[Immunity to SARS CoV-2 - strengths and weaknesses]

In an unprecedented collaborative effort, basic and clinical scientists have provided us with an effective COVID-19 vaccine within less than one year after SARS CoV-2 emergence. Virus or vaccine induced immunity may offer different degrees of protection against infection, transmission and pathology (disease). Immunity decides on the outcome of COVID-19, both at an individual as well as a population level. In this literature analysis, emphasis is put first on the gold standard for evaluating human antiviral immunity: data from high quality, well-designed trials centered on patient outcome as clinical endpoint (morbidity, e. g. severe COVID-19). Next, case reports or case series on humans with inborn errors of immunity (IEI) may provide unique insights into human CoV-2 immunity. Surrogate markers in blood (e. g. antibody titers) are extensively employed for the evaluation of SARS CoV-2 immunity, but are not useful. SARS CoV-2 antibody titers neither indicate local immunity in the nasopharynx/respiratory tract nor do they reliably reflect systemic immunity. Systemic and tissue resident SARS CoV-2 specific effector and memory T-cells are key to immunity but cannot routinely be measured in blood. Based largely on clinical data, this literature analysis suggests that antiviral immunity against Coronaviruses including SARS CoV-2 is waning significantly over time regarding infection and transmission protection. However, in individuals who have recovered from infections with human Coronaviruses (including SARS CoV-2) or been vaccinated against SARS CoV-2, immunity is robust in its most critical quality: protection against pathology/severe disease. Thus, immunologists see the glass half-full and envisage the transition of COVID-19 from an epidemic to an endemic state with semiannual peaks of incidence but, most importantly, protection from severe COVID-19 or death in the vast majority of individuals (as observed in other human Coronavirus infections).