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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323626

ABSTRACT

Background: Coronavirus disease 2019(COVID-19) is a worldwide pandemic.In this study, we aimed to evaluate the risk factors of death from severe and critical COVID-19 patients. Method: A retrospective study of patients diagnosed with severe and critical COVID-19 from four hospitals in Wuhan, China, describing the clinical characteristics and laboratory results, and using Cox regression to study the risk factors was conducted. Results: Four hundred and forty-six patients with COVID-19 showed a high case fatality rate(CFR)(20.2%). All patients required oxygen therapy, and 52(12%) patients required invasive mechanical ventilation,of which 50(96%) patients died.The univariate Cox proportional hazard model showed a white blood cell count of more than 10 × 10⁹/L(HR3.903,95%CI 2.413 to 6.313),patients’ risk of death significantly increased.The multivariate Cox proportional hazard model demonstrated that older age (HR 1.074, 95% CI 1.050 to 1.098) was an independent risk factor and high white blood cell count(HR 1.119, 95% CI 1.056 to 1.186)was a predictive factor for COVID-19 on admission. Conclusions: COVID-19 is a new disease entity that carries significant risk of morbidity and CFR.Older age was an independent risk factor and high white blood cell was a predictive factor for COVID-19.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315786

ABSTRACT

Objectives: Since December 2019, a outbreak of Corona Virus Disease-2019(COVID-19) started in Wuhan, China. Now we comprehended much more about the troublesome disease from studies than the beginning. But more details between admission laboratory test and prognosis of COVID-19 were still confusing. So we focused on the admission biochemical test, and tried to verify their influence to the prognosis of COVID-19. Method: 522 patients from 4 hospitals were enrolled in this retrospective cohort study. We collected demographic information, comorbidities and laboratory biochemical indicators, then compared them between survivors’ and nonsurvivors’ group. Logistic regression methods were used to explore the risk factors associated with in-hospital death. Linear regression and receiver operating characteristic curve(ROC-curve) was applied to assess the efficiency of risk factors and regression model. Results: Age of nonsurvivors’ group(68.9) was older than survivors group(50.0). Diabetes(68.7%) was the most common comorbidity in the nonsurvivors’ group. In univariate regression analysis, most biochemical tests were related to the mortality except lipid metabolic results. Age, fasting blood glucose and blood urea nitrogen(BUN) were with a p-value less than 0.001 in multivariate regression model. Conclusion: Age, BUN and fasting blood glucose were risk factors associated with the prognosis of COVID-19 related pneumonia.Authors Qi Long, Chen-liang Zhou, Ye-ming Wang, Bin Song, Xiao-bin Cheng, Qiu-fen Dong, and Liu-lin Wang contributed equally to this work.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325388

ABSTRACT

Background: During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. In general, continuous negative viral tests are thought to indicate that the virus has been cleared from the body and that the patients can be considered "recovered". However, because these patients were still critically ill, they obviously had not truly recovered from the disease. We sought to investigate why these patients were still critically ill even though they exhibited negative viral tests by analyzing the gene expression profiles of their peripheral immune cells using transcriptome sequencing. Methods: Fourteen severe COVID-19 patients with at least 3 negative virus tests but were still in critical ill and could not be discharged from the ICU were enrolled. Blood samples from 14 patients and 5 healthy donors were collected. Total RNA was extracted from nucleated cells for RNA-Sequencing. FeatureCounts v1.5.0-p3 was used to count the reads numbers mapped to each gene. Results: All enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. This adaptive immune suppression is unlikely due to classic immune checkpoint molecules such as PD-1 or long-term use of glucocorticoids but may be caused by an unknown mechanism that has not yet been discovered. Conclusions: Our findings strongly suggest that an initial recovery of these severe COVID-19 patients, as indicated by negative viral tests, may not indicate actual recovery. They still suffer from secondary infections for a long period of time because of severe adaptive immunosuppression and need to receive a variety of antibiotics, antifungal drugs, or combination therapies. Appropriate methods should be used to detect their adaptive immune function, and appropriate immunotherapy that can activate the adaptive immune response should be developed. Trial registration: Not applicable (this study does not involve intervention on human participants).

