Neurological complications encountered in imaging studies in association with COVID-19 - a single center analysis

Introduction and aim. COVID-19 is a viral infectious disease, which was first reported in patients with unusual pneumonia in December 2019. However, as the pandemic progressed, extrapulmonary manifestations including various neurologic complications have been started to be increasingly reported. In this retrospective study, we tried to search the neurological complications seen in our patients with positive rRT-PCR test for COVID-19 and examine the underlying associated risk factors. Material and methods. We have retrospectively analyzed the neuroimaging studies performed in our patients with positive rRT-PCR test for COVID-19 between April, 2020 and August, 2021. Both computed tomography (CT) scans and magnetic resonance imagings (MRI) of brain, head & neck region and the spine were retrospectively evaluated for the presence of any complications in patients with positive rRT-PCR test for COVID-19. Results. There were 147 patients having neuroradiological imaging studies performed for various neurological symptoms. Among these patients we detected 10 acute neurologicalcomplications.The most common was acute ischemic stroke in 5 patients and intracranial hemorrhage in 3 patients, two of which were intraventricular hemorrhage. The other complications included a preasumed cytotoxic lesion of corpus callosum in a 18 year old girl and lumbar spondylodiscitis complicated with psoas abcess in a 47 year-old man. Conclusion. In COVID-19 patients severe neurological complications can occur even as a presenting manifestation. Early cytotoxic endothelial injury can be the underlying cause in these patients and should be further studied in larger series in terms of what the susceptibility factors in these patients. © 2022 Publishing Office of the University of Rzeszow. All Rights Reserved.

Obesity and COVID-19 - a double blow to the heart

Obesity is one of the main severe COVID-19 risk factors. SARS-CoV-2 causes endothelitis that lead to inflammation and prothrombotic state. Also visceral adipose tissue is a source of different prothrombogenic and proinflammatory cytokines that make prognosis and survival of patients with COVID-19 worse. The synergy of the COVID-19 and obesity pandemics is a double blow to health, especially in young patients. Weight loss due to lifestyle modifications and vaccination are effective methods of the severe COVID-19 prevention in obese patients. This review presents the main pathogenetic aspects of cardiovascular disease development and progression in obese patients with COVID-19 and possible methods of adverse outcomes prevention in this group of patients.Copyright © 2022 Authors. All rights reserved.

Lung pathology

The series of autopsies reported since the beginning of the pandemic have highlighted several patterns of lung damage, both isolated and combined. The factors influencing the occurrence of these different tissue responses to viral aggression by SARS-CoV-2 have not yet been determined. In asymptomatic patients or patients with respiratory symptoms who were not ventilated, lymphocyte pneumonia associated with type II pneumocyte atypical hyperplasia and a few hyaline membranes or focal lesions of acute fibrinous pneumonia have been observed. In critically ill patients, the most frequent pattern is diffuse alveolar damage with interstitial lymphoid infiltration, type II pneumocyte atypia and, very often, capillary or arteriolar microthromboses and/or endothelitis. The precise description of these lesions, which is becoming more and more consensual, makes it possible to understand the favourable effects of corticosteroid therapy in seriously ill patients and the evolution under ventilation towards fibrosis.Copyright © ERS 2021.

