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1.
Respir Res ; 22(1): 317, 2021 Dec 22.
Article in English | MEDLINE | ID: covidwho-1633846

ABSTRACT

BACKGROUND: Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched. METHODS: In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2 < 200 receiving tocilizumab plus usual care versus usual care alone. Tocilizumab was administered at the time point that PaO2/FiO2 < 200 was observed. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10. FINDINGS: Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95% CI: 1.21-9.30), (p = 0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28 day period for patients receiving tocilizumab compared to usual care [11.0 days (95% CI: 9.0 to 16.0) vs 14.0 days (95% CI: 10.0-24.0), HR: 1.32 (95% CI: 0.84-2.08), p = 0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95% CI: 23.0-84.7) vs 15.8 (95% CI: - 19.4-50.3), p = 0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5 ± 2.1 vs 0.6 ± 2.6, p = 0.005). CONCLUSION: Administration of tocilizumab, at the time point that PaO2/FiO2 < 200 was observed, improved survival and other clinical outcomes in hospitalized patients with severe COVID-19 irrespective of systemic inflammatory markers levels.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/drug therapy , COVID-19/mortality , Hospitalization/trends , Patient Acuity , Administration, Intravenous , Aged , COVID-19/diagnosis , Female , Humans , Male , Middle Aged , Prospective Studies , Survival Rate/trends
2.
BMC Endocr Disord ; 22(1): 13, 2022 Jan 06.
Article in English | MEDLINE | ID: covidwho-1613234

ABSTRACT

BACKGROUND: Research regarding the association between severe obesity and in-hospital mortality is inconsistent. We evaluated the impact of body mass index (BMI) levels on mortality in the medical wards. The analysis was performed separately before and during the COVID-19 pandemic. METHODS: We retrospectively retrieved data of adult patients admitted to the medical wards at the Mount Sinai Health System in New York City. The study was conducted between January 1, 2011, to March 23, 2021. Patients were divided into two sub-cohorts: pre-COVID-19 and during-COVID-19. Patients were then clustered into groups based on BMI ranges. A multivariate logistic regression analysis compared the mortality rate among the BMI groups, before and during the pandemic. RESULTS: Overall, 179,288 patients were admitted to the medical wards and had a recorded BMI measurement. 149,098 were admitted before the COVID-19 pandemic and 30,190 during the pandemic. Pre-pandemic, multivariate analysis showed a "J curve" between BMI and mortality. Severe obesity (BMI > 40) had an aOR of 0.8 (95% CI:0.7-1.0, p = 0.018) compared to the normal BMI group. In contrast, during the pandemic, the analysis showed a "U curve" between BMI and mortality. Severe obesity had an aOR of 1.7 (95% CI:1.3-2.4, p < 0.001) compared to the normal BMI group. CONCLUSIONS: Medical ward patients with severe obesity have a lower risk for mortality compared to patients with normal BMI. However, this does not apply during COVID-19, where obesity was a leading risk factor for mortality in the medical wards. It is important for the internal medicine physician to understand the intricacies of the association between obesity and medical ward mortality.


Subject(s)
Body Mass Index , COVID-19/mortality , Hospital Mortality/trends , Hospitalization/statistics & numerical data , Obesity/physiopathology , SARS-CoV-2/isolation & purification , Aged , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Case-Control Studies , Female , Humans , Male , Middle Aged , New York City/epidemiology , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
3.
Sci Rep ; 11(1): 24441, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1585773

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) belongs to the coronavirus family and is characterized by its high transmission competence. Elderly COVID-19 patients are at significantly higher risk of severe course of disease and death. Therefore, outbreaks in nursing homes are particularly challenging for facility managers and health authorities. Here, we report three outbreaks of COVID-19 related to nursing homes (NH01.a, NH02 and NH03) with almost 1000 affected individuals during the first COVID-19 wave in Berlin, Germany. The occurrence of cases and the measures taken were analyzed retrospectively. In all three outbreaks, the index persons were nursing home employees or volunteers. Measures taken were quarantine of contacts, close-meshed tests, separation of the affected housing unit, suspension of admission, ban on visiting, and equipping staff with personal protective equipment, of which there was a shortage in Germany at the beginning of the pandemic. A court-ordered quarantine became necessary for three residents of NH01.a due to cognitive disabilities. In total, 61 persons were tested positive for SARS-CoV-2 in NH01.a, ten persons in NH02, and sixteen persons in NH03. Seventeen patients (27.9%) of NH01.a and three patients (18.8%) of NH03 were referred to hospital. Of all confirmed cases, thirteen (21.3%) related to NH01.a and four (25.0%) related to NH03 died as a result of the infection. Besides one 82 year old volunteer, all deceased persons were residents aged between 66 and 98. Our results emphasize the importance of a previously developed containment and cluster strategy for nursing homes. Due to the particular vulnerability of the residents, immediate action, close cooperation and communication between the facility management, residents, visitors and the health authorities are essential in the case of confirmed COVID-19 cases in healthcare facilities.


