Answer: Is there any evidence for t cell immunity to SARS-COV-2 prior to exposure?
For context, this is a question I answered on Quora
Short answer: yes. I didn’t do this justice the first time I posted it as I only included one study among several evidencing pre-existing t cell immunity to the “novel” coronavirus mainly as a result of cross-reactivity, a concept that isn’t novel, with other endemic coronaviruses. My prior post covered one experimental immunological study that was published in 2021, but prior research published in 2020 and afterwards provides more extensive evidence.
Natural Immunity Can Exist Prior to SARS-COV-2 Infection
A comparative cross-sectional study analyzing peripheral blood mononuclear cells extracted from COVID-19 patients and healthy, SARS-CoV-2-unexposed donors in 2020 (n = 86) detected SARS-CoV-2-reactive T helper cells in healthy unexposed donors. Their t helper cells were reactive to the C-terminal region (S-II) of the spike protein and demonstrated cross-reactivity with spike proteins from endemic human coronaviruses (e.g., OC43, 229E), suggesting prior exposures to common cold coronaviruses.
A cross-sectional observational study comparing T cell immune responses among three groups: people recovered from COVID-19, survivors of the 2003 SARS outbreak, and uninfected controls in 2020 found, also utilizing peripheral blood mononuclear cells isolated from participants (n = 96) found that 19 out of 37 uninfected individuals exhibited T cells reactive to SARS-CoV-2 non-structural proteins (NSP7, NSP13) and, to a lesser degree, the N protein, despite no exposure to SARS or COVID-19. They also found that SARS-COV-1 survivors still had long-lasting memory T cells reactive to the N protein of SARS-Cov-2 17 years later.
Another cross-sectional observational study, published in 2020, that also extracted peripheral blood mononuclear cells from recovered COVID-19 patients and healthy unexposed controls (n = 21) found that 40%-60% of unexposed healthy individuals had t helper cells reactivity to non-spike proteins of SARS-COV-2 suggesting cross-reactivity from exposure to other beta-coronaviruses.
An observational study using pre-pandemic blood samples to extract peripheral blood mononuclear cells for their assessments analyzing 117 distinct SARS-CoV-2–specific T helper cell populations (n = 12) found that a substantial number of SARS-CoV-2–specific T helper cells with memory phenotypes exist in unexposed individuals. T cell clones cross-reacted with commensal bacterial antigens and responded to stool lysates, implying that environmental microbial exposure shapes baseline SARS-CoV-2 T cell repertoires. The abundance of preexisting memory T cells was significantly positively correlated with donor age and total memory frequency and the preexisting repertoire was highly heterogeneous between individuals, with non-spike–specific T cells detected at higher frequencies than spike-specific ones.
A longitudinal cohort study that followed participants over a 3 year period (2020–2024) and assessed their immune response at multiple timepoints (1 month, 6 months, and up to one year or more after infection and vaxx) (n = 44) while including pre-pandemic serum samples taken from healthy donors (n = 18), in their assessment of extracted peripheral blood mononuclear cells, found that about half of pre-pandemic samples had detectable cross-reactive T cell immunity targeting SARS-CoV-2 spike protein segments. Furthermore, participants with cross-reactive T cell immunity from endemic coronaviruses demonstrated significantly stronger and longer-lasting SARS-CoV-2-specific T cell responses than those without which translates into reduced viral load leading to less severe or no viral symptoms.