Intestinal Abnormalities in Patients With SARS-CoV-2 Infection: Histopathologic Changes Reflect Mechanisms of Disease.

Approximately 20% of patients with symptomatic syndrome-associated coronavirus-2 (SARS-CoV-2) infection have gastrointestinal bleeding and/or diarrhea. Most are managed without endoscopic evaluation because the risk of practitioner infection outweighs the value of biopsy analysis unless symptoms are life-threatening. As a result, much of what is known about the gastrointestinal manifestations of coronavirus disease-2019 (COVID-19) has been gleaned from surgical and autopsy cases that suffer from extensive ischemic injury and/or poor preservation. There are no detailed reports describing any other gastrointestinal effects of SARS-CoV-2 even though >3,000,000 people have died from COVID-19 worldwide. The purpose of this study is to report the intestinal findings related to SARS-CoV-2 infection by way of a small case series including one with evidence of direct viral cytopathic effect and 2 with secondary injury attributed to viral infection. Infection can be confirmed by immunohistochemical stains directed against SARS-CoV-2 spike protein, in situ hybridization for spike protein-encoding RNA, and ultrastructural visualization of viruses within the epithelium. It induces cytoplasmic blebs and tufted epithelial cells without inflammation and may not cause symptoms. In contrast, SARS-CoV-2 infection can cause gastrointestinal symptoms after the virus is no longer detected, reflecting systemic activation of cytokine and complement cascades rather than direct viral injury. Reversible mucosal ischemia features microvascular injury with hemorrhage, small vessel thrombosis, and platelet-rich thrombi. Systemic cytokine elaboration and dysbiosis likely explain epithelial cell injury that accompanies diarrheal symptoms. These observations are consistent with clinical and in vitro data and contribute to our understanding of the protean manifestations of COVID-19.

SARS-CoV-2 and Placental Pathology: Malperfusion Patterns Are Dependent on Timing of Infection During Pregnancy.

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at different points in the pregnancy timeline may affect maternal and fetal outcomes remains unknown. We sought to characterize the impact of SARS-CoV-2 infection proximate and remote from delivery on placental pathology. We performed a secondary analysis of placental pathology from a prospective cohort of universally tested SARS-CoV-2 positive women >20 weeks gestation at 1 institution. Subjects were categorized as having acute or nonacute SARS-CoV-2 based on infection <14 or ≥14 days from delivery admission, respectively, determined by nasopharyngeal swab, symptom history, and serologies, when available. A subset of SARS-CoV-2 negative women represented negative controls. Placental pathology was available for 90/97 (92.8%) of SARS-CoV-2 positive women, of which 26 were from women with acute SARS-CoV-2 infection and 64 were from women with nonacute SARS-CoV-2. Fetal vascular malperfusion lesions were significantly more frequent among the acute SARS-CoV-2 group compared with the nonacute SARS-CoV-2 group (53.8% vs. 18.8%; P=0.002), while frequency of maternal vascular malperfusion lesions did not differ by timing of infection (30.8% vs. 29.7%; P>0.99). When including 188 SARS-CoV-2 negative placentas, significant differences in frequency of fetal vascular malperfusion lesions remained between acute, nonacute and control cases (53.8% vs. 18.8% vs. 13.2%, respectively; P<0.001). No differences were noted in obstetric or neonatal outcomes between acutely and nonacutely infected women. Our findings indicate timing of infection in relation to delivery may alter placental pathology, with potential clinical implications for risk of thromboembolic events and impact on fetal health.

Bowel ischemia as onset of COVID-19 in otherwise asymptomatic patients with persistently negative swab.

BACKGROUND: Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS-CoV-2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID-19) and with persistently real-time polymerase chain reaction negative pharyngeal swab. METHODS: Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co-existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID-19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS-CoV-2 on resected tissue was performed. RESULTS: All tested samples were strongly positive for SARS-CoV-2. CONCLUSIONS: This is the first case report in which patients with severe intestinal symptoms presented a marked SARS-CoV-2 positivity in the resected tissues, without any usual clinical manifestations of COVID-19. These results suggest that the patients might be infected with SARS-CoV-2 presenting acute abdominal distress but without respiratory or constitutional symptoms.

Bowel Ischemia in COVID-19 Infection: One-Year Surgical Experience.

