Background/Objectives: SARS-CoV-2 infection increases thrombotic events in hospitalized patients, especially those of greater severity. It has been associated with the cytokine storm and worsening renal and liver function, increased inflammatory markers, and altered coagulation markers. This study analyzes differences in inflammatory, hepatic, renal, and coagulation markers between hospitalized patients with and without COVID-19 who experienced thromboembolic events during the last three years of the pandemic. Methods: This single-center, retrospective observational study, with an inferential component and biomarker analysis, included 663 patients (600 without COVID-19, 63 with COVID-19) admitted between December 2022 and January 2023. Results: Patients with COVID-19 exhibited significantly higher mean glomerular filtration rate (GFR) (100.5 mL/min/1.73 m2; p < 0.01) and alanine aminotransferase (ALT) levels (33.0 IU/L; p < 0.01) compared to those without COVID-19. Ferritin levels were also significantly elevated in COVID-19 patients (441.1; p < 0.01), particularly those with severe disease. Conversely, troponin I was significantly higher in patients without COVID-19 (22.6 × 104 pg/mL; p < 0.001). Among COVID-19 patients, D-dimer levels were significantly higher in those not requiring intensive care unit (ICU) admission (9.0 × 103 ng/mL; p = 0.023). Multivariate analysis revealed a significant association between COVID-19 and sex. Conclusions: Overall, renal function did not differ significantly between COVID-19 and non-COVID-19 patients. However, renal function was better in patients admitted to the ICU, regardless of COVID-19 status. Troponin I levels were elevated in non-COVID-19 patients, while ferritin and ALT levels were higher in COVID-19 patients. D-dimer levels showed no significant difference between the two groups.

Cytokine storm (CS) is a severe systemic inflammatory syndrome characterized by the excessive activation of immune cells and a significant increase in circulating levels of cytokines. This pathological process is implicated in the development of life-threatening conditions such as fulminant myocarditis (FM), acute respiratory distress syndrome (ARDS), primary or secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome (CRS) associated with chimeric antigen receptor-modified T (CAR-T) therapy, and grade III to IV acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. The significant involvement of the JAK-STAT pathway, Toll-like receptors, neutrophil extracellular traps, NLRP3 inflammasome, and other signaling pathways has been recognized in the pathogenesis of CS. Therapies targeting these pathways have been developed or are currently being investigated. While novel drugs have demonstrated promising therapeutic efficacy in mitigating CS, the overall mortality rate of CS resulting from underlying diseases remains high. In the clinical setting, the management of CS typically necessitates a multidisciplinary team strategy encompassing the removal of abnormal inflammatory or immune system activation, the preservation of vital organ function, the treatment of the underlying disease, and the provision of life supportive therapy. This review provides a comprehensive overview of the key signaling pathways and associated cytokines implicated in CS, elucidates the impact of dysregulated immune cell activation, and delineates the resultant organ injury associated with CS. In addition, we offer insights and current literature on the management of CS in cases of FM, ARDS, systemic inflammatory response syndrome, treatment-induced CRS, HLH, and other related conditions.

Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.

One lingering effect of the COVID-19 pandemic created by SARS-CoV-2 is the emergence of Long COVID (LC), characterized by enduring neurological sequelae affecting a significant portion of survivors. This review provides a thorough analysis of these neurological disruptions with respect to cognitive dysfunction, which broadly manifest as chronic insomnia, fatigue, mood dysregulation, and cognitive impairments with respect to cognitive dysfunction. Furthermore, we characterize how diagnostic tools such as PET, MRI, EEG, and ultrasonography provide critical insight into subtle neurological anomalies that may mechanistically explain the Long COVID disease phenotype. In this review, we explore the mechanistic hypotheses of these neurological changes, which describe CNS invasion, neuroinflammation, blood-brain barrier disruption, and gut-brain axis dysregulation, along with the novel vascular disruption hypothesis that highlights endothelial dysfunction and hypoperfusion as a core underlying mechanism. We lastly evaluate the clinical treatment landscape, scrutinizing the efficacy of various therapeutic strategies ranging from antivirals to anti-inflammatory agents in mitigating the multifaceted symptoms of LC.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a respiratory disease that can range in presentation from mild symptoms to severe conditions such as pneumonia and acute respiratory distress syndrome. SARS-CoV-2, a single-stranded RNA virus, spreads through aerosols and respiratory droplets. It enters human cells by binding to the angiotensin-converting enzyme 2 receptor, leading to various complications, including significant alterations in red blood cells and potential disruptions in haemoglobin function and oxygen transport. During infection, the interaction between hypoxia, inflammation, and haematopoiesis affects erythropoiesis at multiple levels. Hypoxia and inflammation, resulting from lung complications and a reduced red blood cell count, influence the regulation of hepcidin, a key regulator of iron levels in the blood. Elevated hepcidin levels are associated with hypoxia and the suppression of erythroferrone, a hormone that normally inhibits hepcidin production. Despite high levels of inflammation, patients in intensive care units often exhibit elevated ferritin levels, which, rather than indicating low hepcidin, suggest disrupted iron metabolism and the development of severe anaemia. Iron is kept in stores, likely due to paradoxically high hepcidin levels, which explains the elevated ferritin measurements. An increase in immature blood cells and a decrease in CD71+ erythroid cells are observed. The elevated levels of CD71+ erythroid cells highlight their dual role in modulating hyper-inflammation and immune response during disease progression. This review examines the pathway by which SARS-CoV-2 affects red blood cell production and the haematopoietic system and how it triggers cytokine storms through interleukins, immature blood cells, and CD71+ erythroid cells. Understanding these processes provides novel pathways for managing haematological manifestations and immune responses in patients with COVID-19.

