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1.
Infect Genet Evol ; 95: 105092, 2021 11.
Article in English | MEDLINE | ID: covidwho-1433676

ABSTRACT

OBJECTIVES: To compare the demographics, clinical characteristics and severity of patients infected with nine different SARS-CoV-2 variants, during three phases of the COVID-19 epidemic in Marseille. METHODS: A single centre retrospective cohort study was conducted in 1760 patients infected with SARS-CoV-2 of Nextstrain clades 20A, 20B, and 20C (first phase, February-May 2020), Pangolin lineages B.1.177 (we named Marseille-2) and B.1.160 (Marseille-4) variants (second phase, June-December 2020), and B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and A.27 (Marseille-501) variants (third phase, January 2021-today). Outcomes were the occurrence of clinical failures, including hospitalisation, transfer to the intensive-care unit, and death. RESULTS: During each phase, no major differences were observed with regards to age and gender distribution, the prevalence of chronic diseases, and clinical symptoms between variants circulating in a given phase. The B.1.177 and B.1.160 variants were associated with more severe outcomes. Infections occurring during the second phase were associated with a higher rate of death as compared to infections during the first and third phases. Patients in the second phase were more likely to be hospitalised than those in the third phase. Patients infected during the third phase were more frequently obese than others. CONCLUSION: A large cohort study is recommended to evaluate the transmissibility and to better characterise the clinical severity of emerging variants.


Subject(s)
COVID-19/pathology , Diabetes Mellitus/pathology , Genome, Viral , Hypertension/pathology , Obesity/pathology , SARS-CoV-2/pathogenicity , Adult , Aged , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Comorbidity , Diabetes Mellitus/epidemiology , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Female , France/epidemiology , Genotype , Heart Diseases/epidemiology , Heart Diseases/mortality , Heart Diseases/pathology , Heart Diseases/virology , Hospitalization/statistics & numerical data , Hospitals , Humans , Hypertension/epidemiology , Hypertension/mortality , Hypertension/virology , Intensive Care Units , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/mortality , Neoplasms/pathology , Neoplasms/virology , Obesity/epidemiology , Obesity/mortality , Obesity/virology , Phylogeny , Retrospective Studies , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sequence Analysis, RNA , Severity of Illness Index , Survival Analysis
2.
Cardiovasc Pathol ; 54: 107370, 2021.
Article in English | MEDLINE | ID: covidwho-1309178

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is commonly associated with myocardial injury and heart failure. The pathophysiology behind this phenomenon remains unclear, with many diverse and multifaceted hypotheses. To contribute to this understanding, we describe the underlying cardiac findings in fifty patients who died with coronavirus disease 2019 (COVID-19). METHODS: Included were autopsies performed on patients with a positive SARS-CoV-2 reverse-transcriptase-polymerase-chain reaction test from the index hospitalization. In the case of out-of-hospital death, patients were included if post-mortem testing was positive. Complete autopsies were performed according to a COVID-19 safety protocol, and all patients underwent both macroscopic and microscopic examination. If available, laboratory findings and echocardiograms were reported. RESULTS: The median age of the decedents was 63.5 years. The most common comorbidities included hypertension (90.0%), diabetes (56.0%) and obesity (50.0%). Lymphocytic inflammatory infiltrates in the heart were present in eight (16.0%) patients, with focal myocarditis present in two (4.0%) patients. Acute myocardial ischemia was observed in eight (16.0%) patients. The most common findings were myocardial fibrosis (80.0%), hypertrophy (72.0%), and microthrombi (66.0%). The most common causes of death were COVID-19 pneumonia in 18 (36.0%), COVID-19 pneumonia with bacterial superinfection in 12 (24.0%), and COVID-19 pneumonia with pulmonary embolism in 10 (20.0%) patients. CONCLUSIONS: Cardiovascular comorbidities were prevalent, and pathologic changes associated with hypertensive and atherosclerotic cardiovascular disease were the most common findings. Despite markedly elevated inflammatory markers and cardiac enzymes, few patients exhibited inflammatory infiltrates or necrosis within cardiac myocytes. A unifying pathophysiologic mechanism behind myocardial injury in COVID-19 remains elusive, and additional autopsy studies are needed.