BACKGROUND: COVID-19 is a deadly multisystemic disease, and bowel ischemia, the most consequential gastrointestinal manifestation, remains poorly described. Our goal is to describe our institution's surgical experience with management of bowel ischemia due to COVID-19 infection over a one-year period. METHODS: All patients admitted to our institution between March 2020 and March 2021 for treatment of COVID-19 infection and who underwent exploratory laparotomy with intra-operative confirmation of bowel ischemia were included. Data from the medical records were analyzed. RESULTS: Twenty patients were included. Eighty percent had a new or increasing vasopressor requirement, 70% had abdominal distension, and 50% had increased gastric residuals. Intra-operatively, ischemia affected the large bowel in 80% of cases, the small bowel in 60%, and both in 40%. Sixty five percent had an initial damage control laparotomy. Most of the resected bowel specimens had a characteristic appearance at the time of surgery, with a yellow discoloration, small areas of antimesenteric necrosis, and very sharp borders. Histologically, the bowel specimens frequently have fibrin thrombi in the small submucosal and mucosal blood vessels in areas of mucosal necrosis. Overall mortality in this cohort was 33%. Forty percent of patients had a thromboembolic complication overall with 88% of these developing a thromboembolic phenomenon despite being on prophylactic pre-operative anticoagulation. CONCLUSION: Bowel ischemia is a potentially lethal complication of COVID-19 infection with typical gross and histologic characteristics. Suspicious clinical features that should trigger surgical evaluation include a new or increasing vasopressor requirement, abdominal distension, and intolerance of gastric feeds.

Timing and causes of death in severe COVID-19 patients.

BACKGROUND: Previous studies reporting the causes of death in patients with severe COVID-19 have provided conflicting results. The objective of this study was to describe the causes and timing of death in patients with severe COVID-19 admitted to the intensive care unit (ICU). METHODS: We performed a retrospective study in eight ICUs across seven French hospitals. All consecutive adult patients (aged ≥ 18 years) admitted to the ICU with PCR-confirmed SARS-CoV-2 infection and acute respiratory failure were included in the analysis. The causes and timing of ICU deaths were reported based on medical records. RESULTS: From March 1, 2020, to April 28, 287 patients were admitted to the ICU for SARS-CoV-2 related acute respiratory failure. Among them, 93 patients died in the ICU (32%). COVID-19-related multiple organ dysfunction syndrome (MODS) was the leading cause of death (37%). Secondary infection-related MODS accounted for 26% of ICU deaths, with a majority of ventilator-associated pneumonia. Refractory hypoxemia/pulmonary fibrosis was responsible for death in 19% of the cases. Fatal ischemic events (venous or arterial) occurred in 13% of the cases. The median time from ICU admission to death was 15 days (25th-75th IQR, 7-27 days). COVID-19-related MODS had a median time from ICU admission to death of 14 days (25th-75th IQR: 7-19 days), while only one death had occurred during the first 3 days since ICU admission. CONCLUSIONS: In our multicenter observational study, COVID-19-related MODS and secondary infections were the two leading causes of death, among severe COVID-19 patients admitted to the ICU.

Concomitant acute limb ischemia and multiple acute ischemic strokes complicating COVID-19: a case report.

Since the spread of the coronavirus disease 2019 (COVID-19) pandemic, cardiovascular complications are interestingly increasing, particularly thrombotic events, especially in those requiring intensive care. Venous thromboembolism is well known to occur in patients infected by the SARS-CoV-2, but only a few arterial thromboembolism cases have been previously reported. Herein, we report the case of a COVID-19 complicated by a concomitant acute right limb ischemia and multiple acute ischemic strokes. This rare case emphasizes the hypercoagulable state described in COVID-19 patients and the need for anticoagulation therapy to prevent these severe complications.

A review of acute limb ischemia in COVID-positive patients.

This literature review discusses the current evidence on acute limb ischemia (ALI) in patients with COVID-19. Throughout the pandemic, these patients have been at increased risk of arterial thrombotic events and subsequent mortality as a result of a hypercoagulable state. The exact mechanism of thrombosis is unknown; however arterial thrombosis may be due to invasion of endothelial cells via angiotensin-converting enzyme 2 (ACE2) receptors, endothelial injury from inflammation, or even free-floating aortic thrombus. Multiple studies have been performed evaluating the medical and surgical management of these patients; the decision to proceed with operative intervention is dependent on the patient's clinical status as it relates to COVID-19 and morbidity of that disease. The interventions afforded typically include anticoagulation in patients undergoing palliation; alternatively, thrombectomy (endovascular and open) is utilized in other patients. There is a high risk of rethrombosis, despite anticoagulation, given persistent endothelial injury from the virus. Postoperative mortality can be high in these patients.

