Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (5)

NSP5 (2)

ProteinN (2)

ProteinS1 (2)

NSP3 (1)


SARS-CoV-2 Proteins
    displaying 21 - 30 records in total 73
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    Anakinra To Prevent Respiratory Failure In COVID-19 MESHD

    Authors: Evdoxia Kyriazopoulou; Periklis Panagopoulos; Simeon Metallidis; George Dalekos; Garyfallia Poulakou; Nikolaos Gatselis; Eleni Karakike; Maria Saridaki; Georgia Loli; Aggelos Stefos; Danai Prasianaki; Sarah Georgiadou; Olga Tsachouridou; Vasileios Petrakis; Konstantinos Tsiakos; Maria Kosmidou; Vassiliki Lygoura; Maria Dareioti; Haralampos Milionis; Ilias C Papanikolaou; Karolina Akinosoglou; Dimitra-Melia Myrodia; Areti Gravani; Aliki Stamou; Theologia Gkavogianni; Konstantina Katrini; Theodoros Marantos; Ioannis P Trontzas; Konstantinos Syrigos; Lukas Chatzis; Stamatios Chatzis; Nikolaos Vechlidis; Christina Avgoustou; Stamatios Chalvatzis; Miltiades Kyprianou; Jos WM van der Meer; jesper eugen-olsen; Mihai Netea; Evangelos Giamarellos-Bourboulis

    doi:10.1101/2020.10.28.20217455 Date: 2020-10-29 Source: medRxiv

    Introduction The management of pneumonia MESHD caused by SARS-CoV-2 should rely on early recognition of the risk for progression to severe respiratory failure MESHD ( SRF HGNC SRF MESHD) and its prevention. We investigated if early suPAR (soluble urokinase plasminogen activator receptor HGNC)-guided anakinra treatment could prevent COVID-19 MESHD-assocated SRF HGNC. Methods In this open-label prospective trial, 130 patients admitted with SARS-CoV-2 pneumonia SARS-CoV-2 MESHD and suPAR levels [≥]6 g/l were assigned to subcutaneous anakinra 100mg once daily for 10 days. The primary outcome was the incidence of SRF MESHD SRF HGNC at day 14. Secondary outcomes were 30-day mortality, changes in sequential organ failure assessment (SOFA) score, of cytokine-stimulation pattern and of circulating inflammatory mediators. Equal number of propensity score-matched comparators for comorbidities, severity on admission and standard-of care (SOC) were studied. Results The incidence of SRF MESHD SRF HGNC was 22.3% (95% CI, 16.0-30.2%) among anakinra-treated patients and 59.2% (95% CI, 50.6-67.3%; P: 4.6 x 10-8) among SOC comparators (hazard ratio, 0.30; 95%CI, 0.20-0.46). 30-day mortality was 11.5% (95% CI, 7.1-18.2%) and 22.3% (95% CI, 16.0-30.2%) respectively (hazard ratio 0.49; 95% CI 0.25-0.97%; P: 0.041). Anakinra treatment was associated with decrease in SOFA score and in circulating interleukin (IL)-6 HGNC, sCD163 and sIL2-R; the serum IL-10 HGNC/ IL-6 HGNC ratio on day 7 was inversely associated with the change in SOFA score. Duration of stay at the intensive care unit and at hospital was shortened compared to the SOC group; the cost of hospitalization was decreased. Conclusions Early suPAR-guided anakinra treatment is associated with decrease of the risk for SRF MESHD SRF HGNC and restoration of the pro- /anti-inflammatory balance.

    sMAdCAM:IL-6 (sMIL Index): A novel signature associated with COVID-19 MESHD disease progression and development of anti-SARS-CoV-2 antibodies

