To describe the experiences of people living with neuropsychological symptomatology associated with long-COVID, as well as identifying the barriers they encounter in their daily lives and the strategies they develop to deal with them.

Descriptive qualitative study following an interpretative phenomenological perspective.

Primary Care Centres in the Northern Metropolitan Area of Barcelona and the Germans Trias i Pujol University Hospital (Badalona), Spain.

34 adults with any persistent neuropsychological symptoms of COVID-19 (>12 weeks since disease onset).

In-depth individual interviews were conducted following a script of open-ended questions to elicit their narratives around the research objective.

3 clusters detailing the life impact of long-COVID and its neuropsychological symptomatology were identified: long-COVID as life-breaking and life-changing; coping strategies; and (ac)knowledge (of) the emerging subjectivity.

From the participants' accounts and the existing literature emerges the relevance of critically integrating lessons learned from analogous syndromes such as fibromyalgia and chronic fatigue, as well as involving patients in the design and implementation (even at the consultation level) of clinical practices that raise awareness of these neuropsychological sequelae (psychoeducation) both to other patients and to caregivers and professionals. This would facilitate a greater and better specialised psychological approach and reduce the stigma that still accompanies the condition.

Emerging and re-emerging viruses are currently known as a major public health issue. These viruses can cause various human complications such as cardiovascular diseases (CVDs), both in adults and pediatric populations. Although various CVDs have been previously reported for emerging and re-emerging viruses, the mechanisms underlying these complications remain relatively unknown. Children and infants, while commonly developing less severe symptoms, may experience notable cardiovascular manifestations during infections caused by emerging and re-emerging viral infections, which can result in both acute and long-term complications. The present review aims to discuss various cardiovascular complications linked to emerging and re-emerging viral pathogens (including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV)) such as arrhythmias, myocarditis, vascular disorders, and thromboembolic conditions, particularly among the pediatric population. This review also addresses the potential mechanisms by which SARS-CoV-2, DENV, ZIKV, and CHIKV may impact the cardiovascular system and their clinical implications. Moreover, it discusses the diagnostic challenges for viral-caused cardiovascular disorders in children, owing to their common subtle or atypical manifestations. Finally, it addresses the present therapeutic specifically used for pediatric cases.

COVID-19, caused by the SARS-CoV-2, poses significant global health challenges. A key player in its pathogenesis is the nucleocapsid protein (NP), which is crucial for viral replication and assembly. While NPs from other coronaviruses, such as SARS-CoV and MERS-CoV, are known to increase inflammation and cause acute lung injury, the specific effects of the SARS-CoV-2 NP on host cells remain largely unexplored. Recent findings suggest that the NP acts as a pathogen-associated molecular pattern (PAMP) that binds to Toll-like receptor 2 (TLR2), activating NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) signaling pathways. This activation is particularly pronounced in severe COVID-19 cases, leading to elevated levels of soluble ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1), which contribute to endothelial dysfunction and multiorgan damage. Furthermore, the NP is implicated in hyperinflammation and thrombosis-key factors in COVID-19 severity and long COVID. Its potential to bind with MASP-2 (mannan-binding lectin serine protease 2) may also be linked to persistent symptoms in long COVID patients. Understanding these mechanisms, particularly the role of the NP in thrombosis, is essential for developing targeted therapies to manage both acute and chronic effects of COVID-19 effectively. This comprehensive review aims to elucidate the multifaceted roles of the NP, highlighting its contributions to viral pathogenesis, immune evasion, and the exacerbation of thrombotic events, thereby providing insights into potential therapeutic targets for mitigating the severe and long-term impacts of COVID-19.

Interstitial capillary congestion and diffuse alveolar damage (DAD) were frequently observed in patients who died from Coronavirus disease-19 (COVID-19). The research question pertains to observing these findings in COVID-19-positive patients lacking pulmonary symptoms. The histological examination of lung samples from COVID-19-positive patients who do not succumb to COVID-19-related pulmonary complications can provide an answer. This study analyzed postmortem lung autopsy samples from individuals who did not succumb to COVID-19-related pulmonary complications. The research article aimed to examine the morphological variations in postmortem lung samples of COVID-19 patients who did not succumb to the disease, and to compare these changes with those observed in cases of COVID-19-related deaths, utilizing existing English literature.

This prospective study included subjects who died without complications from COVID-19-related injuries, had positive real-time polymerase chain reaction throat swabs, and exhibited no pulmonary manifestation of COVID-19 disease. A comprehensive histomorphological analysis of the lung samples was conducted.

A total of 20 subjects were enrolled in this study. Capillary congestion was the most prevalent histomorphological change observed in lung autopsies, seen in 90% (18/20) of cases, followed by emphysema in 75% (15/20) and the acute phase of DAD in 25% (5/20) of cases. Acute bronchopneumonia and fibrotic nodules were identified in 20% (4/20) and 10% (2/20) of the study population, respectively.

In postmortem lung autopsy of COVID-19-positive patients lacking symptomatic pulmonary issues, capillary congestion, diffuse alveolar destruction, and emphysema were prevalent. The findings indicate that COVID-19 exhibits varied responses to damage and inflammation that do not correlate with mortality. This study enhances the understanding of pathophysiological lung tissue variations in COVID-19 patients who have non-COVID-19-related deaths, potentially educating forensic pathologists and supporting future research endeavors.

