The COVID-19 pandemic has caused at least 780 million cases globally. While available treatments and vaccines have reduced the mortality rate, spread and evolution of the virus are ongoing processes. Despite extensive research, the long-term impact of SARS-CoV-2 infection is still poorly understood and requires further investigation. Routine analysis provides limited access to the tissues of patients, necessitating alternative approaches to investigate viral dissemination in the organism. We address this issue by implementing a whole-body in vivo imaging strategy to longitudinally assess the biodistribution of SARS-CoV-2. We demonstrate in a COVID-19 non-human primate model that a single injection of radiolabeled [89Zr]COVA1-27-DFO human monoclonal antibody targeting a preserved epitope of the SARS-CoV-2 spike protein allows longitudinal tracking of the virus by positron emission tomography with computed tomography (PET/CT). Convalescent animals exhibit a persistent [89Zr]COVA1-27-DFO PET signal in the lungs, as well as in the brain, three months following infection. This imaging approach also allows viral detection in various organs, including the airways and kidneys, of exposed animals during the acute infection phase. Overall, the technology we developed offers a comprehensive assessment of SARS-CoV-2 distribution in vivo and provides a promising approach for the non-invasive study of long-COVID pathophysiology.

Coronavirus disease 2019 (COVID-19) was declared a global pandemic in 2019. It remains uncertain to what extent COVID-19 effects the heart in heathy individuals. To evaluate the effect of the COVID-19 on cardiac structure and function in middle-aged and older individuals.

A single-centre prospective observational study enroled a total of 124 participants (84 with history of COVID-19 [COVID-19 group] and 40 without a history of COVID-19 [non-COVID group]). All participants underwent echocardiography with speckle tracking to assess cardiac structure and function at rest and during peak exercise.

There were no differences in left and right ventricular diastolic function (p ≥ 0.05) between the COVID-19 and non-COVID-19 groups. Participants in COVID-19 group demonstrated higher left ventricular mass (130 ± 39.8 vs. 113 ± 27.2 g, p = 0.008) and relative wall thickness (0.38 ± 0.07 vs. 0.36 ± 0.13, p = 0.049). Left ventricular global longitudinal strain was reduced in the COVID-19 group at rest and at peak-exercise (rest: 18.3 ± 2.01 vs. 19.3 ± 1.53%, p = 0.004; peak exercise: 19.1 ± 2.20 vs. 21.0 ± 1.58%, p ≤ 0.001). However, no difference was seen in resting left ventricular ejection fraction (58 ± 2.89 vs. 59 ± 2.51%, p = 0.565) between groups. Right ventricular fractional area change was reduced in the COVID-19 group (p = 0.012).

Cardiac structural and functional remodelling was observed in middle-aged and older otherwise healthy individuals with a history of COVID-19.

Myocarditis is a potentially fatal complication of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 myocarditis appears to have distinct inflammatory characteristics that distinguish it from other viral etiologies. COVID-19 myocarditis can present with symptoms ranging from dyspnea and chest pain to acute heart failure and death. It is critical to detect any cases of myocarditis, especially fulminant myocarditis, which can be characterized by signs of heart failure and arrhythmias. Serial troponins, echocardiography, and electrocardiograms should be performed as part of the initial workup for suspected myocarditis. The second step in detecting myocarditis is cardiac magnetic resonance imaging and endomyocardial biopsy. Treatment for COVID-19 myocarditis is still debatable; however, combining intravenous immunoglobulins and corticosteroids may be effective, especially in cases of fulminant myocarditis. Overall, more research is needed to determine the incidence of COVID-19 myocarditis, and the use of intravenous immunoglobulins and corticosteroids in combination requires large randomized controlled trials to determine efficacy. The purpose of this review is to summarize current evidence on the subject.

Viral myocarditis is associated with the development of dilated cardiomyopathy (DCM), left ventricular dysfunction, and heart failure. This review addresses the mechanisms of viral myocarditis and its treatment.

Electron microscopy (EM) was a popular diagnostic tool in the 1970s and early 80s. With the adoption of newer, less expensive techniques, such as immunohistochemistry, the role of EM in diagnostic surgical pathology has dwindled substantially. Nowadays, even in academic centers, EM interpretation is relegated to renal pathologists and the handful of (aging) pathologists with experience using the technique. As such, EM interpretation is truly arcane-understood by few and mysterious to many. Nevertheless, there remain situations in which EM is the best or only ancillary test to ascertain a specific diagnosis. Thus, there remains a critical need for the younger generation of surgical pathologists to learn EM interpretation. Recognizing this need, cardiac EM was made the theme of the Cardiovascular Evening Specialty Conference at the 2023 United States and Canadian Academy of Pathology (USCAP) annual meeting in New Orleans, Louisiana. Each of the speakers contributed their part to this article, the purpose of which is to review EM as it pertains to myocardial tissue and provide illustrative examples of the spectrum of ultrastructural cardiac pathology seen in storage/metabolic diseases, cardiomyopathies, infiltrative disorders, and cardiotoxicities.

The aim of this study was to see if the CHA2DS2-VASc score (Cardiac failure or dysfunction, Hypertension, Age ≥ 75 [Doubled], Diabetes, Stroke [Doubled]-Vascular disease, Age 65-74 and Sex category [Female] score) could have potential clinical relevance in predicting the outcome of hospitalization time, need for ICU hospitalization, survival time, in-hospital mortality, and mortality at 3 and 6 months after discharge home.