    Authors: Dhanashree Jagtap; Vikrant M Bhor; Shilpa Bhowmick; Nandini Kasarpalkar; Pooja Sagvekar; Bhalchandra Kulkarni; Manish Pathak; Nirjhar Chatterjee; Pranam Dolas; Harsha Palav; Snehal Kaginkar; Sharad Bhagat; Itti Munshi; Swapneil Parikh; Sachee Agrawal; Chandrakant Pawar; Mala Kaneria; Smita Mahale; Jayanthi Shastri; Vainav Patel

    doi:10.1101/2020.10.13.20182949 Date: 2020-10-16 Source: medRxiv

    IMPORTANCE: Recent studies positing the gut as a sanctuary site for viral persistence in SARS-CoV-2 infection MESHD highlight the importance of assimilating profiles of systemic as well as gut inflammatory mediators to understand the pathology of COVID-19 MESHD. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. OBJECTIVE: To evaluate the role of systemic and gut inflammatory markers in disease progression and development of anti-viral humoral immunity following SARS-CoV-2 infection MESHD. DESIGN, SETTING AND PARTICIPANTS: This cohort study (n=58) of SARS-CoV-2 infected MESHD individuals included a group of in-patients (n=36) at various stages of disease progression together with convalescent individuals (n=22) recruited between April and June 2020 (peak of the epidemic) from a tertiary care hospital in Mumbai, India. Follow-up of 11 in-patients at day 7 post diagnosis was carried out, resulting in a total of 47 in-patient samples. EXPOSURES: Diagnosis of SARS-CoV-2 infections MESHD was confirmed by reverse transcriptase-polymerase chain reaction-based testing of nasopharyngeal/oropharyngeal samples. MAIN OUTCOMES AND MEASURES: Primary outcomes were the measurement of inflammatory markers including Th1 HGNC/Th2/Th17 cytokines and levels of soluble mucosal addressin cell adhesion molecule (sMAdCAM) in plasma. Anti-viral humoral response was measured by rapid antibody test (IgG, IgM) and chemiluminescent immunoassay (CLIA) (IgG). Also antibodies binding to SARS-CoV-2 proteins were measured by surface plasmon resonance ( SPR HGNC). Secondary outcomes were correlation of the inflammatory signature with clinical information, including age, sex, disease duration and co-morbidities. RESULTS: Twenty eight of 36 (78%) in-patients and 19 of 22 (86%) convalescents were males. Out of 47 in-patient samples, 22 (46%), 11 (23%) and 14 (30%) were IgG-/IgM-, IgG+/IgM+ and IgG+/IgM- respectively. Of 22 convalescent samples, 3 (14%), 1 (4%) and 17 (77%) were respectively IgG-/IgM-, IgG+/IgM+ and IgG+/IgM-. Two out of 22 (9%) convalescents showed high IL-6 HGNC levels (>100pg/ml) and 4 (18%) had high TNF HGNC levels (>30pg/ml). However, the convalescents (n =22) had significantly lower levels of IL-6 HGNC [Median=27.48 (IQR=23.54-39.92)] compared to followed up in-patients (n = 11) at day 0 [Median=111(IQR=68-129.7), p =0.0002] and higher levels of sMAdCAM [Median=1940 (1711-2174) pg/ml] compared to these individuals at day 0 [Median=1701 (IQR=1532-1836) pg/ml; p=0.032] and day 7 [Median=1534 (IQR=1236-1654) pg/ml; p=0.0007]. Further, IL-6 HGNC and sMAdCAM levels among in-patients inversely correlated with one another (r =-0.374, p = 0.009, CI = 95%). When expressed as a novel integrated marker, sMIL (sMAdCAM/ IL-6 HGNC ratio) index, these levels were incrementally and significantly higher across various disease states with convalescents exhibiting the highest values [Median= 64.74 (IQR=47.33-85.58)]. Also, the sMIL index was significantly higher in convalescents (with class-switched responses) compared to IgG+/IgM+ individuals at early stages of infection [Median=28.65 (IQR=13.63-96.26), p = 0.034]. Real-time measurement by SPR HGNC of plasma antibody binding to viral nucleocapsid (NC), receptor binding domain (RBD) and spike (S) revealed waxing and waning of plasma antibody responses to all 3 targets. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association rates of RBD-binding (r = 0.462, p = 0.03, CI = 95%) and fold change in binding to S (r = 0.68, p = 0.050, CI = 95%) respectively. CONCLUSION AND RELEVANCE: Our results highlight key systemic and gut-associated immune parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19 MESHD.