Subject(s)
COVID-19/epidemiology , Aged , Aged, 80 and over , Berlin/epidemiology , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Disease Outbreaks , Female , Humans , Male , Middle Aged , Nursing Homes , Retrospective Studies , SARS-CoV-2/isolation & purification , Survival Rate
4.
PLoS One ; 16(3): e0248009, 2021.
Article in English | MEDLINE | ID: covidwho-1575841

ABSTRACT

INTRODUCTION: Since the start of the pandemic, millions of people have been infected, with thousands of deaths. Many foci worldwide have been identified in retirement nursing homes, with a high number of deaths. Our study aims were to evaluate the spread of SARS-CoV-2 in the retirement nursing homes, the predictors to develop symptoms, and death. METHODS AND FINDINGS: We conducted a retrospective study enrolling all people living in retirement nursing homes (PLRNH), where at least one SARS-CoV-2 infected person was present. Medical and clinical data were collected. Variables were compared with Student's t-test or Pearson chi-square test as appropriate. Uni- and multivariate analyses were conducted to evaluate variables' influence on infection and symptoms development. Cox proportional-hazards model was used to evaluate 30 days mortality predictors, considering death as the dependent variable. We enrolled 382 subjects. The mean age was 81.15±10.97 years, and males were 140(36.7%). At the multivariate analysis, mental disorders, malignancies, and angiotensin II receptor blockers were predictors of SARS-CoV-2 infection while having a neurological syndrome was associated with a lower risk. Only half of the people with SARS-CoV-2 infection developed symptoms. Chronic obstructive pulmonary disease and neurological syndrome were correlated with an increased risk of developing SARS-CoV-2 related symptoms. Fifty-six (21.2%) people with SARS-CoV-2 infection died; of these, 53 died in the first 30 days after the swab's positivity. Significant factors associated with 30-days mortality were male gender, hypokinetic disease, and the presence of fever and dyspnea. Patients' autonomy and early heparin treatment were related to lower mortality risk. CONCLUSIONS: We evidenced factors associated with infection's risk and death in a setting with high mortality such as retirement nursing homes, that should be carefully considered in the management of PLRNH.


Subject(s)
COVID-19/pathology , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/administration & dosage , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Dyspnea/etiology , Female , Fever/etiology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Male , Mental Disorders/complications , Mental Disorders/pathology , Neoplasms/complications , Neoplasms/pathology , Nursing Homes , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Sex Factors , Survival Rate
5.
Respir Med ; 187: 106538, 2021 10.
Article in English | MEDLINE | ID: covidwho-1574473

ABSTRACT

BACKGROUND: Analyses of COVID-19 infection outcomes in patients with preexisting pulmonary sarcoidosis are lacking and are limited to case reports or small case series with the largest study reporting outcomes of 37 patients. RESEARCH QUESTION: Retrospective cohort study to assess clinical outcomes of 945 patients with pulmonary sarcoidosis, presenting with COVID 19, compared to a propensity matched cohort of patients without sarcoidosis. STUDY DESIGN AND METHODS: Analysis of a multi-center research network TriNETX was performed including patients more than 16 years of age diagnosed with COVID-19. Outcomes in COVID-19 positive patients with concurrent pulmonary sarcoidosis were compared with a propensity score matched cohort of patients without pulmonary sarcoidosis. RESULTS: A total of 278,271 patients with COVID-19 on the research network were identified, 954 patients (0.34 %) carried a diagnosis of pulmonary sarcoidosis. Mean age of patients with sarcoidosis was 56.3 ± 13.2 years, with female predominance (n = 619, 64.89 %). 49.69 % of the participants were African American (n = 474). Co-morbidities including hypertension, chronic lower respiratory diseases, diabetes mellitus, ischemic heart disease, nicotine dependence, and chronic kidney disease were more common in patients with pulmonary sarcoidosis when compared to the non-pulmonary sarcoidosis cohort (all p values < 0.01). In unmatched analysis, pulmonary sarcoidosis group had higher mortality, increased risk for hospitalization, intubation and need for renal replacement therapy. After propensity score matching, no difference in any of the outcome measures was observed. INTERPRETATION: Crude COVID-19 mortality and other clinical outcome measures are poor in pulmonary sarcoidosis cohort; however, propensity-matched analyses revealed no difference in outcomes, showing that higher mortality is driven by higher burden of comorbidities.