Paget-Schroetter Syndrome (PSS) is a rare condition characterized by spontaneous thrombosis of the axillary-subclavian vein that occurs predominantly in young athletes engaged in repetitive overhead upper extremity motion, for instance, weightlifting, swimming, baseball, and tennis. PSS is usually a consequence of chronic repetitive microtrauma to the vein intima due to compression of the axillary-subclavian vein by the thoracic outlet structures. This chronic injury can then be acutely exacerbated by vigorous exercise done over a brief period, accelerating thrombus formation. Lack of PSS awareness leads to underdiagnosis, misdiagnosis, or late diagnosis, which can pose life-threatening risks to patients, including pulmonary embolism (PE) and recurrent thrombosis. This case report of a 20-year-old male college athlete exposes a PE caused by PSS, potentially worsened by a delay in diagnosis. Early suspicion and proper management are crucial for optimizing long-term outcomes and facilitating limb rehabilitation. The recommended approach involves early catheter-directed thrombolysis followed by thoracic outlet decompression.

Platelet-viral interactions are evolving as a new concern. Coagulation disorder is a major consequence of the COVID-19 infection. In chronic hepatitis virus infections, defect in coagulation factors, thrombocytopenia and platelet function abnormalities are common. A SARS-CoV-2 infection on top of chronic viral hepatitis infection can be common in areas where viral hepatitis is endemic. Here, we investigate the platelet ultrastructural changes and estimate the serum platelet factor-4 (PF-4), ferritin, CRP, and D-dimer in COVID-19 patients (n = 60), COVID-19 patients with associated chronic viral hepatitis (n = 20), and healthy subjects (n = 20). Ultrastructural changes were demonstrated in all test groups, denoting platelet activation. In chronic viral hepatitis patients, Platelet ultrastrustural apoptotic changes were also seen. Significantly high levels of PF-4 were confirmed in moderate and severe COVID-19 patients (P.value <0.001), with a cut off value of 17 ng/ml for predicting disease severity. A positive correlation of PF-4 with the level of serum ferritin, CRP, and D-dimer (p value < 0.001) was noted, while negatively correlated with platelet count and platelet granule count (p value < 0.001). In our study, chronic viral hepatitis patients presented mild COVID-19 signs, and their PF-4 level was comparable with the subgroup of mild COVID-19 infection. The platelet's critical role in COVID-19 coagulopathy and chronic viral hepatitis is evidenced by the ultrastructural changes and the high levels of PF4. Moreover, a dual viral infection poses a substantial burden on the platelets, necessitating close monitoring of the patient's coagulation profile.

The symptoms in patients with primary immune thrombocytopenia (ITP) after COVID-19 onset remain largely unclear. The aim of this study was to describe the platelet count fluctuations in ITP patients following the diagnosis of COVID-19. A prospective multicentre observational study was conducted from December 15th, 2022, to January 31st, 2023 in 39 general hospitals across China. Patients with preexisting primary ITP who were newly diagnosed with COVID-19 were enrolled. A total of 1216 ITP patients with newly-diagnosed COVID-19 were enrolled. 375 (30.8%) patients experienced ITP exacerbation within eight weeks after the diagnosis of COVID-19, and most exacerbation (266/375, 70.9%) developed in the first two weeks. Immunosuppressive therapy for ITP and severe/critical COVID-19 infection were independent variables associated with ITP exacerbation. Overall the platelet count had a transient increasing trend, and the platelet peak value occurred at two weeks after COVID-19 infection. Then, the platelet count decreased to the baseline level in the following weeks. The platelet count had a transient increasing trend in ITP patients following the diagnosis of COVID-19. ITP exacerbation only occurred in less than one-third of ITP patients. Nonimmunosuppressive therapy may have an advantage to prevent ITP exacerbation during COVID-19.

The aim of this review was to present the mechanism of infection with severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and its possible effect on the course of arterial hypertension. Another aim was to evaluate the relationship of the renin-angiotensin-aldosterone system with the pathogenetic stages of infection caused by SARS-CoV-2 virus.