Subject(s)
COVID-19/pathology , Heart Diseases/pathology , Myocardium/pathology , SARS-CoV-2/pathogenicity , Adult , Aged , Aged, 80 and over , Atherosclerosis/mortality , Atherosclerosis/pathology , Autopsy , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Comorbidity , Female , Heart Diseases/immunology , Heart Diseases/mortality , Heart Diseases/virology , Host-Pathogen Interactions , Humans , Hypertension/mortality , Hypertension/pathology , Inflammation Mediators/analysis , Male , Middle Aged , Myocardium/immunology , Necrosis , SARS-CoV-2/immunology , Up-Regulation
3.
Diabetes Metab Syndr ; 15(4): 102148, 2021.
Article in English | MEDLINE | ID: covidwho-1284040

ABSTRACT

BACKGROUND: Socio-demographics and comorbidities are involved in determining the severity and fatality in patients with COVID-19 suggested by studies in various countries, but study in Bangladesh is insufficient. AIMS: We designed the study to evaluate the association of sociodemographic and comorbidities with the prognosis of adverse health outcomes in patients with COVID-19 in Bangladesh. METHODS: A multivariate retrospective cohort study was conducted on data from 966 RT-PCR positive patients from eight divisions during December 13, 2020, to February 13, 2021. Variables included sociodemographic, comorbidities, symptoms, Charlson comorbidity index (CCI) and access to health facilities. Major outcome was fatality. Secondary outcomes included hospitalization, duration of hospital stay, requirement of mechanical ventilation and severity. RESULTS: Male (65.8%, 636 of 966) was predominant and mean age was 39.8 ± 12.6 years. Fever (79%), dry cough (55%), and loss of test/smell (51%) were frequent and 74% patients had >3 symptoms. Fatality was recorded in 10.5% patients. Comorbidities were found in 44% patients. Hypertension (21.5%) diabetes (14.6%), and cardiovascular diseases (11.3%) were most prevalent. Age >60 years (OR: 4.83, 95% CI: 2.45-6.49), and CCI >3 (OR: 5.48, 95% CI: 3.95-7.24) were predictors of hospitalizations. CCI >4 (aOR: 3.41, 95% CI: 2.57-6.09) was predictor of severity. Age >60 years (aOR: 3.77, 95% CI: 1.07-6.34), >3 symptoms (aOR: 2.14, 95% CI: 0.97-4.91) and CCI >3 vs. CCI <3 (aOR: 5.23, 95% CI: 3.77-8.09) were independently associated with fatality. CONCLUSIONS: Increased age, >3 symptoms, increasing comorbidities, higher CCI were associated with increased hospitalization, severity and fatality in patients with COVID-19.


Subject(s)
COVID-19/complications , Cardiovascular Diseases/mortality , Diabetes Mellitus/mortality , Hospitalization/statistics & numerical data , Hypertension/mortality , SARS-CoV-2/isolation & purification , Adolescent , Adult , Age Factors , Aged , Bangladesh/epidemiology , COVID-19/transmission , COVID-19/virology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/pathology , Cardiovascular Diseases/virology , Child , Child, Preschool , Comorbidity , Diabetes Mellitus/epidemiology , Diabetes Mellitus/pathology , Diabetes Mellitus/virology , Female , Humans , Hypertension/epidemiology , Hypertension/pathology , Hypertension/virology , Infant , Infant, Newborn , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Survival Rate , Young Adult
4.
PLoS One ; 16(4): e0248080, 2021.
Article in English | MEDLINE | ID: covidwho-1199975

ABSTRACT

BACKGROUND: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses. METHODS AND FINDINGS: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73-0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86-0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30-5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93-1.38, median follow-up 30 days). CONCLUSIONS: This observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/pathology , Hypertension/drug therapy , Aged , COVID-19/mortality , COVID-19/virology , Female , Hospitalization/statistics & numerical data , Humans , Hypertension/pathology , Male , Middle Aged , Propensity Score , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Survival Rate , Veterans
5.
Vascul Pharmacol ; 140: 106861, 2021 10.
Article in English | MEDLINE | ID: covidwho-1180098

