Pooled analysis of monocyte distribution width in subjects with SARS-CoV-2 infection.
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ABSTRACT:
SUBMITTER: Lippi G
PROVIDER: S-EPMC8013932 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceCoronavirus disease 2019 (COVID-19) is an acute respiratory illness with a high rate of hospitalization and mortality. Biomarkers are urgently needed for patient risk stratification. Red blood cell distribution width (RDW), a component of complete blood counts that reflects cellular volume variation, has been shown to be associated with elevated risk for morbidity and mortality in a wide range of diseases.ObjectiveTo investigate whether an association between mortality risk and elevated RDW at hospital admission and during hospitalization exists in patients with COVID-19.Design, setting, and participantsThis cohort study included adults diagnosed with SARS-CoV-2 infection and admitted to 1 of 4 hospitals in the Boston, Massachusetts area (Massachusetts General Hospital, Brigham and Women's Hospital, North Shore Medical Center, and Newton-Wellesley Hospital) between March 4, 2020, and April 28, 2020.Main outcomes and measuresThe main outcome was patient survival during hospitalization. Measures included RDW at admission and during hospitalization, with an elevated RDW defined as greater than 14.5%. Relative risk (RR) of mortality was estimated by dividing the mortality of those with an elevated RDW by the mortality of those without an elevated RDW. Mortality hazard ratios (HRs) and 95% CIs were estimated using a Cox proportional hazards model.ResultsA total of 1641 patients were included in the study (mean [SD] age, 62[18] years; 886 men [54%]; 740 White individuals [45%] and 497 Hispanic individuals [30%]; 276 nonsurvivors [17%]). Elevated RDW (>14.5%) was associated with an increased mortality risk in patients of all ages. The RR for the entire cohort was 2.73, with a mortality rate of 11% in patients with normal RDW (1173) and 31% in those with an elevated RDW (468). The RR in patients younger than 50 years was 5.25 (normal RDW, 1% [n = 341]; elevated RDW, 8% [n = 65]); 2.90 in the 50- to 59-year age group (normal RDW, 8% [n = 256]; elevated RDW, 24% [n = 63]); 3.96 in the 60- to 69-year age group (normal RDW, 8% [n = 226]; elevated RDW, 30% [104]); 1.45 in the 70- to 79-year age group (normal RDW, 23% [n = 182]; elevated RDW, 33% [n = 113]); and 1.59 in those ≥80 years (normal RDW, 29% [n = 168]; elevated RDW, 46% [n = 123]). RDW was associated with mortality risk in Cox proportional hazards models adjusted for age, D-dimer (dimerized plasmin fragment D) level, absolute lymphocyte count, and common comorbidities such as diabetes and hypertension (hazard ratio of 1.09 per 0.5% RDW increase and 2.01 for an RDW >14.5% vs ≤14.5%; P < .001). Patients whose RDW increased during hospitalization had higher mortality compared with those whose RDW did not change; for those with normal RDW, mortality increased from 6% to 24%, and for those with an elevated RDW at admission, mortality increased from 22% to 40%.Conclusions and relevanceElevated RDW at the time of hospital admission and an increase in RDW during hospitalization were associated with increased mortality risk for patients with COVID-19 who received treatment at 4 hospitals in a large academic medical center network.
| S-EPMC7512057 | biostudies-literature
Project description:SARS-CoV-2 has caused a historic pandemic of respiratory disease (COVID-19) and current evidence suggests severe disease is associated with dysregulated immunity within the respiratory tract1,2. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2-dependent infiltration of monocytes restricts viral burden in the lung. We find that a recently developed mouse-adapted MA-SARS-CoV-2 strain, as well as the emerging B.1.351 variant, trigger an inflammatory response in the lung characterized by expression of pro-inflammatory cytokines and interferon-stimulated genes. Using intravital antibody labeling, we demonstrate that MA-SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45+ cells into the lung parenchyma that is dominated by monocyte-derived cells. scRNA-seq analysis of lung homogenates identified a hyper-inflammatory monocyte profile. We utilize this model to demonstrate that mechanistically, CCR2 signaling promotes infiltration of classical monocytes into the lung and expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified a CCR2-monocyte axis that is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection.
2021-10-23 | GSE186360 | GEO
Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
| S-SCDT-10_1038-S44318-024-00061-0 | biostudies-other
Project description:BackgroundThe severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a highly transmittable virus which causes the novel coronavirus disease (COVID-19). Monocyte distribution width (MDW) is an in-vitro hematological parameter which describes the changes in monocyte size distribution and can indicate progression from localized infection to systemic infection. In this study we evaluated the correlation between the laboratory parameters and available clinical data in different quartiles of MDW to predict the progression and severity of COVID-19 infection.MethodsA retrospective analysis of clinical data collected in the Emergency Department of Rashid Hospital Trauma Center-DHA from adult individuals tested for SARS-CoV-2 between January and June 2020. The patients (n = 2454) were assigned into quartiles based on their MDW value on admission. The four groups were analyzed to determine if MDW was an indicator to identify patients who are at increased risk for progression to sepsis.ResultsOur data showed a significant positive correlation between MDW and various laboratory parameters associated with SARS-CoV-2 infection. The study also revealed that MDW ≥ 24.685 has a strong correlation with poor prognosis of COVID-19.ConclusionsMonitoring of monocytes provides a window into the systemic inflammation caused by infection and can aid in evaluating the progression and severity of COVID-19 infection.
| S-EPMC8724663 | biostudies-literature
Project description:To explore the relationship between SARS-CoV-2 infection in different time before operation and postoperative main complications (mortality, main pulmonary and cardiovascular complications) 30 days after operation; To determine the best timing of surgery after SARS-CoV-2 infection.