A retrospective analysis of 2183 patients with COVID-19 hospitalized at the COVID-19 Centre of the University Hospital in Wrocław, Poland, between February 2020 and June 2021, was performed. All medical records were collected as part of the COronavirus in LOwer Silesia-the COLOS registry project. The CHA2DS2-VASc score was applied for all subjects, and the patients were observed from admission to hospital until the day of discharge or death. Further information on patient deaths was prospectively collected following the 90 and 180 days after admission. The new risk stratification derived from differences in survival curves and long-term follow-up of our patients was obtained. Primary outcomes measured included in-hospital mortality and 3-month and 6-month all-cause mortality, whereas secondary outcomes included termination of hospitalization from causes other than death (home discharges/transfer to another facility or deterioration/referral to rehabilitation) and non-fatal adverse events during hospitalization.

It was shown that gender had no effect on mortality. Significantly shorter hospitalization time was observed in the group of patients with low CHA2DS2-VASc scores. Among secondary outcomes, CHA2DS2-VASc score revealed predictive value in both genders for cardiogenic (5.79% vs. 0.69%; p < 0.0001), stroke/TIA (0.48% vs. 9.92%; p < 0.0001), acute heart failure (0.97% vs. 18.18%; p < 0.0001), pneumonia (43% vs. 63.64%; p < 0.0001), and acute renal failure (7.04% vs. 23.97%; p < 0.0001). This study points at the usefulness of the CHA2DS2-VASc score in predicting the severity of the course of COVID-19.

Routine use of this scale in clinical practice may suggest the legitimacy of extending its application to the assessment of not only the risk of thromboembolic events in the COVID-19 cohort.

The risk of cardiovascular complications due to SARS-CoV-2 are significantly increased within the first 6 months of the infection. Patients with COVID-19 have an increased risk of death, and there is evidence that many may experience a wide range of post-acute cardiovascular complications. Our work aims to provide an update on current clinical aspects of diagnosis and treatment of cardiovascular manifestations during acute and long-term COVID-19.

SARS-CoV-2 has been shown to be associated with increased incidence of cardiovascular complications such as myocardial injury, heart failure, and dysrhythmias, as well as coagulation abnormalities not only during the acute phase but also beyond the first 30 days of the infection, associated with high mortality and poor outcomes. Cardiovascular complications during long-COVID-19 were found regardless of comorbidities such as age, hypertension, and diabetes; nevertheless, these populations remain at high risk for the worst outcomes during post-acute COVID-19. Emphasis should be given to the management of these patients. Treatment with low-dose oral propranolol, a beta blocker, for heart rate management may be considered, since it was found to significantly attenuate tachycardia and improve symptoms in postural tachycardia syndrome, while for patients on ACE inhibitors or angiotensin-receptor blockers (ARBs), under no circumstances should these medications be withdrawn. In addition, in patients at high risk after hospitalization due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. In this work we provide a comprehensive review on acute and post-acute COVID-19 cardiovascular complications, symptomatology, and pathophysiology mechanisms. We also discuss therapeutic strategies for these patients during acute and long-term care and highlight populations at risk. Our findings suggest that older patients with risk factors such as hypertension, diabetes, and medical history of vascular disease have worse outcomes during acute SARS-CoV-2 infection and are more likely to develop cardiovascular complications during long-COVID-19.

Coronavirus disease 2019 (COVID-19) has rapidly escalated into a global pandemic that primarily affects older and immunocompromised individuals due to underlying clinical conditions and suppressed immune responses. Furthermore, COVID-19 patients exhibit a spectrum of neurological symptoms, indicating that COVID-19 can affect the brain in a variety of manners. Many studies, past and recent, suggest a connection between viral infections and an increased risk of neurodegeneration, raising concerns about the neurological effects of COVID-19 and the possibility that it may contribute to Alzheimer's disease (AD) onset or worsen already existing AD pathology through inflammatory processes given that both COVID-19 and AD share pathological features and risk factors. This leads us to question whether COVID-19 is a risk factor for AD and how these two conditions might influence each other. Considering the extensive reach of the COVID-19 pandemic and the devastating impact of the ongoing AD pandemic, their combined effects could have significant public health consequences worldwide.

Advances in the etiological classification of myocarditis and inflammatory cardiomyopathy (ICM) have reached a consensus. However, the mechanism of myocarditis/ICM remains unclear, which affects the development of treatment and the improvement of outcome. Cellular transcription and metabolic reprogramming, and the interactions between cardiomyocytes and non-cardiomyocytes, such as the immune cells, contribute to the process of myocarditis/ICM. Recent efforts have been made by multi-omics techniques, particularly in single-cell RNA sequencing, to gain a better understanding of the cellular landscape alteration occurring in disease during the progression. This article aims to provide a comprehensive overview of the latest studies in myocarditis/ICM, particularly as revealed by single-cell sequencing.

Acute necrotizing encephalopathy (ANE) and myocarditis are both acute, life-threatening conditions that can be triggered by COVID-19. We report a case of sequential ANE and myocarditis following a COVID-19 infection.

A 27-year-old female patient was brought to the emergency department due to episodes of fever for two days and a 9-h altered state of consciousness. Her condition rapidly developed into stuporous and hemodynamic instability within serval hours. Veno-arterial extracorporeal membrane oxygenation (ECMO) was rapidly initiated with other supportive treatments. The following-up MRI showed bilateral, symmetrically distributed lesions in the brainstem, bilateral hippocampal regions, and bilateral basal ganglia, consistent with ANE. The diagnosis was confirmed through the detection of SARS-CoV-2 and the exclusion of other potential causes. After weeks of medical treatment, her condition stabilized, and she was transferred for further rehabilitation treatment.

This case study indicates that COVID-19 may simultaneously and rapidly affect the central nervous system and cardiovascular system, leading to poor outcomes. Accurate diagnosis and timely invasive bridging therapy, when necessary, can be lifesaving. Further exploration of potential mechanisms underlying COVID-19 central nervous system (CNS) and cardiovascular system manifestations will be important.

