Neurologic Features in Severe SARS-CoV-2 Infection

Authors: Julie Helms, M.D., Ph.D., Stéphane Kremer, M.D., Ph.D., Hamid Merdji, M.D., Raphaël Clere-Jehl, M.D., Malika Schenck, M.D., Christine Kummerlen, M.D., Olivier Collange, M.D., Ph.D., Clotilde Boulay, M.D., Samira Fafi-Kremer, Pharm.D., Ph.D., Mickaël Ohana, M.D., Ph.D., Mathieu Anheim, M.D., Ph.D. Strasbourg University Hospital, Strasbourg, France, Ferhat Meziani, M.D., Ph.D.
University of Strasbourg, Strasbourg, France

Reported here are the neurologic features in an observational series of 58 of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to Covid-19. The patients received similar evaluations by intensivists in two intensive care units (ICUs) in Strasbourg, France, between March 3 and April 3, 2020.

Six patients were excluded because of paralytic neuromuscular blockade when neurologic data were collected or because they had died without a neurologic examination having been performed. In all 58 patients, reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of nasopharyngeal samples were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The median age of the patients was 63 years, and the median Simplified Acute Physiology Score II at the time of neurologic examination was 52 (interquartile range, 37 to 65, on a scale ranging from 0 to 163, with higher scores indicating greater severity of illness). Seven patients had had previous neurologic disorders, including transient ischemic attack, partial epilepsy, and mild cognitive impairment.

The neurologic findings were recorded in 8 of the 58 patients (14%) on admission to the ICU (before treatment) and in 39 patients (67%) when sedation and a neuromuscular blocker were withheld. Agitation was present in 40 patients (69%) when neuromuscular blockade was discontinued (Table 1). A total of 26 of 40 patients were noted to have confusion according to the Confusion Assessment Method for the ICU; those patients could be evaluated when they were responsive (i.e., they had a score of −1 to 1 on the Richmond Agitation and Sedation Scale, on a scale of −5 [unresponsive] to +4 [combative]). Diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes were present in 39 patients (67%). Of the patients who had been discharged at the time of this writing, 15 of 45 (33%) had had a dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command.

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents A Systematic Review

Authors: Riccardo Castagnoli, MD1,2Martina Votto, MD1,2Amelia Licari, MD1,2et al

Key Points

Question  What are the clinical features of pediatric patients with coronavirus disease 2019 (COVID-19)?

Findings  In this systematic review of 18 studies with 1065 participants, most pediatric patients with SARS-CoV-2 infection presented with fever, dry cough, and fatigue or were asymptomatic; 1 infant presented with pneumonia, complicated by shock and kidney failure, and was successfully treated with intensive care. Most pediatric patients were hospitalized, and symptomatic children received mainly supportive care; no deaths were reported in the age range of 0 to 9 years.

Meaning  Most children with COVID-19 presented with mild symptoms, if any, generally required supportive care only, and typically had a good prognosis and recovered within 1 to 2 weeks.

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19) – anatomic pathology perspective on current knowledge

Authors: Sambit K. MohantyAbhishek SatapathyMachita M. NaiduSanjay MukhopadhyayShivani SharmaLisa M. BartonEdana StrobergEric J. DuvalDinesh PradhanAlexandar Tzankov & Anil V. Parwani 



The world is currently witnessing a major devastating pandemic of Coronavirus disease-2019 (COVID-19). This disease is caused by a novel coronavirus named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). It primarily affects the respiratory tract and particularly the lungs. The virus enters the cell by attaching its spike-like surface projections to the angiotensin-converting enzyme-2 (ACE-2) expressed in various tissues. Though the majority of symptomatic patients have mild flu-like symptoms, a significant minority develop severe lung injury with acute respiratory distress syndrome (ARDS), leading to considerable morbidity and mortality. Elderly patients with previous cardiovascular comorbidities are particularly susceptible to severe clinical manifestations.


Currently, our limited knowledge of the pathologic findings is based on post-mortem biopsies, a few limited autopsies, and very few complete autopsies. From these reports, we know that the virus can be found in various organs but the most striking tissue damage involves the lungs resulting almost always in diffuse alveolar damage with interstitial edema, capillary congestion, and occasional interstitial lymphocytosis, causing hypoxia, multiorgan failure, and death. A few pathology studies have also reported intravascular microthrombi and pulmonary thromboembolism. Although the clinical presentation of this disease is fairly well characterized, knowledge of the pathologic aspects remains comparatively limited.


