Contemporary use of cardiac imaging for COVID-19 patients: a three center experience defining a potential role for cardiac MRI

The pandemic of coronavirus disease 2019 (COVID-19) secondary to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has bestowed an unprecedented challenge upon us, resulting in an international public health emergency. COVID-19 has already resulted in >?1,600,000 deaths worldwide and the fear of a global economic collapse. SARS-CoV-2 is notorious for causing acute respiratory distress syndrome, however emerging literature suggests various dreaded cardiac manifestations associated with high mortality. The mechanism of myocardial damage in COVID-19 is unclear but thought to be multifactorial and mainly driven by the host’s immune response (cytokine storm), hypoxemia and direct myocardial injury by the virus. Cardiac manifestations from COVID-19 include but are not limited to, acute myocardial injury, cardiac arrhythmias, congestive heart failure and acute coronary syndrome. Cardiac imaging is paramount to appropriately diagnose and manage the cardiac manifestations of COVID-19. Herein, we present cardiac imaging findings of COVID-19 patients with biomarker and imaging confirmed myocarditis to provide insight regarding the variable manifestations of COVID-19 myocarditis via Cardiac MRI (CMR) coupled with CMR-edema education along with recommendations on how to incorporate advanced CMR into the clinicians’ COVID-19 armamentarium.

     

冠状病毒疾病2019发病机制若干热点问题的思考

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）所致冠状病毒疾病2019（COVID-19）已构成国际关注的突发公共卫生事件。COVID-19传染性强,可导致患者出现严重呼吸道感染和多器官系统功能损害。COVID-19发病机制尚不明确,我们推测SARS-CoV-2直接致宿主靶细胞损伤及机体免疫炎症反应紊乱可能是COVID-19的主要致病机制。本文基于相关研究领域的进展,对COVID-19发病机制中的若干热点问题进行分析和讨论,并提出思考。     

Hypertransaminasemia in the course of infection with SARS-CoV-2: Incidence and pathogenetic hypothesis

In patients infected with severe acute respiratory syndrome coronavirus 2, the respiratory symptoms, such as fever, cough and dyspnea, are the most frequent clinical manifestations. These patients may also present with less well-defined symptoms like diarrhea, nausea, vomiting and/or abdominal discomfort both at the time of diagnosis and during the clinical course. In a few cases, these symptoms may also present before the appearance of respiratory symptoms. To penetrate the body, Severe acute respiratory syndrome coronavirus 2 uses ACE2 receptors, which are present not only in respiratory epithelium but also in gastrointestinal mucosa and liver cholangiocytes. In several cases, viral RNA is detectable in the stool of patients with coronavirus disease 2019 (COVID-19). The liver damage seems to show a multifactorial origin. About 2%-11% of patients with COVID-19 have known underlying hepatic pathologies. In 14%-53% of COVID-19 cases, there is an alteration of the indices of liver cytolysis and is more frequently observed in severe forms of COVID-19, especially during hospitalization.     

Distinctive features of severe SARS-CoV-2 pneumonia

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.     

Acute myocardial injury in patients with COVID-19: Possible mechanisms and clinical implications

Severe acute respiratory syndrome coronavirus 2 infection affects not only the lungs, but also the cardiovascular system, having a major impact on patients’ outcomes. Myocardial injury (MI) occurs in the context of coronavirus infectious disease 2019 (COVID-19) and is associated with a higher risk of severe clinical outcome and mortality. COVID-19-related MI can have various clinical manifestations, of which the main ones are myocarditis, stress cardiomyopathy, acute coronary syndrome, and pulmonary embolism. The exact mechanisms of how MI occurs in these patients are not yet fully known. Direct injury, through direct viral myocardial invasion, and indirect injury, through interaction with angiotensin I converting enzyme 2, increased inflammation, and thrombocyte and endothelial dysfunction, could be involved in acute MI in patients with COVID-19. A better understanding of these multiple potential mechanisms may help to develop new targeted therapeutic strategies. The purpose of this review is to provide the current understanding of the potential mechanisms involved in MI induced by COVID-19 and to discuss the current progress in the therapeutic strategies.     