An increase in acute myocardial infarction (AMI)-related deaths has been reported during the COVID-19 pandemic. Despite evidence suggesting the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and AMI, the underlying mechanisms remain unclear. Here, we integrated mRNA and microRNA expression profiles related to SARS-CoV-2 infection and AMI from public databases. We then performed transcriptomic analysis using bioinformatics and systems biology approaches to explore the potential molecular mechanisms of SARS-CoV-2 infection affects AMI. First, twenty-one common differentially expressed genes (DEGs) were identified from SARS-CoV-2 infection and AMI patients in endothelial cells datasets and then we performed functional analysis to predict the roles of these DEGs. The functional analysis emphasized that the endothelial cell response to cytokine stimulus due to excessive inflammation was essential in these two diseases. Importantly, the tumor necrosis factor and interleukin-17 signaling pathways appeared to be integral factors in this mechanism. Interestingly, most of these common genes were also upregulated in transcriptomic datasets of SARS-CoV-2-infected cardiomyocytes, suggesting that these genes may be shared in cardiac- and vascular-related injuries. We subsequently built a protein-protein interaction network and extracted hub genes and essential modules from this network. At the transcriptional and post-transcriptional levels, regulatory networks with common DEGs were also constructed, and some key regulator signatures were further identified and validated. In summary, our research revealed that a highly activated inflammatory response in patients with COVID-19 might be a crucial factor for susceptibility to AMI and we identified some candidate genes and regulators that could be used as biomarkers or potential therapeutic targets.

Infectious diseases are a cause of major concern in this twenty-first century. There have been reports of various outbreaks like severe acute respiratory syndrome (SARS) in 2003, swine flu in 2009, Zika virus disease in 2015, and Middle East Respiratory Syndrome (MERS) in 2012, since the start of this millennium. In addition to these outbreaks, the latest infectious disease to result in an outbreak is the SARS-CoV-2 infection. A viral infection recognized as a respiratory illness at the time of emergence, SARS-CoV-2 has wreaked havoc worldwide because of its long-lasting implications like heart failure, sepsis, organ failure, etc., and its significant impact on the global economy. Besides the acute illness, it also leads to symptoms months later which is called long COVID or post-COVID-19 condition. Due to its ever-increasing prevalence, it has been a significant challenge to treat the affected individuals and manage the complications as well. Myocarditis, a long-term complication of coronavirus disease 2019 (COVID-19) is an inflammatory condition involving the myocardium of the heart, which could even be fatal in the long term in cases of progression to ventricular dysfunction and heart failure. Thus, it is imperative to diagnose early and treat this condition in the affected individuals. At present, there are numerous studies which are in progress, investigating patients with COVID-19-related myocarditis and the treatment strategies. This review focuses primarily on myocarditis, a life-threatening complication of COVID-19 illness, and endeavors to elucidate the pathogenesis, biomarkers, and management of long COVID myocarditis along with pipeline drugs in detail.

Coronavirus disease 2019 (COVID-19) has been a major global health concern since its emergence in 2019, with over 680 million confirmed cases as of April 2023. While COVID-19 has been strongly associated with the development of cardiovascular complications, the specific mechanisms by which viral infection induces myocardial dysfunction remain largely controversial as studies have shown that the severe acute respiratory syndrome coronavirus-2 can lead to heart failure both directly, by causing damage to the heart cells, and indirectly, by triggering an inflammatory response throughout the body. In this review, we summarize the current understanding of potential mechanisms that drive heart failure based on in vitro studies. We also discuss the significance of three-dimensional heart-on-a-chip technology in the context of the current and future pandemics.

We sought to determine the impact of right ventricular dysfunction on the outcomes of mechanically ventilated patients with COVID-19 requiring veno-venous extracorporeal membrane oxygenation.

Six academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 stratified by support with veno-venous extracorporeal membrane oxygenation during the first wave of the pandemic (March to August 2020). Echocardiograms performed for clinical indications were reviewed for right and left ventricular function. Baseline characteristics, hospitalization characteristics, and survival were compared.

The cohort included 424 mechanically ventilated patients with COVID-19, 126 of whom were cannulated for veno-venous extracorporeal membrane oxygenation. Right ventricular dysfunction was observed in 38.1% of patients who received extracorporeal membrane oxygenation and 27.4% of patients who did not receive extracorporeal membrane oxygenation with an echocardiogram. Biventricular dysfunction was observed in 5.5% of patients who received extracorporeal membrane oxygenation. Baseline patient characteristics were similar in both the extracorporeal membrane oxygenation and non-extracorporeal membrane oxygenation cohorts stratified by the presence of right ventricular dysfunction. In the extracorporeal membrane oxygenation cohort, right ventricular dysfunction was associated with increased inotrope use (66.7% vs 24.4%, P < .001), bleeding complications (77.1% vs 53.8%, P = .015), and worse survival independent of left ventricular dysfunction (39.6% vs 64.1%, P = .012). There was no significant difference in days ventilated before extracorporeal membrane oxygenation, length of hospital stay, hours on extracorporeal membrane oxygenation, duration of mechanical ventilation, vasopressor use, inhaled pulmonary vasodilator use, infectious complications, clotting complications, or stroke. The cohort without extracorporeal membrane oxygenation cohort demonstrated no statistically significant differences in in-hospital outcomes.

The presence of right ventricular dysfunction in patients with COVID-19-related acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation was associated with increased in-hospital mortality. Additional studies are required to determine if mitigating right ventricular dysfunction in patients requiring veno-venous extracorporeal membrane oxygenation improves mortality.

Myocarditis substantially increases the risk of ventricular arrhythmia. Approximately 30% of all ventricular arrhythmia cases in patients with myocarditis originate from the right ventricular outflow tract (RVOT). However, the role of NLRP3 signaling in RVOT arrhythmogenesis remains unclear.