ABSTRACT

The virus responsible for the coronavirus disease of 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidences suggest that COVID-19 could trigger cardiovascular complications in apparently healthy patients. Coronaviruses are enveloped positive-strand RNA viruses acting as a pathogen-associated molecular pattern (PAMP)/ danger-associated molecular patterns (DAMP). Interestingly, Toll-like receptor (TLR) 3 recognize both PAMPs DAMPs and is activated by viral double-stranded RNA (dsRNA) leading to activation of TIR receptor domain-containing adaptor inducing IFN-ß (TRIF) dependent pathway. New evidence has shown a link between virus dsRNA and increased BP. Hence, we hypothesize that COVID-19 infection may be over activating the TLR3 through dsRNA, evoking further damage to the patients, leading to vascular inflammation and increased blood pressure, favoring the development of several cardiovascular complications, including hypertension.


Subject(s)
COVID-19/genetics , COVID-19/pathology , Hypertension/genetics , RNA, Double-Stranded/genetics , Toll-Like Receptor 3/genetics , Animals , Humans , Hypertension/pathology , Hypertension/virology , Mice , SARS-CoV-2/pathogenicity , Signal Transduction/genetics
6.
Cells ; 10(3)2021 03 03.
Article in English | MEDLINE | ID: covidwho-1129685

ABSTRACT

(1) Background: Recently, influences of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) has gained attention, regarding a possible influence on inflammatory and anti-inflammatory pathways. We aimed to study the effects of newly initiated antihypertensive drugs on angiotensin (Ang) II and Ang (1-7) as representers of two counter-regulatory axes. (2) Methods: In this randomized, open-label trial investigating RAAS peptides after the initiation of perindopril, olmesartan, amlodipine, or hydrochlorothiazide, Ang II and Ang (1-7) equilibrium concentrations were measured at 8 a.m. and 12 a.m. at baseline and after four weeks of treatment. Eighty patients were randomized (1:1:1:1 fashion). (3) Results: Between the four substances, we found significant differences regarding the concentrations of Ang II (p < 0.0005 for 8 a.m., 12 a.m.) and Ang (1-7) (p = 0.019 for 8 a.m., <0.0005 for 12 a.m.) four weeks after treatment start. Ang II was decreased by perindopril (p = 0.002), and increased by olmesartan (p < 0.0005), amlodipine (p = 0.012), and hydrochlorothiazide (p = 0.001). Ang (1-7) was increased by perindopril and olmesartan (p = 0.008/0.002), but not measurably altered by amlodipine and hydrochlorothiazide (p = 0.317/ 0.109). (4) Conclusion: The initiation of all first line antihypertensive treatments causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptides shift upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Antihypertensive Agents/pharmacology , Female , Humans , Hypertension/pathology , Male , Middle Aged
7.
BMC Infect Dis ; 21(1): 175, 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-1085168

ABSTRACT

BACKGROUND: While hypertension is the most common comorbid condition in patients with coronavirus disease 2019 (COVID-19) in Korea, there is a lack of studies investigating risk factors in COVID-19 patients with hypertension in Korea. In this study, we aimed to examine the effects risk factors in hypertensive Korean COVID-19 patients. METHODS: We selected patients from the database of the project #OpenData4Covid19. This information was linked to their 3-year historical healthcare data. The severity of the disease was classified into five levels. We also clustered the levels into two grades. RESULTS: The risk factors associated with COVID-19 severity were old age, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), malignancy, and renal replacement therapy. The use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) both before and after a diagnosis of COVID-19 were not associated with COVID-19 severity. A multivariate analysis revealed that old age, male sex, diabetes mellitus, and renal replacement therapy were risk factors for severe COVID-19. CONCLUSION: The results suggest that in hypertensive patients with COVID-19, older age, male sex, a diagnosis of diabetes mellitus, and renal replacement therapy were risk factors for a severe clinical course. In addition, the use of ARBs and ACEIs before or after COVID-19 infection did not affect a patient's risk of contracting COVID-19 nor did it contribute to a worse prognosis for the disease. These results highlighted that precautions should be considered for hypertensive patients with those risk factors and do not support discontinuation of ARBs and ACEIs during COVID-19 pandemic.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/pathology , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/complications , COVID-19/epidemiology , Diabetes Mellitus/pathology , Female , Humans , Hypertension/complications , Hypertension/pathology , Male , Medical History Taking , Middle Aged , Pandemics , Renin-Angiotensin System/drug effects , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2/physiology
8.
J Korean Med Sci ; 36(2): e15, 2021 Jan 11.
Article in English | MEDLINE | ID: covidwho-1021879

