preVIEW: COVID-19

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MeSH Disease

COVID-19 (25)

Severe Acute Respiratory Syndrome (7)

Inflammation (5)

Neoplasms (5)

Necrosis (5)


HGNC Genes

C-X-C motif chemokine ligand 8 (25)

tumor necrosis factor (25)

interleukin 6 (20)

interleukin 10 (12)

interleukin 1 beta (10)


SARS-CoV-2 proteins

ProteinS (2)

ProteinS1 (1)


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    Exaggerated cytokine production in human peripheral blood mononuclear cells by recombinant SARS-CoV-2 spike PROTEIN glycoprotein S1 and its inhibition by dexamethasone

    Authors: Olumayokun A Olajide; Victoria U Iwuanyanwu; Izabela Lepiarz-Raba; Alaa A Al-Hindawi

    doi:10.1101/2021.02.03.429536 Date: 2021-02-03 Source: bioRxiv

    An understanding of the pathological inflammatory mechanisms involved in SARS CoV-2 virus infection MESHD is necessary in order to discover new molecular pharmacological targets for SARS-CoV-2 spike PROTEIN glycoprotein. In this study, the effects of a recombinant SARS CoV-2 spike PROTEIN glycoprotein S1 was investigated in human peripheral blood mononuclear cells (PBMCs). Stimulation with spike glycoprotein S1 PROTEIN (100 ng/mL) resulted in significant elevation in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and IL-8 HGNC. However, pre-treatment with dexamethasone (100 nM) caused a significant reduction in the release of these cytokines. Further experiments revealed that S1 stimulation of PBMCs increased phosphorylation of NF-{kappa}B HGNC p65 HGNC and I{kappa}B, while increasing I{kappa}B degradation. DNA binding of NF-{kappa}B HGNC p65 HGNC was also significantly increased following stimulation with S1. Treatment of PBMCs with dexamethasone (100 nM) or BAY11-7082 (1 M) resulted in inhibition of S1-induced NF-{kappa}B HGNC activation. Activation of p38 HGNC MAPK by S1 was blocked in the presence of dexamethasone and SKF 86002. CRID3, but not dexamethasone pre-treatment produced significant inhibition of S1-induced activation of NLRP3 HGNC/ caspase 1 HGNC. Further experiments revealed that S1-induced increase in the production of TNF HGNC, IL-6 HGNC, IL-1{beta HGNC} and IL-8 HGNC was reduced in the presence of BAY11-7082 and SKF 86002, while CRID3 pre-treatment resulted in the reduction of IL-1{beta HGNC} production. These results suggest that SARS-CoV-2 spike PROTEIN glycoprotein S1 stimulate PBMCs to release pro inflammatory cytokines through mechanisms involving activation of NF-{kappa}B HGNC, p38 MAPK and NLRP3 HGNC inflammasome. It is proposed that clinical benefits of dexamethasone in COVID-19 MESHD is possibly due to its anti-inflammatory activity in reducing SARS-CoV-2 cytokine storm.

    Humoral and cell-mediated response in colostrum after exposure to severe acute respiratory syndrome coronavirus 2 MESHD

    Authors: Vignesh Narayanaswamy; Brian Pentecost; Dominique Alfandari; Emily Chin; Kathleen Minor; Alyssa Kastrinakis; Tanya Lieberman; Kathleen F Arcaro; Heidi Leftwich