    Host metabolite-cytokine correlation landscape in SARS-CoV-2 infection MESHD

    Authors: Nan Xiao; Meng Nie; Huanhuan Pang; Bohong Wang; Jieli Hu; Xiangjun Meng; Ke Li; Xiaorong Ran; Quanxin Long; Haijun Deng; Ni Tang; Ailong Huang; Zeping Hu

    doi:10.21203/ Date: 2020-10-13 Source: ResearchSquare

    The systemic cytokine release syndrome (CRS) is a major cause of the multi-organ injury MESHD and fatal outcome induced by SARS-CoV-2 infection MESHD in severe COVID-19 MESHD patients. It has been well-known that metabolism plays a role in modulating the immune responses in infectious diseases MESHD. Yet, how the host metabolism correlates with CRS in COVID-19 MESHD patients and how the perturbed metabolites affect the cytokine release remains unclear. Here, we performed both metabolomics and cytokine/chemokine profiling on serum samples from the same cohort of healthy controls, mild and severe COVID-19 MESHD patients and delineated the global metabolic and immune response landscape along disease progression. Intriguingly, the correlation analysis revealed the tight link between metabolites and proinflammatory cytokines and chemokines, such as IL-6 HGNC, M-CSF HGNC, IL-1α HGNC, IL-1β HGNC, implying the potential regulatory role of arginine metabolism, tryptophan metabolism, and purine metabolism in hyperinflammation. Importantly, we demonstrated that targeting metabolism markedly modulated the proinflammatory cytokines release by PBMCs isolated from SARS-CoV-2-infected rhesus MESHD macaques ex vivo. Beyond providing a comprehensive resource of metabolism and immunology data of SARS-CoV-2 infection MESHD, our study showed that metabolic alterations can be potentially exploited to develop novel strategy for the treatment of fatal CRS in COVID-19 MESHD.

    The COVID-19 MESHD Lab Score: An Accurate Dynamic Tool to Predict In-Hospital Outcomes in COVID-19 MESHD Patients

    Authors: Pablo J. Antunez Muiños; Diego López Otero; Ignacio J. Amat-Santos; Javier López Pais; Alvaro Aparisi; Carla E. Cacho Antonio; Pablo Catalá; Teba González Ferrero; Gonzalo Cabezón; Oscar Otero García; José Francisco Gil; Marta Pérez Poza; Jordi Candela; Gino Rojas; Víctor Jiménez Ramos; Carlos Veras; J. Alberto San Román; José R. González-Juanatey

    doi:10.21203/ Date: 2020-10-12 Source: ResearchSquare

    Purpose: Deterioration is sometimes unexpected in SARS-CoV2 infection MESHD. The aim of our study is to establish laboratory predictors of mortality in COVID-19 MESHD disease which can help to identify high risk patients.Methods: All patients admitted to hospital due to Covid-19 MESHD disease were included. Laboratory biomarkers that contributed with significant predictive value for predicting mortality to the clinical model were included. Cut-off points were established, and finally a risk score was built. Results: 893 patients were included. Median age was 68.2 years(CI 95% 53.0-83.4). 87(9.7%) were admitted to Intensive Care Unit(ICU) and 72(8.1%) also needed mechanical ventilation support. 171(19.1%) patients died. A Covid-19 MESHD Lab score ranging from 0 to 30 points was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included haemoglobin, erythrocytes, leukocytes, neutrophils, lymphocytes, creatinine, C-reactive protein HGNC, interleukin-6 HGNC, procalcitonin, lactate dehydrogenase (LDH), and D-dimer. Three groups were established. Low mortality risk group under 12 points, 12 to 18 were included as moderate risk, and high risk group were those with 19 or more points. Low risk group as reference, moderate and high patients showed mortality OR 4.75(CI95% 2.60-8.68) and 23.86(CI 95% 13.61-41.84), respectively. C-statistic was 0-85(0.82-0.88) and Hosmer-Lemeshow p-value 0.63.Conclusion: Covid-19 MESHD Lab score can very easily predict mortality in patients at any moment during admission secondary to SARS-CoV2 infection MESHD. It is a simple and dynamic score, and it can be very easily replicated. It could help physicians to identify high risk patients to foresee clinical deterioration.  

    Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19 MESHD

    Authors: Suzane Ramos da Silva; Enguo Ju; Wen Meng; Alberto E. Paniz Mondolfi; Sanja Dacic; Anthony Green; Clare Bryce; Zachary Grimes; Mary E Fowkes; Emilia M. Sordillo; Carlos Cordon-Cardo; Haitao Guo; Shou-Jiang Gao

    doi:10.1101/2020.09.25.20195818 Date: 2020-09-29 Source: medRxiv

    Background Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection MESHD in patients with Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) prominently manifests with pulmonary symptoms histologically reflected by diffuse alveolar damage MESHD (DAD), excess inflammation MESHD, pneumocyte hyperplasia MESHD and proliferation, and formation of platelet aggregates or thromboemboli MESHD. However, the mechanisms mediating these processes remain unclear. Methods We performed multicolor staining for viral proteins, and lineage cell markers to identify SARS-CoV-2 tropism MESHD and to define the lung pathobiology in postmortem tissues from five patients with fatal SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD. Findings The lung parenchyma showed severe DAD MESHD with thromboemboli MESHD in all cases. SARS-CoV-2 infection MESHD was found in an extensive range of cells including alveolar epithelial type II/pneumocyte type II MESHD (AT2) cells (HT2-280), ciliated cells (tyr--tubulin), goblet cells ( MUC5AC HGNC), club-like cells ( MUC5B HGNC) and endothelial cells ( CD31 HGNC and CD34 HGNC). Greater than 90% of infiltrating immune cells were positive for viral proteins including macrophages and monocytes ( CD68 HGNC and CD163 HGNC), neutrophils ( ELA-2 HGNC), natural killer (NK) cells ( CD56 HGNC), B-cells ( CD19 HGNC and CD20 HGNC), and T-cells (CD3{varepsilon}). Most but not all infected cells were positive for the viral entry receptor angiotensin-converting enzyme-2 HGNC ( ACE2 HGNC). The numbers of infected and ACE2 HGNC-positive cells correlated with the extent of tissue damage. The infected tissues exhibited low numbers of B-cells and abundant CD3{varepsilon}+ T-cells consisting of mainly T helper cells ( CD4 HGNC), few cytotoxic T cells (CTL, CD8 HGNC), and no T regulatory cell ( FOXP3 HGNC). Antigen presenting molecule HLA-DR of B and T cells was abundant in all cases. Robust interleukin-6 HGNC ( IL-6 HGNC) expression was present in most uninfected and infected cells, with higher expression levels observed in cases with more tissue damage. Interpretation In lung tissues from severely affected COVID-19 MESHD patients, there is evidence for broad SARS-CoV-2 cell tropisms, activation of immune cells, and clearance of immunosuppressive cells, which could contribute to severe tissue damage, thromboemboli, excess inflammation MESHD and compromised adaptive immune responses.

