Complement Anaphylatoxins and Inflammatory Cytokines as Prognostic Markers for COVID-19 Severity and In-Hospital Mortality

Alosaimi, Bandar; Mubarak, Ayman; Hamed, Maaweya E.; Almutairi, Abdullah Z.; Alrashed, Ahmed; AlJuryyan, Abdullah; Enani, Mushira; Alenzi, Faris Q.; Alturaiki, Wael

doi:10.3389/fimmu.2021.668725

Cited by 51 publications

(61 citation statements)

References 86 publications

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“…Clinical reports of COVID-19 patients cite a dysregulated immune response characterized by elevated chemokine expression as key in the development of pathogenesis ( 26 , 27 ). Similar to our findings using the K18-hACE2 model, these reports have found upregulation of CCL2 (MCP1), CXCL8 (IL-8), and CXCL10 (IP10) to correlate with severity of disease and have suggested evaluation of these as biomarkers for disease and as targets for therapeutic intervention ( 28 – 30 ). Leronlimab, a CCR5-blocking antibody, is currently in phase 2 clinical trials in the United States.…”

Section: Discussionsupporting

confidence: 88%

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice

Olivarria

Cheng

Furman

et al. 2022

J Virol

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Unlike SARS-CoV-1 and MERS-CoV, infection with SARS-CoV-2, the viral pathogen responsible for COVID-19, is often associated with neurologic symptoms that range from mild to severe, yet increasing evidence argues the virus does not exhibit extensive neuroinvasive properties. We demonstrate SARS-CoV-2 can infect and replicate in human iPSC-derived neurons and that infection shows limited anti-viral and inflammatory responses but increased activation of EIF2 signaling following infection as determined by RNA sequencing. Intranasal infection of K18 human ACE2 transgenic mice (K18-hACE2) with SARS-CoV-2 resulted in lung pathology associated with viral replication and immune cell infiltration. In addition, ∼50% of infected mice exhibited CNS infection characterized by wide-spread viral replication in neurons accompanied by increased expression of chemokine ( Cxcl9, Cxcl10, Ccl2, Ccl5 and Ccl19 ) and cytokine ( Ifn-λ and Tnf-α ) transcripts associated with microgliosis and a neuroinflammatory response consisting primarily of monocytes/macrophages. Microglia depletion via administration of colony-stimulating factor 1 receptor inhibitor, PLX5622, in SARS-CoV-2 infected mice did not affect survival or viral replication but did result in dampened expression of proinflammatory cytokine/chemokine transcripts and a reduction in monocyte/macrophage infiltration. These results argue that microglia are dispensable in terms of controlling SARS-CoV-2 replication in in the K18-hACE2 model but do contribute to an inflammatory response through expression of pro-inflammatory genes. Collectively, these findings contribute to previous work demonstrating the ability of SARS-CoV-2 to infect neurons as well as emphasizing the potential use of the K18-hACE2 model to study immunological and neuropathological aspects related to SARS-CoV-2-induced neurologic disease. Importance Understanding the immunological mechanisms contributing to both host defense and disease following viral infection of the CNS is of critical importance given the increasing number of viruses that are capable of infecting and replicating within the nervous system. With this in mind, the present study was undertaken to evaluate the role of microglia in aiding in host defense following experimental infection of the central nervous system (CNS) of K18-hACE2 with SARS-CoV-2, the causative agent of COVID-19. Neurologic symptoms that range in severity are common in COVID-19 patients and understanding immune responses that contribute to restricting neurologic disease can provide important insight into better understanding consequences associated with SARS-CoV-2 infection of the CNS.

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Section: Discussionsupporting

confidence: 88%

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice

Olivarria

Cheng

Furman

et al. 2022

J Virol

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“…Among these biomarkers, MIP-3-BETA, IFN-β, and BLC were found to be predicting factors, where the upregulation of these biomarkers will increase the patients’ chances of requiring ICU admission. Similar findings were observed in [ 8 ], where patients with COVID-19 experienced the activation of the complement system, which was attributed to disease severity.…”

Section: Discussionsupporting

confidence: 89%

“…Chest CT imaging has been used as a means of determining COVID-19 severity among symptomatic high-risk individuals [ 7 ]. Immune biomarkers’ regulations in COVID-19 patients have been associated with disease severity, complications, and mortality rate [ 8 ]. COVID-19-positive ICU patients had a significant increase in blood coagulation abnormality, which was associated with many inflammatory up/down regulations [ 9 ] and cardiac complications such as acute myocardial infarction [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Prediction and Classification of COVID-19 Admissions to Intensive Care Units (ICU) Using Weighted Radial Kernel SVM Coupled with Recursive Feature Elimination (RFE)

