Reviews and feature articles
COVID-19: Unanswered questions on immune response and pathogenesis

https://doi.org/10.1016/j.jaci.2020.05.001Get rights and content
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The novel coronavirus disease 2019 has rapidly increased in pandemic scale since it first appeared in Wuhan, China, in December 2019. In these troubled days the scientific community is asking for rapid replies to prevent and combat the emergency. It is generally accepted that only achieving a better understanding of the interactions between the virus and the host immune response and of the pathogenesis of infection is crucial to identify valid therapeutic tools to control virus entry, replication, and spread as well as to impair its lethal effects. On the basis of recent research progress of severe acute respiratory syndrome coronavirus 2 and the results on previous coronaviruses, in this contribution we underscore some of the main unsolved problems, mostly focusing on pathogenetic aspects and host immunity to the virus. On this basis, we also touch important aspects regarding the immune response in asymptomatic subjects, the immune evasion of severe acute respiratory syndrome coronavirus 2 in severe patients, and differences in disease severity by age and sex.

Key words

Anti–SARS-CoV-2 immunity
COVID-19 pathogenesis
viral immune evasion

Abbreviations used

ACE2
Angiotensin-converting enzyme 2
COVID-19
Coronavirus disease 2019
IC
Intensive care
IFN-1
Type I interferon
NAb
Neutralizing antibody
NK
Natural killer
RBD
Receptor-binding domain
rCoV
Respiratory coronavirus
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2

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This work was supported by grants from the Ministero della Salute (grant no. RC-2020 OPBG to L.M. and E.M.) and from Associazione Italiana per la Ricerca sul Cancro (project no. 5x1000 2018 Id 21147 and project no. IG 2017 Id 19920 to L.M.).

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.