ABSTRACT

BACKGROUND: Data regarding the association between preexisting cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs) and the outcomes of patients requiring hospitalization for coronavirus disease 2019 (COVID-19) are limited. Therefore, the aim of this study was to investigate the impact of preexisting CVRFs or CVDs on the outcomes of patients with COVID-19 hospitalized in a Korean healthcare system. METHODS: Patients with COVID-19 admitted to 10 hospitals in Daegu Metropolitan City, Korea, were examined. All sequentially hospitalized patients between February 15, 2020, and April 24, 2020, were enrolled in this study. All patients were confirmed to have COVID-19 based on the positive results on the polymerase chain reaction testing of nasopharyngeal samples. Clinical outcomes during hospitalization, such as requiring intensive care and invasive mechanical ventilation (MV) and death, were evaluated. Moreover, data on baseline comorbidities such as a history of diabetes, hypertension, dyslipidemia, current smoking, heart failure, coronary artery disease, cerebrovascular accidents, and other chronic cardiac diseases were obtained. RESULTS: Of all the patients enrolled, 954 (42.0%) had preexisting CVRFs or CVDs. Among the CVRFs, the most common were hypertension (28.8%) and diabetes mellitus (17.0%). The prevalence rates of preexisting CVRFs or CVDs increased with age (P < 0.001). The number of patients requiring intensive care (P < 0.001) and invasive MV (P < 0.001) increased with age. The in-hospital death rate increased with age (P < 0.001). Patients requiring intensive care (5.3% vs. 1.6%; P < 0.001) and invasive MV (4.3% vs. 1.7%; P < 0.001) were significantly greater in patients with preexisting CVRFs or CVDs. In-hospital mortality (12.9% vs. 3.1%; P < 0.001) was significantly higher in patients with preexisting CVRFs or CVDs. Among the CVRFs, diabetes mellitus and hypertension were associated with increased requirement of intensive care and invasive MV and in-hospital death. Among the known CVDs, coronary artery disease and congestive heart failure were associated with invasive MV and in-hospital death. In multivariate analysis, preexisting CVRFs or CVDs (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.07-3.01; P = 0.027) were independent predictors of in-hospital death after adjusting for confounding variables. Among individual preexisting CVRF or CVD components, diabetes mellitus (OR, 2.43; 95% CI, 1.51-3.90; P < 0.001) and congestive heart failure (OR, 2.43; 95% CI, 1.06-5.87; P = 0.049) were independent predictors of in-hospital death. CONCLUSION: Based on the findings of this study, the patients with confirmed COVID-19 with preexisting CVRFs or CVDs had worse clinical outcomes. Caution is required in dealing with these patients at triage.


Subject(s)
COVID-19/complications , COVID-19/mortality , Diabetes Mellitus/mortality , Hypertension/mortality , Aged , COVID-19/pathology , Cardiovascular Diseases/complications , Cardiovascular Diseases/mortality , Cardiovascular Diseases/pathology , Comorbidity , Critical Care/statistics & numerical data , Diabetes Mellitus/pathology , Female , Heart Disease Risk Factors , Hospital Mortality , Humans , Hypertension/pathology , Male , Middle Aged , Prognosis , Republic of Korea , SARS-CoV-2
9.
Nat Biotechnol ; 39(6): 705-716, 2021 06.
Article in English | MEDLINE | ID: covidwho-997913

ABSTRACT

In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial-immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.