4.
Br J Anaesth ; 128(3): 491-500, 2022 03.
Article in English | MEDLINE | ID: covidwho-1608752

ABSTRACT

BACKGROUND: There is a need to assess the long-term outcomes of survivors of critical illness from COVID-19. METHODS: Ninety-two survivors of critical illness from COVID-19 from four hospitals in Hubei Province, China participated in this prospective cohort study. Multiple characteristics, including lung function (lung volumes, diffusing capacity for carbon monoxide, chest computed tomography scores, and walking capacity); immune status (SARS-CoV-2-neutralising antibody and all subtypes of immunoglobulin (Ig) G against SARS-CoV-2, immune cells in response to ex vivo antigen peptide stimuli, and lymphocyte count and its subtypes); liver, coagulation, and kidney functions; quality of life; cognitive function; and mental status, were assessed after 3, 6, and 12 months of follow-up. RESULTS: Amongst the 92 enrolled survivors, 72 (78%) patients required mechanical ventilation. At 12 months, the predicted percentage diffusing capacity of lung for carbon monoxide was 82% (inter-quartile range [IQR]: 76-97%) with a residual volume of 77 (64-88)%. Other lung function parameters and the 6-min walk test improved gradually over time and were almost back to normal by 12 months. The titres of IgG and neutralising antibody to COVID-19 remained high at 12 months compared with those of controls who were not infected with COVID-19, although IgG titres decreased significantly from 34.0 (IQR: 23.8-74.3) to 15.0 (5.8-24.3) AU ml-1 (P<0.001), whereas neutralising antibodies decreased from 29.99 (IQR: 19.43-53.93) AU ml-1 at 6 months to 19.75 (13.1-29.8) AU ml-1 (P<0.001) at 12 months. In general, liver, kidney, physical, and mental functions also improved over time. CONCLUSIONS: Survivors of critical illness from COVID-19 show some persistent long-term impairments in lung function. However, a majority of these tests were normal by 12 months. These patients still had detectable levels of neutralising antibodies against SARS-CoV-2 and all types of IgG at 12 months, but the levels had declined over this time period. CLINICAL TRIAL REGISTRATION: None.


Subject(s)
Antibodies/blood , COVID-19/diagnosis , COVID-19/immunology , Survivors , Aged , Antibodies, Neutralizing/blood , COVID-19/blood , China , Critical Illness , Cytokines/blood , Female , Humans , Kidney/physiopathology , Liver/physiopathology , Lung/diagnostic imaging , Lung/physiopathology , Male , Middle Aged , Prognosis , Prospective Studies , Quality of Life , Respiratory Function Tests , SARS-CoV-2/immunology , Tomography, X-Ray Computed , Walk Test
5.
Front Immunol ; 12: 755579, 2021.
Article in English | MEDLINE | ID: covidwho-1556334

ABSTRACT

During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. To explore the underlying mechanism, we collected blood samples from these patients and analyzed the gene expression profiles of peripheral immune cells. We found that all enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. In addition, no significant change was found in the expression of classic immunosuppression molecules including PD-1, PD-L1, and CTLA-4, suggesting that the adaptive immune suppression may not be due to the change of these genes. According to the published literatures and our data, this adaptive immunosuppression is likely to be caused by the "dysregulated host response" to severe infection, similar to the immunosuppression that exists in other severely infected patients with sepsis.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , Immune Tolerance/immunology , Adaptive Immunity/genetics , Aged , COVID-19/diagnosis , COVID-19/genetics , Coinfection/diagnosis , Coinfection/genetics , Coinfection/immunology , Cross-Sectional Studies , Cytokine Release Syndrome/genetics , Female , Gene Expression Profiling , Humans , Immune Tolerance/genetics , Inflammation/genetics , Intensive Care Units , Male , Middle Aged , Patient Discharge , SARS-CoV-2/isolation & purification , Smell/genetics , Taste/genetics
6.
Vaccine ; 39(48): 7001-7011, 2021 11 26.
Article in English | MEDLINE | ID: covidwho-1488001

