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1.
BMC Pulm Med ; 22(1): 121, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1822183

ABSTRACT

BACKGROUND: The respiratory rate-oxygenation (ROX) index has been increasingly applied to predict the outcome of high-flow nasal cannula (HFNC) in pneumonia patients with acute hypoxemic respiratory failure (AHRF). However, its diagnostic accuracy for the HFNC outcome has not yet been systematically assessed. This meta-analysis sought to evaluate the predictive performance of the ROC index for the successful weaning from HFNC in pneumonia patients with AHRF. METHODS: A literature search was conducted on electronic databases through February 12, 2022, to retrieve studies that investigated the diagnostic accuracy of the ROC index for the outcome of HFNC application in pneumonia patients with AHRF. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy due to the varied cutoff values of the index. We observed the distribution of the cutoff values and estimated the optimal threshold with corresponding 95% confidential interval (CI). RESULTS: Thirteen observational studies comprising 1751 patients were included, of whom 1003 (57.3%) successfully weaned from HFNC. The ROC index exhibits good performance for predicting the successful weaning from HFNC in pneumonia patients with AHRF, with an AUHSROC of 0.81 (95% CI 0.77-0.84), a pooled sensitivity of 0.71 (95% CI 0.64-0.78), and a pooled specificity of 0.78 (95% CI 0.70-0.84). The cutoff values of the ROX index were nearly conically symmetrically distributed; most data were centered between 4.5 and 6.0, and the mean and median values were 4.8 (95% CI 4.2-5.4) and 5.3 (95% CI 4.2-5.5), respectively. Moreover, the AUHSROC in the subgroup of measurement within 6 h after commencing HFNC was comparable to that in the subgroup of measurement during 6-12 h. The stratified analyses also suggested that the ROC index was a reliable predictor of HFNC success in pneumonia patients with coronavirus disease 2019. CONCLUSIONS: In pneumonia patients with AHRF, the ROX index measured within 12 h after HFNC initiation is a good predictor of successful weaning from HFNC. The range of 4.2-5.4 may represent the optimal confidence interval for the prediction of HFNC outcome.


Subject(s)
COVID-19 , Pneumonia , Respiratory Insufficiency , Cannula , Humans , Pneumonia/complications , Pneumonia/diagnosis , Pneumonia/therapy , Respiratory Insufficiency/therapy , Respiratory Rate
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324206

ABSTRACT

COVID -19 has rapidly spread from Wuhan to worldwide, and now has become a global health concern. Hypertension is the most common chronic illness in COVID-19, while the influence on those patients have not been well described. In this retrospective study, 82 confirmed patients with COVID-19 were enrolled, with epidemiological, demographic, clinical, laboratory, radiological, and therapies data analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. Of all 82 patients with COVID-19, the median age of all patients was 60.5 years, including 49 females (59.8%) and 33 (40.2%) males. Hypertension (31[28.2%]) was the most chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). Common symptoms included fatigue (55[67.1%]), dry cough (46 [56.1%]) and fever (≥37.3℃ (46 [56.1%]). The median time from illness onset to positive outcomes of RT-PCR analysis were 13.0 days, ranging from 3-25 days. In hypertension group, 6 (20.7%) patients died compared to 5 (9.4%) died in non-hypertension group. More hypertension patients with COVID-19 (8 [27.6%]) had at least one coexisting disease than those of non-hypertension patients (2 [3.8%]) ( P =0.002). Compared with non-hypertension patients, higher levels of neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP were observed in hypertension group, whereas levels of lymphocyte count and eGFR were decreased. Dynamic observations displayed more significant and worsened outcomes in hypertension group after hospital admission. COVID-19 patients with hypertension take more risks of severe inflammatory reactions, worsened internal organ injuries, and deteriorated progress.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323745

