A Paradigm Gap in Host-Pathogen Interaction Studies: Lesson from the COVID-19 Pandemic.

Introduction: COVID-19 outbreak displayed presumably an increased accumulation of SARS-CoV-2 virus during comorbid complications and a substantial variation in the mortality within and between the countries, which in turn siren us the lack of knowledge in host-pathogen interactions (HPIs). Our aim is to describe the lessons taught by the COVID-19 pandemic in the existing/missing investigations on HPI.

Methods: This was from a retrospective meta-analysis of literature on "COVID-19 and comorbidity" to expose the existing paradigm gap in HPI by highlighting the omitted concepts/areas of research and new approaches to consider for the development of future therapeutics.

Results: Literature on "COVID-19 and comorbidity" apparently depicted the disparity in HPI during comorbid/immune-challenged conditions, which was reflected in the poor prognosis of the disease and failed therapeutics upon clinical trials. Moreover, the entry, adherence, multiplication, and the following establishment of infection were also varied in groups with various comorbidities. This edified that the mode of interaction of an infectious agent could vary according to the immunological and health status of the host system and hence the efficiency/success rate of treatment modalities. In addition, limited number of literature on HPI upon comorbid and immune-challenged conditions of the host manifestly indicated that there is a lack of our focus/attention on consideration of the host immune/health-specific factors in HPI studies. These alert us that the development of unambiguous therapeutic approaches is needed for a better/successful treatment of novel infectious agents in the future.

Conclusion: By understanding the immunological state exhibited in SARS-CoV-2 infection, we conclude that the COVID-19 pandemic has taught us a great lesson that our current understanding of HPI is insufficient to fight and conquer novel infections in real life. Hence, newer approaches are obligatory to understand HPI in order to combat COVID-19-like outbreaks in the future, if any, and also to design novel immunogenic/nutraceutical-based therapeutics.