ABSTRACT

COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases is urgently needed. We have been developing a recombinant vaccine based on a prefusion-stabilized spike trimer of SARS-CoV-2 and formulated with aluminium hydroxide and CpG 7909. The spike protein was expressed in Chinese hamster ovary (CHO) cells, purified, and prepared as a stable formulation with the dual adjuvant. Immunogenicity studies showed that candidate vaccines elicited robust neutralizing antibody responses and substantial CD4+ T cell responses in both mice and non-human primates. And vaccine-induced neutralizing antibodies persisted at high level for at least 6 months. Challenge studies demonstrated that candidate vaccine reduced the viral loads and inflammation in the lungs of SARS-CoV-2 infected golden Syrian hamsters significantly. In addition, the vaccine-induced antibodies showed cross-neutralization activity against B.1.1.7 and B.1.351 variants. These data suggest candidate vaccine is efficacious in preventing SARS-CoV-2 infections and associated pneumonia, thereby justifying ongoing phase I/II clinical studies in China (NCT04982068 and NCT04990544).


Subject(s)
COVID-19 Vaccines , COVID-19 , Alum Compounds , Aluminum Hydroxide , Animals , Antibodies, Neutralizing , Antibodies, Viral , CHO Cells , Cricetinae , Cricetulus , Humans , Mice , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
7.
Sci Rep ; 11(1): 17791, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1397897

ABSTRACT

The purpose of this study is to explore whether uric acid (UA) can independently act as a prognostic factor and critical marker of the 2019 novel corona virus disease (COVID-19). A multicenter, retrospective, and observational study including 540 patients with confirmed COVID-19 was carried out at four designated hospitals in Wuhan. Demographic, clinical, laboratory data were collected and analyzed. The primary end point was in-hospital death of patients with COVID-19. The concentration of admission UA (adUA) and the lowest concentration of uric acid during hospitalization (lowUA) in the dead patients were significantly lower than those in the survivors. Multivariate logistic regression analysis showed the concentration of lowUA (OR 0.986, 95% CI 0.980-0.992, p < 0.001) was able to independently predict the risk of in-hospital death. The mean survival time in the low-level group of lowUA was significantly lower than other groups. When lowUA was ≤ 166 µmol/L, the sensitivity and specificity in predicting hospital short-term mortality were 76.9%, (95% CI 68.5-85.1%) and 74.9% (95% CI 70.3-78.9%). This retrospective study determined that the lowest concentration of UA during hospitalization can be used as a prognostic indicator and a marker of disease severity in severe patients with COVID-19.


Subject(s)
COVID-19/mortality , Uric Acid/blood , Adult , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , China/epidemiology , Feasibility Studies , Female , Hospital Mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment/methods , Risk Factors , Sensitivity and Specificity , Severity of Illness Index
8.
BMC Infect Dis ; 21(1): 371, 2021 Apr 20.
Article in English | MEDLINE | ID: covidwho-1195913