Acute Lower-Extremity Ischemia in a Patient with COVID-19.

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has become a global pandemic. The typical symptoms are fever, cough, and shortness of breath, but the disease can present with atypical signs, including those associated with a hypercoagulable state. These signs include deep venous thrombosis, pulmonary embolism, ischemic stroke, and acute coronary syndrome. Herein, we present the case of acute bilateral lower-extremity ischemia as a thromboembolic complication in a patient with COVID-19. CASE REPORT A 76-year-old woman presented with acute bilateral lower-extremity ulcerations covered with eschar formation of several weeks' duration. During her hospital course, she underwent a test for COVID-19 and the result was positive. An angiogram of the patient's lower extremities showed occlusions of the right distal posterior tibial artery, right mid-distal anterior tibial artery, right dorsalis pedis artery, left mid-distal anterior tibial artery, left dorsalis pedis artery, and left popliteal vein. Tissue plasminogen activator was administered to treat the occlusions. On the following day, the patient had an acute decline in her neurologic state and was emergently intubated. A computed tomography scan of the brain confirmed a subarachnoid hemorrhage requiring reversal of tissue plasminogen activator. The patient was transitioned to comfort care and ultimately died. CONCLUSIONS In conclusion, acute limb ischemia should be acknowledged as a rare complication associated with COVID-19. It is important to raise awareness of arterial thrombosis as a possible complication of the hypercoagulable state caused by SARS-CoV-2 because prompt recognition is essential for early diagnosis and treatment. These actions could have a significant impact on patients' overall outcome.

Bilateral Acute Lower Limb Ischemia Secondary to COVID-19.

COVID-19 has to date affected over 5 million people worldwide and caused in excess of 300000 deaths. One of the principal finding is that of a thrombotic tendency within the lungs leading to high mortality. There have been increasing number of reports of peripheral arterial thrombosis as well. Most cases of arterial thrombosis is noted in patient in intensive care setting. Here-in we report a case of acute bilateral lower limb arterial thrombosis in a patient recovering at home with mild COVID-19 symptoms, highlighting that patients with milder symptoms may also suffer from prothrombotic state resulting in acute arterial occlusions. Arterial thrombosis should be suspected in these patients despite the absence of predisposing factors.

Unusual arterial thrombotic events in Covid-19 patients.

INTRODUCTION: COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated. OBJECTIVES: To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event. MATERIAL AND METHODS: We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis. RESULTS: From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy. CONCLUSION: Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated.

A cross-sectional study evaluating hospitalization rates for chronic limb-threatening ischemia during the COVID-19 outbreak in Campania, Italy.

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown (n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 ± 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32-0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions.

Fisiopatología de la enfermedad cardiovascular en pacientes con COVID-19. Isquemia, trombosis y disfunción cardiaca / Physiopathology of cardiovascular disease in patients with COVID-19. Ischemia, thrombosis and heart failure

Las complicaciones cardiovasculares tienen una alta prevalencia en los pacientes con COVID-19 y son motivo frecuente de hospitalización, mortalidad y secuelas. En está revisión se describen los principales mecanismos fisiopatológicos implicados en la aparición de estas complicaciones. Tras la viremia inicial, se produce una infiltración y reproducción en los pulmónes, con activación del sistema inmunitario, liberación de citocinas y generación de un estado proinflamatorio con sepsis y fallo multiorgánico. El daño miocárdico puede deberse a una afección viral directa con respuesta inflamatoria local, o indirectamente a una inflamación sistémica inapropiada con marcada liberación de citocinas. Además, se genera un estado protrombótico que, junto con la afección viral vascular, pueden desencadenar eventos trombóticos e isquémicos secundarios a daño microvascular o inestabilización de placas de ateroma previas. Son necesarios nuevos estudios para esclarecer la fisiopatología tras estos eventos cardiovasculares y contribuir al desarrollo de nuevos tratamientos efectivos

Cardiovascular complications are highly prevalent in patients with COVID-19 and frequently lead to hospitalization, death and long-term morbidity. This article describes the principle pathophysiological mechanisms involved in the development of these complications. After the initial viremia, viralinvasión and replication occurs in the lungs, accompanied by immune system activation, cytokine release and the induction of a proinflammatory state, with sepsis and multiorgan failure. Myocardial injury could be due to the direct effect of viralinvasión and a local inflammatory response or to the indirect effect of inappropriate systemic inflammation involving a cytokine storm. Furthermore, the development of a prothrombotic state, together with vascular disease due to the virus, could trigger ischemic and thrombotic events secondary to microvascular damage or to the destabilization of pre-existing atheromatous plaque. New research is needed to reveal the pathophysiological mechanisms underlying these cardiovascular events and to support the development of effective new treatments

