COVID-19 Pathogenesis: From Molecular Pathway to Vaccine Administration

Abstract

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease and the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out of the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms of thrombosis following vaccination were also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

Keywords: ACE inhibition; COVID-19; SARS-CoV-2; pathophysiology; thromboembolism.

Figure 1

Depicts the interaction of SARS-CoV2 with the ACE2 receptor and the inflammatory profile pattern before and after Coronavirus 2019 (COVID-19) infection in patients with or without CVD. The initial entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells is shown with involvement mainly of type II pneumocytes. SARS-CoV-2 binds to its functional receptor, the angiotensin-converting enzyme 2 (ACE2). After endocytosis of the viral complex, surface ACE2 is further down-regulated, resulting in unobstructed accumulation of angiotensin II. Local activation of the renin–angiotensin–aldosterone system may mediate lung injury responses to viral insults. The elderly and the young may present with different pathophysiological profiles. The simplified scheme of the pre-infection inflammatory profile among predisposed older individuals compared to their younger counterparts is illustrated. Abbreviations: ACE2, angiotensin-converting enzyme 2; ARB, angiotensin-receptor blocker; CVD, cardiovascular disease; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2

Current Guideline Recommendations for Venous Thromboembolism Prevention in patients With Coronavirus Disease 2019. Abbreviations: DOAC, direct oral anticoagulant; LMWH, low-molecular-weight heparin.

Figure 3

SARS-CoV-2 variants and the respective efficacy of most administered vaccines are shown [120]. B.1.1.7. i.e., the UK variant has recently been studied by investigators: 89.5% and 74.6% efficacies have been demonstrated against the variants by the B1.1.7 + E484K and ChadOx-1 nCoV-19 vaccines respectively.

Figure 4

Variants of Interest (VOI) are illustrated. Every box reflects a country the first variant was discovered in. As for variants of concern, the Spike protein mutations associated with the variant are displayed. The efficacy of vaccines has not been reported due to the lack of data in terms of both literature studies and official national reports. Data are updated until 6 May 2021 [121].

Figure 5

The proposed mechanism of autoantibodies generation is described. Following administration of adenoviral vector encoding the spike protein, a subsequent inflammatory cascade, stimulated by the individual immune response, activates platelets to generate platelet-factor 4 (PF4). In complexes with polyanionic PGs, derived from endothelial cells, they stimulate extrafollicular B cells to antibody production which, in turn, would exert positive feedback on platelet activation. The antibodies generated would resemble HIT autoantibodies from that point on with respect to thrombogenesis and hemostasis disorders. PF4 shares some epitopes with the Spike protein but, despite this, they are not sufficient to induce cross-reactivity. PF4: platelet factor 4, HIT: heparin-induced thrombocytopenia, PGs: proteoglycans.