Neuropathologic findings of patients with COVID-19: a systematic review.

BACKGROUND: Despite the expanding literature that discusses insights into the clinical picture and mechanisms by which the SARS-CoV-2 virus invades the nervous system, data on the neuropathologic findings of patients who died following SARS-CoV-2 infection is limited. METHODS: A broad literature search was done for published articles that reported on histopathological findings of the brain in patients with COVID-19 in PubMed by MEDLINE, Embase, CENTRAL by the Cochrane Library, and SCOPUS from December 31, 2019 to October 31, 2020. RESULTS: The systematic literature search strategy used resulted in a total of 1608 articles of which 14 were included in the analysis (PROSPERO registration number: CRD42020221022). There were ten case series, two case reports, one retrospective cohort, and one prospective cohort. The age of the patients ranged between 38 and 90 years old, most of them older than 65 years old (n=66, 45.2%) and males (n=79, 54.1%). Most tested negative in SARS-CoV-2 immunohistochemistry (n=70, 47.9%). The striking pathologic changes included diffuse edema (n=25, 17.1%), gliosis with diffuse activation of microglia and astrocytes (n=52, 35.6%), infarctions involving cortical and subcortical areas of the brain (n=4, 2.7%), intracranial bleed (subarachnoid hemorrhage and punctate hemorrhages) (n=18, 12.4%), arteriosclerosis (n=43, 29.5%), hypoxic-ischemic injury (n=41, 28.1%), and signs of inflammation (n=52, 35.6%). The cause of death was attributed to the cardiorespiratory system (n=66, 45.2%). CONCLUSIONS: The neuropathologic changes observed likely represent direct cytopathic effects and indirect effects secondary to host-specific inflammatory response induced by the viral infection. Further studies however are required to better elucidate the pathologic mechanism.

Organ-specific manifestations of COVID-19 infection.

Although COVID-19 presents primarily as a lower respiratory tract infection transmitted via air droplets, increasing data suggest multiorgan involvement in patients that are infected. This systemic involvement is postulated to be mainly related to the SARS-CoV-2 virus binding on angiotensin-converting enzyme 2 (ACE2) receptors located on several different human cells. Lung involvement is the most common serious manifestation of the disease, ranging from asymptomatic disease or mild pneumonia, to severe disease associated with hypoxia, critical disease associated with shock, respiratory failure and multiorgan failure or death. Among patients with COVID-19, underlying cardiovascular comorbidities including hypertension, diabetes and especially cardiovascular disease, has been associated with adverse outcomes, whereas the emergence of cardiovascular complications, including myocardial injury, heart failure and arrhythmias, has been associated with poor survival. Gastrointestinal symptoms are also frequently encountered and may persist for several days. Haematological complications are frequent as well and have been associated with poor prognosis. Furthermore, recent studies have reported that over a third of infected patients develop a broad spectrum of neurological symptoms affecting the central nervous system, peripheral nervous system and skeletal muscles, including anosmia and ageusia. The skin, the kidneys, the liver, the endocrine organs and the eyes are also affected by the systemic COVID-19 disease. Herein, we provide a comprehensive overview of the organ-specific systemic manifestations of COVID-19.

COVID-19 and SARS-Cov-2 Infection: Pathophysiology and Clinical Effects on the Nervous System.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-Cov-2, resulting in severe acute respiratory syndrome, with high potential of spreading and infecting humans worldwide. Since December 2019, when the virus was identified in humans, the literature on COVID-19 has grown exponentially and extrarespiratory symptoms including neurologic symptoms are increasingly highlighted. METHODS: Given the high and increasing number of publications reporting neurologic involvements of SARS-Cov-2, we thought that providing an update for neurologic complications of COVID-19 would be useful for physicians and especially young trainees in neurology and neurosurgery. Indeed, in this review we discuss several neurologic aspects reported in the literature to date including the evidence and pathways of neuroinvasion in COVID-19 and the main neurologic disorders reported in the literature to date, as well as future perspectives and the potential long-term consequence of current neuroinfection in COVID-19 patients. RESULTS: Currently, there is convincing evidence that SARS-CoV-2, the etiologic agent of COVID-19, can affect the nervous system, with damage and neurologic alterations. These neurologic disorders are grouped into several categories, ranging from nonspecific and moderate symptoms such as headache, myalgia, and hyposmia to severe symptoms including cerebrovascular disease and intracranial infections. Severe neurologic symptoms such as acute cerebrovascular disease occur only in a minority of patients with usual risk factors and are associated with poor outcome. However, most COVID-19 patients exhibit only minor or mild neurologic symptoms. CONCLUSIONS: Management of COVID-19 patients should include early clinical, radiologic, and laboratory neurologic assessment, with a close follow-up, especially in severe forms. Future studies should assess late and long-term consequences of current COVID-19 patients with neurologic involvement.

COVID-19 and the nervous system.

A pandemic due to novel coronavirus arose in mid-December 2019 in Wuhan, China, and in 3 months' time swept the world. The disease has been referred to as COVID-19, and the causative agent has been labelled SARS-CoV-2 due to its genetic similarities to the virus (SARS-CoV-1) responsible for the severe acute respiratory syndrome (SARS) epidemic nearly 20 years earlier. The spike proteins of both viruses dictate tissue tropism using the angiotensin-converting enzyme type 2 (ACE-2) receptor to bind to cells. The ACE-2 receptor can be found in nervous system tissue and endothelial cells among the tissues of many other organs.Neurological complications have been observed with COVID-19. Myalgia and headache are relatively common, but serious neurological disease appears to be rare. No part of the neuraxis is spared. The neurological disorders occurring with COVID-19 may have many pathophysiological underpinnings. Some appear to be the consequence of direct viral invasion of the nervous system tissue, others arise as a postviral autoimmune process, and still others are the result of metabolic and systemic complications due to the associated critical illness. This review addresses the preliminary observations regarding the neurological disorders reported with COVID-19 to date and describes some of the disorders that are anticipated from prior experience with similar coronaviruses.