8+ T\cell responses based on neutralising antibodies. 18 , 19 , 20 However, there is a lack of longitudinal studies that conduct a combined examination of neutralising antibodies and CD4+ T\cell and CD8+ T\cell responses against SARS\CoV\2 in the same patient population. Addressing these fundamental questions is important in understanding the Tg natural protective immune responses, which may facilitate the development of COVID\19 vaccines. In this study, we aimed to perform a combined assessment of changes in neutralising antibody levels and SARS\CoV\2\specific T\cell responses over time in patients at 7?months after infection. Results Declined, but still detectable, humoral response against Tebuconazole SARS\CoV\2 The levels of IgG and IgM against spike receptor\binding domain (RBD), as well as surrogate markers of neutralising antibodies, were measured in all collected samples. In the 11 samples from healthy controls, the spike\RBD IgM, IgG and neutralising antibodies were undetectable. Spike\RBD IgM was detected in 48.1% (13/27) of the patients, while high titres of spike\RBD\specific IgG were detected in all patients at their first visit (Figure?1a). By contrast, the titres of neutralising antibodies ranged from low to robust (Figure?1b). Despite the detectable levels of neutralising antibodies in all patients, the 50% inhibitory dilutions were below 1:100 in 29.6% (8/27) of the patients. Disease severity was associated with the titres of neutralising antibodies, but not with those of spike\RBD IgG and IgM (Figure?1c). Patients with previous severe diseases had higher titres of neutralising antibodies than those with mild diseases. Other demographic characteristics, including age and sex, did not affect the titres of neutralising antibodies, spike\RBD\specific IgG or IgM. Open in a separate window Figure 1 Dynamic changes in the SARS\CoV\2\specific humoral response. (a) Changes in the spike\RBD IgG titres and (b) neutralising antibody titres at each visit. Each symbol in a and b represents one patient (stimulation with two SARS\CoV\2.