As the world grapples with the coronavirus-19 (COVID) pandemic, more reports are coming in regarding Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in endotheliopathy. It is a vascular condition in which endothelial cell injury or damage inflicts anatomical and functional changes in the endothelium, significantly impacting the physiological process and function. Previously, it was assumed that SARS-CoV-2 infects respiratory epithelial cells via spike glycoproteins present on the surface of the virus. However, severe cases and different autopsy studies described the clandestine role of this virus in infecting endothelial cells other than epithelial cells. It was observed that SARS-CoV-2 targets the pulmonary and extrapulmonary systems to damage the microvasculature and affect respiratory functioning, resulting in the onset of endotheliopathy, thrombosis, inflammation, pulmonary edema, and fibrosis. Such deleterious events are the consequence of the hyperactive immune response initiated by the SARS-CoV-2 infection, leading to pulmonary and extrapulmonary complications. However, the molecular mechanism behind endotheliopathy and other complications caused by this virus is elusive and will be unraveled by covering recent literature in this mini-review.

People with HIV (PWH) are at increased risk of vascular dysfunction and cardiovascular disease (CVD). SARS-CoV-2 infection has been associated with acute CVD complications. The aim of the study was to as-sess macrovascular function as an early indicator of CVD risk in PWH after mild SARS-CoV-2 infection.

PWH aged 20-60 years, with undetectable viral load (RNA < 20 copies/mL), on stable antiretroviral therapy (≥6 months) and history of mild COVID-19 (≥30 days) without any CVD manifestations prior to enrollment were recruited. Participants were excluded if they had history of diabetes mellitus, end-stage renal disease, heart or respiratory disease. Participants were matched 1:1 to pre-pandemic PWH. A health survey, surrogate measures of CVD risk, and macrovascular function (brachial artery flow-mediated vasodilation and arterial stiffness assessments via applanation tonometry) were compared between group.

A total of 17 PWH and history of COVID-19 (PWH/COV+) were matched with 17 PWH without COVID-19 (PWH/COV-) pre-pandemic. Mean age (45.5 years), sex (76.5% male), body mass index (27.3), and duration of HIV infection (12.2 years) were not different between groups. Both groups had comparable CVD risk factors (total cholesterol, LDL, HDL, systolic and diastolic blood pressure). There were no differences in measures of flow mediated arterial dilatation or arterial stiffness after 30 days of SARS-CoV-2 infection.

After recent SARS-CoV-2 infection, PWH did not demonstrate evidence of macrovascular dysfunction and increased CVD risk. Results suggest that CVD risk may not be increased in people with well-controlled HIV who did not manifest CVD complications SARS-CoV-2 infection.

This review article discusses the role of vascular endothelial growth factor A (VEGF-A) in the pathogenesis of SARS-CoV-2 and HIV infection, both conditions being renowned for their impact on the vascular endothelium. The processes involved in vascular homeostasis and angiogenesis are reviewed briefly before exploring the interplay between hypoxia, VEGF-A, neuropilin-1 (NRP-1), and inflammatory pathways. We then focus on SARS-CoV-2 infection and show how the binding of the viral pathogen to the angiotensin-converting enzyme 2 receptor, as well as to NRP-1, leads to elevated levels of VEGF-A and consequences such as coagulation, vascular dysfunction, and inflammation. HIV infection augments angiogenesis via several mechanisms, most prominently, by the trans-activator of transcription (tat) protein mimicking VEGF-A by binding to its receptor, VEGFR-2, as well as upregulation of NRP-1, which enhances the interaction between VEGF-A and VEGFR-2. We propose that the elevated levels of VEGF-A observed during HIV/SARS-CoV-2 co-infection originate predominantly from activated immune cells due to the upregulation of HIF-1α by damaged endothelial cells. In this context, a few clinical trials have described a diminished requirement for oxygen therapy during anti-VEGF treatment of SARS-CoV-2 infection. The currently available anti-VEGF therapy strategies target the binding of VEGF-A to both VEGFR-1 and VEGFR-2. The blocking of both receptors could, however, lead to a negative outcome, inhibiting not only pathological, but also physiological angiogenesis. Based on the examination of published studies, this review suggests that treatment targeting selective inhibition of VEGFR-1 may be beneficial in the context of SARS-CoV-2 infection.

Long COVID (also known as post-acute sequelae of SARS-CoV-2 infection [PASC] or post-COVID syndrome) is characterized by persistent symptoms that extend beyond the acute phase of SARS-CoV-2 infection, affecting approximately 10% to over 30% of those infected. It presents a significant clinical challenge, notably due to pronounced neurocognitive symptoms such as brain fog. The mechanisms underlying these effects are multifactorial, with mounting evidence pointing to a central role of cerebromicrovascular dysfunction. This review investigates key pathophysiological mechanisms contributing to cerebrovascular dysfunction in long COVID and their impacts on brain health. We discuss how endothelial tropism of SARS-CoV-2 and direct vascular infection trigger endothelial dysfunction, impaired neurovascular coupling, and blood-brain barrier disruption, resulting in compromised cerebral perfusion. Furthermore, the infection appears to induce mitochondrial dysfunction, enhancing oxidative stress and inflammation within cerebral endothelial cells. Autoantibody formation following infection also potentially exacerbates neurovascular injury, contributing to chronic vascular inflammation and ongoing blood-brain barrier compromise. These factors collectively contribute to the emergence of white matter hyperintensities, promote amyloid pathology, and may accelerate neurodegenerative processes, including Alzheimer's disease. This review also emphasizes the critical role of advanced imaging techniques in assessing cerebromicrovascular health and the need for targeted interventions to address these cerebrovascular complications. A deeper understanding of the cerebrovascular mechanisms of long COVID is essential to advance targeted treatments and mitigate its long-term neurocognitive consequences.

Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 (NCOA7) deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes. This oxysterol signature overlapped with a plasma metabolite signature associated with human PAH mortality. Mice deficient for endothelial Ncoa7 or exposed to an inflammatory bile acid developed worsened PAH. Genetic predisposition to NCOA7 deficiency was driven by single-nucleotide polymorphism rs11154337, which alters endothelial immunoactivation and is associated with human PAH mortality. An NCOA7-activating agent reversed endothelial immunoactivation and rodent PAH. Thus, we established a genetic and metabolic paradigm that links lysosomal biology and oxysterol processes to endothelial inflammation and PAH.

Acute coronavirus disease 2019 (COVID-19) causes various cardiovascular complications. However, it is unknown if there are cardiovascular sequelae in the medium and long-term. The aim of this study was dual. Firstly, we wanted to investigate symptomatology and health-related quality of life (HRQoL) at medium-term follow-up (6 months post-COVID). Secondly, we wanted to assess whether history of COVID-19 and persistent shortness of breath at medium-term follow-up are associated with ongoing inflammation, endothelial dysfunction, and cardiac injury.

A case-control study was performed. Virologically proven COVID-19 cases and age- and gender-matched controls were interviewed to assess symptoms and HRQoL. Biochemical tests were also performed.

The study comprised 174 cases and 75 controls. The mean age of the participants was 46.1±13.8 years. The median follow-up was 173.5 days (interquartile range 129-193.25 days). There was no significant difference in the demographics between cases and controls. At follow-up, cases had a higher frequency of shortness of breath, fatigue, arthralgia, abnormal taste of food (P <.001), and anosmia. Cases also exhibited worse scores in the general health and role physical domains of the Short Form Survey-36. High-sensitivity C-reactive protein (hsCRP) was significantly higher in the cases, and there was a positive correlation of hsCRP with time. Significant determinants of shortness of breath were age, female gender and white cell count, troponin I, and lower hemoglobin levels at follow-up.

Post-COVID-19 patients have persistent symptomatology at medium-term follow-up. Higher hsCRP in cases and the positive association of hsCRP with time suggest ongoing systemic inflammation in patients persisting for months after COVID-19.

While human autopsy samples have provided insights into pulmonary immune mechanisms associated with severe viral respiratory diseases, the mechanisms that contribute to a clinically favorable resolution of viral respiratory infections remain unclear due to the lack of proper experimental systems. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining successful resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication, histopathological manifestations of lung disease and loss of AT2 program, as reported in human COVID-19 patients. Infection resolution is associated with the activation of a limited number of hematopoietic subsets, including inflammatory monocytes and non-canonical double-negative T-cells with cytotoxic functions, which are highly enriched in viral RNA and dissipate upon infection resolution. Activation of specific human fibroblast and endothelial subsets also elicit robust antiviral and monocyte chemotaxis signatures, respectively. Notably, systemic depletion of human CD4+ cells, but not CD3+ cells, abrogates infection resolution in fLX and induces persistent infection, supporting evidence that peripheral CD4+ monocytes are important contributors to SARS-CoV-2 infection resolution in lung tissues. Collectively, our findings unravel a comprehensive picture of the immunological events defining effective resolution of SARS-CoV-2 infection in human lung tissues, revealing markedly divergent immunological trajectories between resolving and fatal COVID-19 cases.

There is increasing evidence that COVID-19 induces endothelial dysfunction that may precede thrombotic and cardiovascular complications. The aim of this study is to evaluate endothelial function using peripheral arterial tonometry (EndoPAT). The primary endpoint is the hyperemic vascular response index (LnRHI) at two months post-discharge. Secondary endpoints include the LnRHI during hospitalization and at six-month follow-up, the proportion of patients with endothelial dysfunction (LnRHI ≤ 0.51), and the incidence of thrombotic events, cardiovascular complications, and mortality during the follow-up period. The study included 23 COVID-19 patients and 22 COVID-19-negative, matched controls. The patients exhibited a significant reduction in the LnRHI at two months post-discharge compared to the controls (median = 0.55 [IQR: 0.49-0.68] vs. median = 0.70 [IQR: 0.62-0.83]; p = 0.012). The difference in the LnRHI between patients and controls was evident from hospitalization and persisted at two and six months without significant temporal changes. The proportion of COVID-19 patients with endothelial dysfunction (LnRHI ≤ 0.51) was 61% during hospitalization and 55% at six months. There was no significant difference in thrombotic or cardiovascular events, nor in mortality. This study demonstrates that COVID-19 adversely affects endothelial function, as evidenced by a reduction in the hyperemic vascular response index, and endothelial dysfunction may also persist.

The coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 has posed a significant threat to global health since its outbreak in early 2020. Various thrombotic complications have been reported in COVID-19 cases. This study aims to investigate the incidence of various types of thromboses during the COVID-19 pandemic, and explore the potential correlation between the number of COVID-19 infections and occurrence of thrombosis. The present retrospective, single-center study recorded the number of new cases with various types of thromboembolism among all hospital admissions between 2019 and 2023 in a single center. The correlation between the number of total thromboembolism cases and number of inpatients who tested positive for COVID-19 was assessed using Spearman rank correlation coefficient. A total of 3926 thromboembolism cases were recorded in men, while 3657 cases were reported in women. The total number of new thromboembolism cases among all inpatients annually increased from 2019 to 2022, and reached a peak during the "full liberalization" period from December 2022 to January 2023. The most substantial increase was observed in microthrombosis cases, followed by venous and arterial thrombosis cases. In addition, thromboembolism primarily occurred in the lower extremities, followed by the abdomen. The fewest cases were observed in the upper extremities. Furthermore, the correlation coefficient between the total number of thromboembolism cases and number of COVID-19-positive patients between January 2020 and June 2023 was 0.501 (P = .001). The number of thromboembolism cases among all inpatients was correlated to the number of COVID-19-positive patients during the pandemic. Early thromboembolism prophylaxis and thrombotic complications monitoring should be considered for hospitalized patients, when necessary.

COVID-19 patients may experience acute mesenteric ischaemia. Identifying acute mesenteric ischaemia is challenging, particularly as initial symptoms are often vague and easily overlooked. Early detection and immediate intervention to restore blood flow can prevent these severe consequences. Presented in this report are two cases of superior mesenteric artery (SMA) thrombosis following severe acute respiratory syndrome coronavirus 2 infection. CT scans demonstrated SMA thrombosis in both patients, with no evidence of bowel necrosis. Endovascular intervention with self-expanding stent placement was performed after angiographic confirmation of the diagnosis. At 6-month follow-up, both patients remained asymptomatic on dual antiplatelet therapy. Atypical gastrointestinal manifestations in COVID-19 patients should raise suspicion for uncommon complications, such as SMA thrombosis. For SMA occlusion without associated bowel necrosis, endovascular therapy represents a viable treatment approach.

Evidence has shown increased morbidity and mortality for patients with COVID-19 infection within 7 weeks of surgery. However, no studies have specifically investigated the effects of COVID-19 in microsurgical outcomes. This study evaluated thrombotic and overall complications after free tissue transfer for a variety of indications in patients with and without previous COVID-19 infection.

A retrospective cohort study was performed in adult patients with or without a history of COVID-19 infection who underwent microsurgical reconstruction between 2017 and 2022. Patients with a history of COVID-19 infection were matched to controls based on age, gender, race, body mass index, history of diabetes, coronary artery disease, hypertension, Caprini score, tobacco use, and flap indication.

From 2017 to 2022, 35 patients had a documented history of COVID-19. Matched case analysis determined a 4.8 times increased odds ratio of postoperative complications in the COVID-19 group compared with controls (p = 0.002). Significantly, more patients with COVID-19 experienced total or partial flap loss and anastomotic issues (COVID-19: 7/35, Control: 0/35; p < 0.001). There was no significant difference in incidence of VTE (COVID-19: 1/35, Control: 0/35; p = 0.493). Of note, 62.9% of the COVID-19 group were discharged on anticoagulants (versus 14.3% in the control group [p < 0.001]).

COVID-19 has dire, long-lasting effects on virtually every organ system, chief among them, the microcirculation. Further studies are needed to fully determine the extent and influence of COVID-19 on complex procedures such as free tissue transfer and how to optimize the screening, workup, and postoperative care to guard against the associated thrombotic consequences.

While our understanding of coronavirus disease 2019 (COVID-19) has evolved, uncertainty remains regarding utility of previously established pulmonary embolism (PE) screening guidelines in patients with COVID-19. Many studies have investigated the efficacy of D-dimer (DD) screenings for patients with COVID-19 admitted to inpatient services, but few have evaluated patients in the emergency department (ED). The purpose of this study was to investigate utility of DD threshold for PE screening in patients with COVID-19 presenting to the ED.

This was a retrospective, multicenter cohort including patients presenting to three EDs between March 1, 2020 and February 1, 2021 who tested positive for COVID-19 during ED visit or in 60 days prior to presentation and had DD ordered in ED. Patients were grouped by those who underwent computed tomography pulmonary angiogram (CTPA) to evaluate for PE and those who did not, and descriptive statistics were performed. Those who underwent CTPA were further divided into PE-positive and PE-negative groups. The discriminative ability of DD in predicting PE in patients with COVID-19 was analyzed using the receiver operating characteristic (ROC) curve.

A total of 570 patients with COVID-19 were included in the study, of which 107 underwent CTPA to evaluate for PE. History of diabetes, elevated glucose, elevated lactate dehydrogenase, elevated white blood cell count, elevated platelets, elevated respiratory rate, and lower temperature were associated with increased risk for PE. Compared to those without PE, patients with PE were significantly more likely to be hospitalized (100% vs. 82%, p = 0.020) and admitted to the ICU (64% vs. 24%, p = 0.002). Those with PE had a significantly higher median DD value (21,177 ng/mL) compared to PE-negative group (952 ng/mL, p < 0.001). The ROC curve for DD in predicting PE had an area under the curve of 0.91 (95% confidence interval [0.84, 0.98]). In our study population, the optimal DD threshold for predicting PE was 1815 ng/mL (sensitivity 93% and specificity 80%). A conservative threshold of 1089 ng/mL could be used with sensitivity 100% and specificity 58%.

DD is often elevated in patients with COVID-19, regardless of PE. While the classically used DD cutoff is 500 ng/mL, our study demonstrated a threshold of 1089 ng/mL safely predicted PE in patients with COVID-19 .