NK CELLS ARE CRITICAL FOR IN VIVO CONTROL OF SARS-CoV-2 REPLICATION AND DISEASE

Background: Natural killer (NK) cells play a critical role in control of viral infections. However, empirical evidence thus far has been unclear on the role of NK cells in pathogenesis and control of SARS-CoV-2 infection with some research suggesting NK cell accumulation as beneficial while others indicate it as deleterious. To address this crucial deficit in understanding, we employed a non-human primate infection model with a validated experimental NK cell depletion technique. Method(s): A total of 12 experimentally naive (75% female) cynomolgus macaques (CM) of Cambodian origin were used in this study. Six CM were NK cell-depleted using an anti-IL-15 neutralizing antibody, while six controls received placebo, prior to intranasal and intratracheal challenge with the SARS-CoV-2 Delta variant at a TCID50 of 1X105. The cohort was monitored for five weeks with scheduled blood, colorectal (CR) biopsies, and lymph node (LN) collections. Total envelope and sub-genomic viral loads (VL) were measured in the nasal cavity, throat, and bronchoalveolar lavage (BAL). 23-color flow cytometry, pathology, and 27-plex inflammatory analyte Luminex analyses were conducted. Statistical tests used were Mann-Whitney U and Spearman's Correlation. Result(s): Control CM exhibited an increase in the frequency of circulating NK cells, reaching a peak at 10 days post-infection (DPI) and returning to baseline by 22DPI. Simultaneously, NK cells expressing activation and tissue retention marker, CD69, also significantly increased. Cytotoxic NK cells were positively associated with VL (r=0.66;p=0.02), suggestive of a virus-induced mobilization. Total experimental NK cell ablation was verified in blood, CR, and LN of NK celldepleted CM, which had higher VL compared to controls in all tissues evaluated, reaching significance at 10DPI (p=0.01) and demonstrated a longer duration of viremia. Although Luminex measures were similar in plasma, BAL samples from NK cell-depleted CM had universally higher concentrations of inflammatory mediators, most notably a 25-fold higher concentration of IFN-alpha compared to controls. Lung pathology scores were also higher in NK cell-depleted CM with increased evidence of fibrosis, syncytia, pneumocyte hyperplasia, and endothelialitis. Conclusion(s): Overall, we find significant and conclusive evidence for NK cell-mediated control of SARS-CoV-2 virus replication and disease pathology. These data suggest adjunct therapies for infection could largely benefit from NK cell-targeted approaches.

Multivessel Epicardial Coronary Artery Thrombosis after Heart Transplantation

Introduction: Although cardiac allograft vasculopathy (CAV) remains one of the leading causes of graft failure after heart transplantation (HTx), simultaneous thrombosis of multiple epicardial coronary arteries (CA) is an uncommon finding. Case Report: A 43-year-old male patient with non-ischemic dilated cardiomyopathy underwent successful HTx in 2019. The first two years after HTx were uneventful, surveillance endomyocardial biopsies (EMB) did not reveal any rejection episodes, coronary CTA revealed only minimal non-calcified CA plaques. The patient was admitted to hospital due to fever and chest pain in 2021. Immunosuppressive therapy consisted of tacrolimus, mycophenolate-mofetil and methylprednisolone. ECG verified sinus rhythm. Laboratory test revealed elevated hsTroponin T, NT-proBNP and CRP levels. Cytomegalovirus, SARS-CoV-2-virus and hemoculture testing was negative. Several high-titre donor-specific HLA class I and II antibodies (DSAs;including complement-binding DQ7) could have been detected since 2020. Echocardiography confirmed mildly decreased left ventricular systolic function and apical hypokinesis. EMB verified mild cellular and antibody-mediated rejection (ABMR) according to ISHLT grading criteria. Cardiac MRI revealed inferobasal and apical myocardial infarction (MI);thus, an urgent coronary angiography was performed. This confirmed thrombotic occlusions in all three main epicardial CAs and in first diagonal CA. As revascularization was not feasible, antithrombotic therapy with acetylsalicylic acid, clopidogrel and enoxaparin was started for secondary prevention. Tests for immune system disorders, thrombophilia and cancer were negative. Patient suddenly died ten days after admission. Necropsy revealed intimal proliferation in all three main epicardial CAs, endothelitis, thrombosis, chronic pericoronary fat inflammation, fat necrosis, and subacute MI. CA vasculitis owing to persistent high-titre DSAs, chronic ABMR and acute cellular and antibody-mediated rejection led to multivessel CA thrombosis and acute multiple MI. ABMR after HTx may be underdiagnosed with traditional pathological methods. Pathologies affecting coronary vasculature of HTx patients with DSAs, unique manifestations of CAV lesions and occlusive thrombosis of non-stenotic, non-atherosclerotic lesions should be emphasized.Copyright © 2023

Protective effects of COVID-19 vaccination on endothelial function of patients with COVID-19