Rats with myosin peptide-induced myocarditis (experimental group) were treated with an NLRP3 inhibitor (MCC950; 10 mg/kg, daily for 14 days) or left untreated. Then, they were subjected to electrocardiography and echocardiography. Ventricular tissue samples were collected from each rat's RVOT, right ventricular apex (RVA), and left ventricle (LV) and examined through conventional microelectrode and histopathologic analyses. In addition, whole-cell patch-clamp recording, confocal fluorescence microscopy, and Western blotting were performed to evaluate ionic currents, intracellular Ca2+ transients, and Ca2+-modulated protein expression in individual myocytes isolated from the RVOTs.

The LV ejection fraction was lower and premature ventricular contraction frequency was higher in the experimental group than in the control group (rats not exposed to myosin peptide). Myocarditis increased the infiltration of inflammatory cells into cardiac tissue and upregulated the expression of NLRP3; these observations were more prominent in the RVOT and RVA than in the LV. Furthermore, experimental rats treated with MCC950 (treatment group) improved their LV ejection fraction and reduced the frequency of premature ventricular contraction. Histopathological analysis revealed higher incidence of abnormal automaticity and pacing-induced ventricular tachycardia in the RVOTs of the experimental group than in those of the control and treatment groups. However, the incidences of these conditions in the RVA and LV were similar across the groups. The RVOT myocytes of the experimental group exhibited lower Ca2+ levels in the sarcoplasmic reticulum, smaller intracellular Ca2+ transients, lower L-type Ca2+ currents, larger late Na+ currents, larger Na+-Ca2+ exchanger currents, higher reactive oxygen species levels, and higher Ca2+/calmodulin-dependent protein kinase II levels than did those of the control and treatment groups.

Myocarditis may increase the rate of RVOT arrhythmogenesis, possibly through electrical and structural remodeling. These changes may be mitigated by inhibiting NLRP3 signaling.

In December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the COVID-19 pandemic, with millions of deaths worldwide. Vaccine breakthroughs in late 2020 resulted in the authorization of COVID-19 vaccines. While these vaccines have demonstrated efficacy, evidence from vaccine safety monitoring systems around the globe supported a causal association between COVID-19 vaccines, in particular those using mRNA technology, i.e., Moderna's mRNA-1273 and Pfizer-BioNTech's BNT162b2, and myocarditis.

This paper aims to investigate the epidemiology of mRNA COVID-19 vaccine-induced myocarditis, including age, ethnicity, and gender associations with these vaccines. It also discusses the immunopathophysiological mechanisms of mRNA COVID-19 vaccine-associated myocarditis and outlines principles of diagnosis, clinical presentation, and management.

A literature review was conducted using PubMed, Embase, and Queen Mary University of London Library Services databases. Search terms included "myocarditis," "coronavirus disease 2019," "SARS-CoV-2," "mRNA Covid-19 vaccines," "Covid vaccine-associated myocarditis," "epidemiology," "potential mechanisms," "myocarditis diagnosis," and "myocarditis management."

While the definite mechanism of mRNA COVID-19 vaccine-associated myocarditis remains ambiguous, potential mechanisms include molecular mimicry of spike proteins and activation of the adaptive immune response with dysregulated cytokine expression. Male predominance in COVID-19 vaccine-induced myocarditis may be attributed to sex hormones, variations in inflammatory reactions, coagulation states based on gender, and female-specific protective factors. Moreover, an analysis of diagnostic and management strategies reveals a lack of consensus on acute patient presentation management.

In contrast to viral infections that stand as the predominant etiological factor for myocarditis with more severe consequences, the mRNA COVID-19 vaccination elicits a mild and self-limiting manifestation of the condition. There is currently insufficient evidence to confirm the definite underlying mechanism of COVID-19 vaccine-associated myocarditis. Further research is needed to develop preventive and therapeutic solutions in this context.

Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.

In the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, significant attention was given to pulmonary manifestations. However, cardiac involvement is increasingly recognized as a critical factor influencing the prognosis, leading to myocardial damage, heart failure, acute coronary syndromes, potentially lethal arrhythmic events, and sudden cardiac death. Despite these findings, there is a lack of studies detailing the necroscopic, macroscopic, and microscopic cardiac changes associated with SARS-CoV-2. This study aimed to investigate the presence of SARS-CoV-2 viral proteins in cardiac tissue using immunohistochemical techniques to assess viral tropism. The analysis of cardiac tissue samples from deceased subjects, in different stages of conservation, confirmed to be positive for SARS-CoV-2 via reverse transcriptase-polymerase chain reaction (RT-PCR), showed immunopositivity for the SARS-CoV-2-NP viral antigen in 33% of cases. Notably, the presence of leukocyte infiltrates sufficient for diagnosing lymphocytic myocarditis was not observed. The central proinflammatory cytokines involved in the pathogenetic mechanism of coronavirus disease 19 (COVID-19) were researched using the immunohistochemical method. A significant increase in cytokine expression was detected, indicating myocardial involvement and dysfunction during SARS-CoV-2 infection. These findings suggest that the immunohistochemical detection of SARS-CoV-2 viral antigens and inflammatory cytokine expression in cardiac tissue could be crucial for a proper forensic assessment of the cause of death, even in sudden cardiac death.

Despite tremendous progress in the development of mature heart-on-a-chip models, human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip with circulating immune cells to model severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced acute myocarditis. We observed hallmarks of coronavirus disease (COVID-19)-induced myocardial inflammation, as the presence of immune cells augmented the secretion of proinflammatory cytokines, triggered progressive impairment of contractile function, and altered intracellular calcium transients. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the heart-on-a-chip and then validated in COVID-19 patients with low left ventricular ejection fraction, demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation-induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2-induced myocardial inflammation, we established that administration of endothelial cell-derived exosomes effectively rescued the contractile deficit, normalized calcium handling, elevated the contraction force, and reduced the ccf-mtDNA and cytokine release via Toll-like receptor-nuclear factor κB signaling axis.

