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.

Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery

“…The Kaplan–Meier analysis showed not only increased mortality in cluster A patients ( p = 0.034), but also that deaths occurred significantly sooner after hospitalization than in cluster B (4 (3–15) days vs. 21 (19–29) days, p = 0.01) ( Figure 5 E,F). Remarkably, known factors associated with a critical course of the infection, such as age, sex, comorbidities, ARDS, ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2), monocytes, platelets, neutrophil-to-lymphocyte ratio, LDH, albumin, AST, ALT, fibrinogen, D-dimer, viral load (Ct) [ 28 , 29 , 30 , 31 ], days of symptoms and treatment received were not different between clusters. The only parameters that differed were IL-6 and C-reactive protein, which were both significantly increased in cluster A ( Table S1 ), suggesting that cluster A includes a group of patients with higher early inflammation.…”

Molecular Insights of SARS-CoV-2 Antivirals Administration: A Balance between Safety Profiles and Impact on Cardiovascular Phenotypes

“…The pandemic has given rise to a good response from the scientific community with the availability of multiple therapeutic agents and vaccines. Vaccines continue to provide sufficient protection from spread and contagion although their response varies with disease variants [ 58 , 129 , 130 ]. There is an ongoing push towards biological agents and retrovirals to reduce the severity and duration of symptoms with mixed results.…”

“…Baricitinib administration has been associated with an increased risk of thromboembolism when compared with placebo in safety studies for rheumatological diseases and COVID-19 [ 51 , 53 ]. Moreover, it is generally known that COVID-19 might propagate coagulopathies with a thrombotic diathesis [ 54 , 55 , 56 , 57 , 58 ]. The use of tofacitinib is currently suggested for patients with severe COVID-19 on supplemental or high-flow oxygen [ 32 ].…”

“…The tendency is to be cautious with repurposed drugs administration, for COVID-19. However, given the lack of available data, concerns have been raised within the scientific community especially as the mechanism of action of some antivirals remains unclear [ 58 ].…”

Thromboembolic Disease and Cardiac Thrombotic Complication in COVID-19: A Systematic Review

“…Several reports from series by China, Italy, and the United States reveal that most of the affected patients who develop COVID-19 experience a relatively mild clinical form; however, the clinical picture may evolve toward life-threatening disease. The evidence that emerged in the past two years supports the idea that the individuals at the highest risk of serious illness, those requiring intensive care hospitalization and at higher risk of death, are older and with underlying comorbidities, such as cardiovascular diseases [ 34 , 45 , 58 , 62 , 63 , 64 , 65 , 67 , 145 , 146 ]. However, even younger patients have been affected by the serious form of COVID-19, thereby requiring hospitalization.…”