Nonalcoholic fatty liver disease and COVID-19: An epidemic that begets pandemic

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, affecting all the individuals across the planet. COVID-19 has gained significant attention due to its high prevalence among individuals with diabetes, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome. NAFLD is the hepatic manifestation of metabolic syndrome and can be associated with a high risk of developing type 2 diabetes. The association of COVID-19 and NAFLD has also gained more attention because NAFLD is highly associated with the epidemic of obesity. NAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19, independent of metabolic syndrome. Importantly, it is not yet clear whether the epidemics of obesity and NAFLD have perpetuated the current pandemic of COVID-19. Further research is urgently needed to assess the following: (1) Whether NAFLD is a high risk factor for SARS-CoV-2 infection; (2) Whether NAFLD is associated with the severe form of COVID-19; and (3) Whether the presence of NAFLD can explain the racial variation in the morbidity and mortality associated with COVID-19. This review summarizes the interactions between COVID-19 and NAFLD, mechanism of liver injury by COVID-19, and effect of lockdown due to COVID- 19 on patients with NAFLD.     

Prevention,diagnostic evaluation,management and prognostic implications of liver disease in critically ill patients with COVID-19

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.     

Liver injury in COVID-19: Holds ferritinophagy-mediated ferroptosis accountable

Even in patients without a history of liver disease, liver injury caused by coronavirus disease 2019 (COVID-19) is gradually becoming more common. However, the precise pathophysiological mechanisms behind COVID-19's liver pathogenicity are still not fully understood. We hypothesize that inflammation may become worse by cytokine storms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Elevated ferritin levels can initiate ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4), which leads to iron elevation, and ferroptosis. In COVID-19 patients, ferroptosis can be restricted to reduce disease severity and liver damage by targeting NCOA4-mediated ferritinophagy. To confirm the role of ferritinophagy-mediated ferroptosis in SARS-CoV-2 infection, further research is required.     

Remarkable gastrointestinal and liver manifestations of COVID-19: A clinical and radiologic overview

The coronavirus disease 2019 (COVID-19) raging around the world still has not been effectively controlled in most countries and regions. As a severe acute respiratory syndrome coronavirus, in addition to the most common infectious pneumonia, it can also cause digestive system disease such as diarrhea, nausea, vomiting, liver function damage, etc. In medical imaging, it manifests as thickening of the intestinal wall, intestinal perforation, pneumoperitoneum, ascites and decreased liver density. Angiotensin-converting enzyme 2 has great significance in COVID-19-related digestive tract diseases. In this review, we summarized the data on the clinical and imaging manifestations of gastrointestinal and liver injury caused by COVID-19 so far and explored its possible pathogenesis.     

Liver dysfunction-related COVID-19: A narrative review

The coronavirus 2019 disease (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2. This disease was designated by the World Health Organization as a pandemic on March 11, 2020, which is not seen before. There are no classical features among the cases of the disease owing to the involvement of nearly all body tissues by the virus. Hepatic involvement is one of the characteristics of the COVID-19 course. There are six possible mechanisms of such involvement: Direct virus injury, drug-induced effect, inflammatory cytokine storm, hypoxia-ischemic destruction, abnormalities in liver function tests, and pre-existing chronic liver diseases. Liver abnormalities are seen commonly in the severe or critical stage of COVID-19. Therefore, these abnormalities determine the COVID-19 severity and carry a high rate of morbidity and mortality. The elderly and patients with comorbidities like diabetes mellitus and hypertension are more vulnerable to liver involvement. Another issue that needs to be disclosed is the liver manifestations following the COVID-19 vaccination, such as autoimmune hepatitis. Of note, complete vaccination with third and fourth booster doses is necessary for patients with previous chronic liver diseases or those who have been subjected to liver transplantation. This review aims to explore the various aspects of liver dysfunction during the COVID-19 course regarding the epidemiological features, predisposing factors, pathophysiological mechanisms, hepatic manifestations due to COVID-19 or following vaccination, role of liver function tests in the assessment of COVID-19 severity, adverse effects of the therapeutic agents for the disease, and prognosis.     

