AUTHOR=Shafqat Areez , Shafqat Shameel , Salameh Sulaiman Al , Kashir Junaid , Alkattan Khaled , Yaqinuddin Ahmed 

TITLE=Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.835104

DOI=10.3389/fimmu.2022.835104

ISSN=1664-3224

ABSTRACT=Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which causes coronavirus-19 (COVID-19), has caused significant morbidity and mortality globally. In addition to the respiratory manifestations seen in severe cases, multi-organ pathologies are also seen, making management a much-debated issue. In addition, the emergence of new variants can potentially render vaccines with a relatively limited utility. 
A plethora of investigations have been conducted regarding the precise pathophysiological mechanisms causing COVID-19 respiratory and systemic disease. Until recently, a cytokine storm, which results from the spillover of a large magnitude of cytokines from the lung, was considered the cause of systemic disease. However, recent studies have provided contradictory evidence, whereby the magnitude of cytokine storm is insufficient to cause severe illness. These issues are highly relevant, as management approaches considering COVID-19 a classic form of acute respiratory distress syndrome with a cytokine storm could translate to unfounded clinical decisions, detrimental to patient trajectory. Additionally, the precise immune cell signatures characterizing disease of vary severity remains a contentious issue.
We provide an up-to-date review on the immune dysregulation caused by COVID-19, and highlight pertinent discussions being held by the scientific community. The response from the scientific community has been unprecedented regarding the development of highly effective vaccines and cutting-edge research on novel therapies. We hope that this review furthers the conversations being held by scientists and informs the aims of future research projects, which potentially will further our understanding of COVID-19 and its immune pathogenesis.