scholarly journals Pathophysiology of COVID-19: Mechanisms Underlying Disease Severity and Progression

Physiology ◽  
2020 ◽  
Vol 35 (5) ◽  
pp. 288-301 ◽  
Author(s):  
Mary Kathryn Bohn ◽  
Alexandra Hall ◽  
Lusia Sepiashvili ◽  
Benjamin Jung ◽  
Shannon Steele ◽  
...  
Keyword(s):  
Immune Response ◽  
Organ Failure ◽  
Disease Severity ◽  
Viral Entry ◽  
Wide Spectrum ◽  
Underlying Disease ◽  
Viral Clearance ◽  
Clinical Severity ◽  
Global Epidemiology

The global epidemiology of coronavirus disease 2019 (COVID-19) suggests a wide spectrum of clinical severity, ranging from asymptomatic to fatal. Although the clinical and laboratory characteristics of COVID-19 patients have been well characterized, the pathophysiological mechanisms underlying disease severity and progression remain unclear. This review highlights key mechanisms that have been proposed to contribute to COVID-19 progression from viral entry to multisystem organ failure, as well as the central role of the immune response in successful viral clearance or progression to death.

scholarly journals Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections

2021 ◽  
Author(s):  
Karthick Dharmalingam ◽  
Amandeep Birdi ◽  
Sojit Tomo ◽  
Karli Sreenivasulu ◽  
Jaykaran Charan ◽  
...  
Keyword(s):  
Immune Response ◽  
Trace Elements ◽  
Viral Entry ◽  
Viral Infections ◽  
Inhibitory Effect ◽  
Antioxidants Activity ◽  
Host Immune Responses ◽  
Complex Interactions ◽  
Downstream Processes

AbstractNutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words “Trace elements”, “COVID-19”, “Viral Infections” and “Immune Response” (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

scholarly journals Pulmonary transcriptomic responses indicate a dual role of inflammation in pneumonia development and viral clearance during 2009 pandemic influenza infection

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3915 ◽  
Author(s):  
Raquel Almansa ◽  
Pamela Martínez-Orellana ◽  
Lucía Rico ◽  
Verónica Iglesias ◽  
Alicia Ortega ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Pandemic Influenza ◽  
Dual Role ◽  
Viral Clearance ◽  
Cytokine Signaling ◽  
Effective Response ◽  
Pdm09 Virus ◽  
Influenza A H1n1

Background The interaction between influenza virus and the host response to infection clearly plays an important role in determining the outcome of infection. While much is known on the participation of inflammation on the pathogenesis of severe A (H1N1) pandemic 09-influenza virus, its role in the course of non-fatal pneumonia has not been fully addressed. Methods A systems biology approach was used to define gene expression profiles, histology and viral dynamics in the lungs of healthy immune-competent mice with pneumonia caused by a human influenza A (H1N1) pdm09 virus, which successfully resolved the infection. Results Viral infection activated a marked pro-inflammatory response at the lung level paralleling the emergence of histological changes. Cellular immune response and cytokine signaling were the two signaling pathway categories more representative of our analysis. This transcriptome response was associated to viral clearance, and its resolution was accompanied by resolution of histopathology. Discussion These findings suggest a dual role of pulmonary inflammation in viral clearance and development of pneumonia during non-fatal infection caused by the 2009 pandemic influenza virus. Understanding the dynamics of the host’s transcriptomic and virological changes over the course of the infection caused by A (H1N1) pdm09 virus may help identifying the immune response profiles associated with an effective response against influenza virus.

scholarly journals Dissecting the role of genetic modifiers of hemoglobinopathies: A futuristic approach towards precision medicine

2021 ◽  
Author(s):  
Priya Hariharan ◽  
Manju Gorivale ◽  
Pratibha Sawant ◽  
Pallavi Mehta ◽  
Anita Nadkarni
Keyword(s):  
Disease Severity ◽  
Phenotypic Variability ◽  
Globin Gene ◽  
Gene Promoter ◽  
Clinical Severity ◽  
Genetic Modifiers ◽  
Promoter Polymorphisms ◽  
Cumulative Impact ◽  
Remarkable Result

Abstract Introduction: Hemoglobinopathies though a monogenic disorder, show phenotypic variability. Hence, understanding the genetics underlying the heritable sub-phenotypes of hemoglobinopathies, specific to each population, would be prognostically useful and could inform personalized therapeutics. This study aimed to evaluate the role of genetic modifiers leading to higher HbF production with cumulative impact of the modifiers on disease severity. Materials and methods:200 patients [100 β-thalassemia homozygotes,100 Sickle Cell Anemia], and 50 healthy controls were recruited. Primary screening followed with molecular analysis for confirming the β-hemoglobinopathy was performed. Co-existing α-thalassemia and the polymorphisms located in 3 genetic loci linked to HbF regulation were screened.Results: The most remarkable result was the association of SNPs with clinically relevant phenotypic groups. The γ-globin gene promoter polymorphisms [-158 C→T,+25 G→A],BCL11A rs1427407 G→T,-3 bp HBS1L-MYB rs66650371 and rs9399137 T→C polymorphisms were correlated with higher HbF, in group that has lower disease severity score (P<0.00001), milder clinical presentation, and a significant delay in the age of the first transfusion.Conclusion:Our study emphasizes the complex genetic interactions underlying the disease phenotype that may be a prognostic marker for predicting the clinical severity and assist in disease management.