COVID-19 combined with liver injury: Current challenges and management

Coronavirus disease 2019 (COVID-19) combined with liver injury has become a very prominent clinical problem. Due to the lack of a clear definition of liver injury in patients with COVID-19, the different selection of evaluation parameters and statistical time points, there are the conflicting conclusions about the incidence rate in different studies. The mechanism of COVID-19 combined with liver injury is complicated, including the direct injury of liver cells caused by severe acute respiratory syndrome coronavirus 2 replication and liver injury caused by cytokines, ischemia and hypoxia, and drugs. In addition, underlying diseases, especially chronic liver disease, can aggravate COVID-19 liver injury. In the treatment of COVID-19 combined with liver injury, the primary and basic treatment is to treat the etiology and pathogenesis, followed by support, liver protection, and symptomatic treatment according to the clinical classification and severity of liver injury. This article evaluates the incidence, pathogenesis and prevention and treatment of COVID-19 combined with liver injury, and aims to provide countermeasures for the prevention and treatment of COVID-19 combined with liver injury.     

Multiple immune function impairments in diabetic patients and their effects on COVID-19

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, poses a significant threat to public health worldwide, and diabetes is considered a risk factor for the rapid progression and poor prognosis of COVID-19. Limited immune function is a clinical feature of COVID-19 patients, and diabetes patients have defects in innate and adaptive immune functions, which may be an important reason for the rapid progression and poor prognosis of COVID-19 in patients with diabetes. We review the possible multiple effects of immune impairment in diabetic patients on the immune responses to COVID-19 to provide guidance for the diagnosis and treatment of diabetic patients with COVID-19.     

Liver transplantation during global COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory disease respiratory syndrome coronavirus-2 has significantly impacted the health care systems globally. Liver transplantation (LT) has faced an unequivocal challenge during this unprecedented time. This targeted review aims to cover most of the clinical issues, challenges and concerns about LT during the COVID-19 pandemic and discuss the most updated literature on this rapidly emerging subject.     

Recommendations for perinatal and neonatal surgical management during the COVID-19 pandemic

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has spread rapidly around the world and is a significant threat to global health. Patients in the Neonatal Surgery Department have rapidly progressing diseases and immature immunity, which makes them vulnerable to pulmonary infection and a relatively higher mortality. This means that these patients require multidisciplinary treatment including early diagnosis, timely transport, emergency surgery and intensive critical care. The COVID-19 pandemic poses a threat to carrying out these treatments. To provide support for the health protection requirements of the medical services in the Neonatal Surgery Department, we developed recommendations focusing on patient transport, surgery selection and protection requirements with the aim of improving treatment strategies for patients and preventing infection in medical staff during the current COVID-19 pandemic.     

COVID-19 and the digestive system: A comprehensive review

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is spreading at an alarming rate, and it has created an unprecedented health emergency threatening tens of millions of people worldwide. Previous studies have indicated that SARS-CoV-2 ribonucleic acid could be detected in the feces of patients even after smear-negative respiratory samples. However, demonstration of confirmed fecal-oral transmission has been difficult. Clinical studies have shown an incidence rate of gastrointestinal (GI) symptoms ranging from 2% to 79.1% in patients with COVID-19. They may precede or accompany respiratory symptoms. The most common GI symptoms included nausea, diarrhea, and abdominal pain. In addition, some patients also had liver injury, pancreatic damage, and even acute mesenteric ischemia/thrombosis. Although the incidence rates reported in different centers were quite different, the digestive system was the clinical component of the COVID-19 section. Studies have shown that angiotensin-converting enzyme 2, the receptor of SARS-CoV-2, was not only expressed in the lungs, but also in the upper esophagus, small intestine, liver, and colon. The possible mechanism of GI symptoms in COVID-19 patients may include direct viral invasion into target cells, dysregulation of angiotensin-converting enzyme 2, immune-mediated tissue injury, and gut dysbiosis caused by microbiota. Additionally, numerous experiences, guidelines, recommendations, and position statements were published or released by different organizations and societies worldwide to optimize the management practice of outpatients, inpatients, and endoscopy in the era of COVID-19. In this review, based on our previous work and relevant literature, we mainly discuss potential fecal-oral transmission, GI manifestations, abdominal imaging findings, relevant pathophysiological mechanisms, and infection control and prevention measures in the time of COVID-19.     