ABSTRACT

Background: COVID-19 cases with suspected returned-positive SRAS-CoV-2 tests following consecutive negative tests have been reported, but evidence-based explanations for this phenomenon is still lacking. We aimed to describe the clinical and laboratory characteristics of returned-positive COVID-19 patients during treatment in comparison with other patients. Methods: : From January 20 to April 10, 2020, all COVID-19 inpatient with at least three RT-PCR SARS-CoV-2 tests in Renmin Hospital in Wuhan, China were enrolled. Patients with 2 consecutively negative RT-PCR results followed by a positive result were classified as returned-positive patients, and their characteristics and repeatedly measured laboratory results were compared with the rest of the patients. Linear mixed effects models were performed. Results: A total of 789 COVID-19 patients were included and 22.8% patients returned positive in RT-PCR SARS-CoV-2 test. No significant differences were found for general characteristics between the returned-positive and the control groups. The trends of inflammatory and immune factors including the third component of complement (C3), C-reactive protein, procalcitonin (PCT), IL-4, IL-6, the counts of lymphocyte, CD3+, CD8+, white blood cell and immunoglobulin levels during hospitalization were significantly different between the two groups. During the returned-positive period, C3, PCT, serum IgM, anti-SARS-CoV-2 IgM and anti-SARS-CoV-2 IgG were significantly higher in the returned-positive patients at certain time points. Conclusions: : Returned-positive COVID-19 patients appeared to be more sever at admission, and had periodically higher levels in C3, PCT, serum IgM and two specific antibodies during hospitalization. This suggests that positive return of SARS-COV-2 could not be completely explained by false-negative testing and longer observation of these patients is warranted.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312742

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular features, which may be deteriorated in cancer patients.Methods: We retrospectively assessed 1,244 COVID-19 patients from February 1st to August 31st (140 cancer and 1104 non-cancer patients). Clinical data and laboratory findings were obtained and compared between cancer and non-cancer groups. Risk factors for in-hospital mortality were identified by multivariable COX regression models.Findings: The median age of cancer group was older than that in non-cancer patients [61 (57-67) vs. 56 (40-68), p < 0.001]. For cancer group, 56% were in severe and critical status, while the proportion was 10% for non-cancer group. Cancer patients had increased levels of leukocyte, neutrophil count and BUN (all p < 0.01), while lymphocyte count was significantly lower (p < 0.001). The most common solid tumor types were gastrointestinal cancer (26%), lung cancer (21%), breast and reproductive cancer (both 19%). There is a rising for cardiac biomarkers, including Pro-BNP, cTnI, MYO, CK-MB, and D-Dimer in COVID-19 cancer population, especially in deceased cancer subjects. The 30-day in hospital mortality in cancer group was dramatically raised than that in non-cancer group (12.9% vs. 4.0%, p<0.01). In multivariable COX regression models, fever, disease severity status, underlying diseases were risk factors for mortality. The Pro-BNP and D-Dimer levels were significantly increased in cancer subjects with cardiovascular disease.Interpretation: COVID-19 cancer patients relate to deteriorating conditions, increased risk of admission to intensive care units and in-hospital mortality. They display severely impaired myocardium, damaged heart function and imbalanced homeostasis of coagulation, which warrants more aggressive treatment. Funding: The current work was supported by the National Natural Science Foundation Project of China (Grant No. 81670304) and the Fundamental Research Funds for the Central Universities of China (NO.2042019kf0058).Declaration of Interests: All authors report no relationship or conflict of interest to disclose.Ethics Approval Statement: This study was approved by the National Health Commission of China and the institutional review board at Renmin Hospital of Wuhan University (Wuhan, China).

5.
BMC Med ; 20(1): 13, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1639199

ABSTRACT

BACKGROUND: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia. METHODS: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule). RESULTS: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase. CONCLUSION: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov , number NCT03944109.


Subject(s)
Hypercholesterolemia , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hypercholesterolemia/drug therapy , Treatment Outcome
6.
Chem Biol Interact ; 353: 109796, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1611644

ABSTRACT

Coronavirus disease 2019 (COVID-19) was declared a serious global public health emergency. Hospitalization and mortality rates of lung cancer patients diagnosed with COVID-19 are higher than those of patients presenting with other cancers. However, the reasons for the outcomes being disproportionately severe in lung adenocarcinoma (LUAD) patients with COVID-19 remain elusive. The present study aimed to identify the possible causes for disproportionately severe COVID-19 outcomes in LUAD patients and determine a therapeutic target for COVID-19 patients with LUAD. We used publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and various bioinformatics tools to identify and analyze the genes implicated in SARS-CoV-2 infection in LUAD patients. Upregulation of the SARS-CoV-2 infection-related molecules dipeptidyl peptidase 4, basigin, cathepsin B (CTSB), methylenetetrahydrofolate dehydrogenase, and peptidylprolyl isomerase B rather than angiotensin-converting enzyme 2 may explain the relatively high susceptibility of LUAD patients to SARS-CoV-2 infection. CTSB was highly expressed in the LUAD tissues after SARS-CoV-2 infection, and its expression was positively correlated with immune cell infiltration and proinflammatory cytokine expression. These findings suggest that CTSB plays a vital role in the hyperinflammatory response in COVID-19 patients with LUAD and is a promising target for the development of a novel drug therapy for COVID-19 patients.