    Role of IgG against N-protein PROTEIN of SARS-CoV2 in COVID19 MESHD clinical outcomes

    Authors: Mayank Batra; Runxia Tian; Chongxu Zhang; Emile Clarence; Camila Sofia Sacher; Justin Nestor Miranda; Justin Rafa O De La Fuente; Megan Mathew; Desmond Green; Sayari Patel; Maria Virginia Perez Bastidas; Sara Haddadi; Mukunthan Murthi; Miguel Santiago Gonzalez; Shweta Kambali; Kayo HM Santos; Huda Asif; Farzaneh Modarresi; Mohammad Faghihi; Mehdi Mirsaeidi

    doi:10.1101/2020.09.23.20197251 Date: 2020-09-24 Source: medRxiv

    The Nucleocapsid Protein (N PROTEIN Protein) of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) is located in the viral core. Immunoglobulin G (IgG) targeting N protein PROTEIN is detectable in the serum of infected MESHD patients. The effect of high titers of IgG against N-protein PROTEIN on clinical outcomes of SARS-CoV2 disease MESHD has not been described. We studied 400 RT-PCR confirmed SARS-CoV2 patients to determine independent factors associated with poor outcomes, including MICU admission, prolonged MICU stay and hospital admissions, and in-hospital mortality. We also measured serum IgG against the N protein PROTEIN and correlated its concentrations with clinical outcomes. We found that several factors, including Charlson comorbidity Index (CCI), high levels of IL6 HGNC, and presentation with dyspnea MESHD were associated with poor clinical outcomes. It was shown that higher CCI and higher IL6 HGNC levels were independently associated with in-hospital mortality. Anti- N protein PROTEIN IgG was detected in the serum of 55 (55%) patients at the time of admission. A high concentration of antibodies, defined as signal to cut off ratio (S/Co)> 1.5 (75 percentile of all measurements), was found in 25 (25%) patients. The multivariable logistic regression models showed that between being an African American, higher CCI, lymphocyte counts, and S/Co ratio> 1.5, only S/Co ratio were independently associated with MICU admission and longer length of stay in hospital. This study recommends that titers of IgG targeting N-protein PROTEIN of SARS-CoV2 at admission is a prognostic factor for the clinical course of disease and should be measured in all patients with SARS-CoV2 infection MESHD.

    A Meta-analysis of Comorbidities in COVID-19 MESHD: Which Diseases increase the Susceptibility of SARS-CoV-2 Infection MESHD?

    Authors: Srinivasan Ramachandran; Manoj Kumar Singh; Ahmed Mobeen; Amit Chandra; Sweta Joshi

    id:10.20944/preprints202009.0486.v1 Date: 2020-09-21 Source:

    Background: Comorbidities have been frequently reported in COVID-19 MESHD patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection MESHD. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease MESHD(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 HGNC receptor and host proteases, namely FURIN HGNC and TMPRSS2 HGNC that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia MESHD (hereafter, referred as leukemia MESHD). The expression of ACE2 HGNC was also increased in psoriasis MESHD, lung cancer MESHD, Non-alcoholic fatty liver disease MESHD ( NAFLD MESHD), breast cancer MESHD, and pulmonary arterial hypertension MESHD patients. The expression of FURIN HGNC was higher in psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, and in type II diabetic liver MESHD, whereas it was lowered in breast cancer MESHD. Similarly, the expression of TMPRSS2 HGNC was increased during lung cancer MESHD and type II diabetes MESHD; it was decreased during psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, breast cancer MESHD, and cervical cancer MESHD.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia MESHD patients, as shown by the higher expression of IFNA2 HGNC, IFNA8 HGNC, IFNA10 HGNC, IFNA14 HGNC, IFNA16 HGNC, IFNA21 HGNC, IFNB1 HGNC, CXCL10 HGNC, and IL6 HGNC. The expression of JAK1 HGNC, STAT1 HGNC, IL6 HGNC, and CXCL10 HGNC was higher in NAFLD MESHD. Besides, JAK1 HGNC and STAT1 HGNC were upregulated in type II diabetic muscles MESHD. In addition, most of the upregulated genes in COVID-19 MESHD patients showed a similar trend in leukemia MESHD, NAFLD MESHD, and psoriasis MESHD. Furthermore, SARS-CoV-2, SARS-CoV MESHD and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection MESHD are mostly upregulated in leukemia MESHD patients; hence, leukemia MESHD patients are relatively more susceptible to develop COVID-19 MESHD, followed by other chronic disorders MESHD, such as, NAFLD MESHD, type II diabetes MESHD, psoriasis MESHD, and hypertension MESHD. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 MESHD and underlie COVID-19 MESHD associated comorbidities.