| 12454 | ecrin-mdr-crc
Project description:We carried out a prospective observational study to evaluate whether Monocyte Distribution Width (MDW) may play a role in identifying patients with sepsis in comparison with Procalcitonin (PCT). We prospectively enrolled all consecutive patients hospitalized at the Infectious Diseases Unit of Pescara General Hospital for bacterial infection or sepsis. MDW values were collected for all patients. Clinical characteristics, demographic data, past and present medical history, microbiological results, PCT, as well as neutrophil and monocytes indices at entry were compared in the 2 groups. Two-hundred-sixty patients were enrolled, 63.5% males, aged 59.1±19.5 years. Sepsis was diagnosed in 105 (40.4%); in 60 (57.1%) at least 1 microorganism was isolated from blood cultures. In multivariate models, MDW as a continuous variable (OR:1.57 for each unit increase; 95%CI: 1.31-1.87, p<0.001) and PCT˃1 ng/mL (OR: 48.5; 95%CI: 14.7-160.1, p<0.001) were independently associated with sepsis. Statistical best cut points associated with sepsis were 22.0 for MDW and 1.0 ng/mL for PCT whereas MDW values<20 were invariably associated with negative blood cultures. At ROC curve analysis, the AUC of MDW (0.87) was nearly overlapping that of PCT (0.88). Our data suggest that incorporating MDW within current routine WBC counts and indices may be of remarkable use for detection of sepsis. Further research is warranted.
| S-EPMC6953886 | biostudies-literature
Project description:HAE cultures were infected with SARS-CoV, SARS-dORF6 or SARS-BatSRBD and were directly compared to A/CA/04/2009 H1N1 influenza-infected cultures. Cell samples were collected at various hours post-infection for analysis. Time Points = 0, 12, 24, 36, 48, 60, 72, 84 and 96 hrs post-infection for SARS-CoV, SARS-dORF6 and SARS-BatSRBD. Time Points = 0, 6, 12, 18, 24, 36 and 48 hrs post-infection for H1N1. Done in triplicate or quadruplicate for RNA Triplicates/quadruplicates are defined as 3/4 different wells, plated at the same time and using the same cell stock for all replicates. Time matched mocks done in triplicate from same cell stock as rest of samples. Culture medium (the same as what the virus stock is in) will be used for the mock infections. Infection was done at an MOI of 2.
2013-07-31 | E-GEOD-47960 | biostudies-arrayexpress
Project description:HAE cultures were infected with SARS-CoV, SARS-ddORF6 or SARS-BatSRBD and were directly compared to A/CA/04/2009 H1N1 influenza-infected cultures. Cell samples were collected at various hours post-infection for analysis. Time Points = 0, 12, 24, 36, 48, 60, 72, 84 and 96 hrs post-infection for SARS-CoV. Time Points = 0, 24, 48, 60, 72, 84 and 96 hrs post-infection forSARS-ddORF6 and SARS-BatSRBD. Time Points = 0, 6, 12, 18, 24, 36 and 48 hrs post-infection for H1N1. Done in triplicate/quadruplicate for RNA Triplicates/quadruplicates are defined as 3/4 different wells, plated at the same time and using the same cell stock for all replicates. Time matched mocks done in triplicate from same cell stock as rest of samples. Culture medium (the same as what the virus stock is in) will be used for the mock infections. Infection was done at an MOI of 2.
2013-07-31 | E-GEOD-47961 | biostudies-arrayexpress
Project description:HAE cultures were infected with SARS-CoV, SARS-dORF6 or SARS-BatSRBD and were directly compared to A/CA/04/2009 H1N1 influenza-infected cultures. Cell samples were collected at various hours post-infection for analysis. Time Points = 0, 12, 24, 36, 48, 60, 72, 84 and 96 hrs post-infection for SARS-CoV, SARS-dORF6 and SARS-BatSRBD. Time Points = 0, 6, 12, 18, 24, 36 and 48 hrs post-infection for H1N1. Done in triplicate for RNA Triplicates are defined as 3 different wells, plated at the same time and using the same cell stock for all replicates. Time matched mocks done in triplicate from same cell stock as rest of samples. Culture medium (the same as what the virus stock is in) will be used for the mock infections. Infection was done at an MOI of 2 for SARS viruses and an MOI of 1 for H1N1.
2013-07-31 | E-GEOD-47962 | biostudies-arrayexpress
Project description:Interferon-induced transmembrane proteins (IFITMs) restrict infections by many viruses, but a subset of IFITMs enhance infections by specific coronaviruses through currently unknown mechanisms. We show that SARS-CoV-2 Spike-pseudotyped virus and genuine SARS-CoV-2 infections are generally restricted by human and mouse IFITM1, IFITM2, and IFITM3, using gain- and loss-of-function approaches. Mechanistically, SARS-CoV-2 restriction occurred independently of IFITM3 S-palmitoylation, indicating a restrictive capacity distinct from reported inhibition of other viruses. In contrast, the IFITM3 amphipathic helix and its amphipathic properties were required for virus restriction. Mutation of residues within the IFITM3 endocytosis-promoting Yxx? motif converted human IFITM3 into an enhancer of SARS-CoV-2 infection, and cell-to-cell fusion assays confirmed the ability of endocytic mutants to enhance Spike-mediated fusion with the plasma membrane. Overexpression of TMPRSS2, which increases plasma membrane fusion versus endosome fusion of SARS-CoV-2, attenuated IFITM3 restriction and converted amphipathic helix mutants into infection enhancers. In sum, we uncover new pro- and anti-viral mechanisms of IFITM3, with clear distinctions drawn between enhancement of viral infection at the plasma membrane and amphipathicity-based mechanisms used for endosomal SARS-CoV-2 restriction.
| S-SCDT-EMBOJ-2020-106501 | biostudies-other