scholarly journals Metabolomic/lipidomic profiling of COVID-19 and individual response to tocilizumab

2021 ◽  
Vol 17 (2) ◽  
pp. e1009243
Author(s):  
Gaia Meoni ◽  
Veronica Ghini ◽  
Laura Maggi ◽  
Alessia Vignoli ◽  
Alessio Mazzoni ◽  
...  

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.

2020 ◽  
Author(s):  
Gaia Meoni ◽  
Veronica Ghini ◽  
Laura Maggi ◽  
Alessia Vignoli ◽  
Alessio Mazzoni ◽  
...  

AbstractThe current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.Author summaryThe current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is markedly affecting the world population. Here we report about the small-molecule profile of patients hospitalized during the first wave of the COVID-19 pandemic. Using magnetic resonance spectroscopy, we showed that the infection induces profound changes in the metabolome. The analysis of the specific metabolite changes and correlations with clinical data enabled the identification of potential biochemical determinants of the disease fingerprint. We also followed how metabolic alterations revert towards those of the control group upon treatment with tocilizumab, a recombinant humanised monoclonal antibody against the interleukin-6 receptor. These results open up possibilities for the monitoring of novel patients and their individual response to treatment.


2020 ◽  
Vol 10 (01) ◽  
pp. e137-e140
Author(s):  
Mosaad Abdel-Aziz ◽  
Nada M. Abdel-Aziz ◽  
Dina M. Abdel-Aziz ◽  
Noha Azab

AbstractThe clinical manifestations of novel coronavirus disease 2019 (COVID-19) vary from mild flu-like symptoms to severe fatal pneumonia. However, children with COVID-19 may be asymptomatic or may have mild clinical symptoms. The aim of this study was to investigate clinical features of pediatric COVID-19 and to search for the factors that may mitigate the disease course. We reviewed the literature to realize the clinical features, laboratory, and radiographic data that may be diagnostic for COVID-19 among children. Also, we studied the factors that may affect the clinical course of the disease. Fever, dry cough, and fatigue are the main symptoms of pediatric COVID-19, sometimes flu-like symptoms and/or gastrointestinal symptoms may be present. Although some infected children may be asymptomatic, a recent unusual hyperinflammatory reaction with overlapping features of Kawasaki's disease and toxic shock syndrome in pediatric COVID-19 has been occasionally reported. Severe acute respiratory syndrome-coronvirus-2 (SARS-CoV-2) nucleic acid testing is the corner-stone method for the diagnosis of COVID-19. Lymphocyte count and other inflammatory markers are not essentially diagnostic; however, chest computed tomography is highly specific. Factors that may mitigate the severity of pediatric COVID-19 are home confinement with limited children activity, trained immunity caused by compulsory vaccination, the response of the angiotensin-converting enzyme 2 receptors in children is not the same as in adults, and that children are less likely to have comorbidities. As infected children may be asymptomatic or may have only mild respiratory and/or gastrointestinal symptoms that might be missed, all children for families who have a member diagnosed with COVID-19 should be investigated.


2020 ◽  
Author(s):  
Yani Kuang ◽  
Susu He ◽  
Shuangxiang Lin ◽  
Rui Zhu ◽  
Rongzhen Zhou ◽  
...  

Abstract Background: In December 2019, the first case of pneumonia associated with the SARS-CoV-2 was found in Wuhan and rapidly spread throughout China, so data are needed on the affected patients. The purpose of our study was to find the clinical manifestations and CT features of COVID-19.Methods: All patients with COVID-19 in Taizhou city were retrospectively included and divided into non-severe group and severe group according to the severity of the disease. The clinical manifestations, laboratory examinations and imaging features of COVID-19 patients were analyzed, and the differences between the two groups were compared.Results: A total of 143 laboratory-confirmed cases were included in the study, including 110 non-severe patients and 33 severe patients. The median age of patients was 47 (range 4–86 years). Fever (73.4%) and cough (63.6%) were the most common initial clinical symptoms. Between two groups of cases, the results of aspartate transaminase, creatine kinase and lactate dehydrogenase, serum albumin, CR, glomerular filtration rate, amyloid protein A, fibrinogen, calcitonin level and oxygen partial pressure, IL – 10, absolute value of CD3, CD4, CD8 were different, and the difference was statistically significant (P < 0.05). Therefore, these quantitative indicators can be used to help assess the severity. On admission, the CT showed that the lesions were mostly distributed in the periphery of the lung or subpleural (135 cases (98%)), and most of lesions presented as patchy (81%), mixed density (63%) shadow. Consolidation (68% vs 41%), bronchial inflation signs (59% vs 41%), and bronchiectasis (71% vs 39%) were more common in the severe group.Conclusions: Most of the cases of COVID-19 in Taizhou have mild symptoms and no death. In addition to clinical symptoms, some laboratory tests (such as absolute values of CD4 and CD8) and CT findings can be used to assess the severity of the disease.