Acroisquemia aguda en tiempos de COVID-19. Clínica, evolución y hallazgos de laboratorio / Acute acro-ischemia in the child at the time of COVID-19. Clinical, evolution and laboratory findings

Un nuevo coronavirus llamado coronavirus 2 del síndrome respiratorio agudo severo (SARS-CoV-2), causante de una pandemia global, afecta a la población pediátrica con unas características clínicas diferentes a las de los adultos. Las lesiones dermatológicas acroisquémicas que se pueden asociar, se manifiestan más en pacientes jóvenes sin cuadro respiratorio. Se presentan tres casos clínicos con estudios analíticos, que incluyen determinación de anticuerpos neutralizantes por inmunocromatografía. En ninguno de los casos se ha podido demostrar la participación del SARS-CoV-2 como agente implicado. El término de "acroisquemia aguda en el niño en tiempos de COVID-19" parece ser el término más adecuado hasta tener un mayor conocimiento del cuadro

A new coronavirus called coronavirus 2 of severe acute respiratory syndrome (SARSCoV-2), causing a global pandemic, affects the pediatric population with some characteristics different from those of adults. The acro-ischemic dermatological lesions that can be associated, are manifested more in young patients without respiratory symptoms. Three clinical cases with analytical studies that include neutralizing antibody determinations by immunochromatography are presented. In none of these cases the SARS-CoV-2 appears to be an involved agent. The term "acute acro-ischemia in the child in the times of the Covid-19" seems to be the best term until there is a better understanding of the disease

Lesiones cutáneas acro-isquémicas durante la epidemia COVID-19 / Acro-ischemic skin lesions during COVID-19 epidemic

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Rehabilitative of COVID-19 patients with acute lower extremity Ischemia and amputation.

OBJECTIVE: To evaluate the clinical characteristics and rehabilitation management of patients who undergo amputation for COVID-19-associated coagulopathy. METHODS: Clinical and laboratory data for 3 patients were analysed and their rehabilitative management discussed. RESULTS: The medical records of 3 patients who had undergone amputation due to acute lower extremity ischaemia and who were provided with rehabilitation in our COVID-19 unit were reviewed. CONCLUSION: Coagulation changes related to SARS-CoV-2 may complicate recovery from this devastating disease. The rehabilitation management of amputated patients for COVID-19 acute lower extremity ischaemia is based on a multilevel approach for clinical, functional, nutritional and neuropsychological needs. Based on this limited experience, a dedicated programme for this specific group of patients seems advantageous to warrant the best functional outcome and quality of life.

Superior Mesenteric Artery Thrombosis and Acute Intestinal Ischemia as a Consequence of COVID-19 Infection.

BACKGROUND The novel COVID-19 disease caused by the SARS-CoV-2 virus is a highly infectious disease that originated in Wuhan, China, and has rapidly spread throughout the world. In addition to respiratory complications, the virus has also been implicated in damage to other organ systems as well as coagulopathy. The present report describes the first presumptive case of COVID-19-associated acute superior mesenteric artery thrombosis and acute intestinal ischemia. CASE REPORT A 55-year old man presented to the emergency department with nausea, generalized abdominal pain and diarrhea; he denied having a fever or any respiratory symptoms. Computed tomography (CT) of the abdomen and pelvis revealed bilateral pulmonary ground-glass opacities. He tested positive for SARS-CoV-2, and was treated with hydroxychloroquine, azithromycin and ceftriaxone, and was discharged home after five days of inpatient treatment. One week later, the patient returned with recurrent nausea, vomiting and worsening diffuse abdominal pain. A CT scan of the abdomen showed a 1.6-cm clot, causing high grade narrowing of the proximal superior mesenteric artery and bowel ischemia. The patient emergently underwent exploratory laparotomy, thromboembolectomy and resection of the ischemic small bowel. A post-operative complete hypercoagulable workup was unrevealing. CONCLUSIONS Despite the absence of respiratory symptoms, patients infected with SARS-CoV-2 may show atypical presentations, such as gastrointestinal symptoms. Clinicians managing patients with suspected or confirmed SARS-CoV-2 infection during the COVID-19 pandemic should monitor these patients for potential complications that may arise from this disease.