Subject(s)
Adenocarcinoma of Lung/virology , COVID-19/genetics , Cathepsin B/genetics , Lung Neoplasms/virology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/mortality , Angiotensin-Converting Enzyme 2/genetics , Animals , Basigin/genetics , CD8-Positive T-Lymphocytes/virology , COVID-19/immunology , COVID-19/mortality , Cricetinae , Cyclophilins/genetics , Cytokines/blood , Dipeptidyl Peptidase 4/genetics , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Minor Histocompatibility Antigens/genetics , Molecular Targeted Therapy , Prognosis , Protein Interaction Maps/genetics , Up-Regulation
7.
Front Cardiovasc Med ; 8: 738044, 2021.
Article in English | MEDLINE | ID: covidwho-1497031

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has outbroken in China and subsequently spread worldwide since the end of 2019. Chest computed tomography (CT) plays an important role in the diagnosis of lung diseases, but its value in the diagnosis of cardiac injury remains unknown. Methods: We enrolled 241 consecutive hospitalized patients (aged 61 ± 16 years, 115 males) with laboratory-confirmed COVID-19 at Renmin Hospital of Wuhan University from January 11 to March 2, 2020. They were divided into two groups according to whether major adverse cardiovascular events (MACEs) occurred during the follow-up. The anteroposterior diameter of the left atrium (LAD), the length of the left ventricle (LV), and cardiothoracic ratio (CTR) were measured. The values of myocardial CT were also recorded. Results: Of 241 patients, 115 patients (47.7%) had adverse cardiovascular events. Compared with no MACEs, patients with MACEs were more likely to have bilateral lesions (95.7% vs. 86.5%, p = 0.01). In multivariable analysis, bronchial wall thickening would increase the odds of MACEs by 13.42 (p = 0.01). LAD + LV and CTR was the best predictor for MACEs (area under the curve = 0.88, p < 0.001) with a sensitivity of 82.6% and a specificity of 80.2%. Plasma high-sensitivity troponin I levels in patients with cardiac injury showed a moderate negative correlation with minimum CT value (R 2 = -0.636, p < 0.001). Conclusions: Non-contrast chest CT can be a useful modality for detection cardiac injury and provide additional value to predict MACEs in COVID-19 patients.

8.
Clin Infect Dis ; 73(2): 328-331, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1315667

ABSTRACT

To explore any relationship between the ABO blood group and the coronavirus disease 2019 (COVID-19) susceptibility, we compared ABO blood group distributions in 2173 COVID-19 patients with local control populations, and found that blood group A was associated with an increased risk of infection, whereas group O was associated with a decreased risk.


Subject(s)
ABO Blood-Group System , COVID-19 , Disease Susceptibility , Humans , Retrospective Studies , SARS-CoV-2
9.
Immun Inflamm Dis ; 9(4): 1358-1369, 2021 12.
Article in English | MEDLINE | ID: covidwho-1303261