Background: Endotheliilitis COVID-19 related endothelial dysfunction plays a key role in the cardiovascular complications of the disease. Vaccine against SARS-CoV-2 protects against severe COVID-19 and from adverse effects. We evaluated the impact of vaccination on COVID-19 induced endothelial dysfunction. Method(s): We enrolled 45 patients hospitalized for COVID-19 (either vaccinated or not against SARS-CoV-2). Clinical information and laboratory findings were collected, and brachial artery flow-mediated dilation (FMD) was evaluated as a measure of endothelial function. Subjects without COVID- 19 were used as the control group. All patients were hospitalized in a medical ward classified according to the World Health Organization (WHO) scale. Result(s): There was no difference in age (62+/-10 years vs. 65+/-8 years, p=0.12) and male sex prevalence (56% vs. 49%, p=0.53) between patients with COVID-19 and control subjects. Of the patients with COVID-19, 44% (20) were vaccinated against SARS-CoV-2. FMD was impaired in patients with COVID-19 compared to controls (4.35+/-3.56% vs. 7.36+/-2.91%, p<0.001). In patients with COVID-19, FMD was impaired in non-vaccinated subjects compared to vaccinated (2.05+/-2.41% vs. 7.24+/-2.52%, p<0.001). There was no difference in FMD between controls and vaccinated against COVID-19 patients (7.36+/-2.91% vs. 7.24+/-2.52%, p=0.86). There was no difference in the WHO scale clinical status for vaccinated and not vaccinated COVID-19 subjects (For Vaccinated WHO scale 3: 35%;scale 4: 35%;scale 5: 30% vs. For Non-vaccinated WHO scale 3: 20;scale 4: 60%;scale 5: 20%, p=0.24). Conclusion(s): Hospitalized patients with COVID-19 present endothelial dysfunction in the acute phase of the disease. Endothelial function in unvaccinated patients with COVID-19 is impaired compared to control subjects as well as compared to vaccinated patients with COVID-19. This data provides insights on the protective role of vaccination against COVID-19 related endotheliitis. (Figure Presented) .

Acute kidney injury in patient with severe SARS-CoV-2 infection.

Acute kidney injury (AKI) during SARS-CoV-2 infection is frequent and associated with mortality. Pathophysiology of AKI is multifactorial, and encompasses direct (viral invasion, endothelitis and thrombosis, renin-angiotensin-aldosteron system activation, cytokine elevation) and undirect mechanisms (hemodynamic instability, effect of mechanical ventilation, nephrotoxic medications). Acute tubular necrosis is the most frequent histological lesion identified, but glomerular disease can also be observed. To date, there is no specific treatment of SARS-CoV-2 induced AKI.Copyright © SRLF 2021.

FETAL GROWTH RETARDATION AS A COMPLICATION OF POST-COVID ENDOTHELIITIS: CAUSES, CONSEQUENCES, WAYS OF PREVENTION.

The risk of fetal intrauterine growth retardation (IUGR) is increased in women who have experienced acute infections, as well as in pregnant women with gynecological pathology and endocrine diseases. A woman's lack of nutrition also makes a negative contribution to the development of IUGR. The frequency of IUGR in the population is very variable and depends on a number of reasons. In practically healthy pregnant women, IUGR is registered in 3-5% of cases, in case of complicated obstetric and gynecological diagnosis and complicated pregnancy - in 10-25%. Morphofunctional disorders in the chorion/placenta in pregnant women with COVID-19 on the background of post-covid endotheliitis are the main pathogenetic factor in the development of preeclampsia, ectopic pregnancy, antenatal fetal death, and impaired condition of the fetus and newborns. Sufficient saturation of the pregnant woman's body with the nitric oxide donor L-arginine and L-carnitine (main cofactor of fatty acid metabolism in cells) with the improvement of microcirculation and the correction of hypovolemic disorders in the fetoplacental complex can be considered one of the real ways to prevent IUGR in women in the post-covid period. A review of the scientific literature on pathogenesis, diagnosis, impact on the life and health of a newborn with IUGR in women after COVID-19, as well as the possibilities of medical correction of placental dysfunction during pregnancy was performed. This analysis and our own clinical experience allow us to state the fact that after a coronavirus infection during pregnancy, one of the frequent and threatening for the further development of the child is the formation of placental dysfunction and IUGR. One of the ways to prevent these conditions is to saturate the woman's body with the nitric oxide donor L-arginine from the stage of pre-gravid preparation, which will provide the opportunity for adequate angiogenesis and development of the embryo/fetus. In the case of additional risk factors, such as coronavirus disease, complex therapy blood (Rheosorbilact), in combination with a nitric oxide donor and L-carnitine as an endothelium-protective agent (Tivor-L).Copyright © 2022 Authors. All rights reserved.