Subject(s)
COVID-19/drug therapy , Chemokine CCL3/genetics , Chemokine CCL4/genetics , Hypertension/drug therapy , Receptors, CCR1/genetics , Adult , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/complications , COVID-19/genetics , COVID-19/virology , Disease Progression , Female , Gene Expression Regulation/drug effects , Humans , Hypertension/complications , Hypertension/genetics , Hypertension/pathology , Inflammation/complications , Inflammation/drug therapy , Inflammation/genetics , Inflammation/virology , Male , Middle Aged , RNA-Seq , Respiratory System/drug effects , Respiratory System/pathology , Respiratory System/virology , Risk Factors , SARS-CoV-2/pathogenicity , Single-Cell Analysis
10.
Front Immunol ; 11: 596684, 2020.
Article in English | MEDLINE | ID: covidwho-1000092

ABSTRACT

Background: The current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an unprecedented health crisis. The most common chronic illness among patients infected with SARS-CoV-2 is hypertension. Immune dysregulation plays an important role in SARS-CoV-2 infection and in the development of hypertension; however, the dynamic immunological characteristics of COVID-19 patients with hypertension remain largely unclear. Methods: In total, 258 hypertensive patients infected with SARS-CoV-2 were included in this study. CD38+HLA-DR+ and CD38+PD-1+ CD8+ T cells, IFNγ+CD4+ and IFNγ+CD8+ T cells, the titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and SARS-CoV-2 throat viral loads were measured weekly over 4 weeks after the onset of symptoms. Clinical outcomes were also monitored. Findings: CD4+ T lymphopenia was observed in 100% of the severe and critical cases. Compared with the surviving patients, the patients with fatal outcomes exhibited high and prolonged expression of CD38+HLA-DR+ and CD38+PD-1+ on CD8+ T cells, low expression of SARS-CoV-2-specific IFNγ+CD4+ and IFNγ+CD8+ T cells, low titers of IgG, IgM, and IgA against SARS-CoV-2 spike protein, and high SARS-CoV-2 viral load during the illness. In the surviving patients, the viral load was significantly inversely correlated with SARS-CoV-2-specific IFNγ+CD8+and IFNγ+CD4+ T cells, IgG, IgM, and IgA. Interpretation: T lymphopenia is common in critical or severe COVID-19 cases with hypertension. Prolonged activation and exhaustion of CD8+ T cells were associated with severe disease. The delayed SARS-CoV-2-specific antibody responses may be insufficient for overcoming severe SARS-CoV-2 infection in the absence of SARS-CoV-2-specific cellular responses.


Subject(s)
Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Hypertension/pathology , SARS-CoV-2/immunology , COVID-19/pathology , Critical Illness , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Interferon-gamma/blood , Lymphopenia/blood , Retrospective Studies , Spike Glycoprotein, Coronavirus/immunology , Viral Load
11.
PLoS One ; 15(12): e0243600, 2020.
Article in English | MEDLINE | ID: covidwho-977704