This study aimed to investigate factors associated with time-to-referral due to worsening symptoms in patients with laboratory-confirmed COVID-19 in southern Thailand. While underlying diseases have been evaluated to assess COVID-19 severity, the influence of vaccinations and treatments is also crucial.

A cohort of 8,638 patients quarantined in home or community isolation with laboratory-confirmed COVID-19 was analyzed. Survival analysis and the Cox proportional hazard ratio were employed to assess factors influencing time-toreferral.

Age ≥ 60 years, neurologic disorders, cardiovascular disease, and human immunodeficiency virus infection were identified as significant risk factors for severe COVID-19 referral. Patients who received full- or booster-dose vaccinations had a lower risk of experiencing severe symptoms compared to unvaccinated patients. Notably, individuals vaccinated during the Omicron-dominant period had a substantially lower time-to-referral than those unvaccinated during the Delta-dominant period. Moreover, patients vaccinated between 1 and 6 months prior to infection had a significantly lower risk of time-to-referral than the reference group.

These findings demonstrate early intervention in high-risk COVID-19 patients and the importance of vaccination efficacy to reduce symptom severity. The study provides valuable insights for guiding future epidemic management strategies and optimising patient care during infectious disease outbreaks.

One of the severe complications of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is myocarditis. However, the characteristics of fulminant myocarditis with SARS-CoV-2 infection are still unclear. We systematically reviewed the previously reported cases of fulminant myocarditis associated with SARS-CoV-2 infection from January 2020 to December 2022, identifying 108 cases. Of those, 67 were male and 41 female. The average age was 34.8 years; 30 patients (27.8%) were ≤20 years old, whereas 10 (9.3%) were ≥60. Major comorbidities included hypertension, obesity, diabetes mellitus, asthma, heart disease, gynecologic disease, hyperlipidemia, and connective tissue disorders. Regarding left ventricular ejection fraction (LVEF) at admission, 93% of the patients with fulminant myocarditis were classified as having heart failure with reduced ejection fraction (LVEF ≤ 40%). Most of the cases were administered catecholamines (97.8%), and mechanical circulatory support (MCS) was required in 67 cases (62.0%). The type of MCS was extracorporeal membrane oxygenation (n = 56, 83.6%), percutaneous ventricular assist device (Impella®) (n = 19, 28.4%), intra-aortic balloon pumping (n = 12, 12.9%), or right ventricular assist device (n = 2, 3.0%); combination of these devices occurred in 20 cases (29.9%). The average duration of MCS was 7.7 ± 3.8 days. Of the 76 surviving patients whose cardiac function was available for follow-up, 65 (85.5%) recovered normally. The overall mortality rate was 22.4%, and the recovery rate was 77.6% (alive: 83 patients, dead: 24 patients; outcome not described: 1 patient).

Clinical evidence reveals that manifestations of endothelial dysfunction are widely observed in COVID-19 and long-COVID patients. However, whether these detrimental effects are caused by direct infection of the endothelium or are indirectly mediated by systemic inflammation has been a matter of debate. It has been well acknowledged that endothelial cells (ECs) of the cardiovascular system ubiquitously express the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), yet accumulating evidence suggests that it is more predominantly expressed by pericytes and vascular smooth muscle cells of the mammalian blood vessel. Besides, replicative infection of ECs by SARS-CoV-2 has yet to be demonstrated both in vitro and in vivo. In this study, we review latest research on endothelial ACE2 expression in different vascular beds, and the heterogeneity in various EC subsets with differential ACE2 expression in response to SARS-CoV-2. We also discuss ACE2-independent alternative mechanisms underlying endothelial activation in COVID-19, and the clinical manifestations of SARS-CoV-2-induced endothelial dysfunction. Altogether, understanding ACE2-dependent and ACE2-independent mechanisms driving SARS-CoV-2-induced vascular dysfunction would shed light on strategies of more effective therapies targeting cardiovascular complications associated with COVID-19.

To adequately prepare against imminent disease outbreaks from diverse and ever-changing viral pathogens, improved experimental models that can accurately recapitulate host-virus responses and disease pathogenesis in human are essential. Organoid platforms have emerged in recent years as amenable in vitro tools that can bridge the limitations of traditional 2D cell lines and animal models for viral disease research. We highlight in this review the key insights that have contributed by organoid models to virus research, the limitations that exist in current platforms, and outline novel approaches that are being applied to address these shortcomings.

Long coronavirus disease (COVID) is the development or persistence of symptoms after an acute SARS-CoV-2 (COVID-19) infection. Fewer patients are developing acute COVID-19 infections, but patients with long COVID continue to have alarming long-term sequelae. Many cardiac magnetic resonance imaging studies show significant changes in cardiac structure after a COVID-19 infection, suggestive of an increased burden of many cardiovascular diseases, notably myocarditis. The pathophysiology of COVID-19 requires viral binding to angiotensin-converting enzyme 2 protein receptors throughout the body, which are upregulated by inflammation. Consequently, the numerous preexisting conditions that worsen or prolong inflammation enhance this binding and have differing effects on patients based on their unique immune systems. These pathophysiological changes drive long COVID cardiac sequelae such as inappropriate sinus tachycardia, postural orthostatic tachycardia, and other types of orthostatic intolerance. Increased screening for long COVID and low-risk interventions such as exercise regimens could alleviate the suffering endured by patients with long COVID. Many studies such as the Researching COVID to Enhance Recovery Initiative (RECOVER) trials at the National Institutes of Health are exploring potential treatments for long COVID patients.