Phase 3 RCT of C5a-Specific Vilobelimab in Severe COVID-19 Pneumonia

Background: Blocking the C5a-C5aR axis in COVID-19 patients could improve outcomes by limiting myeloid cell infiltration in damaged organs and preventing excessive lung inflammation and endothelialitis. Aims and Objectives: Vilobelimab (VILO), an anti-C5a mAb that preserves the membrane attack complex (MAC), was tested in a Phase III adaptively designed multicenter, double-blind placebo (P)-controlled study for survival in critically ill COVID-19 patients. Method(s): COVID-19 pneumonia patients (N=369;VILO n=178, P n=191) within 48 hrs of intubation were randomly assigned to receive 6, 800 mg infusions of VILO or P on top of standard of care. Primary outcome was 28-day allcause mortality. Result(s): 28-day all-cause mortality was 31.7% VILO vs 41.6% P (Kaplan-Meier estimates;Cox regression site stratified, HR 0.73;95%CI:0.50-1.06;P=0.094) with a 22.7% relative mortality reduction to Day 60. In predefined primary outcome analysis without site stratification, VILO significantly reduced 28-day mortality (HR 0.67;95%CI:0.48-0.96;P=0.027);needed to treat number, 10 to save 1. VILO significantly reduced 28-day mortality in severe patients with baseline WHO ordinal scale score of 7 (n=237, HR 0.62;95%CI:0.40-0.95;P=0.028) or severe ARDS/PaO2/FiO2<=100 mmHg (n=98, HR 0.55;95%CI:0.30-0.98;P=0.044) or eGFR<60 mL/min/1.73m2 (n=108, HR 0.55;95%CI:0.31-0.96;P=0.036). Treatment emergent AEs were 90.9% VILO vs 91.0% P. Infections were comparable;VILO (62.9%), P (59.3%). Serious AEs were 58.9% VILO, 63.5% P. Conclusion(s): VILO reduced mortality at 28 to 60 days in severe COVID-19 pneumonia patients with no increase in infections suggesting the importance of targeting C5a while preserving MAC.

Clinical Evidence and Therapeutic Treatments at the Time of the Coronaviruses Responsible for SARS: A Perspective and Points of view with a Focus on Vascular Endothelium

The clinical outcomes of COVID-19 patients highlight a significant minority of subjects with very rapid lethal outcomes subsequent to the almost complete healing after coronavirus infections for most of the subjects involved. In addition, the reckless use of some drugs and therapeutic protocols that have not shown any efficacy in reducing mortality in those patients where the progression of the disease was unstoppable suggests a different interpretative model in the pathogene-sis of severe cases. Starting from the clinical data already known for almost twenty years on the be-havior of human SARS coronaviruses, it is possible to develop a new hypothesis. The reference points taken into consideration are: i) the comparison of the histological evidence of the autoptic material;ii) the poor pharmacological response in subjects with severe phenotypes of the patholo-gy;iii) the common element of endotheliitis in a subgroup of the population characterized by harm-ful clinical outcomes during the evolution of the pathology. The tendency to develop widespread, massive endothelial lesions not responding to any drug therapy or other interventions necessarily plays a crucial role in the onset of the systemic and severe stage of the disease. The present perspective opens the door to a different therapeutic approach both to the full-blown phase of COVID-19 and to the preventive phase or the very first manifestations of the disease. It is imperative to pay more attention to the protection of the vascular endothelium in subjects who already have a predis-position to the development of a severe evolution of this ailment rather than to give a simple antiviral therapy together with symptomatic drugs.Copyright © 2021 Bentham Science Publishers.

Coagulopathy in COVID-19 and anticoagulation clinical trials.

Severe acute respiratory disease coronavirus 2 (SARS-COV-2) first emerged in Wuhan, China, in December 2019 and has caused a global pandemic of a scale unprecedented in the modern era. People infected with SARS-CoV-2 can be asymptomatic, moderate symptomatic or develop severe COVID-19. Other than the typical acute respiratory distress syndrome (ARDS), patients with moderate or severe COVID-19 also develop a distinctive systemic coagulopathy, known as COVID-19-associated coagulopathy (CAC), which is different from sepsis-related forms of disseminated intravascular coagulation (DIC). Endotheliopathy or endotheliitis are other unique features of CAC. The endothelial cell perturbation can further increase the risk of thrombotic events in COVID-19 patients. In this review, we will summarize the current knowledge on COVID-19 coagulopathy and the possible mechanisms for the condition. We also discuss the results of clinical trials testing methods for mitigating thrombosis events in COVID-19 patients.