Alshanbari

Mehmood

Sami

et al. 2022

Life

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Healthcare systems have been under immense pressure since the beginning of the COVID-19 pandemic; hence, studies on using machine learning (ML) methods for classifying ICU admissions and resource allocation are urgently needed. We investigated whether ML can propose a useful classification model for predicting the ICU admissions of COVID-19 patients. In this retrospective study, the clinical characteristics and laboratory findings of 100 patients with laboratory-confirmed COVID-19 tests were retrieved between May 2020 and January 2021. Based on patients’ demographic and clinical data, we analyzed the capability of the proposed weighted radial kernel support vector machine (SVM), coupled with (RFE). The proposed method is compared with other reference methods such as linear discriminant analysis (LDA) and kernel-based SVM variants including the linear, polynomial, and radial kernels coupled with REF for predicting ICU admissions of COVID-19 patients. An initial performance assessment indicated that the SVM with weighted radial kernels coupled with REF outperformed the other classification methods in discriminating between ICU and non-ICU admissions in COVID-19 patients. Furthermore, applying the Recursive Feature Elimination (RFE) with weighted radial kernel SVM identified a significant set of variables that can predict and statistically distinguish ICU from non-ICU COVID-19 patients. The patients’ weight, PCR Ct Value, CCL19, INF-β, BLC, INR, PT, PTT, CKMB, HB, platelets, RBC, urea, creatinine and albumin results were found to be the significant predicting features. We believe that weighted radial kernel SVM can be used as an assisting ML approach to guide hospital decision makers in resource allocation and mobilization between intensive care and isolation units. We model the data retrospectively on a selected subset of patient-derived variables based on previous knowledge of ICU admission and this needs to be trained in order to forecast prospectively.

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“…Human antibody responses against SARS-CoV-2 4 are generated by viral proteins such as spike glycoprotein (S protein) and nucleocapsid protein, of which the former can induce neutralizing antibodies required for viral neutralization and eradication by inhibiting viral interaction with the host cells. 5 SARS-CoV-2 penetrates host cells similarly to SARS-CoV-1 by binding to angiotensin-converting enzyme 2 (ACE2) using the S protein.…”

Section: Introductionmentioning

confidence: 99%

Durability of SARS-CoV-2 Specific IgG Antibody Responses Following Two Doses of Match and Mixed COVID-19 Vaccines Regimens in Saudi Population

Mubarak¹,

Almutairi²,

Al-Dhabbah³

et al. 2022

IDR

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Background SARS-CoV-2 pandemic continues to threaten the human population with millions of infections and deaths worldwide. Vaccination campaigns undertaken by several countries have resulted in a notable decrease in hospitalization and deaths. However, with the emergence of new virus variants, it is critical to determine the longevity and the protection efficiency provided by the current authorized vaccines. Aim The aims of this study are to provide data about the magnitude of immune responses in individuals fully vaccinated against COVID-19 in Riyadh province of Saudi Arabia. Also, to evaluate the continuity of specific IgG levels and compare the titers in individuals who have been received two doses of the matched and mixed vaccines, including Pfizer and AstraZeneca against SARS-CoV-2 during the period of three to six months. Moreover, we analyze the current state of immune response in terms of antibody responses in thepopulation postvaccination using homogenous or hetrogenous vaccine regimen. Methods A total of 141 healthy volunteers were recruited to our study; blood (n=63) and the saliva samples (n=78) and were collected from fully vaccinated individuals in Riyadh city. We employed a specific ELISA assay in plasma and saliva of fully vaccinated individuals. Results IgG levels varied with age groups with the highest concentration in the age group 19–29 years, but the age group (≥50) had the lowest IgG concentration. The IgG levels in both serum and saliva were higher after three months and start to wane after six months. Individuals who received mixed types of vaccines had significantly better response than Pfizer vaccine alone. Conclusion The current study investigates the status of humoral responses in different age groups, in terms of antibody measurements. These data will help to evaluate the need for further COVID-19 vaccine doses and to what extent a two-dose regimen will protect vaccinated individuals.

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Complement Anaphylatoxins and Inflammatory Cytokines as Prognostic Markers for COVID-19 Severity and In-Hospital Mortality

Cited by 51 publications

References 86 publications

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice

Microglia Do Not Restrict SARS-CoV-2 Replication following Infection of the Central Nervous System of K18-Human ACE2 Transgenic Mice

Prediction and Classification of COVID-19 Admissions to Intensive Care Units (ICU) Using Weighted Radial Kernel SVM Coupled with Recursive Feature Elimination (RFE)

Durability of SARS-CoV-2 Specific IgG Antibody Responses Following Two Doses of Match and Mixed COVID-19 Vaccines Regimens in Saudi Population

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