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1.
J Immunol ; 208(3): 685-696, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1604665

ABSTRACT

Immune response dysregulation plays a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. In this study, we evaluated immune and endothelial blood cell profiles of patients with coronavirus disease 2019 (COVID-19) to determine critical differences between those with mild, moderate, or severe COVID-19 using spectral flow cytometry. We examined a suite of immune phenotypes, including monocytes, T cells, NK cells, B cells, endothelial cells, and neutrophils, alongside surface and intracellular markers of activation. Our results showed progressive lymphopenia and depletion of T cell subsets (CD3+, CD4+, and CD8+) in patients with severe disease and a significant increase in the CD56+CD14+Ki67+IFN-γ+ monocyte population in patients with moderate and severe COVID-19 that has not been previously described. Enhanced circulating endothelial cells (CD45-CD31+CD34+CD146+), circulating endothelial progenitors (CD45-CD31+CD34+/-CD146-), and neutrophils (CD11b+CD66b+) were coevaluated for COVID-19 severity. Spearman correlation analysis demonstrated the synergism among age, obesity, and hypertension with upregulated CD56+ monocytes, endothelial cells, and decreased T cells that lead to severe outcomes of SARS-CoV-2 infection. Circulating monocytes and endothelial cells may represent important cellular markers for monitoring postacute sequelae and impacts of SARS-CoV-2 infection during convalescence and for their role in immune host defense in high-risk adults after vaccination.


Subject(s)
COVID-19/immunology , Endothelial Cells/immunology , Monocytes/immunology , SARS-CoV-2 , Adolescent , Adult , Age Factors , Aged , Antibodies, Viral/biosynthesis , Antibodies, Viral/immunology , Biomarkers , CD56 Antigen/analysis , COVID-19/blood , COVID-19/epidemiology , Child , Comorbidity , Endothelial Cells/chemistry , Female , Flow Cytometry , Humans , Hypertension/epidemiology , Hypertension/immunology , Immunophenotyping , Lymphocyte Activation , Lymphocyte Subsets/immunology , Lymphopenia/etiology , Lymphopenia/immunology , Male , Middle Aged , Monocytes/chemistry , Neutrophils/immunology , Obesity/epidemiology , Obesity/immunology , Platelet Endothelial Cell Adhesion Molecule-1/analysis , SARS-CoV-2/immunology , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Young Adult
2.
Mol Med ; 27(1): 129, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1477255

ABSTRACT

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.


Subject(s)
COVID-19/diagnosis , Chemokine CXCL10/blood , Coronary Artery Disease/diagnosis , Diabetes Mellitus/diagnosis , Hypertension/diagnosis , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/immunology , COVID-19/mortality , Comorbidity , Coronary Artery Disease/blood , Coronary Artery Disease/immunology , Coronary Artery Disease/mortality , Creatine/blood , Diabetes Mellitus/blood , Diabetes Mellitus/immunology , Diabetes Mellitus/mortality , Female , Hospitalization , Humans , Hypertension/blood , Hypertension/immunology , Hypertension/mortality , Immunity, Humoral , Immunity, Innate , Inflammation , Intensive Care Units , L-Lactate Dehydrogenase/blood , Leukocyte Count , Lymphocytes/immunology , Lymphocytes/pathology , Male , Middle Aged , Neutrophils/immunology , Neutrophils/pathology , Prognosis , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
4.
Diabetes Metab Res Rev ; 38(1): e3465, 2022 01.
Article in English | MEDLINE | ID: covidwho-1292067

ABSTRACT

AIMS: To explore variables associated with the serological response following COVID-19 mRNA vaccine. METHODS: Eighty-six healthcare workers adhering to the vaccination campaign against COVID-19 were enrolled in January-February 2021. All subjects underwent two COVID-19 mRNA vaccine inoculations (Pfizer/BioNTech) separated by 3 weeks. Blood samples were collected before the 1st and 1-4 weeks after the second inoculation. Clinical history, demographics, and vaccine side effects were recorded. Baseline anthropometric parameters were measured, and body composition was performed through dual-energy-X-ray absorptiometry. RESULTS: Higher waist circumference was associated with lower antibody (Ab) titres (R = -0.324, p = 0.004); smokers had lower levels compared to non-smokers [1099 (1350) vs. 1921 (1375), p = 0.007], as well as hypertensive versus normotensive [650 ± 1192 vs. 1911 (1364), p = 0.001] and dyslipideamic compared to those with normal serum lipids [534 (972) vs 1872 (1406), p = 0.005]. Multivariate analysis showed that higher waist circumference, smoking, hypertension, and longer time elapsed since second vaccine inoculation were associated with lower Ab titres, independent of BMI, age. and gender. CONCLUSIONS: Central obesity, hypertension, and smoking are associated with lower Ab titres following COVID-19 vaccination. Although it is currently impossible to determine whether lower SARS-CoV-2 Abs lead to higher likelihood of developing COVID-19, it is well-established that neutralizing antibodies correlate with protection against several viruses including SARS-CoV-2. Our findings, therefore, call for a vigilant approach, as subjects with central obesity, hypertension, and smoking could benefit from earlier vaccine boosters or different vaccine schedules.