ABSTRACT

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has emerged as an international pandemic. COVID-19 patients with myocardial injury might need special attention. However, an understanding on this aspect remains unclear. This study aimed to illustrate clinical characteristics and the prognostic value of myocardial injury to COVID-19 patients. METHODS: This retrospective, single-center study finally included 304 hospitalized COVID-19 cases confirmed by real-time reverse-transcriptase polymerase chain reaction from January 11 to March 25, 2020. Myocardial injury was determined by serum high-sensitivity troponin I (Hs-TnI). The primary endpoint was COVID-19-associated mortality. RESULTS: Of 304 COVID-19 patients (median age, 65 years; 52.6% males), 88 patients (27.3%) died (61 patients with myocardial injury, 27 patients without myocardial injury on admission). COVID-19 patients with myocardial injury had more comorbidities (hypertension, chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease); lower lymphocyte counts, higher C-reactive protein (CRP; median, 84.9 vs. 28.5 mg/L; p < .001), procalcitonin levels (median, 0.29 vs. 0.06 ng/ml; p < .001), inflammatory and immune response markers; more frequent need for noninvasive ventilation, invasive mechanical ventilation; and was associated with higher mortality incidence (hazard ratio [HR] = 7.02; 95% confidence interval [CI], 4.45-11.08; p < .001) than those without myocardial injury. Myocardial injury (HR = 4.55; 95% CI, 2.49-8.31; p < .001), senior age, CRP levels, and novel coronavirus pneumonia types on admission were independent predictors to mortality in COVID-19 patients. CONCLUSIONS: COVID-19 patients with myocardial injury on admission is associated with more severe clinical presentation and biomarkers. Myocardial injury and higher Hs-TnI are both strongest independent predictors to COVID-19-related mortality after adjusting confounding factors.


Subject(s)
COVID-19 , Aged , Female , Humans , Male , Pandemics , Prognosis , Retrospective Studies , SARS-CoV-2
10.
J Appl Physiol (1985) ; 131(3): 966-976, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1301730

ABSTRACT

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features, which may be deteriorated in patients with cancer. However, cardiac outcomes of cancer patients with COVID-19 have not been closely examined. We retrospectively assessed 1,244 patients with COVID-19 from February 1 to August 31, 2020 (140 cancer and 1,104 noncancer patients). Demographic and clinical data were obtained and compared between cancer and noncancer groups. Including the cardiac biomarkers, we also analyzed laboratory findings between these two groups. Risk factors for in-hospital mortality were identified by multivariable Cox regression models. For cancer group, 56% were in severe and critical status with more diabetes and immune deficiency, whereas the proportion was 10% for noncancer group. Patients with cancer had increased levels of leukocyte, neutrophil count, and blood urea nitrogen (BUN) (all P < 0.01), whereas lymphocyte count was significantly lower (P < 0.001). The most common solid tumor types were gastrointestinal cancer (26%), lung cancer (21%), and breast and reproductive cancer (both 19%). There is a rising for cardiac biomarkers, including pro-B-type natriuretic peptide (Pro-BNP), sensitive troponin I (cTnI), myoglobin (MYO), creatine kinase-MB (CK-MB), as well as D-Dimer in COVID-19 cancer population, especially in deceased subjects with cancer. The 30-day in-hospital mortality in cancer group was dramatically raised than that in noncancer group (12.9% vs. 4.0%, P < 0.01). In multivariable Cox regression models, fever, disease severity status, and underlying diseases were risk factors for mortality. COVID-19 patients with cancer relate to deteriorating conditions and poor cardiac outcomes accompanied by a high in-hospital mortality, which warrants more aggressive treatment.NEW & NOTEWORTHY Our study indicates that the 30-day mortality is higher in COVID-19 patients with cancer; more COVID-19 patients with cancer are in severe and critical status; age, respiratory rate, neutrophil count, AST, BUN, MYO, Pro-BNP, disease severity status, underlying diseases, and fever are risk factors for in-hospital mortality among COVID-19 cancer cases; COVID-19 patients with cancer display severely impaired myocardium, damaged heart function, and imbalanced homeostasis of coagulation; what is more, those with both cancer and CVD have more significantly increased Pro-BNP and D-Dimer level.


Subject(s)
COVID-19 , Neoplasms , Humans , Retrospective Studies , Risk Factors , SARS-CoV-2
11.
Circ Cardiovasc Qual Outcomes ; 14(5): e007098, 2021 05.
Article in English | MEDLINE | ID: covidwho-1232381