The therapeutic management and short-term consequences of the coronavirus disease 2019 (COVID-19) are well known. However, COVID-19 post-acute sequelae are less known and represent a public health problem worldwide. Patients with COVID-19 who present post-acute sequelae may display immune dysregulation, a procoagulant state, and persistent microvascular endotheliopathy that could trigger microvascular thrombosis. These elements have also been implicated in the physiopathology of postural orthostatic tachycardia syndrome, a frequent sequela in post-COVID-19 patients. These mechanisms, directly associated with post-acute sequelae, might determine the thrombotic consequences of COVID-19 and the need for early anticoagulation therapy. In this context, heparin has several potential benefits, including immunomodulatory, anticoagulant, antiviral, pro-endothelial, and vascular effects, that could be helpful in the treatment of COVID-19 post-acute sequelae. In this article, we review the evidence surrounding the post-acute sequelae of COVID-19 and the potential benefits of the use of heparin, with a special focus on the treatment of postural orthostatic tachycardia syndrome.

Thrombotic events associated with SARS-CoV-2 at the vascular endothelium still remains unclear. The aim of the current study is to determine the relationship between cellular proteins on the (ocular) vascular endothelial surface and the immune thrombotic and/or endotheliopathy process elicited by SARS-CoV-2 using an in-silico modeling. The structural S (spike glycoprotein), N (nucleocapsid protein), M (membrane protein), and E (envelope protein) proteins, an accessory protein (ORF1ab) of SARS-CoV-2 and 158 cellular proteins associated with retinal vascular endothelial cell surface or structure were included in this study for comparison of three-dimensional (3D) structure and sequence. Sixty-nine of the retinal proteins were obtained from the Uniprot database. Remaining proteins not included in the database were included in the study after they were converted into 3D structures using the RaptorX web tool. Sequence and three-dimensional structure of SARS-COV-2 S, N, M, E, ORF1ab proteins and retinal vascular endothelial proteins were compared with mTM-align server. Proteins with significant similarity (score above 0.5) were validated with the TM-align web server. Immune and thrombosis-related protein-receptor interactions of similar proteins was checked with CABS-dock. We detected a high level of structural similarity between E protein and ACE, ACE2, LAT1, and TM9SF4 endothelial proteins. In addition, PECAM-1 was found to be structurally similar to ORF1ab and S protein. When we evaluated the likelihood/potential to stimulate an immune responses/a cytokine release, TLR-2 and TLR-3, which are highly susceptible to SARS-CoV2, showed a potential receptor-protein interaction with retinal vascular endothelial proteins. Our study demonstrates that SARS-CoV-2 proteins may have structural similarities with vascular endothelial proteins, and therefore, as immunological target sites, the counterpart proteins on the endothelial surface of many organs may also be secondarily affected by any immune response against SARS-CoV-2 structural proteins.

Severe SARS-CoV-2 elicits a hyper-inflammatory response that results in intravascular inflammation with endothelial injury, which contributes to increased mortality in COVID-19. To predict the outcome of severe SARS-CoV-2 infection, we analyzed the baseline level of different biomarkers of vascular disorders in COVID-19 subjects upon intensive care unit (ICU) admission and prior to any vaccination. A total of 70 severe COVID-19 patients (37 survivors and 33 non-survivors) were included with 16 age- and sex-matched controls. Vascular dysfunction was monitored via soluble VCAM-1, E-selectin, ACE2 and Lp-PLA2, while abnormal platelet activation was evaluated by soluble P-selectin and CD40L in parallel. These results were correlated with routine laboratory parameters and disease outcomes. Among these parameters, VCAM-1 and ACE2 showed significantly higher serum levels in COVID-19 patients with early death vs. convalescent subjects. VCAM-1 was significantly correlated with the Horowitz index (r = 0.3115) and IL-6 (r = 0.4599), while ACE2 was related to E-selectin (r = 0.4143) and CD40L (r = 0.2948). Lp-PLA2 was altered in none of these COVID-19 subcohorts and showed no relationship with the other parameters. Finally, the pre-treatment level of VCAM-1 (≥1420 ng/mL) and ACE2 activity (≥45.2 μU/mL) predicted a larger risk for mortality (Log-Rank p = 0.0031 and p = 0.0117, respectively). Vascular dysfunction with endothelial cell activation is linked to lethal COVID-19, and highly elevated soluble VCAM-1 and ACE2 at admission to ICU may predict unfavorable outcomes.