Subject(s)
Antibodies, Viral , SARS-CoV-2 , Antibodies, Viral/blood , /immunology , COVID-19/prevention & control , Humans , Hypertension/immunology , Obesity, Abdominal/immunology , SARS-CoV-2/immunology , Smoking/immunology
5.
Clin Nutr ESPEN ; 44: 475-478, 2021 08.
Article in English | MEDLINE | ID: covidwho-1242904

ABSTRACT

BACKGROUND & AIMS: Obesity is associated with low grade systemic inflammation and insulin resistance. Although metabolic and immunological changes may contribute to the increased risk for COVID-19 mortality in obese, little is known about the impact of obesity in the lungs of patients with COVID-19. METHODS: We analyzed gene expression profiles of autopsy lungs of a cohort of 14 COVID-19 patients and 4 control individuals. Patients were divided into 3 groups according to their comorbidities: hypertension, type 2 diabetes (T2D) and obesity. We then identified the molecular alterations associated with these comorbidities in COVID-19 patients. RESULTS: Patients with only hypertension showed higher levels of inflammatory genes and B-cell related genes when compared to those with T2D and obesity. However, the levels of IFN-gamma, IL22, and CD274 (a ligand that binds to receptor PD1) were higher in COVID-19 patients with T2D and obesity. Several metabolic- and immune-associated genes such as G6PD, LCK and IL10 were significantly induced in the lungs of the obese group. CONCLUSION: Our findings suggest that SARS-CoV-2 infection in the lungs may exacerbate the immune response and chronic condition in obese COVID-19 patients.


Subject(s)
COVID-19/complications , COVID-19/genetics , Gene Expression/genetics , Lung/immunology , Obesity/complications , Obesity/genetics , Autopsy , COVID-19/immunology , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/immunology , Humans , Hypertension/complications , Hypertension/genetics , Hypertension/immunology , Obesity/immunology , SARS-CoV-2
6.
Compr Physiol ; 11(1): 1575-1589, 2021 02 12.
Article in English | MEDLINE | ID: covidwho-1082844

ABSTRACT

Uncontrolled immune system activation amplifies end-organ injury in hypertension. Nonetheless, the exact mechanisms initiating this exacerbated inflammatory response, thereby contributing to further increases in blood pressure (BP), are still being revealed. While participation of lymphoid-derived immune cells has been well described in the hypertension literature, the mechanisms by which myeloid-derived innate immune cells contribute to T cell activation, and subsequent BP elevation, remains an active area of investigation. In this article, we critically analyze the literature to understand how monocytes, macrophages, dendritic cells, and polymorphonuclear leukocytes, including mast cells, eosinophils, basophils, and neutrophils, contribute to hypertension and hypertension-associated end-organ injury. The most abundant leukocytes, neutrophils, are indisputably increased in hypertension. However, it is unknown how (and why) they switch from critical first responders of the innate immune system, and homeostatic regulators of BP, to tissue-damaging, pro-hypertensive mediators. We propose that myeloperoxidase-derived pro-oxidants, neutrophil elastase, neutrophil extracellular traps (NETs), and interactions with other innate and adaptive immune cells are novel mechanisms that could contribute to the inflammatory cascade in hypertension. We further posit that the gut microbiota serves as a set point for neutropoiesis and their function. Finally, given that hypertension appears to be a key risk factor for morbidity and mortality in COVID-19 patients, we put forth evidence that neutrophils and NETs cause cardiovascular injury post-coronavirus infection, and thus may be proposed as an intriguing therapeutic target for high-risk individuals. © 2021 American Physiological Society. Compr Physiol 11:1575-1589, 2021.


