Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.

The progress in the development of various vaccine platforms against SARS-CoV-2 have been rather remarkable owing to advancement in molecular and biologic sciences. Most of the current vaccines and those in development focus on targeting the viral spike proteins by generating antibodies of varying spectrum. These vaccines represent a variety of platforms including whole virus vaccines, viral vector vaccines, nucleic acid vaccines representing RNA, DNA, and their hybrid forms. The therapeutic efficacy of these vaccines varies owing to their pharmacodynamic individualities. COVID-19 variants are capable of inducing different pathologic responses and some of which may be resistant to antibodies generated by current vaccines. The current clinical use of these vaccines has been through emergency use authorization until recently. Moreover, the efficacy and safety of these vaccines have been tested in substantial numbers of individuals but studies in special populations that better reflect the global population are pending results. These specialized populations include young children, immunocompromised patients, pregnant individuals, and other specialized groups. Combination approaches, molecularly modified vaccination approaches, and vaccines conferring longer periods of immunity are being currently being investigated, as well as pharmacovigilance studies. The continual transformation of SARS-CoV-2 and its variants are of concern along with the breakthrough infections. These considerations pose new challenges for the development of vaccination platforms. For this purpose, booster doses, combination vaccine approaches, and other modalities are being discussed. This review provides an updated account of currently available vaccines and those in advanced development with reference to their composition and mechanisms of action. A discussion on the use of vaccines in special populations including immunocompromised patients, pregnant women and other specialized populations are also included.

Introduction: Atrial Fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide. Inflammation and structural remodeling of the left atrium are thought to be involved in the pathogenesis of AF. This study explores collagen remodeling and inflammatory biomarkers in AF patients compared to healthy controls to discern their role in AF. Materials and Methods: Plasma samples were collected from AF patients undergoing first AF ablation (n = 72) and compared with commercially available human plasma samples from healthy subjects (n = 62). The collagen remodeling biomarkers and inflammatory biomarkers in the AF patients and control population were quantified using sandwich ELISA kits. GraphPad prism was used to perform statistical analyses. Results: There was a statistically significant elevation in all the collagen remodeling biomarkers and inflammatory biomarkers in the AF patients compared to healthy controls. Spearman correlation analysis demonstrated significant correlations between inflammatory and collagen remodeling biomarkers, and among the collagen biomarkers. Of note, CRP was found to be correlated with TIMP-1, ICTP and PIIINP. IL6 and TIMP-1 were also found to be intercorrelated. Furthermore, correlations were noted among the different collagen remodeling peptides, and between TNFα and IL6, two of the inflammatory markers explored in this study. Conclusions: The elevation of the inflammatory biomarkers and collagen remodeling proteins in AF patients is suggestive of inflammation and increased collagen turnover. The association between inflammatory biomarkers and collagen remodeling proteins may contribute to their regulation and role in the remodeling process.

Type I and type II diabetes are closely associated with a pro-inflammatory state and to a pro-thrombotic state. The role of glycemic control in pulmonary embolism (PE) is poorly understood and requires additional investigation. The aim of this study is to investigate the relationship between glycemic control and thrombo-inflammatory biomarkers in a PE patient cohort compared to normal samples. Demographic and clinical information for 86 diabetic patients and 106 non-diabetic patients presenting with acute PE was collected via retrospective chart review. Plasma levels of pro-inflammatory (C-reactive protein [CRP], tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and pro-thrombotic (d-dimer, plasminogen activator inhibitor-1 [PAI-1], tissue plasminogen activator [tPA], thrombin activatable fibrinolysis inhibitor [TAFI], von-Willebrand factor [vWF], endogenous glycosaminoglycans [GAGs]) biomarkers were drawn within 24 hours of diagnosis of acute PE. Data was also obtained for a population of healthy adult controls. All the pro-inflammatory and pro-thrombotic biomarkers were elevated in diabetic PE patients in comparison to healthy controls. None of the biomarkers were elevated in diabetic PE patients when compared to non-diabetic PE patients. There was no difference in the levels of the pro-inflammatory biomarkers according to glycemic control. The plasma level of TAFI was elevated in diabetic patients with poor glycemic control. Diabetic patients were more likely to have a more severe PE. These studies demonstrate that thrombo-inflammatory biomarkers are elevated in diabetic PE patients with associated comorbidities in comparison to normal individuals. However, there is no difference between the PE cohort alone in comparison to PE with diabetes. The role of TAFI within the continuum of diabetic vascular disease warrants additional investigation.

Atrial Fibrillation (AF) induces proinflammatory processes which incite vascular endothelial activation and dysfunction. This study seeks to examine the potential relationship between various endothelial, inflammatory, thrombotic, and renin-angiotensin-system (RAS) biomarkers in AF patients. Blood samples were from AF patients (n = 110) prospectively enrolled in this study prior to their first AF ablation. Control plasma samples (n = 100) were used as reference. All samples were analyzed for endothelial (NO, ICAM-1, VEGF, TF, TFPI, TM, Annexin V), inflammatory (IL-6, TNFα, CRP), thrombotic (vWF, tPA, PAI-1, TAFI, D-dimer), and RAS (Renin, Ang-II) biomarkers using ELISA methods. Biomarker average comparisons and Spearman correlations were performed. AF patients showed varying levels of biomarker increase compared to controls. We observed a significant decrease of Ang-II in the AF population relative to controls when stratified for the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) upon study enrollment. AF patients showed statistically significant correlations between the following biomarkers: TNFα vs IL-6 (r_s= 0.317, p = .004), ICAM-1 vs TNFα (r_s= 0.527, p = .012), Annexin V vs VEGF (r_s= 0.620, p < .001), CRP vs VEGF (r_s= 0.342, p = .031), Ang-II vs tPA (r_s= −0.592, p = .010), and tPA vs PAI-1 (r_s= 0.672, p < .001). Our study demonstrated significant elevation of endothelial, inflammatory, and thrombotic biomarkers in AF patients compared to controls, with significant correlations between these biomarkers in the AF population. Future investigations are required to better elucidate the mechanistic pathways that lead to endothelial dysfunction and thromboinflammation in AF. This may provide novel therapeutic targets, that in addition to current anticoagulation practices, can best curtail thrombogenicity in AF.