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted clinical care worldwide. Evidence of how this health crisis affected common conditions like blood pressure (BP) control is uncertain. METHODS: We used longitudinal BP data from an ongoing randomized clinical trial to examine variations in home BP monitored via a smartphone-based application (app) in a total of 7394 elderly patients with hypertension aged 60 to 80 years stratified by their location in Wuhan (n=283) compared with other provinces of China (n=7111). Change in morning systolic BP (SBP) was analyzed for 5 30-day phases during the pandemic, including preepidemic (October 21 to November 20, 2019), incubation (November 21 to December 20, 2019), developing (December 21, 2019 to January 20, 2020), outbreak (January 21 to February 20, 2020), and plateau (February 21 to March 21, 2020). RESULTS: Compared with non-Wuhan areas of China, average morning SBP (adjusted for age, sex, body mass index) in Wuhan patients was significantly higher during the epidemic growth phases, which returned to normal at the plateau. Between-group differences in ΔSBP were +2.5, +3.0, and +2.1 mm Hg at the incubation, developing, and outbreak phases of COVID-19 (P<0.001), respectively. Sensitivity analysis showed a similar trend in trajectory pattern of SBP in both the intensive and standard BP control groups of the trial. Patients in Wuhan also had an increased regimen change in antihypertensive drugs during the outbreak compared with non-Wuhan patients. Expectedly, Wuhan patients were more likely to check their BP via the app, while doctors were less likely to monitor the app for BP control during the pandemic. CONCLUSIONS: Our data demonstrate that the COVID-19 pandemic was associated with a short-term increase in morning SBP among elderly patients with hypertension in Wuhan but not other parts of China. Further study will be needed to understand if these findings extended to other parts of the world substantially affected by the virus. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03015311.


Subject(s)
Blood Pressure Determination , COVID-19/epidemiology , Hypertension/diagnosis , Hypertension/physiopathology , Smartphone , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , China , Female , Humans , Hypertension/therapy , Longitudinal Studies , Male , Middle Aged , Self Care
12.
Sci Rep ; 11(1): 3779, 2021 02 12.
Article in English | MEDLINE | ID: covidwho-1084610

ABSTRACT

In less than 6 months, COVID-19 spread rapidly around the world and became a global health concern. Hypertension is the most common chronic disease in COVID-19 patients, but its impact on these patients has not been well described. In this retrospective study, 82 patients diagnosed with COVID-19 were enrolled, and epidemiological, demographic, clinical, laboratory, radiological and therapy-related data were analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. The median age of the included patients was 60.5 years, and the cohort included 49 women (59.8%) and 33 (40.2%) men. Hypertension (31 [28.2%]) was the most common chronic illness, followed by diabetes (16 [19.5%]) and cardiovascular disease (15 [18.3%]). The most common symptoms were fatigue (55 [67.1%]), dry cough (46 [56.1%]) and fever ≥ 37.3 °C (46 [56.1%]). The median time from illness onset to positive RT-PCR test was 13.0 days (range 3-25 days). There were 6 deaths (20.7%) in the hypertension group and 5 deaths (9.4%) in the nonhypertension group, and more hypertensive patients with COVID-19 (8 [27.6%]) than nonhypertensive patients (2 [3.8%]) (P = 0.002) had at least one comorbid disease. Compared with nonhypertensive patients, hypertensive patients exhibited higher neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP and lower lymphocyte counts and eGFR. Dynamic observations indicated more severe disease and poorer outcomes after hospital admission in the hypertension group. COVID-19 patients with hypertension have increased risks of severe inflammatory reactions, serious internal organ injury, and disease progression and deterioration.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Hypertension/epidemiology , Multiple Organ Failure/epidemiology , Aged , Comorbidity , Female , Humans , Male , Middle Aged , Treatment Outcome
13.
Clin Transl Med ; 11(2): e297, 2021 02.
Article in English | MEDLINE | ID: covidwho-1049592

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID-19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID-19, especially for severe and critical patients. Menstrual blood-derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty-four patients were enrolled from January to April 2020 in a multicenter, open-label, nonrandomized, parallel-controlled exploratory trial. Twenty-six patients received allogeneic, menstrual blood-derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 107 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1-month period following MSC infusion. Safety was measured using the frequency of treatment-related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC-based therapy may serve as a promising alternative method for treating severe and critical COVID-19.