Vascular sequelae following (SARS-CoV-2 coronavirus disease) (COVID)-19 infection are considered as "Long Covid (LC)" disease, when occurring 12 weeks after the original infection. The paucity of specific data can be obviated by translating pathophysiological elements from the original Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection (In a microcirculatory system, a first "endotheliitis," is often followed by production of "Neutrophil Extracellular Trap," and can evolve into a more complex leukocytoklastic-like and hyperimmune vasculitis. In medium/large-sized vessels, this corresponds to endothelial dysfunction, leading to an accelerated progression of pre-existing atherosclerotic plaques through an increased deposition of platelets, circulating inflammatory cells and proteins. Associated dysregulated immune and pro-coagulant conditions can directly cause thrombo-embolic arterial or venous complications. In order to implement appropriate treatment, physicians need to consider vascular pathologies observed after SARS-Cov-2 infections as possible "LC" disease.

The advent of the Coronavirus Disease 2019 (COVID-19) has presented a substantial and urgent global public health issue. Biomarkers have the potential to be utilized for the identification of endothelium and/or alveolar epithelial damage in instances of COVID-19 infection.

to evaluate the levels of Intercellular adhesion molecule-1 (ICAM-1) and Vascular cell adhesion molecule (VCAM-1) biomarkers in hospitalized patients who tested positive for COVID-19 infection using Polymerase Chain Reaction (PCR) with the virus specific Immunoglobulins; IgM, and IgG testing. This can help with improved clinical management and treatment programs.

A case-control study that involved 90 hospitalized patients who tested positive for COVID-19 and 40 apparently healthy control patients, subjects in both groups underwent nasopharyngeal swabs for PCR and blood sample collection for evaluation of serum; IgM, IgG, ICAM-1 and VCAM-1 levels.

Males made up the vast majority of the patients (78.9%), with only a minor percentage of females (21.1%) P value 0.1641. Furthermore, every patient in this study had a minimum of one risk factor for COVID-19. The investigator's results show that COVID-19 patients had higher amounts of endothelial cell adhesion indicators (ICAM-1 and VCAM-1) with mean values of 126.27 ± 89.51 ng/mL and 109.74 ± 96.57 ng/mL respectively. While, ICAM-1 and VCAM-1, were present at normal levels in the control group with difference P value 0.0028 and 0.0032 in comparison to the patient's group respectively.

The adhesive markers ICAM and VCAM play a crucial role in the development of COVID-19 and the strong endothelial activation and dysfunction linked to both acute and persistent immunological responses is shown by the substantial correlation found in COVID-19 patients between the presence of IgM and IgG antibodies and higher levels of ICAM-1 and VCAM-1.

High-flow nasal cannula (HFNC) reduces the need for intubation in adult subject with acute respiratory failure. Changes in hypobaric hypoxemia have not been studied for subject with an HFNC in ICUs at altitudes > 2,600 m above sea level. In this study, we investigated the efficacy of HFNC treatment in subjects with COVID-19 at high altitudes. We hypothesized that progressive hypoxemia and the increase in breathing frequency associated with COVID-19 in high altitudes affect the success of HFNC therapy and may also influence the performance of the traditionally used predictors of success and failure.

This was a prospective cohort study of subjects >18 y with a confirmed diagnosis of COVID-19-induced ARDS requiring HFNC who were admitted to the ICU. Subjects were followed up during the 28 d of HFNC treatment or until failure.

One hundred and eight subjects were enrolled. At admission to the ICU, FIO2 delivery between 0.5-0.8 (odds ratio 0.38 [95% CI 0.17-0.84]) was associated with a better response to HFNC therapy than oxygen delivery on admission between 0.8-1.0 (odds ratio 3.58 [95% CI 1.56-8.22]). This relationship continued during follow-ups at 2, 6, 12, and 24 h, with a progressive increase in the risk of failure (odds ratio 24 h 13.99 [95% CI 4.32-45.26]). A new cutoff for the ratio of oxygen saturation (ROX) index (ROX ≥ 4.88) after 24 h of HFNC administration was demonstrated to be the best predictor of success (odds ratio 11.0 [95% CI 3.3-47.0]).

High-altitude subjects treated with HFNC for COVID-19 showed a high risk of respiratory failure and progressive hypoxemia when FIO2 requirements were > 0.8 after 24 h of treatment. In these subjects, personalized management should include continuous monitoring of individual clinical conditions (such as oxygenation indices, with cutoffs adapted to those corresponding to high-altitude cities).

Millions of people were infected by the coronavirus disease (COVID-19) epidemic, which left a huge burden on the care of post COVID-19 survivors around the globe. The self-reported COVID-19 symptoms were experienced by an estimated 1.3 million people in the United Kingdom (2% of the population), and these symptoms persisted for about 4 weeks from the beginning of the infection. The symptoms most frequently reported were exhaustion, shortness of breath, muscular discomfort, joint pain, headache, cough, chest pain, cognitive impairment, memory loss, anxiety, sleep difficulties, diarrhea, and a decreased sense of smell and taste in post-COVID-19 affected people. The post COVID-19 complications were frequently related to the respiratory, cardiac, nervous, psychological and musculoskeletal systems. The lungs, liver, kidneys, heart, brain and other organs had been impaired by hypoxia and inflammation in post COVID-19 individuals. The upregulation of substance "P" (SP) and various cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 1 beta (IL-1β), angiotensin-converting enzyme 2 (ACE2) and chemokine C-C motif ligand 3 (CCL3) has muddled respiratory, cardiac, neuropsychiatric, dermatological, endocrine, musculoskeletal, gastrointestinal, renal and genitourinary complications in post COVID-19 people. To prevent these complications from worsening, it was therefore important to study how these biomarkers were upregulated and block their receptors.