Subject(s)
COVID-19 , Extracellular Traps/immunology , Hypertension/immunology , Immunity, Innate/immunology , Neutrophils/immunology , Animals , COVID-19/complications , COVID-19/immunology , Gastrointestinal Microbiome/immunology , Humans , Hypertension/physiopathology , Inflammation/immunology , Inflammation/physiopathology , Oxidative Stress/immunology , SARS-CoV-2/immunology
7.
Expert Rev Clin Immunol ; 17(3): 201-208, 2021 03.
Article in English | MEDLINE | ID: covidwho-1066078

ABSTRACT

INTRODUCTION: In people living with HIV (PLWH), immune activation and inflammation levels are high even when viral suppression is maintained, potentially contributing to several comorbidities, and hampering the immune response to infections such as the recent SARS-CoV-2 disease 2019 (COVID-19). AREAS COVERED: Immune activation and inflammation play a role in SARS-CoV-2 infection. Severe COVID-19 patients may experience cytokine release syndrome (CRS), leading to alveolar damage, pulmonary fibrinolysis, dysregulated coagulation, and pulmonary injury. Into the systemic circulation, cytokines in excess might leak out of pulmonary circulation, causing systemic symptoms and possibly a multiple-organ dysfunction syndrome. Preexisting comorbidities are also linked to worse COVID-19 outcome: studies suggest that diabetes and hypertension are linked to higher mortality rates. Such comorbidities are more frequent in PLWH, but it is unclear if they have worse outcomes in the case of COVID-19. The literature was searched in PubMed/MEDLINE and EMBASE, and manually in COVID-19 resources. EXPERT OPINION: A body of evidence shows that HIV and SARS-CoV-2 are able to activate inflammatory pathways, acute in the case of SARS-CoV-2, chronic in the case of HIV, while the comorbidities seem to represent, in the first case, a contributory cause, in the second an effect of the virus-induced damage.


Subject(s)
COVID-19/epidemiology , COVID-19/immunology , HIV Infections/epidemiology , HIV Infections/immunology , Blood Coagulation Disorders/epidemiology , Blood Coagulation Disorders/immunology , Comorbidity , Cytokines/immunology , Diabetes Mellitus/epidemiology , Diabetes Mellitus/immunology , Humans , Hyperglycemia/epidemiology , Hyperglycemia/immunology , Hypertension/epidemiology , Hypertension/immunology , Inflammation , Metabolic Syndrome/epidemiology , Metabolic Syndrome/immunology , SARS-CoV-2
9.
Med Hypotheses ; 146: 110448, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-969015

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is able to produce an excessive host immune reaction and may leads to severe disease- a life-threatening condition occurring more often in patients suffering from comorbidities such as hypertension, diabetes and obesity. Infection by human corona viruses highly depends on host microRNA (miR) involved in regulation of host innate immune response and inflammation-modulatory miR-146a is among the first miRs induced by immune reaction to a virus. Moreover, recent analysis showed that miR-146 is predicted to target at the SARS-CoV-2 genome. As the dominant regulator of Toll-like receptors (TLRs) downstream signaling, miR-146a may limit excessive inflammatory response to virus. Downregulation of circulating miR-146a was found in diabetes, obesity and hypertension and it is reflected by enhanced inflammation and fibrosis, systemic effects accompanying severe COVID-19. Thus it could be hypothesized that miR-146a deficiency may contribute to severe COVID-19 state observed in diabetes, obesity and hypertension but further investigations are needed.


Subject(s)
COVID-19/complications , Diabetes Mellitus/genetics , Hypertension/complications , MicroRNAs/genetics , Obesity/complications , Pandemics , SARS-CoV-2 , COVID-19/genetics , COVID-19/immunology , Diabetes Complications/genetics , Diabetes Complications/immunology , Diabetes Mellitus/immunology , Down-Regulation , Humans , Hypertension/genetics , Hypertension/immunology , Immunity, Innate/genetics , Inflammation/complications , Inflammation/genetics , Inflammation/immunology , MicroRNAs/metabolism , Models, Biological , Obesity/genetics , Obesity/immunology , Risk Factors , Severity of Illness Index
10.
Am J Trop Med Hyg ; 103(4): 1590-1592, 2020 10.
Article in English | MEDLINE | ID: covidwho-914663

ABSTRACT

The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.