    Monocytes and macrophages, targets of SARS-CoV-2: the clue for Covid-19 MESHD immunoparalysis

    Authors: Asma Boumaza; Laetitia Gay; Soraya Mezouar; Aissatou Bailo Diallo; Moise Michel; Benoit Desnues; Didier Raoult; Bernard LA SCOLA; Philippe Halfon; Joana Vitte; Daniel Olive; Jean-Louis Mege

    doi:10.1101/2020.09.17.300996 Date: 2020-09-17 Source: bioRxiv

    To date, the Covid-19 pandemic MESHD Covid-19 pandemic MESHD affected more than 18 million individuals and caused more than 690, 000 deaths. Its clinical expression is pleiomorphic and severity is related to age and comorbidities such as diabetes MESHD and hypertension MESHD. The pathophysiology of the disease relies on aberrant activation of immune system and lymphopenia MESHD that has been recognized as a prognosis marker. We wondered if the myeloid compartment was affected in Covid-19 MESHD and if monocytes and macrophages could be infected by SARS-CoV-2. We show here that SARS-CoV-2 efficiently infects MESHD monocytes and macrophages without any cytopathic effect. Infection was associated with the secretion of immunoregulatory cytokines ( IL-6 HGNC, IL-10 HGNC, TGF-b HGNC) and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In addition, we found that in vitro macrophage polarization did not account for the permissivity to SARS-CoV-2, since M1- and M2-type macrophages were similarly infected. Finally, in a cohort of 76 Covid-19 MESHD patients ranging from mild to severe clinical expression, all circulating monocyte subsets were decreased, likely related to massive emigration into tissues. Monocytes from Covid-19 MESHD patients exhibited decreased expression of HLA-DR and increased expression of CD163 HGNC, irrespective of the clinical status. Hence, SARS-CoV-2 drives circulating monocytes and macrophages inducing immunoparalysis of the host for the benefit of Covid-19 MESHD disease progression.

    Daytime variation in SARS-CoV-2 infection MESHD and cytokine production

    Authors: Aissatou Bailo Diallo; Laetitia Gay; Benjamin Coiffard; Marc Leone; Soraya Mezouar; Jean-Louis Mège; Elisa Ghelfi; Chhinder Sodhi; David Hackam; Lester Kobzik; Ben Croker; Douglas Brownfield; Hongpeng Jia; Kristopher A. Sarosiek; Paige D. Hall; Maud Jansen; Kumaran Shanmugarajah; Jessica S. Donington; Florian Krammer; Daved Fremont; Andrzej Joachimiak; Yoshihiro Kawaoka; Vera Tesic; Maria Lucia Madariaga; Patrick C Wilson; Martin Pettersson; Mattew R. Reese; Thomas Rogers; Michelle I Rossulek; Jean G Sathish; Claire Steppan; Martyn Ticehurst; Lawrence W. Updyke; Yuao Zhu; Jun Wang; Arnab K Chatterjee; Andrew D Mesecar; Annaliesa S. Anderson; Charlotte Allerton