The results of thrombectomy from the arteries of the lower extremities in patients infected with SARS-CoV-2 Omicron variant with different severity of respiratory failure.

GOAL: Analysis of the results of thrombectomy from the arteries of the lower extremities in patients with COVID-19 against the background of different severity of respiratory failure. MATERIALS AND METHODS: This retrospective, cohort, comparative study for the period from 05/01/2022 to 20/07/2022 included 305 patients with acute thrombosis of the arteries of the lower extremities against the background of the course of COVID-19 (SARS-CoV-2 Omicron variant). Depending on the type of oxygen support, 3 groups of patients were formed: group 1 (n = 168) - oxygen insufflation through nasal cannulas; group 2 (n = 92) - non-invasive lung ventilation; and group 3 (n = 45) - artificial lung ventilation. RESULTS: Myocardial infarction and ischemic stroke were not detected in the total sample. The highest number of deaths (group 1: 5.3%, n = 9; group 2: 72.8%, n = 67; group 3: 100%, n = 45; p < 0.0001), rethrombosis (group 1 : 18.4%, n = 31; group 2: 69.5%, n = 64; group 3: 91.1%, n = 41; p < 0.0001), and limb amputations (group 1: 9.5%, n = 16; group 2: 56.5%, n = 52; group 3: 91.1%, n = 41; p < 0.0001) was recorded in group 3 (ventilated) patients. CONCLUSION: In patients infected with COVID-19 and on artificial lung ventilation, a more aggressive course of the disease is noted, expressed in an increase in laboratory parameters (C-reactive protein, ferritin, interleukin-6, and D-dimer) of the degree of pneumonia (CT-4 in overwhelming number) and localization of thrombosis of the arteries of the lower extremities, mainly in the tibial arteries.

Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies.

The fight against coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is still raging. However, the pathophysiology of acute and post-acute manifestations of COVID-19 (long COVID-19) is understudied. Endothelial cells are sentinels lining the innermost layer of blood vessel that gatekeep micro- and macro-vascular health by sensing pathogen/danger signals and secreting vasoactive molecules. SARS-CoV-2 infection primarily affects the pulmonary system, but accumulating evidence suggests that it also affects the pan-vasculature in the extrapulmonary systems by directly (via virus infection) or indirectly (via cytokine storm), causing endothelial dysfunction (endotheliitis, endothelialitis and endotheliopathy) and multi-organ injury. Mounting evidence suggests that SARS-CoV-2 infection leads to multiple instances of endothelial dysfunction, including reduced nitric oxide (NO) bioavailability, oxidative stress, endothelial injury, glycocalyx/barrier disruption, hyperpermeability, inflammation/leukocyte adhesion, senescence, endothelial-to-mesenchymal transition (EndoMT), hypercoagulability, thrombosis and many others. Thus, COVID-19 is deemed as a (micro)vascular and endothelial disease. Of translational relevance, several candidate drugs which are endothelial protective have been shown to improve clinical manifestations of COVID-19 patients. The purpose of this review is to provide a latest summary of biomarkers associated with endothelial cell activation in COVID-19 and offer mechanistic insights into the molecular basis of endothelial activation/dysfunction in macro- and micro-vasculature of COVID-19 patients. We envisage further development of cellular models and suitable animal models mimicking endothelial dysfunction aspect of COVID-19 being able to accelerate the discovery of new drugs targeting endothelial dysfunction in pan-vasculature from COVID-19 patients.