Subject(s)
COVID-19/complications , COVID-19/mortality , Sarcoidosis, Pulmonary/complications , Sarcoidosis, Pulmonary/mortality , Adult , Aged , COVID-19/therapy , Critical Care , Female , Hospitalization , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Propensity Score , Respiration, Artificial , Retrospective Studies , Risk Factors , Sarcoidosis, Pulmonary/therapy , Survival Rate
6.
J Med Internet Res ; 23(2): e26257, 2021 02 22.
Article in English | MEDLINE | ID: covidwho-1574035

ABSTRACT

BACKGROUND: As the COVID-19 pandemic continues, an initial risk-adapted allocation is crucial for managing medical resources and providing intensive care. OBJECTIVE: In this study, we aimed to identify factors that predict the overall survival rate for COVID-19 cases and develop a COVID-19 prognosis score (COPS) system based on these factors. In addition, disease severity and the length of hospital stay for patients with COVID-19 were analyzed. METHODS: We retrospectively analyzed a nationwide cohort of laboratory-confirmed COVID-19 cases between January and April 2020 in Korea. The cohort was split randomly into a development cohort and a validation cohort with a 2:1 ratio. In the development cohort (n=3729), we tried to identify factors associated with overall survival and develop a scoring system to predict the overall survival rate by using parameters identified by the Cox proportional hazard regression model with bootstrapping methods. In the validation cohort (n=1865), we evaluated the prediction accuracy using the area under the receiver operating characteristic curve. The score of each variable in the COPS system was rounded off following the log-scaled conversion of the adjusted hazard ratio. RESULTS: Among the 5594 patients included in this analysis, 234 (4.2%) died after receiving a COVID-19 diagnosis. In the development cohort, six parameters were significantly related to poor overall survival: older age, dementia, chronic renal failure, dyspnea, mental disturbance, and absolute lymphocyte count <1000/mm3. The following risk groups were formed: low-risk (score 0-2), intermediate-risk (score 3), high-risk (score 4), and very high-risk (score 5-7) groups. The COPS system yielded an area under the curve value of 0.918 for predicting the 14-day survival rate and 0.896 for predicting the 28-day survival rate in the validation cohort. Using the COPS system, 28-day survival rates were discriminatively estimated at 99.8%, 95.4%, 82.3%, and 55.1% in the low-risk, intermediate-risk, high-risk, and very high-risk groups, respectively, of the total cohort (P<.001). The length of hospital stay and disease severity were directly associated with overall survival (P<.001), and the hospital stay duration was significantly longer among survivors (mean 26.1, SD 10.7 days) than among nonsurvivors (mean 15.6, SD 13.3 days). CONCLUSIONS: The newly developed predictive COPS system may assist in making risk-adapted decisions for the allocation of medical resources, including intensive care, during the COVID-19 pandemic.


Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Age Factors , Aged , Critical Care/statistics & numerical data , Dementia/epidemiology , Female , Humans , Kidney Failure, Chronic/epidemiology , Length of Stay/statistics & numerical data , Male , Middle Aged , Pandemics , Prognosis , Proportional Hazards Models , ROC Curve , Republic of Korea/epidemiology , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Rate
7.
Front Immunol ; 12: 627844, 2021.
Article in English | MEDLINE | ID: covidwho-1573949

ABSTRACT

Background: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. Methods: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. Results: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. Conclusions: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Immunoglobulins, Intravenous/administration & dosage , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/blood , China/epidemiology , Disease-Free Survival , Female , Ferritins/blood , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Middle Aged , Retrospective Studies , Survival Rate
8.
Open Heart ; 8(2)2021 11.
Article in English | MEDLINE | ID: covidwho-1518151

