Box 1.

Investigations needed to further our understanding of the risks of immune enhancement.

The current Covid-19 pandemic with exponential rise in disease cases and deaths urgently calls for both treatment options and efficacious vaccines. However, it cannot be ignored that enhanced immunopathology has been observed with other coronaviruses in animal models, albeit in the absence of convincing clinical evidence. Therefore, in parallel with phase I trials, we suggest urgent clinical evidence to address the gap in clinical evidence for immune enhancement. A list of studies are described below:

•Systematic post-mortem examination with deep immunological and molecular profiling to define the pathology of fatal Covid-19 cases.

•Prospectively enrolled cohort study to determine pre-infection and early post-illness onset immune correlates of Covid-19 disease outcome.

•Develop animal models that replicates the important pathological features found in systematic post-mortem examination of fatal Covid-19 cases.