COVID-19 is primarily a respiratory disease, but numerous studies have indicated the involvement of various organ systems during the course of illness. We conducted a comprehensive review of atypical complications of COVID-19 with their incidence range (IR) and their impact on hospitalization and mortality rates. We identified 97 studies, including 55 research articles and 42 case studies. We reviewed four major body organ systems for various types of atypical complications: (i) Gastro-intestinal (GI) and hepatobiliary system, e.g., bowel ischemia/infarction (IR: 1.49-83.87%), GI bleeding/hemorrhage (IR: 0.47-10.6%), hepatic ischemia (IR: 1.0-7.4%); (ii) Neurological system, e.g., acute ischemic stroke/cerebral venous sinus thrombosis/cerebral hemorrhage (IR: 0.5-90.9%), anosmia (IR: 4.9-79.6%), dysgeusia (IR: 2.8-83.38%), encephalopathy/encephalitis with or without fever and hypoxia (IR: 0.19-35.2%); (iii) Renal system, e.g., acute kidney injury (AKI)/acute renal failure (IR: 0.5-68.8%); (iv) Cardiovascular system, e.g., acute cardiac injury/non-coronary myocardial injury (IR: 7.2-55.56%), arrhythmia/ventricular tachycardia/ventricular fibrillation (IR: 5.9-16.7%), and coagulopathy/venous thromboembolism (IR: 19-34.4%). This review encourages and informs healthcare practitioners to keenly monitor COVID-19 survivors for these atypical complications in all major organ systems and not only treat the respiratory symptoms of patients. Post-COVID effects should be monitored, and follow-up of patients should be performed on a regular basis to check for long-term complications.

Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic fluid removal is disturbed during pathological processes leading to inflammation, but also in hypoxia or due to alterations in vascular perfusion and coagulability. The degradation of the glycocalyx as the main component of the endothelial filtration barrier as well as pericyte disintegration results in the accumulation of interstitial and intracellular water. Moreover, lymphatic dysfunction evokes an increase in metabolic waste products, cytokines and inflammatory cells in the interstitial space contributing to myocardial oedema formation. This leads to myocardial stiffness and impaired contractility, eventually resulting in cardiomyocyte apoptosis, myocardial remodelling and fibrosis. The following article reviews pathophysiological inflammatory processes leading to myocardial oedema including myocarditis, ischaemia-reperfusion injury and viral infections with a special focus on the pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications including potential long-term effects due to viral persistence (long COVID), as well as treatment options, are discussed.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), quickly spread worldwide and led to over 581 million confirmed cases and over 6 million deaths as 1 August 2022. The binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor is the primary mechanism of SARS-CoV-2 infection. Not only highly expressed in the lung, ACE2 is also widely distributed in the heart, mainly in cardiomyocytes and pericytes. The strong association between COVID-19 and cardiovascular disease (CVD) has been demonstrated by increased clinical evidence. Preexisting CVD risk factors, including obesity, hypertension, and diabetes etc., increase susceptibility to COVID-19. In turn, COVID-19 exacerbates the progression of CVD, including myocardial damage, arrhythmia, acute myocarditis, heart failure, and thromboembolism. Moreover, cardiovascular risks post recovery and the vaccination-associated cardiovascular problems have become increasingly evident. To demonstrate the association between COVID-19 and CVD, this review detailly illustrated the impact of COVID-19 on different cells (cardiomyocytes, pericytes, endothelial cells, and fibroblasts) in myocardial tissue and provides an overview of the clinical manifestations of cardiovascular involvements in the pandemic. Finally, the issues related to myocardial injury post recovery, as well as vaccination-induced CVD, has also been emphasized.

Patients diagnosed with coronavirus disease (CVD) who experience cardiovascular complications or have pre-existing cardiovascular disease are at an increased risk of death. The primary heart-related consequences associated with COVID-19 encompass venous thromboembolism, shock, heart failure, arrhythmias, myocarditis, acute myocardial infarction, and acute cardiac damage. The coronavirus has the potential to induce cardiovascular complications or exacerbate pre-existing CVD through various mechanisms. These mechanisms include dysregulation of the renin-angiotensin-aldosterone system; direct viral toxicity; damage to endothelial cells; formation of blood clots and subsequent inflammation, a phenomenon known as thromboinflammation; an excessive immune response known as cytokine storm; and an imbalance between the demand and supply of oxygen in the body. In this study, we comprehensively analyze the cardiovascular symptoms, histology, and underlying mechanisms associated with COVID-19. Our aim is to contribute to the identification of future research objectives and aid in the advancement of therapeutic management approaches.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a global health threat in 2019. An important feature of the disease is that multiorgan symptoms of SARS-CoV-2 infection persist after recovery. Evidence indicates that people who recovered from COVID-19, even those under the age of 65 years without cardiovascular risk factors such as smoking, obesity, hypertension, and diabetes, had a significantly increased risk of cardiovascular disease for up to one year after diagnosis. Therefore, it is important to closely monitor individuals who have recovered from COVID-19 for potential cardiovascular damage that may manifest at a later stage. Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the production of reactive oxygen species (ROS) and increased lipid peroxide levels. Several studies have demonstrated that ferroptosis plays an important role in cancer, ischemia/reperfusion injury (I/RI), and other cardiovascular diseases. Altered iron metabolism, upregulation of reactive oxygen species, and glutathione peroxidase 4 inactivation are striking features of COVID-19-related cardiovascular injury. SARS-CoV-2 can cause cardiovascular ferroptosis, leading to cardiovascular damage. Understanding the mechanism of ferroptosis in COVID-19-related cardiovascular injuries will contribute to the development of treatment regimens for preventing or reducing COVID-19-related cardiovascular complications. In this article, we go over the pathophysiological underpinnings of SARS-CoV-2-induced acute and chronic cardiovascular injury, the function of ferroptosis, and prospective treatment approaches.