ABSTRACT

OBJECTIVE: To determine the prevalence of cardiac abnormalities and their relationship to markers of myocardial injury and mortality in patients admitted to hospital with COVID-19. METHODS: A retrospective and prospective observational study of inpatients referred for transthoracic echocardiography for suspected cardiac pathology due to COVID-19 within a London NHS Trust. Echocardiograms were performed to assess left ventricular (LV), right ventricular (RV) and pulmonary variables along with collection of patient demographics, comorbid conditions, blood biomarkers and outcomes. RESULT: In the predominant non-white (72%) population, RV dysfunction was the primary cardiac abnormality noted in 50% of patients, with RV fractional area change <35% being the most common marker of this RV dysfunction. By comparison, LV systolic dysfunction occurred in 18% of patients. RV dysfunction was associated with LV systolic dysfunction and the presence of a D-shaped LV throughout the cardiac cycle (marker of significant pulmonary artery hypertension). LV systolic dysfunction (p=0.002, HR 3.82, 95% CI 1.624 to 8.982), pulmonary valve acceleration time (p=0.024, HR 0.98, 95% CI 0.964 to 0.997)-marker of increased pulmonary vascular resistance, age (p=0.047, HR 1.027, 95% CI 1.000 to 1.055) and an episode of tachycardia measured from admission to time of echo (p=0.004, HR 6.183, 95% CI 1.772 to 21.575) were independently associated with mortality. CONCLUSIONS: In this predominantly non-white population hospitalised with COVID-19, the most common cardiac pathology was RV dysfunction which is associated with both LV systolic dysfunction and elevated pulmonary artery pressure. The latter two, not RV dysfunction, were associated with mortality.


Subject(s)
COVID-19/ethnology , Heart Diseases/ethnology , Heart Ventricles/diagnostic imaging , Population Surveillance , Comorbidity , Cross-Sectional Studies , Echocardiography, Doppler , Heart Diseases/diagnosis , Hospitalization/trends , Humans , Pandemics , Prevalence , Quebec/epidemiology , Retrospective Studies , Survival Rate/trends
9.
Sci Rep ; 11(1): 21522, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500507

ABSTRACT

There is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Receptors, Interleukin-6/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/immunology , COVID-19/mortality , COVID-19/virology , Humans , Odds Ratio , Respiration, Artificial , SARS-CoV-2/isolation & purification , Survival Rate
10.
Arch Iran Med ; 24(4): 333-338, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1498430

ABSTRACT

BACKGROUND: Decision-making on allocating scarce medical resources is crucial in the context of a strong health system reaction to the coronavirus disease 2019 (COVID-19) pandemic. Therefore, understanding the risk factors related to a high mortality rate can enable the physicians for a better decision-making process. METHODS: Information was collected regarding clinical, demographic, and epidemiological features of the definite COVID-19 cases. Through Cox regression and statistical analysis, the risk factors related to mortality were determined. The Kaplan-Meier curve was used to estimate survival function and measure the mean length of living time in the patients. RESULTS: Among about 3000 patients admitted in the Taleghani hospital as outpatients with suspicious signs and symptoms of COVID-19 in 2 months, 214 people were confirmed positive for this virus using the polymerase chain reaction (PCR) technique. Median time to death was 30 days. In this population, 24.29% of the patients died and 24.76% of them were admitted to the ICU (intensive care unit) during hospitalization. The results of Multivariate Cox regression Analysis showed that factors including age (HR, 1.031; 95% CI, 1.001-1.062; P value=0.04), and C-reactive protein (CRP) (HR, 1.007; 95% CI, 1.000-1.015; P value=0.04) could independently predict mortality. Furthermore, the results showed that age above 59 years directly increased mortality rate and decreased survival among our study population. CONCLUSION: Predictor factors play an important role in decisions on public health policy-making. Our findings suggested that advanced age and CRP were independent mortality rate predictors in the admitted patients.


Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Adult , Age Factors , Aged , COVID-19/complications , Clinical Decision-Making , Female , Hospital Mortality , Hospitalization , Humans , Iran , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Survival Rate
11.
Rev Invest Clin ; 73(4): 259-264, 2021 06 02.
Article in English | MEDLINE | ID: covidwho-1498287