    doi:10.1101/2021.01.03.20248715 Date: 2021-01-04 Source: medRxiv

    BackgroundColostrum provides an immune sharing between a mother and her infant. The transfer in colostrum of antibodies against SARS-CoV-2 and the elicited cytokines may provide crucial protection to the infant. There is limited literature on the immune response to SARS-CoV-2 present in colostrum. ObjectiveTo evaluate the presence of antibodies specific to SARS-CoV-2 and the associated cytokines in colostrum from women who tested positive for the virus. Study DesignBetween March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Five of these 15 COVID-19 MESHD positive women also provided bilateral liquid colostrum within 1-2 days of providing the spot card samples. Archived bilateral colostrum samples collected from 8 women during 2011-2013 were used as pre- COVID-19 MESHD controls. All samples were tested for reactivity to the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike PROTEIN protein using an ELISA that measures SARS-CoV-2 RBD-specific IgA, IgG, and IgM, and for concentrations of 10 inflammatory cytokines ( IFN{gamma HGNC}, TNF HGNC, IL-1{beta HGNC}, IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, IL-12, IL-13 HGNC) using a multiplex electrochemiluminescent sandwich assay. ResultsBilateral colostrum samples from 73%, 73% and 33% of the 15 COVID-19 MESHD mothers exhibited IgA, IgG, and IgM reactivity to RBD respectively. Colostrum samples from two of the 8 pre-pandemic controls showed IgA and IgG reactivity to RBD. Additionally, COVID-19 MESHD mothers had significantly higher levels of 9 of the 10 inflammatory markers (all except IFN{gamma HGNC}) as compared to the pre- COVID-19 MESHD controls. Comparable results were obtained with both the spot card-eluates and liquid samples. ConclusionsA strong humoral immune response is present in the colostrum of women who were infected with SARS-CoV-2 before delivering. High levels of 9 inflammatory markers were also present in the colostrum. The evolution and duration of the antibody response, as well as dynamics of the cytokine response, remain to be determined. Our results also indicate that future large-scale studies can be conducted with milk easily collected on paper spot cards.

    Kinetics of Plasma Cytokines During and After Two Different Modalities of Extracorporeal Blood Purification in Critically Ill COVID-19 MESHD Patients

    Authors: Daniela Ponce; Welder Zamoner; Luis Eduardo Magalhães; Paula Gabriela Souza de Oliveira; Patricia Polla; Alexandre Naime Barbosa; Marjorie de Assis Golim; Andre Luis Balbi

    doi:10.21203/rs.3.rs-136018/v1 Date: 2020-12-25 Source: ResearchSquare

    Cytokine storm syndrome ( CSS MESHD) has been documented in coronavirus disease 2019 MESHD ( COVID-19 MESHD) since the first reports of this disease. In the absence of vaccines or direct therapy for COVID-19 MESHD, extracorporeal blood treatment (EBT) could represent an option for the removal of cytokines and may be beneficial to improve the clinical outcome of critically ill MESHD patients. Intermittent haemodialysis ( IHD MESHD), using high flux (HF) or high cut-off membranes, and continuous renal replacement therapy (CRRT) could be used for blood purification in COVID-19 MESHD patients with CSS. To the best of our knowledge, cytokine kinetics during and after different types of EBT on COVID-19 MESHD patients have never been studied. In this study, we describe cytokine variation and removal during and after IHD MESHD and CRRT in COVID-19 MESHD patients with acute kidney injury MESHD ( AKI MESHD). Methods: Patients with COVID-19 MESHD-related AKI MESHD according to Kidney Disease MESHD Improving Global Outcomes (KDIGO) criteria and admitted at Intensive Care Unit (ICU) were studied. Blood samples were collected at the start and end of both IHD MESHD using HF membranes (10 patients) and continuous venovenous haemodiafiltration (CVVHDF: 10 patients) in two sessions for measuring 13 different plasma interleukins and calculating the cytokine removal rate. Results: We evaluated cytokine removal in patients with COVID-19 MESHD-related AKI MESHD undergoing either prolonged IHD MESHD (10 patients) or CRRT (CVVHDF: 10 patients). There was no difference between the IHD MESHD and CVVHDF groups regarding mechanical ventilation, vasoactive drug use, age or prognostic scores. Patients treated by CRRT presented higher levels of IL-2 HGNC and IL-8 HGNC than patients treated by prolonged IHD at the start of dialysis. Cytokine removal ranged from 9–78%. Patients treated by CRRT presented higher cytokine removal rates than those treated by prolonged IHD for IL-2 HGNC, IL-6 IL-8, IP-10 HGNC and TNF HGNC. The removal rates of IL-4 HGNC, IL-10 HGNC, IL-1β HGNC, IL-17A HGNC, IFN HGNC, MCP-1 HGNC and free active TGF-B1 HGNC were similar in the two groups. After one session of CVVHDF (24 h) the IL-2 HGNC and IL-1β HGNC levels did not vary significantly, whereas IL-4 HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, IL-17A HGNC, TNF HGNC, IFN HGNC, IP-10 HGNC, MCP-1 HGNC, IL-12p70 and free active TGF-B1 HGNC decreased by 33.8–76%, and this decrease was maintained over the next 24 h. In the prolonged IHD groups, IL-2 HGNC, IL-6 HGNC, TNF HGNC, IP-10 HGNC and IL-1β HGNC levels did not decrease significantly whereas IL-4 HGNC, IL-8 HGNC, IL-10 HGNC, IL-17A HGNC, IFN HGNC, MCP-1 HGNC, IL-12p70 and free active TGF-B1 HGNC decreased by 21.8–72%. However, all cytokine levels returned to their initial values after 24 h, despite their removal. Conclusions: Cytokine removal is lower using prolonged IHD MESHD with HF membranes than by using CVVHDF, and IHD MESHD allows a transient and selective decrease in cytokines that can be correlated with mortality during CSS-related COVID-19 MESHD.