In this review, we discuss clinical, pathologic, and genomic features of COVID-19, review current hypotheses regarding the pathogenesis, and briefly discuss the clinical characteristics. We also compare the salient features of COVID-19 with other coronavirus-related illnesses that have posed significant public health issues in the past, including SARS and the Middle East Respiratory Syndrome (MERS).

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COVID-19: Current understanding of its Pathophysiology, Clinical presentation and Treatment

Authors: Anant Parasher


Background The severe acute respiratory syndrome (SARS) coronavirus-2 is a novel coronavirus belonging to the family Coronaviridae and is now known to be responsible for the outbreak of a series of recent acute atypical respiratory infections originating in Wuhan, China. The disease caused by this virus, termed coronavirus disease 19 or simply COVID-19, has rapidly spread throughout the world at an alarming pace and has been declared a pandemic by the WHO on March 11, 2020. In this review, an update on the pathophysiology, clinical presentation and the most recent management strategies for COVID-19 has been described.

Results and Conclusions COVID-19 has now spread globally with increasing morbidity and mortality among all populations. In the absence of a proper and effective antibody test, the diagnosis is presently based on a reverse-transcription PCR of nasopharyngeal and oropharyngeal swab samples. The clinical spectrum of the disease presents in the form of a mild, moderate or severe illness. Most patients are either asymptomatic carriers who despite being without symptoms have the potential to be infectious to others coming in close contact, or have a mild influenza-like illness which cannot be differentiated from a simple upper respiratory tract infection. Moderate and severe cases require hospitalisation as well as intensive therapy which includes non-invasive as well as invasive ventilation, along with antipyretics, antivirals, antibiotics and steroids. Complicated cases may require treatment by immunomodulatory drugs and plasma exchange therapy. The search for an effective vaccine for COVID-19 is presently in full swing, with pharmaceutical corporations having started human trials in many countries.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the COVID-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

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The role of extracorporeal membrane oxygenation in critically ill patients with COVID-19: a narrative review

Authors: Shiqian HuangShuai ZhaoHuilin LuoZhouyang WuJing WuHaifa Xia & Xiangdong Chen BMC Pulmonary Medicine volume 21, Article number: 116 (2021)


Extracorporeal life support treatments such as extracorporeal membrane oxygenation (ECMO) have been recommended for the treatment of severe acute respiratory distress syndrome (ARDS) patients with coronavirus disease 2019 (COVID-19). To date, many countries, including China, have adopted ECMO as a treatment for severe COVID-19. However, marked differences in patient survival rates have been reported, and the underlying reasons are unclear. This study aimed to summarize the experience of using ECMO to treat severe COVID-19 and provide suggestions for improving ECMO management. The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the pathophysiology of COVID-19 and the effects of ECMO on the clinical outcomes in patients with severe cases of COVID-19 were reviewed. Recent data from frontline workers involved in the use of ECMO in Wuhan, China, and those experienced in the implementation of artificial heart and lung support strategies were analyzed. There is evidence that ECMO may complicate the pathophysiological state in COVID-19 patients. However, many studies have shown that the appropriate application of ECMO improves the prognosis of such patients. To expand our understanding of the benefits of ECMO for critically ill patients with COVID-19, further prospective, multicenter clinical trials are needed.

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The Severe Acute Respiratory Syndrome

Authors: Joseph S.M. Peiris, M.D., D.Phil., Kwok Y. Yuen, M.D., Albert D.M.E. Osterhaus, Ph.D., and Klaus Stöhr, Ph.D.

The severe acute respiratory syndrome (SARS) is responsible for the first pandemic of the 21st century. Within months after its emergence in Guangdong Province in mainland China, it had affected more than 8000 patients and caused 774 deaths in 26 countries on five continents. It illustrated dramatically the potential of air travel and globalization for the dissemination of an emerging infectious disease and highlighted the need for a coordinated global response to contain such disease threats. We review the cause, epidemiology, and clinical features of the disease.


An unusual atypical pneumonia emerged in Foshan, Guangdong Province, mainland China, in November 2002.1,2 In February and March 2003, the disease spread to Hong Kong and then to Vietnam, Singapore, Canada, and elsewhere (Table 1).3,4 The new disease was named the severe acute respiratory syndrome (SARS), and a preliminary case definition was established.4 A novel coronavirus (SARS-CoV) was identified as the causative agent.5-10 Coronaviruses are a family of enveloped, single-stranded–RNA viruses causing disease in humans and animals, but the other known coronaviruses that affect humans cause only the common cold.

