Coagulation Profile of COVID-19 Patients

Abstract

Coronavirus disease is a viral infection that can affect multiple systems and be expressed with many-or no-symptoms. The viral infection begins when the virus binds to the host's receptor and from that point on, it is transmitted to the rest of the body, where it causes inflammatory reactions. Among other tissues and systems, SARS-CoV-2 impacts the coagulation system, where it triggers the immunothrombotic response. Its effects are rather intense and can lead to many complications. COVID-19-associated coagulopathy is frequently observed in hospitalized patients, especially ICU patients, and can be proven detrimental. It is usually accompanied by other complications, such as sepsis-induced coagulopathy, disseminated intravascular coagulation and venous thromboembolism. Since all these conditions lead to poor prognosis for severely ill patients, thromboprophylaxis and coagulopathy prognosis are just as important as the therapeutic handling of these patients. Since the beginning of the pandemic, many biomarkers have been considered useful when trying to assess the thrombotic risk of hospitalized patients or evaluate the severity of their situation. At the same time, many drugs have already been tested-while others are still being trialed-in order to find the optimal therapy for each urgent situation.

Keywords: COVID-19; COVID-19 biomarkers; coagulopathy; complement system; cytokine storm; microthrombosis; thromboinflammation.

Figure 1

SARS-CoV-2’s binding to the host receptor. SARS-CoV-2 binds to the host cell ACE2 receptor, after TMPRSS2 primes the viral S protein. Abbreviations used: TMPRSS2: transmembrane protease serine-2; ACE2: angiotensin-converting enzyme 2.

Figure 2

ACE2 converts AngII to Ang1-7. Ang1-7 then binds to MAS, causes an elevation of NO and prostacyclin and thus has anti-inflammatory, antioxidant and anti-thrombotic effects. When SARS-CoV-2 binds to the ACE2 receptor, this pathway is downregulated. Abbreviations used: MAS: a transmembrane G-protein coupled receptor; AngII: angiotensin II; Ang1-7: angiotensins 1-7; NO: nitric oxide.

Figure 3

SARS-CoV-2 infection and alterations in the RAAS and KKS axis. SARS-CoV-2 binds to the ACE2 receptor causing its internalization. ACE2 no longer converts AngII to Ang1-7 and AngII binds to the AT1 receptor and subsequently triggers the production of p83 MAPK, caspase 3, ROS and Cyt C, which promotes apoptosis, hyperinflammation and hypertrophy. ACE2 also affects the KKS axis by affecting DEABK’s and LDEABK’s attachment to BRB1, thus leading to inflammation and coagulation. Abbreviations used: RAAS: Renin-Angiotensin-Aldosterone-System; AT1R: Angiotensin type 1 receptor; p83 MAPK: p83 mitogen activated protein kinase; Cyt C: Cytochrome C; ROS: Reactive oxygen species; KKS: Kinin-Kallikrein system; DEABK: [des-Arg9]-BK; LDEABK: Lys-[des-Arg9]-BK; NADPH: nicotinamide adenine dinucleotide phosphate; COX2: cyclooxygenase 2; IL-6, IL-1β, TNFa30: proinflammatory cytokines; BRB1/2: bradykinin receptor B1/B2; BK: bradykinin; Lys-BK: Lys- bradykinin.

Figure 4

The cytokine storm. Viral entry in the cell after binding to the ACE2 receptor. After entry, the virus replicates inside the cell and activation of host innate immunity occurs. This contains the release of pro-inflammatory cytokines, which when uncontrolled leads to the cytokine storm. Abbreviations used: IL: interleukin; IP: interferon gamma-induced protein; MCP-1: monocyte chemoattractant protein 1; MIP: macrophage inflammatory protein; IFN-γ: interferon gamma, TNF-α: tumor necrosis factor alpha.

Figure 5

Cases of coagulation complications severity during COVID-19 infections. Every level of severity (low, intermediate, and high) is characterized by different aspects which help both in the diagnosis as well as in the treatment process.