Pulmonary and Extra-Pulmonary Clinical Manifestations of COVID-19.
ABSTRACT: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been recently identified as the culprit of the highly infectious, outbreak named coronavirus disease 2019 (COVID-19) in China. Now declared a public health emergency, this pandemic is present in more than 200 countries with over 14 million cases and 600,000 deaths as of July 18, 2020. Primarily transmitted through the respiratory tract, the most common clinical presentations of symptomatic individuals infected with SARS-CoV-2 include fever, dyspnea, cough, fatigue, and sore throat. In advanced cases, patients may rapidly develop respiratory failure with acute respiratory distress syndrome, and even progress to death. While it is known that COVID-19 manifests similarly to the 2003 Severe Acute Respiratory Syndrome (SARS) and the 2012 Middle East Respiratory Syndrome (MERS), primarily affecting the pulmonary system, the impact of the disease extends far beyond the respiratory system and affects other organs of the body. The literature regarding the extrapulmonary manifestations (cardiovascular, renal, hepatic, gastrointestinal, ocular, dermatologic, and neurological) of COVID-19 is scant. Herein, we provide a comprehensive review of the organ-specific clinical manifestations of COVID-19, to increase awareness about the various organs affected by SARS-CoV-2 and to provide a brief insight into the similarities and differences in the clinical manifestations of COVID-19 and the earlier SARS and MERS.
Project description:Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths.1 COVID-19 causes a severe pneumonia characterized by fever, cough and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extrapulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multiorgan manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What is more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.
Project description:Highlights • MERS is characterized by fever, encephalopathy, and a reversible splenium lesion.• MERS has been associated with infection, potentially as an autoimmune response.• MERS has not previously been described in conjunction with COVID-19.• We present the first reported case of MERS in the setting of SARS-CoV-2 antibodies. Neurological complications of coronavirus 2019 (COVID-19) are common, and novel manifestations are increasingly being recognized. Mild encephalopathy with reversible splenium lesion (MERS) is a syndrome that has been associated with viral infections, but not previously with COVID-19. In this report, we describe the case of a 69 year-old man who presented with fever and encephalopathy in the setting of a diffusion-restricting splenium lesion, initially mimicking an ischemic stroke. A comprehensive infectious workup revealed positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies, and a pro-inflammatory laboratory profile characteristic of COVID-19 infection. His symptoms resolved and the brain MRI findings completely normalized on repeat imaging, consistent with MERS. This case suggests that MERS may manifest as an autoimmune response to SARS-CoV-2 infection and should be considered in a patient with evidence of recent COVID-19 infection and the characteristic MERS clinico-radiological syndrome.
Project description:BACKGROUND:The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta-coronavirus entitled 2019 novel coronavirus (2019-nCoV), has become a global threat. Awareness of the biological features of 2019-nCoV should be updated in time and needs to be comprehensively summarized to help optimize control measures and make therapeutic decisions. METHODS:Based on recently published literature, official documents and selected up-to-date preprint studies, we reviewed the virology and origin, epidemiology, clinical manifestations, pathology and treatment of 2019-nCoV infection, in comparison with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. RESULTS:The genome of 2019-nCoV partially resembled SARS-CoV and MERS-CoV, and indicated a bat origin. The COVID-19 generally had a high reproductive number, a long incubation period, a short serial interval and a low case fatality rate (much higher in patients with comorbidities) than SARS and MERS. Clinical presentation and pathology of COVID-19 greatly resembled SARS and MERS, with less upper respiratory and gastrointestinal symptoms, and more exudative lesions in post-mortems. Potential treatments included remdesivir, chloroquine, tocilizumab, convalescent plasma and vaccine immunization (when possible). CONCLUSION:The initial experience from the current pandemic and lessons from the previous two pandemics can help improve future preparedness plans and combat disease progression.
Project description:Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) in the twenty-first century. In this minireview, we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis, diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections, which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.
Project description:Clinical manifestations of coronavirus disease 2019 (COVID-19) vary from asymptomatic virus shedding, nonspecific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells and macrophages are sentinel cells for innate and adaptive immunity that affect the pathogenesis of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The interplay between SARS-CoV-2 and these cell types remains unknown. We investigated infection and host responses of monocyte-derived dendritic cells (moDCs) and macrophages (MDMs) infected by SARS-CoV-2. MoDCs and MDMs were permissive to SARS-CoV-2 infection and protein expression but did not support productive virus replication. Importantly, SARS-CoV-2 launched an attenuated interferon response in both cell types and triggered significant proinflammatory cytokine/chemokine expression in MDMs but not moDCs. Investigations suggested that this attenuated immune response to SARS-CoV-2 in moDCs was associated with viral antagonism of STAT1 phosphorylation. These findings may explain the mild and insidious course of COVID-19 until late deterioration.
Project description:After the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in the last two decades, the world is facing its new challenge in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic with unprecedented global response. With the expanding domain of presentations in COVID-19 patients, the full range of manifestations is yet to unfold. The classical clinical symptoms for SARS-CoV-2 affected patients are dry cough, high fever, dyspnoea, lethal pneumonia whereas many patients have also been found to be associated with a few additional signs and clinical manifestations of isolated vasculopathy. Albeit a deep and profound knowledge has been gained on the clinical features and management of COVID-19, less clear association has been provided on SARS-CoV-2 mediated direct or indirect vasculopathy and its possible correlation with disease prognosis. The accumulative evidences suggest that novel coronavirus, apart from its primary respiratory confinement, may also invade vascular endothelial cells of several systems including cerebral, cardio-pulmonary as well as renal microvasculature, modulating multiple visceral perfusion indices. Here we analyse the phylogenetic perspective of SARS-CoV-2 along with other strains of ?-coronaviridae from a standpoint of vasculopathic derangements. Based on the existing case reports, literature and open data bases, we also analyse the differential pattern of vasculopathy related changes in COVID-19 positive patients. Besides, we debate the need of modulation in clinical approach from a hemodynamical point of view, as a measure towards reducing disease transmission, morbidity and mortality in SARS-CoV-2 affected patients.
Project description:BACKGROUND:The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood. AIMS:To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS. SOURCES:The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics. CONTENT:COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0-2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7-1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation. IMPLICATIONS:There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.
Project description:Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that is responsible for the 2019-2020 pandemic. In this comprehensive review, we discuss the current published literature surrounding the SARS-CoV-2 virus. We examine the fundamental concepts including the origin, virology, pathogenesis, clinical manifestations, diagnosis, laboratory, radiology, and histopathologic findings, complications, and treatment. Given that much of the information has been extrapolated from what we know about other coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), we identify and provide insight into controversies and research gaps for the current pandemic to assist with future research ideas. Finally, we discuss the global response to the coronavirus disease-2019 (COVID-19) pandemic and provide thoughts regarding lessons for future pandemics.
Project description:The 2019 novel coronavirus disease (COVID-19), which is caused by the novel beta coronavirus, SARS-CoV-2, is currently prevalent all over the world, causing thousands of deaths with relatively high virulence. Like two other notable beta coronaviruses, severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 can lead to severe contagious respiratory disease. Due to impaired cellular immunity and physiological changes, pregnant women are susceptible to respiratory disease and are more likely to develop severe pneumonia. Given the prevalence of COVID-19, it is speculated that some pregnant women have already been infected. However, limited data are available for the clinical course and management of COVID-19 in pregnancy. Therefore, we conducted this review to identify strategies for the obstetric management of COVID-19. We compared the clinical course and outcomes of COVID-19, SARS, and MERS in pregnancy and discussed several drugs for the treatment of COVID-19 in pregnancy.