ABSTRACT

BACKGROUND: Patients with monoclonal gammopathy of undetermined significance (MGUS) have clinical features including older age, presence of medical comorbidities, susceptibility to infections, and thrombotic tendencies which are relevant when assessing their risk during the coronavirus disease (COVID-19) pandemic. OBJECTIVE: To study the vulnerability of patients with MGUS during the COVID-19 pandemic, we assessed the local management of MGUS patients and their clinical outcomes. METHODS: Retrospective chart reviews were performed for all patients with MGUS seen at a university medical center clinic (2014-2020). RESULTS: A total of 228 MGUS patients were included; 211 patients are alive, 7 patients died before the pandemic, and 10 patients died since the pandemic declaration. The mean age and the overall survival (OS) of the patients who died before versus during the pandemic were 83.0 versus 75.2 years, p = 0.4, and OS 40.6 versus 53.2 months, p = 0.3, respectively. One patient died of COVID-19. Nine patients had venous thromboembolisms (VTE), all of which occurred before the pandemic onset. CONCLUSIONS: There were no significant differences found in the mean age or OS of the MGUS patients who died before versus after the pandemic onset. An increase in VTE rates was not seen. Study results are limited by small patient numbers.


Subject(s)
COVID-19 , Monoclonal Gammopathy of Undetermined Significance/therapy , Venous Thromboembolism/epidemiology , Academic Medical Centers , Age Factors , Aged , Aged, 80 and over , Female , Humans , Male , Monoclonal Gammopathy of Undetermined Significance/epidemiology , Monoclonal Gammopathy of Undetermined Significance/mortality , Retrospective Studies , Survival Rate , Venous Thromboembolism/etiology , Vulnerable Populations
12.
Biomark Med ; 15(17): 1581-1588, 2021 12.
Article in English | MEDLINE | ID: covidwho-1496869

ABSTRACT

Introduction: SARS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2) to enter the cell. In our study, we aimed to investigate the role of angiotensin-converting enzyme 2 and angiotensin II plasma levels on prognosis and mortality in patients with isolated hypertension, patients with chronic diseases in addition to hypertension and patients with COVID-19 without comorbidities, in accordance with the use of renin-angiotensin-aldosterone system inhibitor. Materials & methods: In the study, patients diagnosed with COVID-19 were divided into three groups. Angiotensin II and ACE2 levels were compared by comorbidities, antihypertensive drugs used, intensive care hospitalization and termination of patients. The relationship between angiotensin II and ACE2 levels and service and intensive care times was investigated. Findings: A total of 218 patients were enrolled in our study, including 68 patients diagnosed with COVID-19 without comorbidities, 33 patients diagnosed with isolated hypertension and 117 patients with other chronic diseases in addition to hypertension. There was no statistically significant difference between the comorbid disease groups between angiotensin II and ACE2 levels of the patients enrolled in the study. The rate of patients admitted to the intensive care unit was 17.9%, and the mortality rate was 11.5%. Results: In our study, we did not obtain significant findings regarding angiotensin II and ACE2 levels on presentation that can be used in prognosis and mortality of COVID-19 patients and development of future treatment methods.


Subject(s)
Angiotensin II/blood , Angiotensin-Converting Enzyme 2/blood , COVID-19 , Hypertension , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/mortality , Disease-Free Survival , Female , Humans , Hypertension/blood , Hypertension/mortality , Male , Middle Aged , Prospective Studies , Survival Rate
13.
Crit Care Med ; 49(7): 1149-1158, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1494026

ABSTRACT

OBJECTIVES: Circulating nucleosomes and their component histones have been implicated as pathogenic in sepsis and acute respiratory distress syndrome in adults. However, their role in pediatric acute respiratory distress syndrome is unknown. DESIGN: We performed a prospective cohort study in children with acute respiratory distress syndrome, with plasma collection within 24 hours of acute respiratory distress syndrome onset. We associated nucleosome levels with severity of acute respiratory distress syndrome and with nonpulmonary organ failures and tested for association of nucleosomes with PICU mortality and ventilator-free days at 28 days in univariate and multivariable analyses. We also performed proteomics of DNA-bound plasma proteins in a matched case-control study of septic children with and without acute respiratory distress syndrome in order to identify specific histone proteins elevated in acute respiratory distress syndrome. SETTING: Large academic tertiary-care PICU. PATIENTS: Intubated children meeting Berlin criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled 333 children with acute respiratory distress syndrome, with 69 nonsurvivors (21%). Plasma nucleosomes were correlated with acute respiratory distress syndrome severity and with the number of nonpulmonary organ failures at acute respiratory distress syndrome onset. Nucleosomes were higher (p < 0.001) in nonsurvivors (0.40 [interquartile range, 0.20-0.71] arbitrary units) relative to survivors (0.10 [interquartile range, 0.04-0.25] arbitrary units). Nucleosomes were associated with PICU mortality in multivariable analysis (adjusted odds ratio 1.84 per 1 sd increase; 95% CI, 1.38-2.45; p < 0.001). Nucleosomes were also associated with a lower probability of being extubated alive by day 28 after multivariable adjustment (adjusted subdistribution hazard ratio, 0.74; 95% CI, 0.63-0.88; p = 0.001). Proteomic analysis demonstrated higher levels of the core nucleosome histones H2A, H2B, H3, and H4 in septic children with acute respiratory distress syndrome, relative to septic children without acute respiratory distress syndrome. CONCLUSIONS: Plasma nucleosomes are associated with acute respiratory distress syndrome severity, nonpulmonary organ failures, and worse outcomes in pediatric acute respiratory distress syndrome.