The presence of SARS-CoV has been demonstrated by reverse-trancriptase polymerase chain reaction (RT-PCR) and the isolation of the virus from respiratory secretions, feces, urine, and tissue specimens from lung biopsy,11,12 indicating that the infection is not confined to the respiratory tract. The experimental infection of cynomolgus macaques with SARS-CoV produced a pneumonia that was pathologically similar to SARS in humans.8,9 Other pathogens, including human metapneumovirus13,14 and chlamydia,7,15 have been detected together with SARS-CoV in some patients with SARS, but they have not been found consistently.5,9 The experimental infection of macaques with human metapneumovirus did not lead to a SARS-like disease, and coinfection of macaques with human metapneumovirus and SARS-CoV did not enhance the pathogenicity of the SARS-CoV in this animal model.8 Thus, all the information that is available to date suggests that SARS-CoV is necessary and sufficient for the causation of SARS in humans, but it remains to be determined whether microbial or other cofactors enhance the severity or transmissibility of the disease. The complete genetic sequence of the SARS-CoV genome was determined, and it provided confirmation that SARS-CoV belongs to a new group within the coronavirus family.

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Rapid detection of novel coronavirus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcription-loop-mediated isothermal amplification

Authors: Laura E. Lamb ,Sarah N. Bartolone,Elijah Ward,Michael B. Chancellor


Novel Corona virus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV), and the subsequent disease caused by the virus (coronavirus disease 2019 or COVID-19), is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for SARS-CoV-2 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in 30–45 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the SARS-CoV-2 nucleic sequence. RNA isolated from nasopharyngeal swabs collected from actual COVID-19 patients was also tested. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected SARS-CoV-2 in both simulated patient samples and clinical specimens. This test was performed in 30–45 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.


The recent Novel Corona virus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV) pandemic, and the subsequent disease caused by the virus (coronavirus disease 2019 or COVID-19), has generated global concern given its rapid spread in multiple countries and possible fatal progression of the infection. Initially, many patients reported exposure at a large seafood and animal market in Wuhan, China, suggesting animal-to-person transmission of the virus. However, since then many patients have reported no exposure to animal markets, indicating that person-to-person transmission is occurring.

SARS-CoV-2 infection is difficult to diagnose early in infection as patients can remain asymptomatic or present with non-specific clinical symptoms including fever, cough, or shortness of breath. Symptoms may appear in as few as 2 days or up to 2 weeks after exposure [1]. Quantitative reverse transcription PCR (qRT-PCR) for COVID-19 in respiratory samples is currently the standard for diagnostic molecular testing. However, this requires expensive equipment and trained personnel.

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Pathophysiology of acute respiratory syndrome coronavirus 2 infection: a systematic literature review to inform EULAR points to consider

Authors: Aurélie Najm1 Alunno2, Xavier Mariette3,4 Terrier5,6 De Marco7,8, Jenny Emmel9, Laura Mason9, Dennis G McGonagle7,10 and M Machado11,12,13


Background The SARS-CoV-2 pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Our objective was to summarise the available information on the pathophysiology of COVID-19.

Methods Two reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection; I (intervention): any intervention/no intervention; C (comparator): any comparator; O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration.

Results Of the 55 496 records yielded, 84 articles were eligible for inclusion according to question-specific research criteria. Proinflammatory cytokine expression, including interleukin-6 (IL-6), was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. The myeloid and lymphoid compartments were differentially affected by SARS-CoV-2 infection depending on disease phenotype. Failure to maintain high interferon (IFN) levels was characteristic of severe forms of COVID-19 and could be related to loss-of-function mutations in the IFN pathway and/or the presence of anti-IFN antibodies. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalisation, disease progression or severity, and mortality.

Conclusions SARS-CoV-2 infection affects both humoral and cellular immunity depending on both disease severity and individual parameters. This systematic literature review informed the EULAR ‘points to consider’ on COVID-19 pathophysiology and immunomodulatory therapies.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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COVID-19 pathophysiology: A review

Authors: COVID-19 pathophysiology: A review Koichi Yuki, Miho Fujiogi, and Sophia Koutsogiannaki


In December 2019, a novel coronavirus, now named as SARS-CoV-2, caused a series of acute atypical respiratory diseases in Wuhan, Hubei Province, China. The disease caused by this virus was termed COVID-19. The virus is transmittable between humans and has caused pandemic worldwide. The number of death tolls continues to rise and a large number of countries have been forced to do social distancing and lockdown. Lack of targeted therapy continues to be a problem. Epidemiological studies showed that elder patients were more susceptible to severe diseases, while children tend to have milder symptoms. Here we reviewed the current knowledge about this disease and considered the potential explanation of the different symptomatology between children and adults.