Vaso-occlusion in sickle cell disease (SCD) leads to a myriad of manifestations driving morbidity and mortality in patients with SCD. Increased leucocyte adhesion and P-selectin expression on platelets and endothelial cells is an inciting event that leads to obstruction of microcirculation by adhesion with rigid sickled red blood cells. Crizanlizumab is a first-in-class monoclonal antibody that inhibits P-selectin and has been shown to decrease the frequency of vaso-occlusive pain crises in patients with SCD in clinical trials. The role of crizanlizumab in other manifestations of SCD still needs further investigation.

Currently, worldwide, the coronavirus disease 2019 (COVID-19) pandemic, which first appeared in Wuhan, China, in December 2019, is capsizing the medical system and turning the attention of the entire healthcare system through the many aspects it presents, both from a pathophysiological and from a semiological view, insufficiently studied aspects. With a high rate of morbidity and mortality, the COVID-19 pandemic was initially observed as a pathology leading to a severe acute respiratory syndrome, but over time gastrointestinal and hepatic manifestations have been reported. The study includes an analysis of 21 patients in the stage of the clinical disease of COVID-19 or in the stage of recovery, hospitalized in the Departments of General Surgery II or Gastroenterology, Emergency Clinical County Hospital of Craiova, Romania, with predominantly digestive symptoms, with the clinical expression of infectious enterocolitis, although stool culture was negative for pathogenic bacteria. The evolution of patients was influenced by the appearance of peritonitis through colonic necrosis or remission of clinical symptoms under empirical therapy.

COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality.

This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID.

One-hundred-seventy-seven patients were recruited from clinical cohorts at 2 Israeli centers: acute COVID-19 (mild/moderate, severe/critical), convalescent COVID-19 (recovered and long COVID), along with 54 non-COVID controls. Plasma was examined for markers of platelet activation, coagulation, and NETs. Ex vivo NETosis induction capability was evaluated after neutrophil incubation with patient plasma.

Soluble P-selectin, factor VIII, von Willebrand factor, and platelet factor 4 were significantly elevated in patients with COVID-19 versus controls. Myeloperoxidase (MPO)-DNA complex levels were increased only in severe COVID-19 and did not differentiate between COVID-19 severities or correlate with thrombotic markers. NETosis induction levels strongly correlated with illness severity/duration, platelet activation markers, and coagulation factors, and were significantly reduced upon dexamethasone treatment and recovery. Patients with long COVID maintained higher NETosis induction, but not NET fragments, compared to recovered convalescent patients.

Increased NETosis induction can be detected in patients with long COVID. NETosis induction appears to be a more sensitive NET measurement than MPO-DNA levels in COVID-19, differentiating between disease severity and patients with long COVID. Ongoing NETosis induction capability in long COVID may provide insights into pathogenesis and serve as a surrogate marker for persistent pathology. This study emphasizes the need to explore neutrophil-targeted therapies in acute and chronic COVID-19.

COVID-19 is associated with acute and longer-term cardiovascular manifestations including myocardial injury, myopericarditis, stress-induced cardiomyopathy, myocardial infarction, and thromboembolic disease. Although the morbidity and mortality related to acute COVID-19 have decreased substantially, there is growing concern about the longer-term cardiovascular effects of the disease and postacute sequelae. Myocarditis has also been reported after messenger ribonucleic acid (mRNA)-based COVID-19 vaccination, with the highest risk among adolescent boys and young adult men. Noninvasive imaging including cardiac MRI has a key role in identifying the presence of cardiovascular disease, evaluating for potential mechanisms of injury, stratifying risk of future adverse cardiovascular events, and potentially guiding treatment in patients with suspected cardiovascular injury after COVID-19 and vaccination. Patterns of injury identified at cardiac MRI after COVID-19 include myocarditis and pericarditis, myocardial ischemia, and infarction. Myocardial edema and late gadolinium enhancement have been described months after the initial infection in a minority of patients with persistent cardiac symptoms after COVID-19. In patients with myocarditis after receiving a COVID-19 vaccination, the most common pattern of late gadolinium enhancement is subepicardial at the basal inferolateral wall, and patients tend to have milder imaging abnormalities compared with those from other causes of myocarditis. This article describes the role of multimodality cardiac imaging and imaging findings in patients with acute and longer-term cardiovascular manifestations of COVID-19 and in patients with myocarditis after receiving an mRNA-based COVID-19 vaccination. ©RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has claimed the lives of 6.9 million people and infected over 765 million. It has become a major worldwide health problem and is also known to cause abnormalities in various systems, including the hematologic system. COVID-19 infection primarily affects the lower respiratory tract and can lead to a cascade of events, including a cytokine storm, intravascular thrombosis, and subsequent complications such as arterial and venous thromboses. COVID-19 can cause thrombocytopenia, lymphopenia, and neutrophilia, which are associated with worse outcomes. Prophylactic anticoagulation is essential to prevent complications and death rates associated with the virus's effect on the coagulation system. It is crucial to recognize these complications early and promptly start therapeutic anticoagulation to improve patient outcomes. While rare, COVID-19-induced disseminated intravascular coagulation (DIC) exhibits some similarities to DIC induced by sepsis. Lactate dehydrogenase (LDH), D-dimer, ferritin, and C-reactive protein (CRP) biomarkers often increase in serious COVID-19 cases and poor prognosis. Understanding the pathophysiology of the disease and identifying risk factors for adverse outcomes is critical for effective management of COVID-19.

Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems.

The capacity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to wreak havoc on the inflammatory and coagulation pathways via the cytokine storm has led to over 6.3 million fatalities globally. Based on recent data, the mechanism predominately involves the formation of microvascular thrombosis when pertaining to cardiovascular disease. However, a subset of coronavirus disease-2019 (COVID-19)-positive patients present emergently with acute ST-elevation myocardial infarction (STEMI) are found to have severe epicardial thrombosis which is refractory to traditional coronary revascularization. We have noted mortality in these patients presenting to our facility to be as high as 90% and all angiographically confirmed to have thrombus which was refractory to traditional therapy. We present a case series of COVID-19-positive patients presenting with STEMI found to have epicardial thrombus who were treated with different traditional STEMI therapies but with fatal outcomes. Other possible techniques including mechanical thrombectomy, optimizing traditional and nontraditional anticoagulation therapy with the use of early hemodynamic support may prove more efficacious to destroy thrombus and potentially improve mortality.

Globally, over 650 million people have had COVID-19 due to infection with the SARS-Cov-2 virus. Cardiac complications in the acute infectious and early recovery phase were recognized early in the pandemic, including myocardial injury and inflammation. With a decrease in the number of acute COVID-19 related deaths, there has been increased interest in postacute sequela of COVID-19 (PASC) and other longer-term cardiovascular complications. A proportion of patients recovered from COVID-19 have persistent cardiac symptoms and are at risk of cardiovascular disease. Cardiovascular imaging, including MRI, plays an important role in the detection of cardiovascular manifestations of COVID-19 in both the acute and longer-term phases after COVID-19. The purpose of this review is to highlight the role of cardiovascular imaging in the diagnosis and risk stratification of patients with acute and chronic cardiovascular manifestations of COVID-19 with a focus on cardiac MRI. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 3.

The novel coronavirus infection (COVID-19) causes a severe acute illness with the development of respiratory distress syndrome in some cases. COVID-19 is a global problem of mankind to this day. Among its most important aspects that require in-depth study are pathogenesis and molecular changes in severe forms of the disease. A lot of literature data is devoted to the pathogenetic mechanisms of COVID-19. Without dwelling in detail on some paths of pathogenesis discussed, we note that at present there are many factors of development and progression. Among them, this is the direct role of both viral non-coding RNAs (ncRNAs) and host ncRNAs. One such class of ncRNAs that has been extensively studied in COVID-19 is microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Moreover, Initially, it was believed that this COVID-19 was limited to damage to the respiratory system. It has now become clear that COVID-19 affects not only the liver and kidneys, but also the nervous system. In this review, we summarized the current knowledge of mechanisms, risk factors, genetics and neurologic impairments in COVID-19. In addition, we discuss and evaluate evidence demonstrating the involvement of miRNAs and lnRNAs in COVID-19 and use this information to propose hypotheses for future research directions.

Infection with SARS-CoV-2, the virus that causes COVID, is associated with numerous potential secondary complications. Global efforts have been dedicated to understanding the myriad potential cardiovascular sequelae which may occur during acute infection, convalescence, or recovery. Because patients often present with nonspecific symptoms and laboratory findings, cardiac imaging has emerged as an important tool for the discrimination of pulmonary and cardiovascular complications of this disease. The clinician investigating a potential COVID-related complication must account not only for the relative utility of various cardiac imaging modalities but also for the risk of infectious exposure to staff and other patients. Extraordinary clinical and scholarly efforts have brought the international medical community closer to a consensus on the appropriate indications for diagnostic cardiac imaging during this protracted pandemic. In this review, we summarize the existing literature and reference major societal guidelines to provide an overview of the indications and utility of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging for the diagnosis of cardiovascular complications of COVID.