ABSTRACT

OBJECTIVE: Based on the epidemiologic findings of Covid-19 incidence; illness and mortality seem to be associated with metabolic risk factors. This systematic review and meta-analysis aimed to assess the association of metabolic risk factors and risk of Covid-19. METHODS: This study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Cochrane Library, and Scopus. The search terms developed focusing on two main roots of "Covid-19" and "metabolic risk factors". All relevant observational, analytical studies, review articles, and a meta-analysis on the adult population were included in this meta-analysis. Meta-analysis was performed using the random effect model for pooling proportions to address heterogeneity among studies. Data were analyzed using STATA package version 11.2, (StataCorp, USA). RESULTS: Through a comprehensive systematic search in the targeted databases we found 1124 papers, after running the proses of refining, 13 studies were included in the present meta-analysis. The pooled prevalence of obesity in Covid-19 patients was 29% (95% CI: 14-47%). For Diabetes and Hypertension, these were 22% (95% CI: 12% 33%) and 32% (95% CI: 12% 56%), respectively. There was significant heterogeneity in the estimates of the three pooled prevalence without any significant small-study effects. Such warning points, to some extent, guide physicians and clinicians to better understand the importance of controlling co-morbid risk factors in prioritizing resource allocation and interventions. CONCLUSION: The meta-analysis showed that hypertension is more prevalent than obesity and diabetes in patients with Covid-19 disease. The prevalence of co-morbid metabolic risk factors must be adopted for better management and priority settings of public health vaccination and other required interventions. The results may help to improve services delivery in COVID-19 patients, while helping to develop better policies for prevention and response to COVID-19 and its critical outcomes.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Hypertension/epidemiology , Metabolism , COVID-19/metabolism , COVID-19/virology , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Diabetes Mellitus/virology , Humans , Hypertension/complications , Hypertension/pathology , Hypertension/virology , Risk Factors , SARS-CoV-2
12.
FEBS J ; 287(17): 3681-3688, 2020 09.
Article in English | MEDLINE | ID: covidwho-960853

ABSTRACT

In coronavirus disease 2019 (COVID-19), higher morbidity and mortality are associated with age, male gender, and comorbidities, such as chronic lung diseases, cardiovascular pathologies, hypertension, kidney diseases, diabetes mellitus, and obesity. All of the above conditions are characterized by increased sympathetic discharge, which may exert significant detrimental effects on COVID-19 patients, through actions on the lungs, heart, blood vessels, kidneys, metabolism, and/or immune system. Furthermore, COVID-19 may also increase sympathetic discharge, through changes in blood gases (chronic intermittent hypoxia, hyperpnea), angiotensin-converting enzyme (ACE)1/ACE2 imbalance, immune/inflammatory factors, or emotional distress. Nevertheless, the potential role of the sympathetic nervous system has not yet been considered in the pathophysiology of COVID-19. In our opinion, sympathetic overactivation could represent a so-far undervalued mechanism for a vicious circle between COVID-19 and comorbidities.


Subject(s)
COVID-19/metabolism , Coronary Disease/metabolism , Diabetes Mellitus/metabolism , Hypertension/metabolism , Kidney Failure, Chronic/metabolism , Obesity/metabolism , Respiratory Insufficiency/metabolism , Sympathetic Nervous System/metabolism , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Comorbidity , Coronary Disease/mortality , Coronary Disease/pathology , Coronary Disease/virology , Diabetes Mellitus/mortality , Diabetes Mellitus/pathology , Diabetes Mellitus/virology , Female , Humans , Hypertension/mortality , Hypertension/pathology , Hypertension/virology , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/virology , Male , Obesity/mortality , Obesity/pathology , Obesity/virology , Respiratory Insufficiency/mortality , Respiratory Insufficiency/pathology , Respiratory Insufficiency/virology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Severity of Illness Index , Sex Factors , Survival Analysis , Sympathetic Nervous System/physiopathology , Sympathetic Nervous System/virology
13.
Am J Trop Med Hyg ; 103(6): 2164-2167, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-895568

ABSTRACT

Despite myriad improvements in the care of COVID-19 patients, atypical manifestations are least appreciated during the current pandemic. Because COVID-19 is primarily manifesting as an acute respiratory illness with interstitial and alveolar pneumonia, the possibility of viral invasions into the other organs cannot be disregarded. Acute kidney injury (AKI) has been associated with various viral infections including dengue, chikungunya, Zika, and HIV. The prevalence and risks of AKI during the course of COVID-19 have been described in few studies. However, the existing literature demonstrate great disparity across findings amid variations in methodology and population. This article underscores the propensity of AKI among COVID-19 patients, limitations of the exiting evidence, and importance of timely identification during the case management. The prevalence of AKI is variable across the studies ranging from 4.7% to 81%. Evidence suggest old age, comorbidities, ventilator support, use of vasopressors, black race, severe infection, and elevated levels of baseline serum creatinine and d-dimers are independent risk factors of COVID-19 associated with AKI. COVID-19 patients with AKI also showed unsatisfactory renal recovery and higher mortality rate as compared with patients without AKI. These findings underscore that AKI frequently occurs during the course of COVID-19 infection and requires early stratification and management.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Hypertension/epidemiology , Pandemics , Respiratory Distress Syndrome/epidemiology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/pathology , Acute Kidney Injury/virology , Age Factors , COVID-19/diagnosis , COVID-19/pathology , COVID-19/virology , Comorbidity , Diabetes Mellitus/diagnosis , Diabetes Mellitus/pathology , Diabetes Mellitus/virology , Hospitalization , Humans , Hypertension/diagnosis , Hypertension/pathology , Hypertension/virology , Kidney/pathology , Kidney/virology , Respiration, Artificial/adverse effects , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , Risk Factors , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , Vasoconstrictor Agents/adverse effects
15.
Pathog Dis ; 79(1)2021 01 09.
Article in English | MEDLINE | ID: covidwho-857624