ABSTRACT

BACKGROUND: The current coronavirus disease 2019 (COVID-19) is a public health emergency. In this study, we aimed to evaluate the risk factors for mortality in severe and critical COVID-19 patients. METHODS: We performed a retrospective study of patients diagnosed with severe and critical COVID-19 from four hospitals in Wuhan, China, by evaluating the clinical characteristics and laboratory results, and using Cox proportional hazards model to assess the risk factors involved in disease progression. RESULTS: In total, 446 patients with COVID-19 were enrolled. The study indicated a high mortality rate (20.2%) in severe and critical COVID-19 patients. At the time of admission, all patients required oxygen therapy, and 52 (12%) required invasive mechanical ventilation, of which 50 (96%) died. The univariate Cox proportional hazards model showed a white blood cell count of more than 10 × 109/L (HR 3.993,95%CI 2.469 to 6.459) that correlated with an increased mortality rate. The multivariable Cox proportional hazards model demonstrated that older age (HR 1.066, 95% CI 1.043 to 1.089) and higher white blood cell count (HR 1.135, 95% CI 1.080 to 1.192) were independent risk factors for determining COVID-19 associated mortality. CONCLUSIONS: COVID-19 is associated with a significant risk of morbidity and mortality in the population. Older age and higher white blood cell count were found to be independent risk factors for mortality.


Subject(s)
Age Factors , COVID-19/diagnosis , Leukocyte Count , Adult , Aged , COVID-19/physiopathology , China/epidemiology , Female , Hospitalization , Humans , Male , Middle Aged , Proportional Hazards Models , Respiration, Artificial , Retrospective Studies , Risk Factors
9.
Medicine (Baltimore) ; 100(16): e25619, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1195757

ABSTRACT

ABSTRACT: The coronavirus disease (COVID-19) outbreak was first reported in December 2019 in Wuhan, China. Specific information about critically ill COVID-19 patients receiving invasive mechanical ventilation (IMV) is rare.To describe the clinical course and complications of critically ill patients with COVID-19 who received IMV and were successfully weaned from it.This retrospective study included patients admitted to 3 intensive care units (ICUs) and 1 sub-ICU of Renmin Hospital of Wuhan University and Wuhan Jin Yin-tan Hospital between December 24, 2019, and March 12, 2020. Eleven patients who had been diagnosed with critically ill COVID-19 according to the World Health Organization interim guidance, received invasive ventilation, and were finally successfully weaned from it, were enrolled in our study. Their presenting symptoms, comorbidity conditions, laboratory values, ICU course, ventilator parameters, treatments, and relative complications were recorded.Of 108 critically ill COVID-19 patients who received invasive ventilation, 11 patients who underwent tracheal extubation or terminal weaning were included. The mean age of the 11 patients was 52.8 years (range, 38-70 years), 8 (72.7%) were male, and 2 were health care workers. The median time from onset of symptoms to dyspnea was 6.6 days (range, 3-13 days), and the median duration of IMV was 15.7 days (range, 6-29 days). All 11 patients presented with acute severe hypoxemic respiratory failure and received IMV, and 1 patient switched to extracorporeal membrane oxygenation assistance. A lung-protective strategy with lower tidal volume ventilation and proper driving pressure is the main strategy of IMV. All patients had extrapulmonary manifestations, including acute kidney injury, hepatic dysfunction, myocardial damage, and/or lymphopenia. Hospital-acquired infections occurred in 7 (63.6%) patients.Critical COVID-19 illness is characterized by acute hypoxemic respiratory failure and subsequent dysfunction of other organs with a high mortality rate. Correct ventilation strategies and other clinical strategies to improve oxygenation based on the skilled trained group and the availability of equipment are the key methods to rescue lives.


Subject(s)
Coronavirus Infections/therapy , Critical Care/methods , Respiration, Artificial , Ventilator Weaning , Adult , Aged , China , Coronavirus Infections/complications , Extracorporeal Membrane Oxygenation , Female , Humans , Hypoxia/therapy , Hypoxia/virology , Male , Middle Aged , Respiration, Artificial/adverse effects , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Retrospective Studies
10.
Virulence ; 12(1): 1199-1208, 2021 12.
Article in English | MEDLINE | ID: covidwho-1192789