    doi:10.1101/2020.09.09.290718 Date: 2020-09-12 Source: bioRxiv

    S. Ray and A. Reddy recently anticipated the implication of circadian rhythm in severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which is the causative agent of the coronavirus disease MESHD ( Covid-19 MESHD). In addition to its key role in the regulation of biological functions, the circadian rhythm has been suggested as a regulator of viral infections MESHD. Specifically, the time of day of infection was found critical for illness progression, as has been reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. We analyzed circadian rhythm implication in SARS-CoV-2 virus infection MESHD of isolated human monocytes, key actor cells in Covid-19 MESHD disease, from healthy subjects. The circadian gene expression of Bmal1 HGNC and Clock genes was investigated with q-RTPCR. Monocytes were infected with SARS-CoV-2 virus strain and viral infection MESHD was investigated by One-Step qRT-PCR and immunofluorescence. Interleukin (IL)-6 HGNC, IL-1{beta HGNC} and IL-10 HGNC levels were also measured in supernatants of infected monocytes. Using Cosinor analysis, we showed that Bmal1 HGNC and Clock transcripts exhibited circadian rhythm in monocytes with an acrophase and a bathyphase at Zeitgeber Time (ZT)6 and ZT17. After forty-eight hours, the amount of SARS-CoV-2 virus increased in the monocyte infected at ZT6 compared to ZT17. The high virus amount at ZT6 was associated with significant increased release in IL-6 HGNC, IL-1{beta HGNC} and IL-10 HGNC compared to ZT17. Our results suggest that time day of SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHD affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease MESHD progression and we propose circadian rhythm as a novel target for managing viral progression. ImportanceThe implication of circadian rhythm (CR) in pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been recently anticipated. The time of day of infection is critical for illness progression as reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. In this study, we wondered if SARS-CoV-2 infection MESHD and cytokine production by human monocytes, innate immune cells affected by Covid-19 MESHD, were regulated by CR. Our results suggest that time day of SARS-CoV-2 infection MESHD affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression.

    Induction of a regulatory myeloid program in bacterial sepsis and severe COVID-19 MESHD

    Authors: Miguel Reyes; Michael R. Filbin; Roby P. Bhattacharyya; Abraham Sonny; Arnav Mehta; Kianna Billman; Kyle R. Kays; - MGH COVID-19 Collection & Processing Team; Alexandra-Chloe Villani; Moshe Sade-Feldman; Marcia B. Goldberg; Paul C. Blainey; Nir Hacohen

    doi:10.1101/2020.09.02.280180 Date: 2020-09-02 Source: bioRxiv

    A recent estimate suggests that one in five deaths globally are associated with sepsis MESHD. To date, no targeted treatment is available for this syndrome, likely due to substantial patient heterogeneity and our lack of insight into sepsis MESHD immunopathology. These issues are highlighted by the current COVID-19 MESHD COVID-19 MESHD pandemic, wherein many clinical manifestations of severe SARS-CoV-2 infection parallel bacterial sepsis MESHD. We previously reported an expanded CD14 HGNC+ monocyte state, MS1, in patients with bacterial sepsis MESHD or non-infectious critical illness, and validated its expansion in sepsis MESHD across thousands of patients using public transcriptomic data. Despite its marked expansion in the circulation of bacterial sepsis MESHD patients, its relevance to viral sepsis MESHD and association with disease outcomes have not been examined. In addition, the ontogeny and function of this monocyte state remain poorly characterized. Using public transcriptomic data, we show that the expression of the MS1 program is associated with sepsis mortality MESHD and is up-regulated in monocytes from patients with severe COVID-19 MESHD. We found that blood plasma from bacterial sepsis MESHD or COVID-19 MESHD patients with severe disease induces emergency myelopoiesis and expression of the MS1 program, which are dependent on the cytokines IL-6 HGNC and IL-10 HGNC. Finally, we demonstrate that MS1 cells are broadly immunosuppressive, similar to monocytic myeloid-derived suppressor cells (MDSCs), and have decreased responsiveness to stimulation. Our findings highlight the utility of regulatory myeloid cells in sepsis MESHD prognosis, and the role of systemic cytokines in inducing emergency myelopoiesis during severe bacterial and SARS-CoV-2 infections MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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