ABSTRACT

BACKGROUND: despite being in the 5th month of pandemic, knowledge with respect to viral dynamics, infectivity and RT-PCR positivity continues to evolve. AIM: to analyse the SARS CoV-2 nucleic acid RT-PCR profiles in COVID-19 patients. DESIGN: it was a retrospective, observational study conducted at COVID facilities under AIIMS, New Delhi. METHODS: patients admitted with laboratory confirmed COVID-19 were eligible for enrolment. Patients with incomplete details, or only single PCR tests were excluded. Data regarding demographic details, comorbidities, treatment received and results of SARS-CoV-2 RT-PCR performed on nasopharyngeal and oropharyngeal swabs, collected at different time points, was retrieved from the hospital records. RESULTS: a total of 298 patients were included, majority were males (75·8%) with mean age of 39·07 years (0·6-88 years). The mean duration from symptom onset to first positive RT-PCR was 4·7 days (SD 3·67), while that of symptom onset to last positive test was 17·83 days (SD 6·22). Proportions of positive RT-PCR tests were 100%, 49%, 24%, 8·7% and 20·6% in the 1st, 2nd, 3rd, 4th and >4 weeks of illness. A total of 12 symptomatic patients had prolonged positive test results even after 3 weeks of symptom onset. Age > = 60 years was associated with prolonged RT-PCR positivity (statistically significant). CONCLUSION: this study showed that the average period of PCR positivity is more than 2 weeks in COVID-19 patients; elderly patients have prolonged duration of RT-PCR positivity and requires further follow up.


Subject(s)
COVID-19/diagnosis , Diabetes Mellitus/diagnosis , Hypertension/diagnosis , RNA, Viral/genetics , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Aged, 80 and over , Asymptomatic Diseases , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , COVID-19 Nucleic Acid Testing/methods , Child , Child, Preschool , Comorbidity , Diabetes Mellitus/epidemiology , Diabetes Mellitus/pathology , Diabetes Mellitus/virology , Humans , Hypertension/epidemiology , Hypertension/pathology , Hypertension/virology , India/epidemiology , Infant , Infectious Disease Incubation Period , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Severity of Illness Index
18.
Infection ; 49(1): 15-28, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-734048