2016 ◽  
Vol 4 (1) ◽  
pp. 226
Author(s):  
Alok Kumar M. K. ◽  
Timmangouda R. Patil ◽  
Santhosh Veerabadhraiah

Background: Dengue fever is an acute febrile illness caused by 4 closely related viral serotypes of the genus Flavivirus. Dengue has a broad range of clinical manifestations and often with unpredictable clinical evaluation and outcome. So this study has been done to see the wide range of clinical presentation of dengue and its outcome.Methods: It is a retrospective study done in tertiary hospital during the period of 8 months. Study was done by collecting the previous records from hospital record section. There were 48 cases of serologically confirmed cases of dengue which satisfied the inclusion and exclusion criteria were included in the study. Results: In our study there were 52% of the cases of dengue fever, 16.6% of cases were dengue fever with warning signs and remaining 31.4% of patients were severe dengue. Common Clinical symptoms at admission were fever (100%), vomiting (77%), respiratory distress (56.25%), generalised weakness (54.1%) and pain abdomen (33.3%). Less common symptoms were loose stools (6.25%), periorbital puffiness (6.25%), altered sensorium (4.1%), oliguria (2%) and bleeding manifestations (2%). Out of these dengue children 70.8% of these children improved without complication, 20.8 % of children improved with complication, in the form of ARDS, acute liver failure, DSS, meningitis, 6.25 % of these children went DAMA and  2 % of children expired.Conclusions: In our study atypical presentations like respiratory distress, loose stools meningitis were commonly noted and bleeding manifestation at admission was rare in our study. Platelet transfusions have little role in management of dengue patients. Early diagnosis, careful monitoring and proper fluid management goes a long way in reducing the mortality due to dengue hemorrhagic fever and shock syndrome.  


2020 ◽  
Vol 10 (4) ◽  
pp. 303-311
Author(s):  
Gundu H. R. Rao

The first human case of COVID-19, caused by the novel coronavirus, was reported by health officials in the city of Wuhan, China, in December of 2019. The virus was identified as a novel coronavirus in early January 2020, and its genetic sequence was shared publicly on January 11, 2020. The novel virus, previously called 2019-novel coronavirus (2019-nCoV), is currently designated as the severe respiratory syndrome coronavirus-2 (SARS-CoV-2). On January 23, Wuhan was locked down, and the World Health Organization (WHO) declared a “public health emergency of international concern.” The viral genome of SARS-CoV-2 is around 29.8 kilobase, containing six major open reading frames. The most common clinical symptoms were fever, cough, fatigue, shortness of breath, dyspnea, muscle ache, headache, chest pain, vomiting, sore throat, and sputum production. The main mode of transmission is through respiratory particles. The incubation period is 3 to 7 days. Both asymptomatic and symptomatic patients seem to be infectious. Spike (S) proteins of SARS-CoV-2 seem to have a 10- to 20-fold higher affinity to the human angiotensin enzyme 2 (ACE2) receptor than that of SARS-CoV. The high affinity of S protein to theACE2 receptor, and the additional advantages offered by the transfection facilitators Furin and Neutropilin-1, likely, contributes to the rapid spreading of this novel virus. Since these receptors are highly expressed on a variety of cells, including vascular endothelial cells and adipose tissue, individuals with compromised function of these tissues drive greater infection and severity in patients with COVID-19. Global health experts estimate that one in five individuals worldwide could be at risk for severe COVID-19, due to underlying health conditions. There is a great need for a rapid, specific, cost-effective test for monitoring the infected individuals. Even though a 15- minute, antigen test was made available by Abbott recently, it seems that the schools, colleges, and business establishments lack the ability to use these tests effectively to keep their businesses open safely. Management of the infected individuals seems to be based on clinical symptoms that manifest as the disease progresses. The US Food & Drug Administration (FDA), has created a special emergency program for possible therapies, the Coronavirus Treatment Acceleration Program (CTAP). The program uses every available method to move new and emerging treatments as quickly as possible, keeping in mind the safety and efficacy of such therapies. According to the WHO report, there are currently more than 150 COVID-19 vaccine candidates under development. Several vaccines are in Phase 3 clinical trials. In an unprecedented effort, one of the experimental monoclonal antibody cocktails of Regeneron was used for therapeutic purposes when the US president was tested positive for COVID-19. There are no drugs or other therapeutics approved by the US FDA to prevent or treat COVID-19. The National Institutes of Health (NIH) have published interim guidelines for the medical management of COVID-19. In the absence of a cure, the only choice we all have is to follow the best practices recommended by the public health experts—use of face masks (coverings), frequent hand washing with soap, contact tracing of infected individuals, and quarantining COVID-19 positive individuals, till they are free of the highly infectious virus.