ABSTRACT

Background: COVID-19 has rapidly become a major health emergency worldwide. The characteristic, outcome, and risk factor of COVID-19 in patients with decompensated cirrhosis remain unclear.Methods: Medical records were collected from 23 Chinese hospitals. Patients with decompensated cirrhosis and age- and sex-matched non-liver disease patients were enrolled with 1:4 ratio using stratified sampling.Results: There were more comorbidities with higher Chalson Complication Index (p < 0.001), higher proportion of patients having gastrointestinal bleeding, jaundice, ascites, and diarrhea among those patients (p < 0.05) and in decompensated cirrhosis patients. Mortality (p < 0.05) and the proportion of severe ill (p < 0.001) were significantly high among those patients. Patients in severe ill subgroup had higher mortality (p < 0.001), MELD, and CRUB65 score but lower lymphocytes count. Besides, this subgroup had larger proportion of patients with abnormal (PT), activated partial thromboplatin time (APTT), D-Dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) and Creatinine (Cr) (p < 0.05). Multivariate logistic regression for severity shown that MELD and CRUB65 score reached significance. Higher Child-Pugh and CRUB65 scores were found among non-survival cases and multivariate logistic regression further inferred risk factors for adverse outcome. Receiver Operating Characteristic (ROC) curves also provided remarkable demonstrations for the predictive ability of Child-Pugh and CRUB65 scores.Conclusions: COVID-19 patients with cirrhosis had larger proportion of more severely disease and higher mortality. MELD and CRUB65 score at hospital admission may predict COVID-19 severity while Child-Pugh and CRUB65 score were highly associated with non-survival among those patients.


Subject(s)
COVID-19/mortality , Liver Cirrhosis/complications , SARS-CoV-2 , Severity of Illness Index , Adult , Aged , COVID-19/etiology , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
11.
Front Pharmacol ; 11: 603830, 2020.
Article in English | MEDLINE | ID: covidwho-1058447

ABSTRACT

The global spread of the novel coronavirus SARS-CoV-2 urgently requires discovery of effective therapeutics for the treatment of COVID-19. The spike (S) protein of SARS-CoV-2 plays a key role in receptor recognition, virus-cell membrane fusion and virus entry. Our previous studies have reported that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) serves as a viral entry inhibitor to prevent several kinds of virus infection. Here, our results reveal that HP-OVA can effectively inhibit SARS-CoV-2 replication and S protein-mediated cell-cell fusion in a dose-dependent manner without obvious cytopathic effects. Further analysis suggests that HP-OVA can bind to both the S protein of SARS-CoV-2 and host angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and disrupt the S protein-ACE2 interaction, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that HP-OVA can serve as a potential therapeutic agent for the treatment of deadly COVID-19.

12.
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
13.
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
14.
Aging (Albany NY) ; 12(22): 22399-22404, 2020 11 20.
Article in English | MEDLINE | ID: covidwho-940434

ABSTRACT

BACKGROUND: The aim of this study was to investigate the host factors of patients with COVID-19 that were associated with delayed viral RNA clearance in specimens obtained from the upper respiratory tract. RESULTS: A median of a 32-day period of viral RNA shedding was observed, ranging from 4 days to 111 days. On multivariate analysis, elderly age was independently associated with prolonged viral shedding (OR = 1.02, 95% CI: 1.01-1.04, P = 0.003). An incremental increase in the duration of viral RNA shedding was observed with increasing age (P < 0.05). The median (quartile) duration of viral RNA shedding was 23 (22) days (≤ 40 years), 30 (18) days (41-50 years), 33 (21) days (51-60 years), 34 (17) days (61-70 years) and 34 (17) days (> 70 years). CONCLUSIONS: Viral RNA shedding can persist for as long as 111 days in the upper respiratory tract. Increasing age is associated with viral RNA persistence. METHOD: The demographic and virological data of patients with laboratory-confirmed COVID-19 were retrospectively analyzed. A multivariate logistic regression analysis was performed to identify significant risk factors associated with delayed viral RNA clearance. The duration of viral shedding was compared among age-stratified groups.