Subject(s)
Histones/blood , Nucleosomes/metabolism , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/mortality , Adolescent , Airway Extubation , Case-Control Studies , Child , Child, Preschool , DNA/blood , Female , Hospital Mortality , Humans , Intensive Care Units, Pediatric , Male , Multiple Organ Failure/mortality , Prognosis , Prospective Studies , Proteomics , Respiration, Artificial , Respiratory Distress Syndrome/complications , Sepsis/blood , Sepsis/complications , Severity of Illness Index , Survival Rate
14.
Int J Mol Sci ; 22(21)2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1488619

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to global public health and the economy. The enzymatic product of cholesterol 25-hydroxylase (CH25H), 25-Hydroxycholesterol (25-HC), was reported to have potent anti-SARS-CoV-2 activity. Here, we found that the combination of 25-HC with EK1 peptide, a pan-coronavirus (CoV) fusion inhibitor, showed a synergistic antiviral activity. We then used the method of 25-HC modification to design and synthesize a series of 25-HC-modified peptides and found that a 25-HC-modified EK1 peptide (EK1P4HC) was highly effective against infections caused by SARS-CoV-2, its variants of concern (VOCs), and other human CoVs, such as HCoV-OC43 and HCoV-229E. EK1P4HC could protect newborn mice from lethal HCoV-OC43 infection, suggesting that conjugation of 25-HC with a peptide-based viral inhibitor was a feasible and universal strategy to improve its antiviral activity.


Subject(s)
Antiviral Agents/pharmacology , Hydroxycholesterols/chemistry , Lipopeptides/chemistry , SARS-CoV-2/drug effects , Amino Acid Sequence , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Body Weight/drug effects , COVID-19/drug therapy , COVID-19/virology , Coronavirus 229E, Human/drug effects , Coronavirus 229E, Human/pathogenicity , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/virology , Coronavirus OC43, Human/drug effects , Coronavirus OC43, Human/pathogenicity , Disease Models, Animal , Drug Synergism , Humans , Hydroxycholesterols/pharmacology , Hydroxycholesterols/therapeutic use , Lipopeptides/pharmacology , Lipopeptides/therapeutic use , Mice , Mice, Inbred BALB C , Polyethylene Glycols/chemistry , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Survival Rate , Virus Internalization/drug effects
15.
Front Immunol ; 12: 744696, 2021.
Article in English | MEDLINE | ID: covidwho-1485054

ABSTRACT

Background: Little is known about the mortality of hospital-acquired (nosocomial) COVID-19 infection globally. We investigated the risk of mortality and critical care admission in hospitalised adults with nosocomial COVID-19, relative to adults requiring hospitalisation due to community-acquired infection. Methods: We systematically reviewed the peer-reviewed and pre-print literature from 1/1/2020 to 9/2/2021 without language restriction for studies reporting outcomes of nosocomial and community-acquired COVID-19. We performed a random effects meta-analysis (MA) to estimate the 1) relative risk of death and 2) critical care admission, stratifying studies by patient cohort characteristics and nosocomial case definition. Results: 21 studies were included in the primary MA, describing 8,251 admissions across 8 countries during the first wave, comprising 1513 probable or definite nosocomial COVID-19, and 6738 community-acquired cases. Across all studies, the risk of mortality was 1.3 times greater in patients with nosocomial infection, compared to community-acquired (95% CI: 1.005 to 1.683). Rates of critical care admission were similar between groups (Relative Risk, RR=0.74, 95% CI: 0.50 to 1.08). Immunosuppressed patients diagnosed with nosocomial COVID-19 were twice as likely to die in hospital as those admitted with community-acquired infection (RR=2.14, 95% CI: 1.76 to 2.61). Conclusions: Adults who acquire SARS-CoV-2 whilst already hospitalised are at greater risk of mortality compared to patients admitted following community-acquired infection; this finding is largely driven by a substantially increased risk of death in individuals with malignancy or who had undergone transplantation. These findings inform public health and infection control policy and argue for individualised clinical interventions to combat the threat of nosocomial COVID-19, particularly for immunosuppressed groups. Systematic Review Registration: PROSPERO CRD42021249023.