Coronavirus disease 2019 (COVID-19) has been declared a new pandemic in March 2020. Although most patients are asymptomatic, those with underlying cardiovascular comorbidities may develop a more severe systemic infection which is often associated with fatal pneumonia. Nonetheless, neurological and cardiovascular manifestations could be present even without respiratory symptoms. To date, no COVID-19-specific drugs are able for preventing or treating the infection and generally, the symptoms are relieved with general anti-inflammatory drugs. Angiotensin-converting-enzyme 2 (ACE2) may function as the receptor for virus entry within the cells favoring the progression of infection in the organism. On the other hand, ACE2 is a relevant enzyme in renin angiotensin system (RAS) cascade fostering Ang1-7/Mas receptor activation which promotes protective effects in neurological and cardiovascular systems. It is known that RAS is composed by two functional countervailing axes the ACE/AngII/AT1 receptor and the ACE/AngII/AT2 receptor which counteracts the actions mediated by AngII/AT1 receptor by inducing anti-inflammatory, antioxidant and anti-growth functions. Subsequently an "alternative" ACE2/Ang1-7/Mas receptor axis has been described with functions similar to the latter protective arm. Here, we discuss the neurological and cardiovascular effects of COVID-19 highlighting the role of the stimulation of the RAS "alternative" protective arm in attenuating pulmonary, cerebral and cardiovascular damages. In conclusion, only two clinical trials are running for Mas receptor agonists but few other molecules are in preclinical phase and if successful these drugs might represent a successful strategy for the treatment of the acute phase of COVID-19 infection.

One of the most common complications of coronavirus disease 2019 (COVID-19) is myocardial injury, and although its cause is unclear, it can alter the heart's contractility. This study aimed to characterize the ventricular and atrial strain in patients who recovered from COVID-19 using cardiovascular magnetic resonance feature-tracking (CMR-FT).

In this single-center study, we assessed left ventricle (LV) and right ventricular (RV) global circumferential strain (GCS), global longitudinal strain (GLS), global radial strain (GRS), left atrial (LA) and right atrial (RA) longitudinal strain (LS) parameters by CMR-FT. The student's t-test and Wilcoxon rank-sum test were used to compare the variables.

We compared seventy-two patients who recovered from COVID-19 (49 ± 16 years) to fifty-four controls (49 ± 12 years, p = 0.752). The patients received a CMR examination 48 (34 to 165) days after the COVID-19 diagnosis. 28% had LGE. Both groups had normal LV systolic function. Strain parameters were significantly lower in the COVID-19 survivors than in controls.

Patients who recovered from COVID-19 exhibited significantly lower strain in the left ventricle (through LVGCS, LVGLS, LVGRS), right ventricle (through RVGLS and RVGRS), left atrium (through LALS), and right atrium (through RALS) than controls.

The COVID-19 pandemic has impacted the world that was not previously conceivable. In early 2020, hospitals on all continents were overwhelmed with patients afflicted with this novel virus, with unanticipated mortality worldwide. The virus has had a deleterious effect, particularly the respiratory and cardiovascular systems. Cardiovascular biomarkers demonstrated an array of cardiovascular insults from hypoxia to inflammatory and perfusion abnormalities of the myocardium to life-threatening arrhythmias and heart failure. Patients were at increased risk of a pro-thrombotic state early in the course of the disease. Cardiovascular imaging became a primary tool in diagnosing, prognosing and risk-stratifying patients. Transthoracic echocardiography became the initial imaging modality in management of cardiovascular implications. In addition to cardiac function, LV longitudinal strain (LVLS) and right ventricular free wall strain (RVFWS) were indicators of increased morbidly and mortality. Cardiac MRI has become the diagnostic cardiovascular imaging for myocardial injury and tissue evaluation in the age of COVID-19.

Myocardial injury (MI) is frequent in critically ill patients with COVID-19, but its pathogenesis remains unclear. We hypothesized that MI is not solely due to viral infection by SARS-CoV-2 but rather due to the common pathophysiological mechanisms associated with severe pulmonary infections and respiratory failure. This contemporary cohort study was designed to compare the incidence of MI in patients with acute respiratory failure caused by COVID-19 to patients with other pulmonary infections. In addition, we aimed to investigate whether MI was a distinct risk factor for in-hospital mortality in patients with COVID-19 compared to those with non-COVID-19 infections. This study included 1444 patients with COVID-19 (55.5% men; age 58 (46;68) years) and 182 patients with other pulmonary infections (46.9% men; age 62 (44;73) years). The incidence of MI at ICU admission was lower in COVID-19 patients (36.4%) compared to non-COVID-19 patients (56%), and this difference persisted after adjusting for age, sex, coronary artery disease, heart failure, SOFA score, lactate, and C-reactive protein (RR 0.84 (95% CI, 0.71-0.99)). MI at ICU admission was associated with a 59% increase in mortality (RR 1.59 (1.36-1.86); p < 0.001), and there was no significant difference in the mortality between patients with COVID-19 and those with other pulmonary infections (p = 0.271). We concluded that MI is less frequent in patients with critical COVID-19 pneumonia and respiratory failure compared to those with other types of pneumonia. The occurrence of MI is a significant risk factor for in-hospital mortality, regardless of the etiology of the pulmonary infection.

Desmoglein-2 (DSG2) has emerged as a potential biomarker for coronavirus disease 2019 (COVID-19) complications, particularly cardiac and cardiovascular involvement. The expression of DSG2 in lung tissues has been detected at elevated levels, and circulating DSG2 levels correlate with COVID-19 severity. DSG2 may contribute to myocardial injury, cardiac dysfunction and vascular endothelial dysfunction in COVID-19. Monitoring DSG2 levels could aid in risk stratification, early detection and prognostication of COVID-19 complications. However, further research is required to validate DSG2 as a biomarker. Such research will aim to elucidate its precise role in pathogenesis, establishing standardized assays for its measurement and possibly identifying therapeutic targets.

