Immune responses during COVID-19 infection

Abstract

Over the past 16 years, three coronaviruses (CoVs), severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012 and 2015, and SARS-CoV-2 in 2020, have been causing severe and fatal human epidemics. The unpredictability of coronavirus disease-19 (COVID-19) poses a major burden on health care and economic systems across the world. This is caused by the paucity of in-depth knowledge of the risk factors for severe COVID-19, insufficient diagnostic tools for the detection of SARS-CoV-2, as well as the absence of specific and effective drug treatments. While protective humoral and cellular immune responses are usually mounted against these betacoronaviruses, immune responses to SARS-CoV2 sometimes derail towards inflammatory tissue damage, leading to rapid admissions to intensive care units. The lack of knowledge on mechanisms that tilt the balance between these two opposite outcomes poses major threats to many ongoing clinical trials dealing with immunostimulatory or immunoregulatory therapeutics. This review will discuss innate and cognate immune responses underlying protective or deleterious immune reactions against these pathogenic coronaviruses.

Correcting the imbalanced protective RAS in COVID-19 with angiotensin AT2-receptor agonists

“…As would be expected, COVID-19 infection elicits activation of the innate and adaptive immune systems, and in a majority of cases their combined actions result in disease resolution [49][50][51][52][53]. In patients with more severe COVID-19 disease, those displaying ARDS and pneumonia, clinical findings indicate that multiple aspects of the innate and adaptive immune systems are compromised or dysregulated [50,51,53].…”

“…In patients with more severe COVID-19 disease, those displaying ARDS and pneumonia, clinical findings indicate that multiple aspects of the innate and adaptive immune systems are compromised or dysregulated [50,51,53]. Of importance for the current article is the observation that this group of COVID-19 patients exhibits massively increased levels of circulating pro-inflammatory cytokines, including interleukin (IL)-1β (IL-1β), IL-6, tumour necrosis factor (TNFα), IL-17 and interferon-γ, (IFN-γ) [53,54]. The resulting chronic pro-inflammatory milieu, termed as a 'cytokine storm' , is likely responsible for the uncontrolled inflammation within the lungs, heart, vascular endothelium and kidney, and recruitment of immune cells (macrophages, neutrophils, T cells) to these sites [7,55].…”

“…In general, initial COVID-19 infection will result in activation of the innate immune system, including monocytes, macrophages, dendritic cells and the complement system [50,51,53]. Human monocytes, macrophages and dendritic cells contain AT 2 R [75][76][77] and a number of studies indicate that activation of this angiotensin receptor subtype interferes with certain aspects of the innate immune system response.…”

“…COVID-19 infection also results in activation of the adaptive immune system, albeit over a more delayed time frame [50,51,53]. T helper (CD4 + ) and cytotoxic (CD8 + ) T cells are central to the adaptive immune response [86].…”

No impact of cancer and plague-relevant FPR1 polymorphisms on COVID-19

“…1,2 In nonsusceptible individuals lacking discernible risk factors, 3,4 infection by SARS-CoV-2, the agent responsible for COVID-19 is usually asymptomatic or paucisymptomatic, although exceptions have been reported. [5][6][7][8][9] For this reason, strategies for identifying individuals at risk might help to guide strategies for the selective confinement or vaccination of those persons who are at risk of severe or lethal SARS-CoV-2. 5 Formyl peptide receptor 1 (FPR1) is a patternrecognition receptor (PRR) 10 that is mostly expressed by myeloid cells including granulocytes, macrophages, and dendritic cells.…”