The deregulated immune reaction and cytokines release storm (CRS) in COVID-19 disease

Quantitative plasma proteomics of survivor and non-survivor COVID-19 patients admitted to hospital unravels potential prognostic biomarkers and therapeutic targets

“…In the initial stages of inflammation, IL-6 expression is restricted. However, in later stages it is also expressed in the liver, where it elicits the production of acute phase proteins, such as fibrinogen and serum amyloid A (SAA) (30) that were also increased in the present study in critical patients, compared to mild ones ( Table 4 ). SAA was also increased in severe patients when compared to mild ones ( Table 3 ).…”

“…High production of IFNs in 18-24 h post infection leads to effective innate and acquired immune responses. On the other hand, a delay in the production of IFNs (3-4 days post infection) results in ineffective innate and acquired immune responses (30), despite persistent IL-6 and TNF-α release by several cells, infiltrating monocytes, inflammatory reactions and a dysfunctional response amplified by macrophages (31), which may lead to the critical form of COVID-19. In this case, there is a huge increase in cytokines release, which is known as cytokines release syndrome (CRS), or “cytokines storm”.…”

Vitamin D and COVID‐19 in an immunocompromised patient with multiple comorbidities—A Case Report

“…In most groups of risk patients, common mechanism favoring development of excessive inflammation and cytokine storm is persistently present proinflammatory milieu 7 . Such chronic proinflammatory state can arise either due to hypersecretion of proinflammatory adipokines in obese patients, 7 lack of anti‐inflammatory signaling in diabetic, and insulin‐resistant patients 7,8 or dysregulation of renin‐angiotensin system (RAS) with increased proinflammatory angiotensin II (Ang II) production in hypertensive patients 6,9,10 . Patients on immunosuppressive therapy are considered to be at risk due to the facilitated viral multiplication and dissemination during the initial phase, enabling in turn more vigorous ignition of hyperinflammatory phase 6,10,11 .…”

“…Such chronic proinflammatory state can arise either due to hypersecretion of proinflammatory adipokines in obese patients, 7 lack of anti‐inflammatory signaling in diabetic, and insulin‐resistant patients 7,8 or dysregulation of renin‐angiotensin system (RAS) with increased proinflammatory angiotensin II (Ang II) production in hypertensive patients 6,9,10 . Patients on immunosuppressive therapy are considered to be at risk due to the facilitated viral multiplication and dissemination during the initial phase, enabling in turn more vigorous ignition of hyperinflammatory phase 6,10,11 . In the other hand, hyperactive inflammatory processes could be kept under control to some extent by immunosuppressants, but conclusions and recommendations on their use in COVID‐19 patients are inconsistent and unclear 12 .…”

High-dose ACEi might be harmful in COVID-19 patients with serious respiratory distress syndrome by leading to excessive bradykinin receptor activation

“…The high mortality rate of elderly vulnerable hypertensive patients infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often associated with cytokine storm [1]. Several cytokines were measured or suggested to contribute to the development of serious pulmonary inflammation [2][3][4] but no direct information is available on the plasma or tissue concentrations of bradykinin and kallidin (lysine-bradykinin), and their active metabolites (bradykinin-related peptides). The kallikrein-kinin system (KKS) is upregulated in many inflammatory diseases [5], and in the bronchoalveolar lavage fluid of COVID-19 patients [6].…”