    Altered Transcript Levels of Cytokines in COVID-19 MESHD Patients

    Authors: Majid Samsami; Alireza Fatemi; Reza Jalili Khoshnoud; Karim Kohansal; Arezou Sayad; Shabnam Soghala; Shahram Arsang-Jang; Mohammad Taheri; Soudeh Ghafouri-Fard

    doi:10.21203/rs.3.rs-126215/v1 Date: 2020-12-10 Source: ResearchSquare

    The pandemic caused by severe acute respiratory syndrome coronavirus 2 MESHD and the related disorder i.e. “ coronavirus disease 2019 MESHD” ( COVID-19 MESHD) have encouraged researchers to unravel the molecular mechanism of disease severity. Several lines of evidence support the impact of "cytokine storm" in the pathogenesis of severe forms of the disorder MESHD. We aimed to assess the expression levels of nine cytokine coding in COVID-19 MESHD patients admitted in a hospital. Expression levels of IFN-G HGNC, IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-17 HGNC, TGF-B HGNC, IL-8 HGNC and IL-1B HGNC were significantly higher in COVID-19 MESHD patients compared with healthy controls and in both female and male patients compared with sex-matched controls. However, expression of none of these cytokines was different between ICU-admitted patients and other patients except for IL-6 HGNC whose expression was lower in the former group compared with the latter (ratio of means = 0.33, P value = 4.82E-02). Expression of TNF-A HGNC was not different between COVID-19 MESHD patients and healthy controls. Then, we assessed diagnostic power of cytokine coding genes in differentiating between COVID-19 MESHD patients and controls. The area under curve (AUC) values range from 0.94 for IFN-G HGNC to 1.0 for IL-2 HGNC and IL-1B HGNC. After combining the transcript levels of all cytokines, AUC, sensitivity and specificity values reached 1.0, 1.0 and 0.99, respectively. For differentiation between ICU-admitted patients and other patients, IL-4 HGNC with AUC value of 0.68, had the best diagnostic power among cytokine coding genes. Expression of none of cytokine coding genes was correlated with the assessed clinical/demographic data including age, gender, ICU admission, or CRP HGNC/ESR levels. Our study provides further evidence for contribution of “cytokine storm” in the pathobiology of moderate/severe forms of COVID-19 MESHD.