The coronavirus disease 2019 (COVID-19) pandemic has caused the death of almost 7 million people worldwide. While vaccinations and new antiviral drugs have greatly reduced the number of COVID-19 cases, there remains a need for additional therapeutic strategies to combat this deadly disease. Accumulating clinical data have discovered a deficiency of circulating glutamine in patients with COVID-19 that associates with disease severity. Glutamine is a semi-essential amino acid that is metabolized to a plethora of metabolites that serve as central modulators of immune and endothelial cell function. A majority of glutamine is metabolized to glutamate and ammonia by the mitochondrial enzyme glutaminase (GLS). Notably, GLS activity is upregulated in COVID-19, favoring the catabolism of glutamine. This disturbance in glutamine metabolism may provoke immune and endothelial cell dysfunction that contributes to the development of severe infection, inflammation, oxidative stress, vasospasm, and coagulopathy, which leads to vascular occlusion, multi-organ failure, and death. Strategies that restore the plasma concentration of glutamine, its metabolites, and/or its downstream effectors, in conjunction with antiviral drugs, represent a promising therapeutic approach that may restore immune and endothelial cell function and prevent the development of occlusive vascular disease in patients stricken with COVID-19.

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.

This article provides an overview of various aspects related to post-COVID syndrome. Apart from its prevalence, symptoms and sequelae, risk determinants, and psychosocial implications, the pathogenesis of post-COVID condition is discussed in more detail. A focus on thrombo-inflammation in SARS-CoV-2 infection, the role of neutrophil extracellular traps, and the prevalence of venous thromboembolism is made. Moreover, COVID-19 and post-COVID syndrome in immunocompromising conditions, and the impact of vaccination on the prevention and treatment of post-COVID symptoms are reviewed. Autoimmunity is a hallmark of post-COVID syndrome, and, therefore, is another focus of this article. Thus, misdirected cellular and humoral immune responses can enhance the risk of latent autoimmunity in post-COVID syndrome. Facing the high prevalence of COVID-19 cases worldwide, it can be assumed that autoimmune disorders will increase globally over the next few years. Recent advances in identifying genetically determined variants may open the avenue for a better understanding of the susceptibility to and severity of SARS-CoV-2 infection and post-COVID syndrome.

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.

Venous thromboembolism (VTE) is known to be a common respiratory and/or cardiovascular complication in hospitalized patients with viral infections. Numerous studies have proven human immunodeficiency virus infection to be a prothrombotic condition. An elevated VTE risk has been observed in critically ill H1N1 influenza patients. VTE risk is remarkably higher in patients infected with the Hepatitis C virus in contrast to uninfected subjects. The elevation of D-dimer levels supported the association between Chikungunya and the Zika virus and the rise of clinical VTE risk. Varicella-zoster virus is a risk factor for both cellulitis and the consequent invasive bacterial disease which may take part in thrombotic initiation. Eventually, hospitalized patients infected with the coronavirus disease of 2019 (COVID-19), the cause of the ongoing worldwide pandemic, could mainly suffer from an anomalous risk of coagulation activation with enhanced venous thrombosis events and poor quality clinical course. Although the risk of VTE in nonhospitalized COVID-19 patients is not known yet, there are a large number of guidelines and studies on thromboprophylaxis administration for COVID-19 cases. This study aims to take a detailed look at the effect of viral diseases on VTE, the epidemiology of VTE in viral diseases, and the diagnosis and treatment of VTE.

Over the last few years, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) unleashed a global public health catastrophe that had a substantial influence on human physical and mental health, the global economy, and socio-political dynamics. SARS-CoV-2 is a respiratory pathogen and the cause of ongoing COVID-19 pandemic, which testified how unprepared humans are for pandemics. Scientists and policymakers continue to face challenges in developing ideal therapeutic agents and vaccines, while at the same time deciphering the pathology and immunology of SARS-CoV-2. Challenges in the early part of the pandemic included the rapid development of diagnostic assays, vaccines, and therapeutic agents. The ongoing transmission of COVID-19 is coupled with the emergence of viral variants that differ in their transmission efficiency, virulence, and vaccine susceptibility, thus complicating the spread of the pandemic. Our understanding of how the human immune system responds to these viruses as well as the patient groups (such as the elderly and immunocompromised individuals) who are often more susceptible to serious illness have both been aided by this epidemic. COVID-19 causes different symptoms to occur at different stages of infection, making it difficult to determine distinct treatment regimens employed for the various clinical phases of the disease. Unsurprisingly, determining the efficacy of currently available medications and developing novel therapeutic strategies have been a process of trial and error. The global scientific community collaborated to research and develop vaccines at a neck-breaking speed. This review summarises the overall picture of the COVID-19 pandemic, different mutations in SARS-CoV-2, immune response, and the treatment modalities against SARS-CoV-2.