ENDOTHELIAL INFLAMMATION AND DYSFUNCTION INDUCED BY SARS-COV-2 SPIKE PROTEIN 1 INVOLVE ADAM17 AND INTERFERON ACTIVATION PATHWAYS

Objective: COVID19 is associated with vascular inflammation. IFN-alpha (IFNa) and IFN-lambda3 (IFNl3) are potent cytokines produced in viral infections. Their effects involve interferon-stimulated genes (ISGs) and may influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. We hypothesized that S1P-induced immune/inflammatory responses in endothelial cells (EC) are mediated via IFN-activated pathways Design and methods: Human ECs were stimulated with S1P (1 mg/mL), IFNa (100ng/mL) or IFNl3 (100IU/mL). Because ACE2, ADAM17 and TMPRSS2 are important for SARS-CoV-2 infection, we used inhibitors of ADAM17 (marimastat, 3.8 nM), ACE2 (MLN4760, 440pM), and TMPRSS2 (camostat, 50 mM). Gene and protein expression was investigated by real-time PCR and immunoblotting, respectively. Vascular function was assessed in mesenteric arteries from wild-type (WT) normotensive and hypertensive (LinA3) mice and in ISG15-deficient (ISG15KO) mice. Results: S1P increased expression of IFNa (3-fold), IFNl3 (4-fold) and ISGs (2-fold) in EC (p < 0.05). EC responses to IFNa (ISG15: 16-fold) were greater than to IFNl3 (ISG15: 1.7-fold) (p < 0.05). S1P increased gene expression of IL-6 (1.3-fold), TNFa (6.2-fold) and IL-1b (3.3-fold), effects that were amplified by IFNs. Only the ADAM17 inhibitor marimastat inhibited S1P effects. IFNa and IFNl3 increase protein expression of ADAM17 (27%) and TMPRSS2 (38%). No changes were observed on ACE2 expression. This was associated with increased phosphorylation of Stat1 (134%), Stat2 (102%), ERK1/2 (42%). EC production of IL-6 was increased by IFNa (1,230pg/mL) and IFNl3 (1,124pg/mL) vs control (591pg/mL). Nitric oxide generation and eNOS phosphorylation (Ser1177) were reduced by IFNa (40%) and IFNl3 (40%). Vascular functional responses demonstrated that endothelium-dependent vasorelaxation (% Emax) in vessels from WT-mice stimulated with IFNa (67%) and IFNl3 (71%) were reduced vs control (82%) (p < 0.05). Responses were not altered in vessels from ISG15KO mice. Increased contraction was observed only in vessels from hypertensive mice treated with IFNa (9.1 ± 0.5mN vs control: 7.3 ± 0.3mN) (p < 0.05). Conclusions: In ECs, S1P, IFNa and IFNl3 increased ISG15 and IL-6 by mechanisms dependent on ADAM17. IFNs amplifies endothelial cell inflammatory responses and induced vascular dysfunction through ISG15-dependent mechanisms, with augmented effects in hypertension. Our findings demonstrate that S1P induces immune/inflammatory responses that may be important in endotheliitis associated with COVID-19. This may be especially important in the presence of cardiovascular risk factors, including hypertension.

COVID-19 and Cardiac Complication: what is new?

Coronavirus disease 2019 (COVID-19) has been reported to cause cardiovascular complications such as myocardial injury, thromboembolic events, arrhythmia, and heart failure. Multiple mechanisms-some overlapping, notably the role of inflammation and IL-6-potentially underlie these complications. The reported cardiac injury may be a result of direct viral invasion of cardiomyocytes with consequent unopposed effects of angiotensin II, increased metabolic demand, immune activation, or microvascular dysfunction. Thromboembolic events have been widely reported in both the venous and arterial systems that have attracted intense interest in the underlying mechanisms. These could potentially be due to endothelial dysfunction secondary to direct viral invasion or inflammation. Additionally, thromboembolic events may also be a consequence of an attempt by the immune system to contain the infection through immunothrombosis and neutrophil extracellular traps. Cardiac arrhythmias have also been reported with a wide range of implicated contributory factors, ranging from direct viral myocardial injury, as well as other factors, including at-risk individuals with underlying inherited arrhythmia syndromes. Heart failure may also occur as a progression from cardiac injury, precipitation secondary to the initiation or withdrawal of certain drugs, or the accumulation of des-Arg9-bradykinin (DABK) with excessive induction of pro-inflammatory G protein coupled receptor B1 (BK1). The presenting cardiovascular symptoms include chest pain, dyspnoea, and palpitations. There is currently intense interest in vaccine-induced thrombosis and in the treatment of Long COVID since many patients who have survived COVID-19 describe persisting health problems. This review will summarise the proposed physiological mechanisms of COVID-19-associated cardiovascular complications. Copyright © 2022, Anka Publishers. All rights reserved.