Subject(s)
COVID-19/transmission , RNA, Viral/isolation & purification , SARS-CoV-2/isolation & purification , Virus Shedding , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Risk Factors , SARS-CoV-2/genetics , Time Factors
15.
Clin Nutr ; 40(4): 2154-2161, 2021 04.
Article in English | MEDLINE | ID: covidwho-808531

ABSTRACT

OBJECTIVE: To evaluate the nutritional risk and therapy in severe and critical patients with COVID-19. METHODS: A total of 523 patients enrolled from four hospitals in Wuhan, China. The inclusion time was from January 2, 2020 to February 15. Clinical characteristics and laboratory values were obtained from electronic medical records, nursing records, and related examinations. RESULTS: Of these patients, 211 (40.3%) were admitted to the ICU and 115 deaths (22.0%). Patients admitted to the ICU had lower BMI and plasma protein levels. The median Nutrition risk in critically ill (NUTRIC) score of 211 patients in the ICU was 5 (4, 6) and Nutritional Risk Screening (NRS) score was 5 (3, 6). The ratio of parenteral nutrition (PN) therapy in non-survivors was greater than that in survivors, and the time to start nutrition therapy was later than that in survivors. The NUTRIC score can independently predict the risk of death in the hospital (OR = 1.197, 95%CI: 1.091-1.445, p = 0.006) and high NRS score patients have a higher risk of poor outcome in the ICU (OR = 1.880, 95%CI: 1.151-3.070, p = 0.012). After adjusted age and sex, for each standard deviation increase in BMI, the risk of in-hospital death was reduced by 13% (HR = 0.871, 95%CI: 0.795-0.955, p = 0.003), and the risk of ICU transfer was reduced by 7% (HR = 0.932, 95%CI:0.885-0.981, p = 0.007). The in-hospital survival time of patients with albumin level ≤35 g/L was significantly decreased (15.9 d, 95% CI: 13.7-16.3, vs 24.2 d, 95% CI: 22.3-29.7, p < 0.001). CONCLUSION: Severe and critical patients with COVID-19 have a high risk of malnutrition. Low BMI and protein levels were significantly associated with adverse events. Early nutritional risk screening and therapy for patients with COVID-19 are necessary.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Critical Illness/epidemiology , Critical Illness/therapy , Malnutrition/epidemiology , Malnutrition/therapy , Nutritional Support , Adult , Aged , COVID-19/mortality , China/epidemiology , Critical Illness/mortality , Female , Hospital Mortality , Hospitalization , Humans , Intensive Care Units , Kaplan-Meier Estimate , Male , Malnutrition/mortality , Middle Aged , Nutrition Assessment , Nutritional Status , Proportional Hazards Models , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Severity of Illness Index , Time-to-Treatment
16.
Hum Vaccin Immunother ; 16(10): 2366-2369, 2020 Oct 02.
Article in English | MEDLINE | ID: covidwho-786981

ABSTRACT

The recent outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been characterized by the World Health Organization (WHO) as a controllable global pandemic. The spike (S) glycoprotein mediates binding to the angiotensin-converting enzyme 2 (ACE2) receptor for virus entry and also services as the target of virus-neutralizing antibodies, making it an attractive and leading viral antigen for vaccine development. No vaccine against any human coronavirus is available to date. In learning from the experience of developing Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV vaccine candidates in preclinical and clinical trials, the most promising strategies for SARS-CoV-2 vaccines should employ viral-vector platforms, properly adjuvanted recombinant protein or DNA/mRNA encoding an engineered sequence of trimeric S protein in pre-fusion conformation.