Subject(s)
COVID-19/immunology , COVID-19/mortality , Hospitalization , Immunocompromised Host , Inpatients , SARS-CoV-2 , Adult , COVID-19/therapy , Disease-Free Survival , Humans , Risk Factors , Survival Rate
16.
PLoS One ; 16(10): e0258684, 2021.
Article in English | MEDLINE | ID: covidwho-1480452

ABSTRACT

AIMS: Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity. METHODS AND RESULTS: We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59-0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43-0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators. CONCLUSION: These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.


Subject(s)
Angiotensin Receptor Antagonists/administration & dosage , COVID-19 , Hypertension , Registries , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Biomarkers/blood , COVID-19/blood , COVID-19/drug therapy , COVID-19/mortality , Comorbidity , Disease-Free Survival , Female , Humans , Hypertension/blood , Hypertension/drug therapy , Hypertension/mortality , Inflammation/blood , Inflammation/drug therapy , Inflammation/mortality , Male , Middle Aged , Severity of Illness Index , Survival Rate
17.
Biomark Med ; 15(16): 1509-1517, 2021 11.
Article in English | MEDLINE | ID: covidwho-1477715

ABSTRACT

Background: The contribution of endothelial injury in the pathogenesis of COVID-19-associated acute respiratory distress syndrome (ARDS) and resulting respiratory failure remains unclear. Plasma endostatin, an endogenous inhibitor of angiogenesis and endothelial dysfunction is upregulated during hypoxia, inflammation and progress of pulmonary disease. Aim: To investigate if plasma endostatin is associated to hypoxia, inflammation and 30-day mortality in patients with severe COVID-19 infection. Method: Samples for blood analysis and plasma endostatin quantification were collected from adult patients with ongoing COVID-19 (n = 109) on admission to intensive care unit (day 1). Demographic characteristics and 30-day mortality data were extracted from medical records. The ability of endostatin to predict mortality was analyzed using receiving operating characteristics and Kaplan-Meier analysis with a cutoff at 46.2 ng/ml was used to analyze the association to survival. Results: Plasma endostatin levels correlated with; PaO2/FiO2 (r = -0.3, p < 0.001), arterial oxygen tension (r = -0.2, p = 0.01), lactate (r = 0.2, p = 0.04), C-reactive protein (r = 0.2, p = 0.04), ferritin (r = 0.2, p = 0.09), D-dimer (r = 0.2, p = 0.08) and IL-6 (r = 0.4, p < 0.001). Nonsurvivors at 30 days had higher plasma endostatin levels than survivors (72 ± 26 vs 56 ± 16 ng/ml, p = 0.01). Receiving operating characteristic curve (area under the curve 0.7) showed that plasma endostatin >46.2 ng/ml predicts mortality with a sensitivity of 92% and specificity of 71%. In patients with plasma endostatin >46.2 ng/ml probability of survival was lower (p = 0.02) in comparison to those with endostatin <46.2 ng/ml. Conclusion: Our results suggest that plasma endostatin is an early biomarker for disease severity in COVID-19.


Subject(s)
COVID-19 , Endostatins/blood , Hypoxia , Respiratory Distress Syndrome , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/mortality , Disease-Free Survival , Female , Humans , Hypoxia/blood , Hypoxia/mortality , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/mortality , Survival Rate
18.
Crit Care ; 25(1): 363, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1477449