The recent COVID-19 (Coronavirus Disease 2019) pandemic by SARS-CoV2 infection has caused millions of deaths and hospitalizations across the globe. In the early pandemic phases, the infection had been initially considered a primary pulmonary disease. However, increasing evidence has demonstrated a wide range of possible cardiac involvement. Most of systemic and cardiac damage is likely sustained by a complex interplay between inflammatory, immune-related and thrombotic mechanisms. Biventricular failure and myocardial damage with elevation of cardiac biomarkers have been reported in COVID-19 patients, although histological demonstration of acute myocarditis has been rarely documented. Indeed while cardiac magnetic resonance findings include different patterns of myocardial involvement in terms of late gadolinium enhancement, histological data from necropsy and endomyocardial biopsy showed peculiar inflammatory patterns, mostly composed by macrophages. On the other hand COVID-19 vaccines based on mRN technology have been also associated with increased risk of myocarditis. COVID-19 and mRNA vaccine-related myocarditis present different clinical and imaging presentations and recent data suggest the presence of distinctive immunological mechanisms involved.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV-2 variants, has become a global pandemic resulting in significant morbidity and mortality. Severe cases of COVID-19 are characterized by hypoxemia, hyper-inflammation, cytokine storm in lung. Clinical studies have reported an association between COVID-19 and cardiovascular disease (CVD). Patients with CVD tend to develop severe symptoms and mortality if contracted COVID-19 with further elevations of cardiac injury biomarkers. Furthermore, COVID-19 itself can induce and promoted CVD development, including myocarditis, arrhythmia, acute coronary syndrome, cardiogenic shock, and venous thromboembolism. Although the direct etiology of SARS-CoV-2 induced cardiac injury remains unknown and under-investigated, it is suspected that it is related to myocarditis, cytokine-mediated injury, microvascular injury, and stress-related cardiomyopathy. Despite vaccinations having provided the most effective approach to reducing mortality overall, an adapted treatment paradigm and regular monitoring of cardiac injury biomarkers is critical for improving outcomes in vulnerable populations at risk for severe COVID-19. In this review, we focus on the latest progress in clinic and research on the cardiovascular complications of COVID-19 and provide a perspective of treating cardiac complications deriving from COVID-19 in Emergency Medicine.

Cardiovascular disease continues to take more human lives than all cancer combined, prompting the need for improved research models and treatment options. Despite a significant progress in development of mature heart-on-a-chip models of fibrosis and cardiomyopathies starting from induced pluripotent stem cells (iPSCs), human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip system with circulating immune cells to model SARS-CoV-2-induced acute myocarditis. Briefly, we observed hallmarks of COVID-19-induced myocardial inflammation in the heart-on-a-chip model, as the presence of immune cells augmented the expression levels of proinflammatory cytokines, triggered progressive impairment of contractile function and altered intracellular calcium transient activities. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the in vitro heart-on-a-chip model and then validated in COVID-19 patients with low left ventricular ejection fraction (LVEF), demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2 induced myocardial inflammation, we established that administration of human umbilical vein-derived EVs effectively rescued the contractile deficit, normalized intracellular calcium handling, elevated the contraction force and reduced the ccf- mtDNA and chemokine release via TLR-NF-kB signaling axis.

This review aims to comprehensively explore the clinical characteristics of COVID-19-related cardiac injury and examine the potential mechanisms underlying cardiac injury in patients affected by COVID-19.

The COVID-19 pandemic has primarily been associated with severe respiratory symptoms. However, emerging evidence has indicated that a significant number of COVID-19 patients also experience myocardial injury, leading to conditions such as acute myocarditis, heart failure, acute coronary syndrome, and arrhythmias. The incidence of myocardial injury is notably higher in patients with preexisting cardiovascular diseases. Myocardial injury often manifests with elevated levels of inflammation biomarkers, as well as abnormalities observed on electrocardiograms and echocardiograms. COVID-19 infection has been found to be associated with myocardial injury, which can be attributed to several pathophysiological mechanisms. These mechanisms include injury caused by hypoxia, resulting from respiratory compromise, a systemic inflammatory response triggered by the infection, and direct attack on the myocardium by the virus itself. Furthermore, the angiotensin-converting enzyme 2 (ACE2) receptor plays a crucial role in this process. Early recognition, prompt diagnosis, and a comprehensive understanding of the underlying mechanisms are essential for effectively managing and reducing the mortality associated with myocardial injury in COVID-19 patients.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has enveloped the world into an unprecedented pandemic since 2019. Significant damage to multiple organs, such as the lungs and heart, has been extensively reported. Cardiovascular injury by ACE2 downregulation, hypoxia-induced myocardial injury, and systemic inflammatory responses complicate the disease. This virus causes multisystem inflammatory syndrome in children with similar symptoms to adult SARS-CoV-2-induced myocarditis. While several treatment strategies and immunization programs have been implemented to control the menace of this disease, the risk of long-term cardiovascular damage associated with the disease has not been adequately assessed. In this review, we surveyed and summarized all the available information on the effects of COVID-19 on cardiovascular health as well as comorbidities. We also examined several case reports on post-immunization cardiovascular complications.

The diagnosis and specific and causal treatment of myocarditis and inflammatory cardiomyopathy remain a major clinical challenge. Despite the rapid development of new imaging techniques, endomyocardial biopsies remain the gold standard for accurate diagnosis of inflammatory myocardial disease. With the introduction and continued development of immunohistochemical inflammation diagnostics in combination with viral nucleic acid testing, myocarditis diagnostics have improved significantly since their introduction. Together with new technologies such as miRNA and gene expression profiling, quantification of specific immune cell markers, and determination of viral activity, diagnostic accuracy and patient prognosis will continue to improve in the future. In this review, we summarize the current knowledge on the pathogenesis and diagnosis of myocarditis and inflammatory cardiomyopathies and highlight future perspectives for more in-depth and specialized biopsy diagnostics and precision, personalized medicine approaches.