Subject(s)
COVID-19/therapy , Menstruation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , SARS-CoV-2/metabolism , Adolescent , Adult , Aged , Allografts , COVID-19/blood , COVID-19/mortality , Critical Illness , Disease-Free Survival , Female , Humans , Male , Middle Aged , Severity of Illness Index , Survival Rate
14.
Artif Organs ; 45(7): 762-769, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-978684

ABSTRACT

Our aim was to investigate the effect of artificial liver blood purification treatment on the survival of severe/critical patients with coronavirus disease 2019 (COVID-19). A total of 101 severe and critical patients with coronavirus SARS-CoV-2 infection were enrolled in this open, case-control, multicenter, prospective study. According to the patients' and their families' willingness, they were divided into two groups. One was named the treatment group, in which the patients received artificial liver therapy plus comprehensive treatment (n = 50), while the other was named the control group, in which the patients received only comprehensive treatment (n = 51). Clinical data and laboratory examinations, as well as the 28-day mortality rate, were collected and analyzed. Baseline data comparisons on average age, sex, pre-treatment morbidity, initial symptoms, vital signs, pneumonia severity index score, blood routine examination and biochemistry indices etc. showed no difference between the two groups. Cytokine storm was detected, with a significant increase of serum interleukin-6 (IL-6) level. The serum IL-6 level decreased from 119.94 to 20.49 pg/mL in the treatment group and increased from 40.42 to 50.81 pg/mL in the control group (P < .05), indicating that artificial liver therapy significantly decreased serum IL-6. The median duration of viral nucleic acid persistence was 19 days in the treatment group (ranging from 6 to 67 days) and 17 days in the control group (ranging from 3 to 68 days), no significant difference was observed (P = .36). As of 28-day follow-up,17 patients in the treatment group experienced a median weaning time of 24 days, while 11 patients in the control group experienced a median weaning time of 35 days, with no significant difference between the two groups (P = .33). The 28-day mortality rates were 16% (8/50) in the treatment group and 50.98% (26/51) in the control group, with a significant difference (z = 3.70, P < .001). Cytokine storm is a key factor in the intensification of COVID-19 pneumonia. The artificial liver therapy blocks the cytokine storm by clearing inflammatory mediators, thus preventing severe cases from progressing to critically ill stages and markedly reducing short-term mortality.


Subject(s)
COVID-19/therapy , Cytokine Release Syndrome/prevention & control , Liver, Artificial , Plasma Exchange/instrumentation , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , COVID-19/virology , Case-Control Studies , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Cytokines/blood , Female , Hospital Mortality , Host-Pathogen Interactions , Humans , Male , Middle Aged , Plasma Exchange/adverse effects , Plasma Exchange/mortality , Prospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness Index , Time Factors , Treatment Outcome , Viral Load
15.
Crit Care Explor ; 2(10): e0263, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-900573

ABSTRACT

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 infections commonly lead to respiratory failure and potentially fatal systemic inflammation and organ failure. Nebulized DAS181, a host-directed biologics with sialidase activity, is an investigational drug with antiviral activities on parainfluenza and influenza under phase 3 and phase 2 development. The objective of this study (NCT04324489) is to investigate the safety and effects of nebulized DAS181 on hypoxic coronavirus disease 2019 patients. DESIGN: Single-center, prospective, open-label, compassionate use. SETTING: Renmin Hospital of Wuhan University, Department of Respiratory and Critical Care Medicine and Department of Infectious Diseases. SUBJECTS: Patients 18 to 70 years old who met Chinese criteria for severe coronavirus disease 2019 pneumonia and required supplemental oxygen but not on mechanical ventilator at screening. INTERVENTIONS: Nebulized DAS181 (4.5 mg) twice a day for 10 days. MEASUREMENTS AND MAIN RESULTS: Three male coronavirus disease 2019 hypoxic patients with bilateral lung involvement completed DAS181 treatment for 10 days. By day 14, all achieved return to room air (primary endpoint) and their nasopharyngeal swabs were negative for severe acute respiratory syndrome coronavirus 2. Clinical severity improved from severe coronavirus disease 2019 at baseline to moderate or mild disease by day 5, consistent with rapid reduction of inflammatory cytokines by days 2-3 and radiologic improvement by days 5-10. No DAS181-related adverse events were reported. CONCLUSIONS: Inhalation of DAS181 was well tolerated and potential clinical benefit of DAS181 on hypoxic coronavirus disease 2019 is the reduction of supplemental oxygen need. Efficacy and safety, including pharmacokinetics and viral studies of DAS181 in severe, hypoxic coronavirus disease 2019, should be examined by a double-blind, randomized controlled study.