Endothelial dysfunction plays a central role in the severity of COVID-19, since the respiratory, thrombotic and myocardial complications of the disease are closely linked to vascular endothelial damage. To address this issue, we evaluate here the effect of conditioned media from spike S1-activated macrophages (CM_S1) on the proliferation of human umbilical endothelial cells (HUVECs), focusing on the specific role of interleukin-1-beta (IL-1β), interleukin-6 (IL-6), interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Results obtained demonstrate that the incubation with CM_S1 for 72 h hinders endothelial cell proliferation and induces signs of cytotoxicity. Comparable results are obtained upon exposure to IFN-γ + TNF-α, which are thus postulated to play a pivotal role in the effects observed. These events are associated with an increase in p21 protein and a decrease in Rb phosphorylation, as well as with the activation of IRF-1 and NF-kB transcription factors. Overall, these findings further sustain the pivotal role of a hypersecretion of inflammatory cytokines as a trigger for endothelial activation and injury in the immune-mediated effects of COVID-19.

Evidence suggests that coronavirus disease 2019 (COVID-19) is associated with the risk of cardiovascular diseases (CVDs). However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between COVID-19 and CVDs by using two-sample Mendelian randomization (MR) analysis.

Summary-level data for COVID-19 and CVDs including myocarditis, heart failure (HF), acute myocardial infarction (AMI), arrhythmia and venous thromboembolism (VTE) were obtained from the IEU OpenGWAS project, a public genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) were used as instrumental variables. Five complementary MR methods were performed, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode and simple mode methods. IVW method was considered as the primary approach. Besides, sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis, were performed to evaluate the robustness of the results.

According to the IVW results, our MR study indicated that genetically predicted COVID-19 was not causally connected with the risk of CVDs [myocarditis: odds ratio (OR) = 1.407, 95% confidence interval (CI) = 0.761-2.602, p-value = 0.277; HF: OR = 1.180, 95% CI = 0.980-1.420, p-value = 0.080; AMI: OR = 1.002, 95% CI = 0.998-1.005, p-value = 0.241; arrhythmia: OR = 0.865, 95% CI = 0.717-1.044, p-value = 0.132; VTE: OR = 1.013, 95% CI = 0.997-1.028, p-value = 0.115]. The supplementary MR methods showed similar results. Sensitivity analyses suggested that the causal estimates were robust.

This two-sample MR analysis did not provide sufficient evidence for a causal relationship between COVID-19 and the risk of acute CVDs, which may provide new insights into the prevention of acute CVDs in COVID-19 patients.

The aim of this study was to examine the impact of the pentraxin 3 (PTX3) serum level and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on the severity of radiographic pulmonary infiltrates and the clinical outcomes of COVID-19.

The severity of COVID-19 pulmonary infiltrates was evaluated within a week of admission by analyzing chest X-rays (CXR) using the modified Brixia (MBrixa) scoring system. The insertion (I)/deletion (D) polymorphism of the ACE gene and the serum levels of PTX3 were determined for all patients included in the study.

This study included 80 patients. Using a cut-off serum level of PTX3 ≥ 2.765 ng/mL, the ROC analysis (AUC 0.871, 95% CI 0.787-0.954, p < 0.001) showed a sensitivity of 85.7% and specificity of 78.8% in predicting severe MBrixa scores. Compared to ACE I/I polymorphism, D/D polymorphism significantly increased the risk of severe CXR infiltrates, OR 7.7 (95% CI: 1.9-30.1), and p = 0.002. Significant independent predictors of severe CXR infiltrates include hypertension (OR 7.71), PTX3 (OR 1.20), and ACE D/D polymorphism (OR 18.72). Hypertension (OR 6.91), PTX3 (OR 1.47), and ACE I/I polymorphism (OR 0.09) are significant predictors of poor outcomes.

PTX3 and ACE D/D polymorphism are significant predictors of the severity of COVID-19 pneumonia. PTX3 is a significant predictor of death.

To analyze the accuracy of the defining characteristics of four respiratory nursing diagnoses (ND) in patients with COVID-19 and on oxygen therapy.

This is a cross-sectional study conducted in four Brazilian public hospitals in two regions of the country. A total of 474 patients with COVID-19 receiving oxygen therapy were assessed. Latent-adjusted class analysis with random effects was used to establish the sensitivity (Se) and specificity (Sp) of the defining characteristics evaluated for each ND.

Among the ND that constituted the study (impaired spontaneous ventilatory, impaired gas exchange, ineffective airway clearance, and dysfunctional ventilatory weaning response), the following defining characteristics had the highest simultaneous Se and Sp (>0.8): decrease in tidal volume, confusion, irritability, dyspnea, decreased breath sounds, orthopnea, impaired ability to cooperate and respond to coaching, and decrease in the level of consciousness.

Recognizing the clinical signs that predict respiratory ND in patients affected by COVID-19 can contribute to the nurse's accurate diagnostic inference and designate the appropriate nursing interventions to achieve the desired results and avoid complications.

It is well-described that the coronavirus disease 2019 (COVID-19) infection is associated with an increased risk of thrombotic complications. While there have been many cases of pulmonary emboli and deep vein thrombosis in these patients, reports of COVID-19 associated portal vein thrombosis (PVT) have been uncommon. We present a unique case of concomitant PVT and splenic artery thrombosis in a COVID-19 patient.