Herbs for Heart: Benefits for Post-Covid Cardiac Protection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused coronavirus disease 2019 (COVID-19) pandemic, which began in early December 2019, has spread quickly over the world and presented an unprecedented threat to human health. The disease is characterized by cytokine storm, resulting in endothelial inflammation/dysfunction, micro- and macro-vascular thrombosis, which may damage organs other than the lung. COVID-19 substantially impairs the cardiovascular system. According to the study published in the journal Nature Medicine, patients with COVID-19 were more likely to have a wide range of cardiovascular conditions. Thus, one of the most useful tools in the therapeutic management of post-covid cardiovascular illnesses will be cardio-protection and treatment. Despite improvements in CVD management and therapy, CVDs continue to claim more lives than other cancer types combined. As a result, there has been significant enforcement of CVD prevention in recent years. Since ancient times, people have used herbs to treat cardiovascular conditions. The journal of Clinical Phytoscience published an article in 2021 that used cluster analysis to choose 128 plants. These herbs effectively protected the heart. This study and subsequent analysis revealed that herbal remedies like Arjuna, Tribulus, and Tinospora have potent cardioprotective characteristics. The evidence for these herbs' cardiovascular protection is highlighted in the current review.

The "footprints" of COVID-19 in the tissues: Only in the lungs?

COVID-19 was identified in late 2019 and spread rapidly to become a pandemic. The causative agent is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-virus, which affects mainly the respiratory tract. SARS-CoV-2 enters the host's alveolar lung cells through the angiotensin converting enzyme (ACE2) receptor. During infection, in addition to abnormal activation of the immune system, an acute decrease in the ACE2 expression level occurs, result-ing in acute respiratory distress syndrome (ARDS) and acute lung damage. Histopathologically, diffuse alveolar damage is observed, and vascular injury appears to be very important, as the pulmonary vessels demonstrate extensive thrombosis with microangiopathy and endothelitis. The virus has also been shown to affect heart tissue, and some patients develop acute cardiovascular syndrome. Endothelitis has also been found in the heart, kidney, spleen, liver and small intestine, and thrombogenic angiopathy is observed in the skin. Vascular injury also affects the brain. In placentas from COVID-19 positive mothers, inflammation and infarcts have been observed. The aim of this literature review is to summarize emerging data on the pathophysiology of SARS-CoV-2 disease in the lungs and other target organs, with an emphasis on microscopic findings in the tissues. Progress in understanding the pathophysiology of COVID-19 is of great importance for comprehension of clinical condition and administration of optimal treatment. Copyright © Athens Medical Society.

Covid Related Thrombus or Vasculitis?

COVID is associated with cardiovascular manifestations. It worsens the pre-existing cardiovascular diseases, and newly diagnosed cardiovascular diseases are being reported with it. In our we present a case with unusual cardiac manifestation with COVID. 63-years-old, covid positive male with hypertension, hyperlipidemia and coronary artery disease with prior RCA stent was admitted for inferior STEMI.The angiogram showed instent stenosis, with distal vessels narrowing. Stent was placed in RCA. Despite this, he had persistent chest pain and ST elevation, so he was taken back to Cath lab. It confirmed patent stent. For distal vessel narrowing with ongoing pain intra-aortic balloon pump was placed. Aggrastat and heparin was continued. At the time of discharge, he had ongoing dyspnea and chest pain, which was thought to be associated with COVID. He was readmitted in six days for pericardial effusion with constriction and echocardiographic finding of tamponade. He had elevated inflammatory markers and liver enzyme. With recent COVID infection, elevated inflammatory markers, echo findings and known distal coronary artery narrowing there was a concern of vasculitis and pericarditis. He was started on steroid and colchicine with significant improvement. COVID can cause direct myocardial injury or indirect injury due to altered myocardial demandsupply. The pericardial involvement is associated with heightened inflammation and increased vascularity. Interestingly, our patient who initially presented as ACS had resolution of symptoms with steroids. Could ACS symptoms not resolving with antiplatelets and stenting be a part of inflammatory picture of COVID? In post-COVID autopsy and surgical tissue diffuse lymphocytic endotheliitis and apoptotic bodies are seen in the vascular beds. Vasculitis lesion in skin and Kawasaki's disease is reported in adolescents and children. However, adult-onset vasculitis is still to be studied.