1. Introduction

In December 2019, a series of acute atypical respiratory disease occurred in Wuhan, China. This rapidly spread from Wuhan to other areas. It was soon discovered that a novel coronavirus was responsible. The novel coronavirus was named as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCoV) due to its high homology (~80%) to SARS-CoV, which caused acute respiratory distress syndrome (ARDS) and high mortality during 2002–2003 [1]. The outbreak of SARS-CoV-2 was considered to have originally started via a zoonotic transmission associated with the seafood market in Wuhan, China. Later it was recognized that human to human transmission played a major role in the subsequent outbreak [2]. The disease caused by this virus was called Coronavirus disease 19 (COVID-19) and a pandemic was declared by the World Health Organization (WHO). COVID-19 has been impacting a large number of people worldwide, being reported in approximately 200 countries and territories [3,4]. As of April 7th, 2020, around 1,400,000 cases worldwide have been reported according to the Center for Systems Science and Engineering (CSSE) at John Hopkins University [5].

SARS-CoV-2 virus primarily affects the respiratory system, although other organ systems are also involved. Lower respiratory tract infection related symptoms including fever, dry cough and dyspnea were reported in the initial case series from Wuhan, China [6]. In addition, headache, dizziness, generalized weakness, vomiting and diarrhea were observed [7]. It is now widely recognized that respiratory symptoms of COVID-19 are extremely heterogeneous, ranging from minimal symptoms to significant hypoxia with ARDS. In the report from Wuhan mentioned above, the time between the onset of symptoms and the development of ARDS was as short as 9 days, suggesting that the respiratory symptoms could progress rapidly [6]. This disease could be also fatal. A growing number of patients with severe diseases have continued to succumb worldwide. Epidemiological studies have shown that mortalities are higher in elder population [8] and the incidence is much lower in children [9,10]. Current medical management is largely supportive with no targeted therapy available. Several drugs including lopinavir-ritonavir, remdesivir, hydroxychloroquine, and azithromycin have been tested in clinical trials [8,11,12], but none of them have been proven to be a definite therapy yet. More therapies are being tested in clinical trials. A large number of countries have implemented social distancing and lockdown to mitigate further spread of the virus. Here we will review our current knowledge of COVID-19 and consider the underlying mechanism to explain the heterogeneous symptomatology, particularly focusing on the difference between children and adult patients.

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Acute Respiratory Distress Syndrome and COVID-19: A Scoping Review and Meta-analysis

Authors: Mehdi Jafari-Oori 1Fatemeh Ghasemifard 2Abbas Ebadi 3Leila Karimi 3Farshid Rahimi-Bashar 4Tannaz Jamialahmadi 5 6Paul C Guest 7Amir Vahedian-Azimi 8Amirhossein Sahebkar 9 10 11 12


Acute respiratory distress syndrome (ARDS) is a fatal complication of the new severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes COVID-19 disease. This scoping review was carried out with international, peer-reviewed research studies and gray literature published up to July 2020 in Persian and English languages. Using keywords derived from MESH, databases including Magiran, IranMedex, SID, Web of Sciences, PubMed, Embase via Ovid, Science Direct, and Google Scholar were searched. After screening titles and abstracts, the full texts of selected articles were evaluated, and those which passed the criteria were analyzed and synthesized with inductive thematic analysis. Study quality was also evaluated using a standard tool. The overall prevalence of ARDS was estimated using a random-effects model. This led to identification of 23 primary studies involving 2880 COVID-19 patients. All articles were observational with a cross-sectional, retrospective, case report, and cohort design with moderate to strong quality. The main findings showed that COVID-19-related ARDS has a high prevalence and is different to ARDS due to other etiologies. Elderly and patients with comorbidities and organ failure should be closely surveyed for respiratory organ indications for several weeks after the onset of respiratory symptoms. There is currently no definitive treatment for ARDS in COVID-19 disease, and supportive therapies and their effects are somewhat controversial.

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