16.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-932

ABSTRACT

Background: Since December, 2019, the outbreak of COVID-19, epidemiological and clinical characteristics of patients with COVID-19 have been reported to be a fe

18.
Front Med ; 14(5): 664-673, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-696783

ABSTRACT

The Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was identified in December 2019. The symptoms include fever, cough, dyspnea, early symptom of sputum, and acute respiratory distress syndrome (ARDS). Mesenchymal stem cell (MSC) therapy is the immediate treatment used for patients with severe cases of COVID-19. Herein, we describe two confirmed cases of COVID-19 in Wuhan to explore the role of MSC in the treatment of COVID-19. MSC transplantation increases the immune indicators (including CD4 and lymphocytes) and decreases the inflammation indicators (interleukin-6 and C-reactive protein). High-flow nasal cannula can be used as an initial support strategy for patients with ARDS. With MSC transplantation, the fraction of inspired O2 (FiO2) of the two patients gradually decreased while the oxygen saturation (SaO2) and partial pressure of oxygen (PO2) improved. Additionally, the patients' chest computed tomography showed that bilateral lung exudate lesions were adsorbed after MSC infusion. Results indicated that MSC transplantation provides clinical data on the treatment of COVID-19 and may serve as an alternative method for treating COVID-19, particularly in patients with ARDS.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections , Critical Care/methods , Mesenchymal Stem Cell Transplantation/methods , Pandemics , Pneumonia, Viral , Adult , Aged , Blood Cells/physiology , Blood Coagulation Tests/methods , COVID-19 , COVID-19 Testing , China , Clinical Laboratory Techniques/methods , Combined Modality Therapy , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Humans , Male , Monitoring, Immunologic/methods , Oximetry/methods , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Preliminary Data , SARS-CoV-2 , Severity of Illness Index , Symptom Assessment/methods , Treatment Outcome
19.
Front Mol Biosci ; 7: 157, 2020.
Article in English | MEDLINE | ID: covidwho-689155

ABSTRACT

Introduction: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients at a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared between severe and non-severe patients. Immune response phenotyping based on the late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratified patients into different disease severities and outcomes. Results: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those with low IgG levels (51.8 vs. 32.3%; p = 0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype were 72.3, 48.5, 33.3, and 15.6%, respectively (p < 0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher inflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p < 0.05). Recovery rates for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype were 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p = 0.0592). Dead cases only occurred in NLRhiIgGhi and NLRhiIgGlo phenotypes. Conclusions: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on the late IgG response and NLR could act as a simple complementary tool to discriminate between severe and non-severe COVID-19 patients, and further predict their clinical outcome.

20.
PLoS One ; 15(7): e0235458, 2020.
Article in English | MEDLINE | ID: covidwho-638588

ABSTRACT

A recently developed pneumonia caused by SARS-CoV-2 bursting in Wuhan, China, has quickly spread across the world. We report the clinical characteristics of 82 cases of death from COVID-19 in a single center. Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. All patients were local residents of Wuhan, and a large proportion of them were diagnosed with severe illness when admitted. Due to the overwhelming of our system, a total of 14 patients (17.1%) were treated in the ICU, 83% of deaths never received Critical Care Support, only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. Most of the patients who died were male (65.9%). More than half of the patients who died were older than 60 years (80.5%), and the median age was 72.5 years. The bulk of the patients who died had comorbidities (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), followed by sepsis/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhagic, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), and increased C-reactive protein (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%) levels. A high level of IL-6 (>10 pg/ml) was observed in all detected patients. The median time from initial symptoms to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p = 0.002), alanine aminotransferase (p = 0.037) and time from initial symptoms to death was remarkably observed. Older males with comorbidities are more likely to develop severe disease and even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but the virus itself and cytokine release syndrome-mediated damage to other organs, including cardiac, renal, hepatic, and hemorrhagic damage, should be taken seriously as well.


Subject(s)
Coronavirus Infections/mortality , Coronavirus Infections/pathology , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Adult , Age Factors , Aged , Betacoronavirus , COVID-19 , Cause of Death , China/epidemiology , Comorbidity , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Respiratory Insufficiency/pathology , Retrospective Studies , SARS-CoV-2
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