Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools

Abstract

Currently there is no effective antiviral therapy for SARS-CoV-2 infection, which frequently leads to fatal inflammatory responses and acute lung injury. Here, we discuss the various mechanisms of SARS-CoV-mediated inflammation. We also assume that SARS-CoV-2 likely shares similar inflammatory responses. Potential therapeutic tools to reduce SARS-CoV-2 -induced inflammatory responses include various methods to block FcR activation. In the absence of a proven clinical FcR blocker, the use of intravenous immunoglobulin to block FcR activation may be a viable option for the urgent treatment of pulmonary inflammation to prevent severe lung injury. Such treatment may also be combined with systemic anti-inflammatory drugs or corticosteroids. However, these strategies, as proposed here, remain to be clinically tested for effectiveness.

Nervous system involvement after infection with COVID-19 and other coronaviruses

“…The pathology of severe viral infections is closely linked to the development of a systemic inflammatory response syndrome (SIRS). SIRS could be abnormally initiated in severe pneumonia caused by CoV infection, while early antiinflammatory intervention effectively prevent immune damage and reduce the risk of injury in the nervous system (Mehta et al, 2020;Fu et al, 2020). Furthermore, SARS and COVID-19 have resulted in a large number of fatalities, most of which have been due to multiple organs failure (MOF) caused by virus-induced SIRS or SIRS-like immune disorders (Yin et al, 2004;Chen et al, 2020).…”

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19

“…On the other way, Ig specific serum antibodies could be also associated with an increased risk of infection by promoting viral entry in susceptible cells through a mechanism of antibody-dependent enhancement (ADE), firstly described for Flaviviridae, HIV and Ebola viruses, which involves specific cellular receptors like Fc receptor (FcR) or complement receptor type 3 (CR3) [275,276]. This process has been recently proposed by Fu et al as a possible mechanism of lung damage in SARS-CoV pneumonia [277].…”

Old and new antirheumatic drugs for the treatment of COVID-19

“…This loss of ACE2 activity caused by shedding has been associated with lung injury as a consequence of increased activity of the renin-angiotensin system [22]. Although mainly demonstrated for SARS-CoV, the homology between S protein structures suggests that SARSCoV-2 protein S may also exhibit a similar mechanism [23]. Increased TNF␣ production could consequently facilitate viral infection and cause organ damage.…”