# Back to the Future: Immune Protection or Enhancement of Future Coronaviruses

## TL;DR

This paper explores whether immunity from past coronaviruses can protect against future ones or worsen outcomes through immune mechanisms like antibody-dependent enhancement.

## Contribution

The paper provides a novel analysis of immune memory's role in protection or enhancement against future coronaviruses.

## Key findings

- Evidence suggests that cytotoxic memory T cells may offer partial protection against future coronaviruses.
- Antibody-dependent enhancement and original antigenic sin are considered unlikely in the context of human coronaviruses.
- Immunity from prior infections like SARS-CoV-1 or MERS-CoV may not significantly protect against SARS-CoV-2.

## Abstract

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently, SARS-CoV-2, four other coronaviruses (the alpha coronaviruses NL63 and 229E and the beta coronaviruses OC43 and HKU1) had already been circulating in the human population. These circulating coronaviruses all cause mild respiratory illness during the winter seasons, and most people are already infected in early life. Could antibodies and/or T cells, especially against the beta coronaviruses, have offered some form of protection against (severe) COVID-19 caused by infection with SARS-CoV-2? Related is the question of whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory generated during the SARS-CoV-2 pandemic, either by infection or vaccination, offer protection against future coronaviruses? Or rather than protection, could antibody-dependent enhancement have taken place, a mechanism by which circulating corona antibodies enhance the severity of COVID-19? Another related phenomenon, the original antigenic sin, would also predict that the effectiveness of the immune response to future coronaviruses would be impaired because of the reactivation of memory against irrelevant epitopes. The currently available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.