Providing Coloproctological Care in Conditions of Covid-19: Surgical Treatment Methods, Clinical and Morphological Characteristics of Patients with Exacerbation of Chronic Hemorrhoids, after a Previous Coronavirus Infection (Covid-19)

Aim: to compare and evaluate the experience gained in the surgical treatment of patients with complicated forms of chronic hemorrhoids, after suffering from Covid-19, taking into account the clinical and morphological picture, and justifying pre-and postoperative rehabilitation programs. Method(s): This study presents our own research results, analysis of experts, and rehabilitation documentation obtained from 12 persons with medium and severe Covid-19, stage 3-4, who underwent pre-and postoperative rehabilitation with transrectal low-intensity laser therapeutic device ALP-01 "Laton" intravenous ozone therapy using the "TEOZON" medical Ozonator. Macroscopically -fixed in a buffered formalin solution, hemorrhoids from 1 to 4 cm in diameter, dense elastic consistency, gray-brown in color, t-sections show subtotal acutely dilated vessels filled with dark brown, dryish, crumbling blood convolutions. The signs of endotheliitis and destructive-productive thrombovasculitis in hemorrhoids identified in all cases confirmed systemic endothelial dysfunction in Covid-19 with damage not only to important organs and systems but also leading to an exacerbation of chronic processes in any region of the human body. Result(s): The observation results allowed not only to confirm the good effect of minimally invasive technologies for surgical treatment of hemorrhoids with pre-and postoperative rehabilitation programs, but also to study the morphological picture of chronic hemorrhoid exacerbation in patients who underwent COVID-19. Conclusion(s): COVID-19 has a rather frequent, yet scarcely described complication in the form of exacerbation or manifestation of chronic hemorrhoids. Pathomorphological examination of hemorrhoids following a hemorrhoidectomy confirms the correctness of the patient-oriented approach using minimally invasive surgical treatment technologies with pre-and postoperative rehabilitation programs in patients with exacerbations of chronic hemorrhoids after suffering from COVID-19.

Characterization of the Proteomic Changes via SARS-CoV-2 Infection or Vaccination in the COVID-19 Community Research Partnership (CCRP)

Background. There remain important gaps in knowledge concerning the effects of SARS-CoV-2 infection or vaccination on the human blood proteome. Methods. The CCRP is a longitudinal surveillance study with information on SARS-CoV-2 infections, vaccinations and associated humoral immune responses in over 37,000 individuals. We selected a sample of blood spots cards (n=510) from serum antibody studies obtained between October 2020 and April 2021 for mass spectrometry proteomics analysis covering 540 unique plasma proteins. We analyzed the quantified protein differences based on dried blood samples obtained before and after infection or vaccination among previously non-infected individuals (immune naive) after adjustment for batch effects, age, sex, or prior diagnosis of cancer, cardiovascular or autoimmune disease, or diabetes. The majority of infected individuals were minimally symptomatic. Differentially expressed proteins were considered significant with an FDR adjusted p-value of < 0.05 and log2 fold change (L2FC) >0.2. Results. We found 11 and 12 proteins differentially expressed proteins in the naive/infected and naive/vaccinated people respectively, of which 10 were shared. Hepatocyte growth factor receptor (HGF) was upregulated (L2FC 0.24;p < 0.001) only in those who were infected while fibrillarin (L2FC -0.24;p< 0.001) and lambdacrystallin homolog (L2FC -0.29, p < 0.001) were downregulated only in the vaccinated samples (Fig 1). The remaining DE protein were associated with a wide array of functions including metabolic, cytostructural, extracellular matrix and DNA regulatory processes. Conclusion. We found changes in the proteome both from infection and vaccination. HGF, elevated in the infected, has been associated with endothelial inflammation, upregulation of pro-inflammatory cytokines to reduce lung fibrosis and is known to promote tissue repair. Fibrillarin, downregulated in the vaccinated, has been associated with higher rates of bacterial and viral clearance, inflammation reduction, and increased cell survival. These findings suggest detectable complex inflammation from mild to moderate infections. Further investigation is required to understand the mechanism of action and clinical implication of these findings.