scholarly journals Perspectives and Challenges in the Fight Against COVID-19: The Role of Genetic Variability

2021 ◽  
Vol 11 ◽  
Author(s):  
Mariana Guilger-Casagrande ◽  
Cecilia T. de Barros ◽  
Vitória A. N. Antunes ◽  
Daniele R. de Araujo ◽  
Renata Lima
Keyword(s):  
Disease Severity ◽  
Viral Entry ◽  
Expression Profiles ◽  
Clinical Signs ◽  
Pharmacological Therapy ◽  
Genetic Features ◽  
Inflammatory Processes ◽  
Clinical Responses ◽  
Infection Mechanisms

In the last year, the advent of the COVID-19 pandemic brought a new consideration for the multidisciplinary sciences. The unknown mechanisms of infection used by SARS-CoV-2 and the absence of effective antiviral pharmacological therapy, diagnosis methods, and vaccines evoked scientific efforts on the COVID-19 outcome. In general, COVID-19 clinical features are a result of local and systemic inflammatory processes that are enhanced by some preexistent comorbidities, such as diabetes, obesity, cardiovascular, and pulmonary diseases, and biological factors, like gender and age. However, the discrepancies in COVID-19 clinical signs observed among those patients lead to investigations about the critical factors that deeply influence disease severity and death. Herein, we present the viral infection mechanisms and its consequences after blocking the angiotensin-converting enzyme 2 (ACE2) axis in different tissues and the progression of inflammatory and immunological reactions, especially the influence of genetic features on those differential clinical responses. Furthermore, we discuss the role of genotype as an essential indicator of COVID-19 susceptibility, considering the expression profiles, polymorphisms, gene identification, and epigenetic modifications of viral entry factors and their recognition, as well as the infection effects on cell signaling molecule expression, which amplifies disease severity.

scholarly journals COVID-19 and Hyperinflammation: Role of Steroid in Mild Disease

2020 ◽  
pp. 18-22
Author(s):  
Jhasaketan Meher ◽  
Manish Kumar Nayak
Keyword(s):  
Immune Response ◽  
Wide Spectrum ◽  
Case Series ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Cytokine Storm ◽  
Multiorgan Dysfunction ◽  
Mild Disease ◽  
Persistent Symptoms

Current COVID-19 has become a major public health problem because of its pandemicity, with wide spectrum of disease manifestation. SARS-COV-2 can have a varied clinical manifestation ranging from asymptomatic, mild symptomatic to severe disease like acute respiratory distress syndrome, cytokine storm, and multiorgan dysfunction. It has been described in literature that cytokine storm/hyperinflammation arises as result of dysregulated immune response leading to excessive release of various cytokines which causes multiorgan dysfunction. But there is paucity of literature describing the immune response and hyperinflammation in mild disease which may cause unremitting symptoms. Here we describe a case series of three patients with mild disease, who had persistent symptoms beyond 1 week and managed with low dose steroid after confirming it to be hyperinflammation. So it is imperative to detect the hyperinflammatory phase to halt the disease progression. Also we have discussed the role of immune system and role of steroid in COVID-19.

scholarly journals Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience

2020 ◽  
Author(s):  
Sarfraz A Saleemi ◽  
Abdulrahman Alrajhi ◽  
Mohammed Alhajji ◽  
Areej Alfattani ◽  
Faisal Albaiz
Keyword(s):  
Disease Severity ◽  
Median Time ◽  
Symptom Onset ◽  
Viral Clearance ◽  
P Value ◽  
Nasopharyngeal Swab ◽  
Multivariate Regression Model ◽  
Mild Disease ◽  
Virus Clearance