A 77-year-old-male with no history of liver disease presented with three days of left-sided abdominal pain. One week earlier, the patient was diagnosed with mildly symptomatic COVID-19 and was treated with nirmatrelvir/ritonavir. Physical exam revealed mild right and left lower quadrant tenderness, but was otherwise unremarkable. Significant laboratory findings included white blood cell count 12.5 K/μL, total bilirubin 1.6 mg/dL, aminoaspartate transferase 40 U/L, and alanine aminotransferase 61 U/L. Computed tomography of the abdomen and pelvis revealed acute PVT with thrombus extending from the distal portion of the main portal vein into the right and left branches. Also noted was a thrombus within the distal portion of the splenic artery with resulting splenic infarct. Hypercoagulable workup including prothrombin gene analysis, factor V Leiden, cardiolipin antibody, and JAK2 mutation were all negative. Anticoagulation with enoxaparin was initiated, and the patient's pain improved. He was discharged on apixaban.

It is quite uncommon for PVT to present simultaneously with an arterial thrombotic occlusion, as in the case of our patient. Unusual thrombotic manifestations are classically linked to hypercoagulable states including malignancy and hereditary and autoimmune disorders. Viral infections such as Epstein-Barr virus, cytomegalovirus, viral hepatitis, and COVID-19 have all been found to increase the risk of splanchnic venous occlusions, including PVT. In our patient, prompt abdominal imaging led to early detection of thrombus, early treatment, and an excellent outcome. This case is unique in that it is the second known case within the literature of simultaneous PVT and splenic artery thrombosis in a COVID-19 patient.

Background/Objectives: The newly emergent COVID-19 pandemic involved primarily the respiratory system and had also major cardiovascular system (CVS) implications, revealed by acute myocardial infarction (AMI), arrhythmias, myocardial injury, and thromboembolism. CVS involvement is done through main mechanisms-direct and indirect heart muscle injury, with high mortality rates, worse short-term outcomes, and severe complications. AMI is the echo of myocardial injury (revealed by increases in CK, CK-MB, and troponin serum markers-which are taken into consideration as possible COVID-19 risk stratification markers). When studying myocardial injury, physicians can make use of imaging studies, such as cardiac MRI, transthoracic (or transesophageal) echocardiography, coronary angiography, cardiac computed tomography, and nuclear imaging (which have been used in cases where angiography was not possible), or even endomyocardial biopsy (which is not always available or feasible). Two-case-series presentations: We present the cases of two COVID-19 positive male patients who were admitted into the Clinical Department of Cardiology in "Sfântul Apostol Andrei" Emergency Clinical Hospital of Galați (Romania), who presented with acute cardiac distress symptoms and have been diagnosed with ST elevation AMI. The patients were 82 and 57 years old, respectively, with moderate and severe forms of COVID-19, and were diagnosed with anteroseptal left ventricular AMI and extensive anterior transmural left ventricular AMI (with ventricular fibrillation at presentation), respectively. The first patient was a non-smoker and non-drinker with no associated comorbidities, and was later discharged, while the second one died due to AMI complications. Conclusions: From this two-case series, we extract the following: old age alone is not a significant risk factor for adverse outcomes in COVID-19-related CVS events, and that the cumulative effects of several patient-associated risk factors (be it either for severe forms of COVID-19 and/or acute cardiac injury) will most probably lead to poor patient prognosis (death). At the same time, serum cardiac enzymes, dynamic ECG changes, along with newly developed echocardiographic modifications are indicators for poor prognosis in acute cardiac injury in COVID-19 patients with acute myocardial injury, regardless of the presence of right ventricular dysfunction (due to pulmonary hypertension).

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was the main pathogen in the COVID-19 pandemic. This viral infection has been associated with several respiratory and non-respiratory complications contributing to a higher mortality rate, especially in patients with underlying heart diseases worldwide. Once considered a respiratory tract disease, it is now well-known that COVID-19 patients may experience a wide range of cardiac manifestations. Because of its remarkable direct and indirect effects on the cardiovascular system, herein, we examined the published literature that studied the hypothetical mechanisms of injury, manifestations, and diagnostic modalities, including changes in molecular biomarkers with a predictive value in the prognostication of the disease, as well as emerging evidence regarding the long-term cardiac complications of the disease.

The primary targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the lungs are type I pneumocytes, macrophages, and endothelial cells. We aimed to identify lung cells targeted by SARS-CoV-2 using viral nucleocapsid protein staining and morphometric features on patients with fatal COVID-19. We conducted a retrospective analysis of fifty-one autopsy cases of individuals who tested positive for SARS-CoV-2. Demographic and clinical information were collected from forensic reports, and lung tissue was examined for microscopic lesions and the presence of specific cell types. Half of the evaluated cohort were older than 71 years, and the majority were male (74.5%). In total, 24 patients presented diffuse alveolar damage (DAD), and 50.9% had comorbidities (56.9% obesity, 33.3% hypertension, 15.7% diabetes mellitus). Immunohistochemical analysis showed a similar pattern of infected macrophages, infected type I pneumocytes, and endothelial cells, regardless of the presence of DAD (p > 0.5). The immunohistochemical reactivity score (IRS) was predominantly moderate but without significant differences between patients with and without DAD (p = 0.633 IRS for type I pneumocytes, p = 0.773 IRS for macrophage, and p = 0.737 for IRS endothelium). The nucleus/cytoplasm ratio shows lower values in patients with DAD (median: 0.29 vs. 0.35), but the difference only reaches a tendency for statistical significance (p = 0.083). Our study confirms the presence of infected macrophages, type I pneumocytes, and endothelial cells with a similar pattern in patients with and without diffuse alveolar damage.