Subject(s)
Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/immunology , Angiotensin-Converting Enzyme 2 , Betacoronavirus/immunology , COVID-19 , Humans , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
17.
Trials ; 21(1): 738, 2020 Aug 24.
Article in English | MEDLINE | ID: covidwho-727297

ABSTRACT

OBJECTIVES: This study aims to determine the protection provided by Shenfu injection (a traditional Chinese medicine) against development of organ dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19). TRIAL DESIGN: This study is a multicenter, randomized, controlled, open-label, two-arm ratio 1:1, parallel group clinical trial. PARTICIPANTS: The patients, who are aged from 18 to 75 years old, with a confirmed or suspected diagnosis of severe or critical COVID-19, will be consecutively recruited in the study, according to the guideline on diagnosis and treatment of COVID-19 (the 7th version) issued by National Health Commission of the People's Republic of China. Exclusion criteria include pregnant and breastfeeding women, atopy or allergies to Shenfu Injection (SFI), severe underlying disease (malignant tumor with multiple metastases, uncontrolled hemopathy, cachexia, severe malnutrition, HIV), active bleeding, obstructive pneumonia caused by lung tumor, severe pulmonary interstitial fibrosis, alveolar proteinosis and allergic alveolitis, continuous use of immunosuppressive drugs in last 6 months, organ transplantation, expected death within 48 hours, the patients considered unsuitable for this study by researchers. The study is conducted in 11 ICUs of designated hospitals for COVID-19, located in 5 cities of China. INTERVENTION AND COMPARATOR: The enrolled patients will randomly receive 100 ml SFI (study group) or identical volume of saline (control group) twice a day for seven consecutive days. Patients in the both groups will be given usual care and the necessary supportive therapies as recommended by the latest edition of the management guidelines for COVID-19 (the 7th version so far). MAIN OUTCOMES: The primary endpoint is a composite of newly developed or exacerbated organ dysfunction. This is defined as an increase in the sequential organ failure assessment (SOFA) score of two or more, indicating sepsis and involvement of at least one organ. The SOFA score will be measured for the 14 days after enrolment from the baseline (the score at randomization). The secondary endpoints are shown below: • SOFA score in total • Pneumonia severity index score • Dosage of vasoactive drugs • Ventilation free days within 28 days • Length of stay in intensive care unit • Total hospital costs to treat the patient • 28-day mortality • The incidence of adverse drug events related to SFI RANDOMISATION: The block randomization codes were generated by SAS V.9.1 for allocation of participants in this study. The ratio of random distribution is 1:1. The sealed envelope method is used for allocation concealment. BLINDING (MASKING): The patients and statistical personnel analyzing study data are both blinded. The blinding of group assignment is not adopted for the medical staff. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study is expected to recruit 300 patients with COVID-19, (150 in each group). TRIAL STATUS: Protocol version 2.0, February 15, 2020. Patient recruitment started on February 25, and will end on August 31, 2020. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000030043. Registered February 21, 2020, http://www.chictr.org.cn/showprojen.aspx?proj=49866 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Subject(s)
Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Organ Dysfunction Scores , Pneumonia, Viral/drug therapy , Betacoronavirus , COVID-19 , China , Coronavirus Infections/physiopathology , Critical Illness , Humans , Pandemics , Pneumonia, Viral/physiopathology , SARS-CoV-2
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.
Infection ; 48(5): 715-722, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-688761

ABSTRACT

OBJECTIVE: To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). METHODS: The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. RESULTS: The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z1 = - 1.426, P = 0.154. The Z1 values (Z1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were - 5.569, - 6.967, and - 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. CONCLUSION: SAA can be used as a predictor of the prognosis in patients with COVID-19.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/diagnosis , Cough/diagnosis , Fever/diagnosis , Pharyngitis/diagnosis , Pneumonia, Viral/diagnosis , Serum Amyloid A Protein/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19 , China , Coronavirus Infections/blood , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Cough/blood , Cough/mortality , Cough/physiopathology , Female , Fever/blood , Fever/mortality , Fever/physiopathology , Hemoglobins/metabolism , Humans , Leukocyte Count , Male , Middle Aged , Pandemics , Pharyngitis/blood , Pharyngitis/mortality , Pharyngitis/physiopathology , Pneumonia, Viral/blood , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
20.
Trials ; 21(1): 520, 2020 Jun 12.
Article in English | MEDLINE | ID: covidwho-595058