Background: The role of hydroxychloroquine (HCQ) and azithromycin in the treatment of COVID-19 and its effect on SARS-CoV-2 viral clearance is not known. Methods: This is a retrospective observational study to assess the effect of HCQ and Azithromycin on duration from symptom onset to negative SARS-CoV-2 PCR using nasopharyngeal swab in hospitalized patient with COVID-19. Eighty-five patients were included in the study, 65 in HCQ (Hydroxychloroquine + Azithromycin) and 20 in non-HCQ group. Measurement of duration from symptom onset to negative PCR and effect of gender, age and disease severity on time to viral clearance was measured. Results: Median time to negative PCR in HCQ group was 23 days (IQR: 9, Mean 24+8, N=65) compared with non-HCQ group, 19 days (IQR: 8, Mean 18+6, N=20), (p <0.05). Forty-one (63%) patients in HCQ group and all patients (100%) in non-HCQ group had mild disease. Multivariate regression model (F=6.8, P<0.002, R2=0.20) shows that being in HCQ group would delay the time to negative PCR by 7 days (95%CI: 2-12) and with every year increase in the age, the time to negative PCR would be delayed by 0.12 days (95%CI: 0.017-0.22). Among HCQ sub-groups, gender and disease severity had no effect on duration (p 0.142 and 0.156 respectively) but older patients >60 year had longer duration compared to patients <60 year of age although p value did not reach significance (p 0.073). Median time to negative PCR in mild-HCQ group (23 days, IQR: 9, Mean 23+8, N=41) was longer when compared with non-HCQ group (p <0.05). On day 28, all patients in non-HCQ group had negative PCR while only 50/65 (77%) were negative in HCQ group. Conclusion: Hydroxychloroquine (HCQ) and azithromycin delay SARS-CoV-2 virus clearance in hospitalized patients with COVID-19 and it is correlated with older age. Larger studies are needed to confirm this finding.

scholarly journals Role of Lung Ultrasound in Predicting Clinical Severity and Fatality in COVID-19 Pneumonia

2021 ◽  
Vol 11 (8) ◽  
pp. 757
Author(s):  
Ivan Skopljanac ◽  
Mirela Pavicic Ivelja ◽  
Ognjen Barcot ◽  
Ivan Brdar ◽  
Kresimir Dolic ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Disease Severity ◽  
Predictive Power ◽  
Lung Ultrasound ◽  
Clinical Severity ◽  
Imaging Method ◽  
High Flow Nasal Cannula ◽  
Severity Of The Disease

Background: Lung ultrasound (LUS) is a useful imaging method for identifying COVID-19 pneumonia. The aim of this study was to explore the role of LUS in predicting the severity of the disease and fatality in patients with COVID-19. Methods: This was a single-center, follow-up study, conducted from 1 November 2020, to 22 March 2021. The LUS protocol was based on the assessment of 14 lung zones with a total score up to 42, which was compared to the disease severity and fatality. Results: A total of 133 patients with COVID-19 pneumonia confirmed by RT-PCR were enrolled, with a median time from hospital admission to lung ultrasound of one day. The LUS score was correlated with clinical severity at hospital admission (Spearman’s rho 0.40, 95% CI 0.24 to 0.53, p < 0.001). Patients with higher LUS scores were experiencing greater disease severity; a high flow nasal cannula had an odds ratio of 1.43 (5% CI 1.17–1.74) in patients with LUS score > 29; the same score also predicted the need for mechanical ventilation (1.25, [1.07–1.48]). An LUS score > 30 (1.41 [1.18–1.68]) and age over 68 (1.26 [1.11–1.43]) were significant predictors of fatality. Conclusions: LUS at hospital admission is shown to have a high predictive power of the severity and fatality of COVID-19 pneumonia.

scholarly journals Role of Type I Interferon (IFN) in the Respiratory Syncytial Virus (RSV) Immune Response and Disease Severity

2019 ◽  
Vol 10 ◽  
Author(s):  
Diego R. Hijano ◽  
Luan D. Vu ◽  
Lawrence M. Kauvar ◽  
Ralph A. Tripp ◽  
Fernando P. Polack ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Disease Severity ◽  
Type I Interferon ◽  
Type I ◽  
Syncytial Virus

The Role of Immune Response to Staphylococcus aureus Superantigens and Disease Severity in Relation to the Sensitivity to Tacrolimus in Atopic Dermatitis

2006 ◽  
Vol 141 (3) ◽  
pp. 281-289 ◽  
Author(s):  
Hisayo Fukushima ◽  
Toshihiko Hirano ◽  
Naoko Shibayama ◽  
Keishi Miwa ◽  
Tomonobu Ito ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Atopic Dermatitis ◽  
Disease Severity

scholarly journals Predictive SNPs for β0-thalassemia/HbE disease severity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thongperm Munkongdee ◽  
Sissades Tongsima ◽  
Chumpol Ngamphiw ◽  
Pongsakorn Wangkumhang ◽  
Chayanon Peerapittayamongkol ◽  
...  
Keyword(s):  
Disease Severity ◽  
Risk Score ◽  
Wide Spectrum ◽  
Association Studies ◽  
Treatment Decision ◽  
Clinical Severity ◽  
Predictive Score ◽  
Blood Transfusions ◽  
Treatment Decision Making ◽  
Snp Interaction

Abstractβ-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β0-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β0-thalassemia/HbE population.

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