    Transcriptome Profiling of different types of human respiratory tract cells infected by SARS-CoV-2 Highlight an unique Role for Inflammatory and Interferon Response

    Authors: Luping Lei; Qiumei Cao; Yu Wang; Mario Hensen; Anu V. Chandran; Michelle L. Hill; J.L. Kiappes; Raymond A. Dwek; Dominic S. Alonzi; Weston B. Struwe; Nicole Zitzmann; Florian M Wurm; Xin Zheng; Jia Liu; Davey Smith; Daniela Weiskopf; Alessandro Sette; Shane Crotty; Jian Jin; Xian Chen; Andrew Pekosz; Sabra Klein; Irina Burd

    doi:10.1101/2020.11.15.383927 Date: 2020-11-16 Source: bioRxiv

    The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease MESHD ( COVID-19 MESHD) at the end of 2019 has caused a large global outbreak and now become a major public health issue. Lack of data underlying how the human host interacts with SARS-CoV-2 virus. In the current study, We performed Venn-analysis, Gene ontology (GO), KEGG pathway analysis and Protein-protein interaction analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during human respiratory tract cells infected with SARS-CoV-2. We selected four studies through a systematic search of the Gene Expression Omnibus (GEO) database or published article about SARS-CoV-2 infection MESHD in different types of respiratory tract cells. We found 36 overlapping upregulated genes among different types of cells after viral infection. Further functional enrichment analysis revealed these DEGs are most likely involved in biological processes related to inflammatory response and response to cytokine, cell component related to extracellular space and I-kappaB/NF-kappaB complex, molecular function related to protein binding and cytokine activity. KEGG pathways analysis highlighted altered conical and casual pathways related to TNF HGNC, NF-kappa B HGNC, Cytokine-cytokine receptor interaction and IL17 HGNC signaling pathways during SARS-CoV-2 infection MESHD with CXCL1 HGNC, CXCL2 HGNC, CXCL3 HGNC, CXCL8 HGNC, CXCL10 HGNC, IL32 HGNC, CX3CL1 HGNC, CCL20 HGNC, IRF1 HGNC, NFKB2 HGNC and NFKB1A up-regulated which may explain the inflammatory cytokine storms associated with severe cases of COVID-19 MESHD.

    Dynamic changes in serum IL-6 HGNC, IL-8 HGNC, and IL-10 HGNC are associated with the outcome of patients with severe COVID-19 MESHD in ICU

    Authors: Jia Li; Liu Rong; Ran Cui; Jiaqi Feng; Yuyang Jin; Yuetian Yu; Xiaoxiang Chen; Renying Xu

    doi:10.21203/rs.3.rs-83336/v1 Date: 2020-09-25 Source: ResearchSquare

    Background: Biomarkers that would help prognosticate outcomes and guide treatment of patients with severe coronavirus disease 2019 MESHD ( COVID-19 MESHD) are currently required. We aimed to investigate whether the dynamic variation of cytokines was associated with the survival of patients admitted to an intensive care unit (ICU).Methods: A retrospective study was performed on 40 patients with COVID-19 MESHD admitted to an ICU in Wuhan, China. Demographic, clinical, and laboratory variables were collected, and serum cytokines were kinetically assessed. A multivariable- adjusted generalized linear regression model was used to evaluate the differences in serum cytokine levels between survivor and non-survivors.Results: Among the 40 patients included, a significant positive correlation was found between multiple cytokines. Serum levels of IL-6 HGNC, IL-10 HGNC, and tumor MESHD tumor HGNC necrosis MESHD factor alpha in non-survivors were consistently elevated compared to that of the survivors. Kinetic variations of IL-6 HGNC, IL-8 HGNC, and IL-10 HGNC were associated with a fatal outcome in severe patients with COVID-19 MESHD, independent of sex, age, absolute lymphocyte count, direct bilirubin, hypertension MESHD, chronic obstructive pulmonary disease MESHD, and cancer MESHD.Conclusion: Dynamic changes in serum IL-6 HGNC, IL-8 HGNC, and IL-10 HGNC levels were associated with survival in ICU and could serve as a predictive biomarker in patients with severe COVID-19 MESHD to determine therapeutic options.

