In this antigen-specific analysis we confirmed that approximately 50% of adult South African women, who had not been exposed to SARS-CoV-2, had cellular immune responses against peptides derived from SARS-CoV-2. This is similar to the frequency reported in studies from the USA (40–60%), Singapore (51%) and Europe (35%) [9–11]. Notably, adult plasma samples collected prior to 2020 from a similar cohort in South Africa as used in this study showed no reactivity to the receptor binding domain of the immunogenic SARS-CoV-2 spike protein when tested by an in-house Luminex assay (submitted manuscript).
The differential magnitude of response elicited by CD8-A and CD8-B pools in convalescent individuals has been noted before and may be related to the fact that CD8-A pool contains immunodominant spike epitopes and other structural proteins . Notably, in SARS-CoV-2 naive individuals the IFNγ response to CD8-B pool was higher than to any of the other stimulants, suggesting highest cross reactivity between common CCoV and SARS-CoV-2 at the level of CD8 T-cell epitopes in non-structural proteins. These findings are consistent with the observation that the SARS-CoV-2 nucleocapsid protein may induce an immunodominant response in both COVID-19-recovered individuals and in subjects that have not been exposed to SARS-CoV-2 .
The IFNγ predominantly measures effector responses, while the IL2 mainly measures memory responses. As such, IL2 responses were slightly higher than IFNγ responses to the whole virus inactivated antigen, typically processed and presented in the context of HLA Class II. IL2 production in response to spike and non-spike pools was also higher than IFNγ, consistent with memory CD4 T-cell stimulation. In contrast, the CD8 pools elicited slightly higher IFNγ responses. The higher proportion of SARS-CoV-2 naive women with IL2 production after SARS-CoV-2 antigenic stimulation, suggests that memory responses may be more sensitive than effector responses for the detection of SARS-CoV-2 cross-reactive responses generated by past infection with CCoV. Moreover, the majority of PBMCs analysed were collected from pregnant women and it is well established that IFNγ production decreases in pregnancy .
Although women living with HIV had lower responses compared to women without HIV, cross-reactivity was still detected among women with HIV that might explain why many reports, albeit not all, did not identify HIV infection as a risk factor for severe COVID-19 [14, 15].
In conclusion, in this pilot study we demonstrate the presence of cross-reactive immunity to SARS-CoV-2 among South African women that has possibly been induced by past exposure to CCoV. Whether this immunity is relevant in influencing clinical outcomes still needs to be demonstrated.