The severity of COVID-19 commonly depends on age-related tissue stiffness. The aim was to review publications that explain the effect of microenvironmental extracellular matrix stiffness on cellular processes. Platelets and endothelial cells are mechanosensitive. Increased tissue stiffness can trigger cytokine storm with the upregulated expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin IL-6, and tissue integrity disruption, leading to enhanced virus entry and disease severity. Increased tissue stiffness in critically ill COVID-19 patients triggers platelet activation and initiates plague formation and thrombosis development. Cholesterol content in cell membrane increases with aging and further enhances tissue stiffness. Membrane cholesterol depletion decreases virus entry to host cells. Membrane cholesterol lowering drugs, such as statins or novel chitosan derivatives, have to be further developed for application in COVID-19 treatment. Statins are also known to decrease arterial stiffness mitigating cardiovascular diseases. Sulfated chitosan derivatives can be further developed for potential use in future as anticoagulants in prevention of severe COVID-19. Anti-TNF-α therapies as well as destiffening therapies have been suggested to combat severe COVID-19. The inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells pathway must be considered as a therapeutic target in the treatment of severe COVID-19 patients. The activation of mechanosensitive platelets by higher matrix stiffness increases their adhesion and the risk of thrombus formation, thus enhancing the severity of COVID-19.

The aim was to describe the small bowel morphology with conventional B-mode and elastography and additionally to evaluate dynamic effects of COVID-19 associated small bowel microvascularization using CEUS with color coded perfusion parameters.Thirteen patients with severe COVID-19 acute respiratory distress syndrome (ARDS) were investigated. 13 patients required intensive care treatment with mechanical ventilation. Five patients required extracorporeal membrane oxygenation (ECMO). Contrast-enhanced ultrasound (CEUS) was performed by an experienced investigator as a bolus injection of up to 2.4 ml sulfur hexafluoride microbubbles via a central venous catheter. In the parametric analysis of CEUS, the flare of microbubbles over time is visualized with colors. This is the first work using parametric analysis of CEUS to detect perfusion differences in the small bowel.Parametric analysis of CEUS in the intestinal phase was carried out, using DICOM loops for 20 seconds. In 5 patients, parametric analysis revealed intraindividual differences in contrast agent behavior in the small bowel region. Analogous to the computed tomography (CT) images parametric analysis showed regions of simultaneous hyper- and hypoperfusion of the small intestine in a subgroup of patients. In 5 patients, the parametric image of transmural global contrast enhancement was visualized.Our results using CEUS to investigate small bowel affection in COVID-19 suggest that in severe COVID-19 ARDS systemic inflammation and concomitant micro embolisms may lead to disruption of the epithelial barrier of the small intestine.This is the first study using parametric analysis of CEUS to evaluate the extent of small bowel involvement in severe COVID-19 disease and to detect microemboli. In summary, we show that in COVID-19 the small bowel may also be an important interaction site. This is in line with the fact that enterocytes have been shown to a plenitude of angiotensin converting enzyme (ACE)-2 receptors as entry sites of the virus.

Arterial dissections, which involve an abrupt tear in the wall of a major artery resulting in the intramural accumulation of blood, are a family of catastrophic disorders causing major, potentially fatal sequelae. Involving diverse vascular beds, including the aorta or coronary, cervical, pulmonary, and visceral arteries, each type of dissection is devastating in its own way. Traditionally they have been studied in isolation, rather than collectively, owing largely to the distinct clinical consequences of dissections in different anatomical locations - such as stroke, myocardial infarction, and renal failure. Here, we review the shared and unique features of these arteriopathies to provide a better understanding of this family of disorders. Arterial dissections occur commonly in the young to middle-aged, and often in conjunction with hypertension and/or migraine; the latter suggesting they are part of a generalized vasculopathy. Genetic studies as well as cellular and molecular investigations of arterial dissections reveal striking similarities between dissection types, particularly their pathophysiology, which includes the presence or absence of an intimal tear and vasa vasorum dysfunction as a cause of intramural hemorrhage. Pathway perturbations common to all types of dissections include disruption of TGF-β signaling, the extracellular matrix, the cytoskeleton or metabolism, as evidenced by the finding of mutations in critical genes regulating these processes, including LRP1, collagen genes, fibrillin and TGF-β receptors, or their coupled pathways. Perturbances in these connected signaling pathways contribute to phenotype switching in endothelial and vascular smooth muscle cells of the affected artery, in which their physiological quiescent state is lost and replaced by a proliferative activated phenotype. Of interest, dissections in various anatomical locations are associated with distinct sex and age predilections, suggesting involvement of gene and environment interactions in disease pathogenesis. Importantly, these cellular mechanisms are potentially therapeutically targetable. Consideration of arterial dissections as a collective pathology allows insight from the better characterized dissection types, such as that involving the thoracic aorta, to be leveraged to inform the less common forms of dissections, including the potential to apply known therapeutic interventions already clinically available for the former.