Author(s):  
MURUGAN NANDAGOPAL ◽  
ARULMOZHI BALAKRISHNAN ◽  
CHIRAYU PADHIAR

The coronavirus disease-2019 (COVID-19) outbreak by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or a novel coronavirus (2019-CoV) has prompted global health concerns. A pandemic resulted from the disease’s transmission through many routes. In this pandemic, the interaction between coronavirus and the host immune system, particularly the innate immune system, is becoming more prominent. Against viruses and pathogens, innate immunity serves as a first line of defense. Our understanding of pathogenesis will benefit from a better grasp of the mechanisms of immune evasion techniques. The origin, classification, structure, and method of transmission of SARS-CoV-2 were summarized in this paper. We have discussed the importance of important communications. In this review, we have discussed the function of important components of the innate immune system in COVID-19 infection, as well as how the virus evades innate immunity through multiple tactics and contributes to a wide range of clinical symptoms and outcomes.


2021 ◽  
Vol 8 ◽  
Author(s):  
Rongjun Wan ◽  
Wenzhe Yang ◽  
Xinhua Ma ◽  
Wei Yang ◽  
Pinhua Pan ◽  
...  

Granulomatosis with polyangiitis (GPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis with a wide range of clinical symptoms related to the systemic involvement of small blood vessels. The respiratory system is one of the most frequently involved, and life-threatening acute respiratory failure could occur due to diffusive alveolar hemorrhage and tracheal stenosis. When maximum mechanical ventilation is unable to maintain oxygenation, extracorporeal membrane oxygenation (ECMO) should be considered as the final respiratory supportive method, if available. Here we present a 32-year-old male patient with acute respiratory failure (ARF) related to GPA, who was rescued by winning time for accurate diagnosis and appropriate treatment. Additionally, we reviewed more than 60 GPA-related ARF cases on multiple online databases, summarized the clinical manifestations of these patients, and concluded that ECMO plays an important role in further respiratory support for ARF patients with GPA and assists in accurate and timely diagnosis and appropriate treatment, thus helping them recuperate.


Author(s):  
Nicole A. P. Lieberman ◽  
Vikas Peddu ◽  
Hong Xie ◽  
Lasata Shrestha ◽  
Meei-Li Huang ◽  
...  

AbstractDespite limited genomic diversity, SARS-CoV-2 has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA-sequencing profiles of nasopharyngeal swabs from 430 individuals with PCR-confirmed SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong antiviral response with upregulation of antiviral factors such as OAS1-3 and IFIT1-3, and Th1 chemokines CXCL9/10/11, as well as a reduction in transcription of ribosomal proteins. SARS-CoV-2 culture in human airway epithelial cultures replicated the in vivo antiviral host response. Patient-matched longitudinal specimens (mean elapsed time = 6.3 days) demonstrated reduction in interferon-induced transcription, recovery of transcription of ribosomal proteins, and initiation of wound healing and humoral immune responses. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load, while transcripts for B cell-specific proteins and neutrophil chemokines were elevated in patients with lower viral load. Older individuals had reduced expression of Th1 chemokines CXCL9/10/11 and their cognate receptor, CXCR3, as well as CD8A and granzyme B, suggesting deficiencies in trafficking and/or function of cytotoxic T cells and natural killer (NK) cells. Relative to females, males had reduced B and NK cell-specific transcripts and an increase in inhibitors of NF-κB signaling, possibly inappropriately throttling antiviral responses. Collectively, our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time course, with observed differences due to age and sex that may contribute to disease severity.


2020 ◽  
Vol 18 (6) ◽  
pp. 63-68
Author(s):  
O. I. PIKUSA ◽  
◽  
E. A. SAMORODNOVA ◽  

The purpose — to present the information on the main causes of lymphadenopathies in children and the stages of differential-diagnostic search which complicate diagnosing and determining the treatment tactics. Material and methods. Analysis of literature data on lymphadenopathies in children, features of clinical manifestations under tumorous and non-tumorous etiology of the disease, and approaches to differential diagnostics. Results. The article presents the general information on etiology and classification of the characteristic clinical symptoms of lymphadenopathies in children, which are necessary for a pediatrician to determining the treatment tactics of a patient with this pathology. Conclusion. For duly diagnosing a child with lymphadenopathy, a pediatrician should be aware of a wide range of nosologies and be attentive to any detail of the case history, clinical picture and laboratory examination data, as it may influence not only the treatment efficiency but even life forecast for the patient.


Author(s):  
Francisco Montenegro ◽  
Luis Unigarro ◽  
Gustavo Paredes ◽  
Tatiana Moya ◽  
Ana Romero ◽  
...  

Introduction: The exponential growth of the SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on health systems worldwide. The complications derived from the novel coronavirus disease (COVID-19) vary in due to comorbidities, sex and age, with more than 50% of the patients who require some level of intensive care developing acute respiratory distress syndrome (ARDS). Areas covered: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological and radiological presentation as well as the current treatment strategies. Expert Opinion Elevation of inflammatory biomarkers is a common trend among seriously ill patients. The information available strongly suggests that in COVID-19 patients, their altered immune response, including a massive cytokine storm, is responsible for the further damage evidenced among ARDS patients. The increasingly high number of scientific articles and evidence available can only suggest that the individualization of each case is the norm, not all patients with acute respiratory failure due to COVID-19 meet the Berlin definition and therefore ARDS should be considered as a heterogeneous disease, with a wide range in the expression of its severity and clinical manifestations.


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