    LOX-1 HGNC+ immature neutrophils predict severe COVID-19 MESHD patients at risk of thrombotic complications

    Authors: Behazine Combadiere; Lucille Adam; Paul Quentric; Pierre Rosenbaum; Karim Dorgham; Olivia Bonduelle; Christophe Parizot; Delphine Sauce; Julien Mayaux; Charles-Edouard Luyt; Alexandre Boissonnas; Zahir Amoura; Valerie Pourcher; Makoto Miyara; Guy Gorochov; Amelie Guihot; Christophe Combadiere; Duraipandian Thavaselvam; Devendra Kumar Dubey; Paul Lin; Hila Shaim; Sean G Yates; David Marin; Indreshpal Kaur; Sheetal Rao; Duncan Mak; Angelique Lin; Qi Miao; Jinzhuang Dou; Ken Chen; Richard Champlin; Elizabeth J Shpall; Katayoun Rezvani

    doi:10.1101/2020.09.15.293100 Date: 2020-09-15 Source: bioRxiv

    Rational: Lymphopenia MESHD and neutrophil/lymphocyte ratio may have prognostic value in coronavirus disease 2019 MESHD ( COVID-19 MESHD) severity. Objective: We sought to investigate the representation of neutrophil subsets in severe and critical COVID-19 MESHD patients based on Intensive Care Units (ICU) and non-ICU admission. Methods: We developed a multi-parametric neutrophil profiling strategy based on known neutrophil markers to distinguish COVID-19 MESHD phenotypes in critical and severe patients. Results: Our results showed that 80 percent of ICU patients develop strong myelemia with CD10 HGNC- CD64 HGNC+ immature neutrophils. Cellular profiling revealed two distinct neutrophil subsets expressing either the lectin-like oxidized low-density lipoprotein receptor-1 ( LOX-1 HGNC) or the Interleukin-3 receptor alpha ( CD123 HGNC), both significantly overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1 HGNC-expressing immature neutrophils positively correlated with clinical severity, with the cytokine storm ( IL-1{beta HGNC}, IL-6 HGNC, IL-8 HGNC, TNF HGNC), and with intravascular coagulation MESHD. Importantly, high proportions of LOX-1 HGNC+-immature neutrophils are associated with high risks of severe thrombosis MESHD. Conclusions: Together these data suggest that point of care enumeration of LOX-1 HGNC-immature neutrophils might help distinguish patients at risk of thrombosis MESHD complication and most likely to benefit from intensified anticoagulant therapy.

    Lymphocyte May Be a Reference Index of the Outcome of Cancer Patients in COVID-19 MESHD Infection

    Authors: Xun Yuan; Yuan Gao; Qian Chu

    doi:10.21203/rs.3.rs-58047/v1 Date: 2020-08-12 Source: ResearchSquare

    Background: The novel coronavirus ( COVID-19 MESHD)– infected pneumonia MESHD is an international concern as it spreads through human populations and across national and international borders.Methods: In this retrospective study, we consecutively included all cancer MESHD cases who had been identified as having a nucleic acid-confirmed COVID-19 MESHD infection from two designated hospitals in Wuhan, China. Non-cancer MESHD patients were also enrolled for comparison. The clinical data were gathered from the medical recordsfrom Jan 14 to March 12.Results: Among the 117 cancer MESHD patients infected with COVID19 MESHD, the median age was 63 years and 48.7% were male. Male, hematologic cancer MESHD, dyspnea MESHD on admission, and anti- cancer MESHD therapy significantly increased the risk of death MESHD. The amounts of cytokines and immune cells were correlated with the outcomeofcancer patients infected with COVIP-19. However, high level of TNF-a HGNC, IL-2R HGNC, IL-6 HGNC, IL-8 HGNC did not increase the risk of death in non-cancer MESHD patients. Moreover, IL-2R HGNC and IL-6 HGNC markedly decreased in cancer MESHD patients recovered from COVID-19 MESHD.Conclusions: Cancer MESHD patients with COVID-19 MESHD were associated with high mortality (23.9%).The amounts of cytokines and lymphocytes could be utilized as the reference index in predicting the survival outcome of cancer MESHD patients with COVID-19 MESHD.