Subject(s)
Coronavirus Infections/parasitology , Diabetes Mellitus/parasitology , Hypertension/parasitology , Peripheral Nervous System Diseases/parasitology , Pneumonia, Viral/parasitology , Strongyloides stercoralis/pathogenicity , Strongyloidiasis/parasitology , Adrenal Cortex Hormones/administration & dosage , Aged , Animals , Anthelmintics/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Betacoronavirus/pathogenicity , COVID-19 , Coinfection , Connecticut , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/virology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/immunology , Diabetes Mellitus/virology , Ecuador , Humans , Hypertension/drug therapy , Hypertension/immunology , Hypertension/virology , Immunologic Factors/administration & dosage , Male , Pandemics , Peripheral Nervous System Diseases/drug therapy , Peripheral Nervous System Diseases/immunology , Peripheral Nervous System Diseases/virology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Strongyloidiasis/drug therapy , Strongyloidiasis/immunology , Strongyloidiasis/virology
11.
Clin Immunol ; 221: 108611, 2020 12.
Article in English | MEDLINE | ID: covidwho-856558

ABSTRACT

Since December 2019, Coronavirus Disease 2019 (COVID-19) has emerged as a global pandemic. We aimed to investigate the clinical characteristics and analyzed the risk factors for prolonged viral RNA shedding. We retrospectively collected data from 112 hospitalized COVID-19 patients in a single center in Wuhan, China. Factors associated with prolonged viral RNA shedding (≥28 days) were investigated. Forty-nine (43.8%) patients had prolonged viral RNA shedding. Patients with prolonged viral shedding were older and had a higher rate of hypertension. Proinflammatory cytokines, including interleukin-2R (IL-2R) and tumor necrosis factor-α (TNF-α), were significantly elevated in patients with prolonged viral shedding. Multivariate analysis revealed that hypertension, older age, lymphopenia and elevated serum IL-2R were independent risk factors for prolonged viral shedding. This comprehensive investigation revealed the distinct characteristics between patients with or without prolonged viral RNA shedding. Hypertension, older age, lymphopenia and high levels of proinflammatory cytokines may be correlated with prolonged viral shedding.


Subject(s)
COVID-19/virology , Cytokine Release Syndrome/virology , Diabetes Mellitus/virology , Hypertension/virology , Lymphopenia/virology , RNA, Viral/blood , SARS-CoV-2/pathogenicity , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/immunology , China , Comorbidity , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Diabetes Mellitus/diagnosis , Diabetes Mellitus/drug therapy , Diabetes Mellitus/immunology , Drug Combinations , Female , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/immunology , Interferons/therapeutic use , Lopinavir/therapeutic use , Lymphopenia/diagnosis , Lymphopenia/drug therapy , Lymphopenia/immunology , Male , Middle Aged , Receptors, Interleukin-2/biosynthesis , Retrospective Studies , Risk Factors , Ritonavir/therapeutic use , Severity of Illness Index , Tumor Necrosis Factor-alpha/biosynthesis , Virus Shedding
13.
Immunity ; 53(4): 864-877.e5, 2020 10 13.
Article in English | MEDLINE | ID: covidwho-693493

ABSTRACT

The SARS-CoV-2 pandemic has resulted in millions of infections, yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, natural killer, monocyte, and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and ratios of conventional DCs to plasmacytoid DCs were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks after symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, could contribute to acute COVID-19 pathogenesis and have implications for vaccine development.


Subject(s)
Betacoronavirus/pathogenicity , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/immunology , Dendritic Cells/immunology , Diabetes Mellitus/immunology , Hypertension/immunology , Pneumonia, Viral/immunology , Adult , Aged , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Betacoronavirus/immunology , CD4-Positive T-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/virology , COVID-19 , Convalescence , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Dendritic Cells/pathology , Dendritic Cells/virology , Diabetes Complications , Diabetes Mellitus/diagnosis , Diabetes Mellitus/virology , Disease Progression , Female , Humans , Hypertension/complications , Hypertension/diagnosis , Hypertension/virology , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Killer Cells, Natural/virology , Lymphocyte Activation , Lymphocyte Count , Male , Middle Aged , Monocytes/immunology , Monocytes/pathology , Monocytes/virology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index
15.
Am J Trop Med Hyg ; 102(6): 1205-1207, 2020 06.
Article in English | MEDLINE | ID: covidwho-602003