Stem cell therapy: A promising treatment for COVID-19

Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. SARS-CoV-2 is an RNA virus and has a glycosylated spike (S) protein used for genome encoding. COVID-19 can lead to a cytokine storm and patients usually have early respiratory signs and further secondary infections, which can be fatal. COVID-19 has entered an emergency phase, but there are still no specific effective drugs for this disease. Mesenchymal stem cells (MSCs) are multipotent stromal cells, which cause antiapoptosis and can repair damaged epithelial cells. Many clinical trials have proved that MSC therapy could be a potential feasible therapy for COVID-19 patients, especially those with acute respiratory distress syndrome, without serious adverse events or toxicities. However, more studies are needed in the future, in order to confirm the effect of this therapy.     

Non-pulmonary involvement in COVID-19: A systemic disease rather than a pure respiratory infection

During the early phase of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), diagnosis was difficult due to the diversity in symptoms and imaging findings and the variability of disease presentation. Pulmonary manifestations are reportedly the main clinical presentations of COVID-19 patients. Scientists are working hard on a myriad of clinical, epidemiological, and biological aspects to better understand SARS-CoV-2 infection, aiming to mitigate the ongoing disaster. Many reports have documented the involvement of various body systems and organs apart from the respiratory tract including the gastrointestinal, liver, immune system, renal, and neurological systems. Such involvement will result in diverse presentations related to effects on these systems. Other presentations such as coagulation defects and cutaneous manifestation may also occur. Patients with specific comorbidities including obesity, diabetes, and hypertension have increased morbidity and mortality risks with COVID-19.     

Use of convalescent plasma in COVID-19 patients with immunosuppression

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID-19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune-deficient and immune-suppressed patients with COVID-19 warrants further investigation.     

Post-COVID-19 interstitial lung disease presenting with profound hypoxemia: Report of three cases demonstrating a good response to high-dose corticosteroid therapy

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to critical pneumonia, although the clinical courses vary. In some cases, COVID-19 pneumonia causes secondary pulmonary fibrosis, which can retain radiological changes and prolong respiratory symptoms. Interstitial lung disease (ILD) secondary to COVID-19 is thought to be caused by multiple pathologies, such as excessive cytokines and abnormal repair processes elaborated by lung cells (epithelium, mesenchyme, and alveolar macrophages) after lung injury rather than viral invasion itself. Immunosuppression therapy may improve chronic respiratory symptoms and radiological changes in post-COVID-19 ILD, although the treatment is not yet established. Herein, we report three patients with post-COVID-19 ILD who presented with profound hypoxemia that had a good response to high-dose corticosteroid therapy. Further and larger studies are needed to establish post-COVID-19 ILD.     

Management of neurosurgical patients during coronavirus disease 2019 pandemics: The Ljubljana,Slovenia experience

The novel coronavirus disease 2019 (COVID-19) is an emerging disease, caused by severe acute respiratory syndrome coronavirus-2. It bears unique biological characteristics, clinical symptoms and imaging manifestations, therefore presenting an important and urgent threat to global health. As a result, a new public health crisis arose, threatening the world with the spread of the 2019 novel coronavirus. Despite the maximal worldwide public health responses aimed at containing the disease and delaying its spread, many countries have been confronted with a critical care crisis, and even more, countries will almost certainly follow. In Slovenia, the COVID-19 has struck the health system immensely and among all the specialities, neurosurgery has also been experiencing difficulties in the service, not only in regular, elective surgeries but especially during emergencies. The management of these neurosurgical patients has become more difficult than ever. We describe our protocol in the management of neurosurgical patients in the University Medical Centre Ljubljana, Slovenia and how neurosurgical pathology was tackled during the pandemics.