To analyze the evidence of content validity of the Nursing Outcomes "Mechanical Ventilation Response: Adult" and "Mechanical Ventilation Weaning Response: Adult", for patients with severe COVID-19.

Methodological study developed in two stages: literature review to construct the definitions of the indicators and analysis of the evidence of content validity of the nursing outcomes by a focus group.

All the conceptual and operational definitions developed for the 56 indicators were considered clear and precise. However, 17 indicators were excluded because they were deemed not to be relevant. The definitions of the magnitudes for 17 indicators of the Nursing Outcome "Mechanical Ventilation Response: Adult" and 22 indicators "Mechanical Ventilation Weaning Response: Adult" were thus constructed.

The development of definitions and validation by experts makes the use of these outcomes and their indicators more understandable and precise, favoring their use in clinical practice and providing greater detail in assessment and recording.

Emerging evidence indicates that the relationship between coronavirus disease 2019 (COVID-19) and diabetes is 2-fold: 1) it is known that the presence of diabetes and other metabolic alterations poses a considerably high risk to develop a severe COVID-19; 2) patients who survived a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have an increased risk of developing new-onset diabetes. However, the mechanisms underlying this association are mostly unknown, and there are no reliable biomarkers to predict the development of new-onset diabetes. In the present study, we demonstrate that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells reliably predicts the risk of developing new-onset diabetes in COVID-19. This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. SIGNIFICANCE STATEMENT: We demonstrate for the first time that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells is able to reliably predict the risk of developing diabetes after having contracted coronavirus disease 2019 (COVID-19). This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. Our findings are also relevant when considering the emerging importance of post-acute sequelae of COVID-19, with systemic manifestations observed even months after viral negativization (long COVID).

Early since the onset of the COVID-19 pandemic, the medical and scientific community were aware of extra respiratory actions of SARS-CoV-2 infection. Endothelitis, hypercoagulation, and hypofibrinolysis were identified in COVID-19 patients as subsequent responses of endothelial dysfunction. Activation of the endothelial barrier may increase the severity of the disease and contribute to long-COVID syndrome and post-COVID sequelae. Besides, it may cause alterations in primary, secondary, and tertiary hemostasis. Importantly, these responses have been highly decisive in the evolution of infected patients also diagnosed with diabetes mellitus (DM), who showed previous endothelial dysfunction. In this review, we provide an overview of the potential triggers of endothelial activation related to COVID-19 and COVID-19 under diabetic milieu. Several mechanisms are induced by both the viral particle itself and by the subsequent immune-defensive response (i.e., NF-κB/NLRP3 inflammasome pathway, vasoactive peptides, cytokine storm, NETosis, activation of the complement system). Alterations in coagulation mediators such as factor VIII, fibrin, tissue factor, the von Willebrand factor: ADAMST-13 ratio, and the kallikrein-kinin or plasminogen-plasmin systems have been reported. Moreover, an imbalance of thrombotic and thrombolytic (tPA, PAI-I, fibrinogen) factors favors hypercoagulation and hypofibrinolysis. In the context of DM, these mechanisms can be exacerbated leading to higher loss of hemostasis. However, a series of therapeutic strategies targeting the activated endothelium such as specific antibodies or inhibitors against thrombin, key cytokines, factor X, complement system, the kallikrein-kinin system or NETosis, might represent new opportunities to address this hypercoagulable state present in COVID-19 and DM. Antidiabetics may also ameliorate endothelial dysfunction, inflammation, and platelet aggregation. By improving the microvascular pathology in COVID-19 and post-COVID subjects, the associated comorbidities and the risk of mortality could be reduced.

The scientific and medical community faced an unprecedented global health hazard that led to nearly 7 million deaths attributable to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In spite of the development of efficient vaccines against SARS-CoV-2, many people remain at risk of developing severe symptoms as the virus continues to spread without beneficial patient therapy. The hyper-inflammatory response to SARS-CoV-2 infection progressing to acute respiratory distress syndrome remains an unmet medical need for improving patient care. The viral infection stimulates alveolar macrophages to adopt an inflammatory phenotype regulated, at least in part, by the cluster of differentiation 36 receptor (CD36) to produce unrestrained inflammatory cytokine secretions. We suggest herein that the modulation of the macrophage response using the synthetic CD36 ligand hexarelin offers potential as therapy for halting respiratory failure in SARS-CoV-2-infected patients.

Sepsis-induced cardiac injury represents a major clinical challenge, amplifying the urgency for effective therapeutic interventions. This study aimed to delve into the individual and combined prophylactic effects of Vitamin C (Vit C) and Coenzyme Q10 (CoQ10) against inflammatory heart injury in a cecal ligation and puncture (CLP) induced polymicrobial sepsis rat model. Thirty adult female Sprague-Dawley rats were randomly divided into five groups: Control, CLP, Vitamin C, CoQ10, and Vit C + CoQ10, each consisting of six rats. Treatments were administered orally via gavage for 10 days prior to the operation. Eighteen hours post-sepsis induction, the animals were euthanized, and specimens were collected for analysis. The study examined variations in oxidative (TOS, OSI, MDA, MPO) and antioxidative markers (TAS, SOD, CAT, GSH), histopathological changes, inflammatory cytokine concentrations (TNF-α, IL-1β), nitric oxide (NO) dynamics, and cardiac indicators such as CK-MB. Impressively, the combined regimen markedly diminished oxidative stress, and antioxidative parameters reflected notable enhancements. Elevated NO levels, a central player in sepsis-driven inflammatory cascades, were effectively tempered by our intervention. Histological examinations corroborated the biochemical data, revealing diminished cardiac tissue damage in treated subjects. Furthermore, a marked suppression in pro-inflammatory cytokines was discerned, solidifying the therapeutic potential of our intervention. Interestingly, in certain evaluations, CoQ10 exhibited superior benefits over Vit C. Collectively, these findings underscore the potential therapeutic promise of Vit C and CoQ10 combination against septic cardiac injuries in rats.