ABSTRACT

BACKGROUND: Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The role of zinc in critically ill patients with COVID-19 remains unclear. This study aims to evaluate the efficacy and safety of zinc sulfate as adjunctive therapy in critically ill patients with COVID-19. METHODS: Patients aged ≥ 18 years with COVID-19 who were admitted to the intensive care unit (ICU) in two tertiary hospitals in Saudi Arabia were retrospectively assessed for zinc use from March 1, 2020 until March 31, 2021. After propensity score matching (1:1 ratio) based on the selected criteria, we assessed the association of zinc used as adjunctive therapy with the 30-day mortality. Secondary outcomes included the in-hospital mortality, ventilator free days, ICU length of stay (LOS), hospital LOS, and complication (s) during ICU stay. RESULTS: A total of 164 patients were included, 82 patients received zinc. Patients who received zinc sulfate as adjunctive therapy have a lower 30-day mortality (HR 0.52, CI 0.29, 0.92; p = 0.03). On the other hand, the in-hospital mortality was not statistically significant between the two groups (HR 0.64, CI 0.37-1.10; p = 0.11). Zinc sulfate use was associated with a lower odds of acute kidney injury development during ICU stay (OR 0.46 CI 0.19-1.06; p = 0.07); however, it did not reach statistical significance. CONCLUSION: The use of zinc sulfate as an additional treatment in critically ill COVID-19 patients may improve survival. Furthermore, zinc supplementation may have a protective effect on the kidneys.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Critical Illness/therapy , Neoadjuvant Therapy/methods , Zinc Sulfate/therapeutic use , Aged , Female , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Saudi Arabia , Survival Rate
19.
Int J Hematol ; 114(6): 709-718, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1474138

ABSTRACT

Polymerase chain reaction (PCR) tests cannot always detect the SARS-CoV-2 virus, possibly due to differences in sensitivity between sample types. Under these circumstances, immunochromatography may serve as an alternative method to detect anti-SARS-CoV-2 IgG antibodies that indicate a history of infection. In our analysis of patients with severe COVID-19 infection, we found that 14 of 19 serum samples were positive for IgG antibodies, whereas 6 of 10 samples from patients with asymptomatic or mild cases were negative. Two patients with immune thrombocytopenia who were treated with prednisolone experienced aggressive COVID-19-related respiratory failure and eventually died. Patients not in remission and those who received steroid-based chemotherapy had a higher risk of death, and patients with lymphoid malignancies including lymphoma and myeloma died in larger numbers than those with myeloid malignancies. A stricter cohorting strategy based on repeat PCR tests or isolation to a private room should be adopted in routine care in hematology departments to prevent viral spread to the environment.


Subject(s)
COVID-19 , Cross Infection/prevention & control , Hematologic Diseases/therapy , Antibodies, Viral/blood , Biomarkers/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , COVID-19/prevention & control , Female , Hematologic Diseases/complications , Hematologic Diseases/mortality , Humans , Immunoassay/methods , Immunoglobulin G/blood , Infection Control/methods , Japan , Male , Patient Isolation , Polymerase Chain Reaction , Risk , SARS-CoV-2/immunology , Severity of Illness Index , Survival Rate
20.
JCI Insight ; 6(18)2021 09 22.
Article in English | MEDLINE | ID: covidwho-1467778

ABSTRACT

The importance of the adaptive T cell response in the control and resolution of viral infection has been well established. However, the nature of T cell-mediated viral control mechanisms in life-threatening stages of COVID-19 has yet to be determined. The aim of the present study was to determine the function and phenotype of T cell populations associated with survival or death of patients with COVID-19 in intensive care as a result of phenotypic and functional profiling by mass cytometry. Increased frequencies of circulating, polyfunctional CD4+CXCR5+HLA-DR+ stem cell memory T cells (Tscms) and decreased proportions of granzyme B-expressing and perforin-expressing effector memory T cells were detected in recovered and deceased patients, respectively. The higher abundance of polyfunctional PD-L1+CXCR3+CD8+ effector T cells (Teffs), CXCR5+HLA-DR+ Tscms, and anti-nucleocapsid (anti-NC) cytokine-producing T cells permitted us to differentiate between recovered and deceased patients. The results from a principal component analysis show an imbalance in the T cell compartment that allowed for the separation of recovered and deceased patients. The paucity of circulating PD-L1+CXCR3+CD8+ Teffs and NC-specific CD8+ T cells accurately forecasts fatal disease outcome. This study provides insight into the nature of the T cell populations involved in the control of COVID-19 and therefore might impact T cell-based vaccine designs for this infectious disease.


Subject(s)
B7-H1 Antigen/immunology , CD4-Positive T-Lymphocytes/immunology , CD8 Antigens/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunity, Cellular , Receptors, CXCR3/immunology , Adult , COVID-19/mortality , COVID-19/pathology , Epitopes, T-Lymphocyte/immunology , Female , France/epidemiology , Humans , Immunologic Memory , Lymphocyte Activation , Male , SARS-CoV-2 , Survival Rate/trends
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