ABSTRACT

The initial cases of novel coronavirus disease-19 (COVID-19) in a country are of utmost importance given their impact on healthcare providers, the country's preparedness response, and the initial molding of the public perception toward this pandemic. In Bhutan, the index case was a 76-year-old immunocompromised man who had traveled from the United States and entered Bhutan as a tourist. He presented initially with vague gastrointerestinal symptoms and later a cough. His atypical presentation led to a delay in diagnosis, but ultimately he was isolated and tested. On confirming the diagnosis of COVID-19, the patient was isolated in a separate hospital with a dedicated medical care team. All contacts were traced and quarantined. The patient's respiratory status deteriorated despite broad-spectrum antivirals, antibiotics, and intensive supportive care. He required intubation and was given a trial of intravenous immunoglobulin to modulate his likely aberrant immune response. Subsequently, the patient's clinical status improved, and after 8 days of hospitalization, he was transferred out of the country, where he recovered. This was a learning experience for the treating medical staff, the government, and the people of Bhutan.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/diagnostic imaging , Hyperlipidemias/diagnostic imaging , Hypertension/diagnostic imaging , Lung/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Aged , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Bhutan , COVID-19 , Contact Tracing , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Humans , Hyperlipidemias/drug therapy , Hyperlipidemias/immunology , Hyperlipidemias/pathology , Hypertension/drug therapy , Hypertension/immunology , Hypertension/pathology , Immunocompromised Host , Immunoglobulins, Intravenous/therapeutic use , Lung/drug effects , Lung/pathology , Lung/virology , Male , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , SARS-CoV-2 , Tomography, X-Ray Computed , Travel , Treatment Outcome , Ultrasonography , United States
16.
Med Hypotheses ; 144: 109999, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-598567

ABSTRACT

The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin "COVID-19 Clinical Guidance for the CV Care Team", there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% ≥80 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention.


Subject(s)
COVID-19/epidemiology , Immunity, Innate , Pandemics , Adult , Aging/immunology , COVID-19/etiology , COVID-19/immunology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/immunology , Child , Diabetes Mellitus/epidemiology , Diabetes Mellitus/immunology , Disease Susceptibility , Humans , Hydrogen Peroxide/metabolism , Hypertension/epidemiology , Hypertension/immunology , Hypochlorous Acid/metabolism , Lung/blood supply , Lung/immunology , Microcirculation , Microvessels/physiopathology , Neutrophils/immunology , Neutrophils/metabolism , Peroxidase/metabolism , Risk Factors , United States/epidemiology
17.
Clin Immunol ; 217: 108509, 2020 08.
Article in English | MEDLINE | ID: covidwho-597932

ABSTRACT

BACKGROUND: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. METHODS: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. RESULTS: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO2/FiO2 ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. CONCLUSION: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.


Subject(s)
Coronary Disease/diagnosis , Coronavirus Infections/diagnosis , Diabetes Mellitus/diagnosis , Hypertension/diagnosis , Kidney Failure, Chronic/diagnosis , Pneumonia, Viral/diagnosis , Pulmonary Edema/diagnosis , Severe Acute Respiratory Syndrome/diagnosis , Age Factors , Aged , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Comorbidity , Coronary Disease/epidemiology , Coronary Disease/immunology , Coronary Disease/mortality , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Diabetes Mellitus/epidemiology , Diabetes Mellitus/immunology , Diabetes Mellitus/mortality , Female , Hospitalization , Humans , Hypertension/epidemiology , Hypertension/immunology , Hypertension/mortality , Infectious Disease Incubation Period , Italy/epidemiology , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/immunology , Kidney Failure, Chronic/mortality , Lymphocyte Count , Lymphocytes/immunology , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pulmonary Edema/epidemiology , Pulmonary Edema/immunology , Pulmonary Edema/mortality , Risk Factors , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/mortality , Severity of Illness Index , Survival Analysis
19.
Allergy ; 75(11): 2829-2845, 2020 11.
Article in English | MEDLINE | ID: covidwho-526792

ABSTRACT

BACKGROUND: Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. METHODS: We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147-related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID-19 morbidity and severity patterns.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , Basigin/immunology , COVID-19/epidemiology , Chronic Disease/epidemiology , Dipeptidyl Peptidase 4/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Age Factors , Aged , Angiotensin-Converting Enzyme 2/genetics , Asthma/epidemiology , Asthma/genetics , Asthma/immunology , Basigin/genetics , COVID-19/genetics , COVID-19/immunology , Child , Child, Preschool , Comorbidity , Dipeptidyl Peptidase 4/genetics , Female , Gene Expression/genetics , Humans , Hypertension/epidemiology , Hypertension/genetics , Hypertension/immunology , Immunity, Innate/immunology , Infant , Male , Middle Aged , Obesity/epidemiology , Obesity/genetics , Obesity/immunology , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/immunology , Risk Factors , SARS-CoV-2/genetics , Young Adult
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