A new perspective for mitigation of SARS-CoV-2 infection: priming the innate immune system for viral attack.

The course of infection by SARS-CoV-2 frequently includes a long asymptomatic period, followed in some individuals by an immune dysregulation period that may lead to complications and immunopathology-induced death. This course of disease suggests that the virus often evades detection by the innate immune system. We suggest a novel therapeutic approach to mitigate the infection's severity, probability of complications and duration. We propose that priming an individual's innate immune system for viral attack shortly before it is expected to occur may allow pre-activation of the preferable trajectory of immune response, leading to early detection of the virus. Priming can be carried out, for example, by administering a standard vaccine or another reagent that elicits a broad anti-viral innate immune response. By the time that the expected SARS-CoV-2 infection occurs, activation cascades will have been put in motion and levels of immune factors needed to combat the infection will have been elevated. The infection would thus be cleared faster and with less complication than otherwise, alleviating adverse clinical outcomes at the individual level. Moreover, priming may also mitigate population-level risk by reducing need for hospitalizations and decreasing the infectious period of individuals, thus slowing the spread and reducing the impact of the epidemic. In view of the latter consideration, our proposal may have a significant epidemiological impact even if applied primarily to low-risk individuals, such as young adults, who often show mild symptoms or none, by shortening the period during which they unknowingly infect others. The proposed view is, at this time, an unproven hypothesis. Although supported by robust bio-medical reasoning and multiple lines of evidence, carefully designed clinical trials are necessary.