Inflammasome Activation and Molecular Mechanisms Involved in COVID-19 Severity: A Systematic Review
Bárbara Luisa Fermino *
State University of Midwest, Guarapuava, Paraná, Brazil.
Fernanda Ivanski
State University of Midwest, Guarapuava, Paraná, Brazil.
Katiuscia de Oliveira Francisco Gabriel
State University of Midwest, Guarapuava, Paraná, Brazil.
Bárbara Mendes Paz Chao
State University of Midwest, Guarapuava, Paraná, Brazil.
Marcieli Borba do Nascimento
State University of West, Francisco Beltrão, Paraná, Brazil.
Emerson Carraro
State University of Midwest, Guarapuava, Paraná, Brazil.
David Livingstone Alves Figueiredo
State University of Midwest, Guarapuava, Paraná, Brazil.
*Author to whom correspondence should be addressed.
Abstract
Introduction: In recent decades, three significant coronaviruses have posed threats to public health: Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and in December 2019, a novel SARS-CoV-2 type coronavirus was reported in patients with viral pneumonia in Wuhan province. It was later named COVID-19 in March 2020 when the World Health Organization (WHO) declared the outbreak a pandemic. SARS-CoV-2 infections primarily manifest as respiratory illnesses leading to Acute Respiratory Distress Syndrome (ARDS). There is hyperactivation of the inflammatory response that results in increased production of inflammatory cytokines, such as interleukin IL-1β, and its downstream molecule IL-6, which serves as an aggravating factor of this disease. The inflammasome is a multiprotein complex involved in caspase-1 activation that leads to IL-1β activation in various diseases and infections, such as SARS-CoV-2 infection, and in different tissues.
Methodology: A systematic review was conducted to investigate the mechanism of inflammasome activation by SARS-CoV-2 infection, the role of the inflammasome in ARDS, and other potential mechanisms of inflammasome involvement in the severity of pathogenesis in patients with COVID-19. We conducted searches in the following databases: PubMed, LitCovid, MedRxiv, and ScienceDirec, in addition to manually searching for key materials.
Results: A total of 101 references were included. Regarding general characteristics, 57.7% were directly related to COVID-19 and SARS-CoV-2; 7.7% addressed aspects of the pandemic, including discussions about social aspects, and 34.6% covered general theoretical aspects related to the subjects included in this review.
Conclusion: This review highlights the inflammasome in interfering with different aspects associated with SARS-CoV-2. The simultaneous activation of inflammasomes and the inhibition of negative regulatory mechanisms that suppress them can lead to severe uncontrolled inflammation.
Keywords: Coronavirus, severe acute respiratory syndrome, SARS-CoV-2, COVID-19, Inflammasome, cytokine storm