ABSTRACT

PURPOSE: Covid-19 is a global threat that pushes health care to its limits. Since there is neither a vaccine nor a drug for Covid-19, people with an increased risk for severe and fatal courses of disease particularly need protection. Furthermore, factors increasing these risks are of interest in the search of potential treatments. A systematic literature review on the risk factors of severe and fatal Covid-19 courses is presented. METHODS: The review is carried out on PubMed and a publicly available preprint dataset. For analysis, risk factors are categorized and information regarding the study such as study size and location are extracted. The results are compared to risk factors listed by four public authorities from different countries. RESULTS: The 28 records included, eleven of which are preprints, indicate that conditions and comorbidities connected to a poor state of health such as high age, obesity, diabetes and hypertension are risk factors for severe and fatal disease courses. Furthermore, severe and fatal courses are associated with organ damages mainly affecting the heart, liver and kidneys. Coagulation dysfunctions could play a critical role in the organ damaging. Time to hospital admission, tuberculosis, inflammation disorders and coagulation dysfunctions are identified as risk factors found in the review but not mentioned by the public authorities. CONCLUSION: Factors associated with increased risk of severe or fatal disease courses were identified, which include conditions connected with a poor state of health as well as organ damages and coagulation dysfunctions. The results may facilitate upcoming Covid-19 research.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Disseminated Intravascular Coagulation/epidemiology , Hypertension/epidemiology , Obesity/epidemiology , Pandemics , Tuberculosis, Pulmonary/epidemiology , Age Factors , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Comorbidity , Diabetes Mellitus/mortality , Diabetes Mellitus/pathology , Diabetes Mellitus/virology , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/pathology , Disseminated Intravascular Coagulation/virology , Heart/physiopathology , Heart/virology , Hospitalization/statistics & numerical data , Humans , Hypertension/mortality , Hypertension/pathology , Hypertension/virology , Kidney/pathology , Kidney/virology , Liver/pathology , Liver/virology , Obesity/mortality , Obesity/pathology , Obesity/virology , Risk Factors , SARS-CoV-2/pathogenicity , Severity of Illness Index , Survival Analysis , Tuberculosis, Pulmonary/mortality , Tuberculosis, Pulmonary/pathology , Tuberculosis, Pulmonary/virology
19.
Cytokine Growth Factor Rev ; 54: 32-42, 2020 08.
Article in English | MEDLINE | ID: covidwho-694176

ABSTRACT

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.


Subject(s)
BCG Vaccine/therapeutic use , Coronavirus Infections/prevention & control , Cytokine Release Syndrome/prevention & control , Cytokines/blood , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Antiviral Agents/therapeutic use , Betacoronavirus/immunology , COVID-19 , Cardiovascular Diseases/pathology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Diabetes Mellitus/pathology , Humans , Hypertension/pathology , Middle East Respiratory Syndrome Coronavirus/immunology , Mycobacterium bovis/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Pulmonary Disease, Chronic Obstructive/pathology , Risk Factors , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Vaccination
20.
Stem Cell Rev Rep ; 17(1): 132-143, 2021 02.
Article in English | MEDLINE | ID: covidwho-692570

ABSTRACT

Severe acute respiratory syndrome corona virus - 2 (SARS-CoV-2) is a single stranded RNA virus and responsible for infecting human being. In many cases the individual may remain asymptomatic. Some recently reported studies revealed that individuals of elderly age group and with pre-existing medical conditions such as hypertension, diabetes mellitus had severe consequences, even may lead to death. However, it is not clearly delineated whether hypertension itself or associated comorbidities or antihypertensive therapy contributes to the grave prognosis of COVID-19 infections. This review is aimed to decipher the exact mechanisms involved at molecular level from existing evidence and as reported. It has been reported that SARS-CoV-2 enters into the host cell through interaction between conserved residues of viral spike protein and angiotensin converting enzyme 2 (ACE2) receptor which is highly expressed in host's cardiac and pulmonary cells and finally transmembrane protease, serine-2 (TMPRSS2), helps in priming of the surface protein. Subsequently, symptom related to multi organ involvement is primarily contributed by cytokine storm. Although various clinical trials are being conducted on renin- angiotensin- system inhibitor, till to date there is no standard treatment protocol approved for critically ill COVID-19 positive cases with pre-existing hypertension. Recently, several studies are carried out to document the safety and efficacy outcome of mesenchymal stem cell transplantation based on its immunomodulatory and regenerative properties. Therefore, identification of future novel therapeutics in the form of mesenchymal stem cell either alone or in combination with pharmacological approach could be recommended for combating SARS-CoV-2 which might be dreadful to debilitating elderly people. Graphical Abstract.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/therapy , Hypertension/therapy , SARS-CoV-2/genetics , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Humans , Hypertension/genetics , Hypertension/pathology , Hypertension/virology , Mesenchymal Stem Cells/metabolism , SARS-CoV-2/pathogenicity , Serine Endopeptidases/genetics
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