    Age-severity matched cytokine profiling reveals specific signatures in Covid-19 MESHD patients

    Authors: Roberta Angioni; Ricardo Sanchez-Rodriguez; Fabio Munari; Nicole Bertoldi; Diletta Arcidiacono; Silvia Cavinato; Davide Marturano; Annamaria Cattelan; Antonella Viola; Barbara Molon

    doi:10.1101/2020.07.28.20162735 Date: 2020-07-29 Source: medRxiv

    A global effort is currently undertaken to restrain the COVID-19 pandemic MESHD COVID-19 pandemic MESHD. Host immunity has come out as a determinant for COVID-19 MESHD clinical outcome, and several studies investigated the immune profiling of SARS-CoV-2 infected people MESHD to properly direct the clinical management of the disease. Thus, lymphopenia MESHD, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 MESHD patients, in particular in severe cases1. Age represents a key factor in COVID-19 MESHD morbidity and mortality2. Understanding age-associated immune signatures of patients is therefore important to identify preventive and therapeutic strategies. In this study, we investigated the immune profile of COVID-19 MESHD hospitalized patients identifying a distinctive age-dependent immune signature associated with disease severity. Indeed, defined circulating factors - CXCL8 HGNC, IL-10 HGNC, IL-15 HGNC, IL-27 HGNC and TNF HGNC- - positively correlate with older age, longer hospitalization, and a more severe form of the disease and may thus represent the leading signature in critical COVID-19 MESHD patients.

    Circulating cytokines and lymphocyte subsets in patients who have recovered from COVID-19 MESHD

    Authors: Hasi Chaolu; Xinri Zhang; Xin Li; Xin Li; Dongyan Li

    doi:10.1101/2020.07.22.20160259 Date: 2020-07-24 Source: medRxiv

    To investigate the immune status of people who previously had COVID-19 MESHD infections, we recruited patients 2 weeks post-recovery and analyzed circulating cytokines and lymphocyte subsets. We measured levels of total lymphocytes, CD4+ T cells, CD8+ T cells, CD19 HGNC+ B cells, CD56 HGNC+ NK cells, and the serum concentrations of interleukin (IL)-1, IL-4 HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, transforming growth factor beta HGNC (TGF-{beta}), tumor MESHD necrosis MESHD factor alpha (TNF-), and interferon gamma ( IFN-{gamma HGNC}) by flow cytometry. We found that in most post-recovery patients, levels of total lymphocytes (66.67%), CD3+ T cells (54.55%), CD4+ T cells (54.55%), CD8 + T cells (81.82%), CD19 HGNC+ B cells (69.70%), and CD56 HGNC+ NK cells(51.52%) remained lower than normal, whereas most patients showed normal levels of IL-2 HGNC (100%), IL-4 HGNC (80.88%), IL-6 HGNC (79.41%), IL-10 HGNC (98.53%), TNF HGNC- (89.71%), IFN-{gamma HGNC} (100%) and IL-17 HGNC (97.06%). Compared to healthy controls, 2-week post-recovery patients had significantly lower absolute numbers of total lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19 HGNC+ B cells, and CD56 HGNC+ NK cells, along with significantly higher levels of IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-10 HGNC, TNF HGNC-, IFN-{gamma} and IL-17. Among post-recovery patients, T cells, particularly CD4+ T cells, were positively correlated with CD19 HGNC+ B cell counts. Additionally, CD8+ T cells positively correlated with CD4+ T cells and IL-2 HGNC levels, and IL-6 HGNC positively correlated with TNF HGNC- and IFN-{gamma HGNC}. These correlations were not observed in healthy controls. By ROC curve analysis, post-recovery decreases in lymphocyte subsets and increases in cytokines were identified as independent predictors of rehabilitation efficacy. These findings indicate that the immune system has gradually recovered following COVID-19 MESHD infection; however, the sustained hyper-inflammatory response for more than 14 days suggests a need to continue medical observation following discharge from the hospital. Longitudinal studies of a larger cohort of recovered patients are needed to fully understand the consequences of the infection.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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