SARS-CoV-2, the causative agent of COVID-19, primarily affects the epithelial compartment in the upper and lower airways. There is evidence that the microvasculature in both the pulmonary and extrapulmonary systems is a major target of SARS-CoV-2. Consistent with this, vascular dysfunction and thrombosis are the most severe complications in COVID-19. The proinflammatory milieu triggered by the hyperactivation of the immune system by SARS-CoV-2 has been suggested to be the main trigger for endothelial dysfunction during COVID-19. More recently, a rapidly growing number of reports have indicated that SARS-CoV-2 can interact directly with endothelial cells through the spike protein, leading to multiple instances of endothelial dysfunction. Here, we describe all the available findings showing the direct effect of the SARS-CoV-2 spike protein on endothelial cells and offer mechanistic insights into the molecular basis of vascular dysfunction in severe COVID-19.

At the beginning of 2020, coronavirus disease 2019 (COVID-19) emerged as a new pandemic, leading to a worldwide health crisis and overwhelming healthcare systems due to high numbers of hospital admissions, insufficient resources, and a lack of standardized therapeutic protocols. Multiple genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected since its first public declaration in 2020, some of them being considered variants of concern (VOCs) corresponding to several pandemic waves. Nevertheless, a growing number of COVID-19 patients are continuously discharged from hospitals, remaining symptomatic even months after their first episode of COVID-19 infection. Long COVID-19 or 'post-acute COVID-19 syndrome' emerged as the new pandemic, being characterized by a high variability of clinical manifestations ranging from cardiorespiratory and neurological symptoms such as chest pain, exertional dyspnoea or cognitive disturbance to psychological disturbances, e.g., depression, anxiety or sleep disturbance with a crucial impact on patients' quality of life. Moreover, Long COVID is viewed as a new cardiovascular risk factor capable of modifying the trajectory of current and future cardiovascular diseases, altering the patients' prognosis. Therefore, in this review we address the current definitions of Long COVID and its pathophysiology, with a focus on cardiovascular manifestations. Furthermore, we aim to review the mechanisms of acute and chronic cardiac injury and the variety of cardiovascular sequelae observed in recovered COVID-19 patients, in addition to the potential role of Long COVID clinics in the medical management of this new condition. We will further address the role of future research for a better understanding of the actual impact of Long COVID and future therapeutic directions.

Critical illness is often accompanied by a hemodynamic imbalance between macrocirculation and microcirculation, as well as mitochondrial dysfunction. Microcirculatory disorders lead to abnormalities in the supply of oxygen to tissue cells, while mitochondrial dysfunction leads to abnormal energy metabolism and impaired tissue oxygen utilization, making these conditions important pathogenic factors of critical illness. At the same time, there is a close relationship between the microcirculation and mitochondria. We introduce here the concept of a "critical unit", with two core components: microcirculation, which mainly comprises the microvascular network and endothelial cells, especially the endothelial glycocalyx; and mitochondria, which are mainly involved in energy metabolism but perform other non-negligible functions. This review also introduces several techniques and devices that can be utilized for the real-time synchronous monitoring of the microcirculation and mitochondria, and thus critical unit monitoring. Finally, we put forward the concepts and strategies of critical unit-guided treatment.

Uncontrolled inflammation is a pathological state that underlies many diseases. Despite the development of numerous anti-inflammatory agents, the treatment of uncontrolled inflammation remains a challenging task. We developed a targeted delivery system for [5-(p-fluorophenyl)-2-ureido]thiophene-3-carboxamide (TPCA-1), a potent inhibitor of the NF-κB signaling pathway. The system comprises TPCA-1-loaded nanoparticles (NPs) functionalized with a monoclonal antibody (mAb) that specifically binds to the break point of the IgD6 region of the platelet/endothelial cell adhesion molecule-1 (PECAM-1) extracellular segment that is overexposed on the injured endothelium and activated macrophages during the pathogenesis of inflammation. In vitro binding and cellular uptake experiments revealed that the mAb modification on NPs could significantly enhance uptake by both Raw264.7 and HUVEC compared with unmodified NPs. In studies conducted at the cellular level focusing on anti-inflammatory and antioxidant effects, this formulation was found to effectively inhibit M1 polarization of macrophages, downregulate the secretion of pro-inflammatory cytokines, and reduce the production of reactive oxygen species (ROS) and nitric oxide (NO). In an animal model of vascular endothelial injury with acute inflammation, these NPs were capable of delivering TPCA-1 to inflammatory lesions in a targeted manner. Compared with the free agent-treated group, the NP-treated group exhibited reduced infiltration of inflammatory cells. In conclusion, our study demonstrates that this targeted delivery of TPCA-1-loaded NPs represents a promising strategy for improved mitigation of uncontrolled inflammation.