ABSTRACT

OBJECTIVES: To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. TRIAL DESIGN: This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. PARTICIPANTS: Twenty serious COVID-19 cases will be enrolled in the trial from April 6th to December 31st 2020. INCLUSION CRITERIA: hospitalised patients at Renmin Hospital of Wuhan University satisfy all criteria as below: 1)Adults aged 18-65 years;2)Voluntarily participate in this clinical trial and sign the "informed consent form" or have consent from a legal representative.3)Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg).4)COVID-19 featured lung lesions in chest X-ray image. EXCLUSION CRITERIA: Patients will be excluded from the study if they meet any of the following criteria. 1.Patients have received other experimental treatment for COVID-19 within the last 30 days;2.Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit);3.Patients with severe renal insufficiency (estimated glomerular filtration rate <=30mL / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis;4.Patients who are co-infected with HIV, hepatitis B, tuberculosis, influenza virus, adenovirus or other respiratory infection viruses;5.Female patients who have no sexual protection in the last 30 days prior to the screening assessment;6.Pregnant or lactating women or women using estrogen contraception;7.Patients who are planning to become pregnant during the study period or within 6 months after the end of the study period;8.Other conditions that the researchers consider not suitable for participating in this clinical trial. INTERVENTION AND COMPARATOR: There will be two study groups: experimental and control. Both will receive all necessary routine treatment for COVID-19. The experimental group will receive an intravenous injection of dental pulp stem cells suspension (3.0x107 human DPSCs in 30ml saline solution) on day 1, 4 and 7; The control group will receive an equal amount of saline (placebo) on the same days. Clinical and laboratory observations will be performed for analysis during a period of 28 days for each case since the commencement of the study. MAIN OUTCOMES: 1. Primary outcome The primary outcome is Time To Clinical Improvement (TTCI). By definition, TTCI is the time (days) it takes to downgrade two levels from the following six ordered grades [(grade 1) discharge to (grade 6) death] in the clinical state of admission to the start of study treatments (hDPSCs or placebo). Six grades of ordered variables: GradeDescriptionGrade 1:Discharged of patient;Grade 2:Hospitalized without oxygen supplement;Grade 3:Hospitalized, oxygen supplement is required, but NIV / HFNC is not required;Grade 4:Hospitalized in intensive care unit, and NIV / HFNC treatment is required;Grade 5:Hospitalized in intensive care unit, requiring ECMO and/or IMV;Grade 6:Death. ABBREVIATIONS: NIV, non-invasive mechanical ventilation; HFNC, high-flow nasal catheter; IMV, invasive mechanical ventilation. 2. Secondary outcomes 2.1 vital signs: heart rate, blood pressure (systolic blood pressure, diastolic blood pressure). During the screening period, hospitalization every day (additional time points of D1, D4, D7 30min before injection, 2h ± 30min, 24h ± 30min after the injection) and follow-up period D90 ± 3 days. 2.2 Laboratory examinations: during the screening period, 30 minutes before D1, D4, D7 infusion, 2h ± 30min, 24h ± 30min after the end of infusion, D10, D14, D28 during hospitalization or discharge day and follow-up period D90 ± 3 days. 2.3 Blood routine: white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, neutrophils, lymphocytes, monocytes, eosinophils Acidic granulocyte count, basophil count, red blood cell, hemoglobin, hematocrit, average volume of red blood cells, average red blood cell Hb content, average red blood cell Hb concentration, RDW standard deviation, RDW coefficient of variation, platelet count, platelet specific platelet average Volume, platelet distribution width,% of large platelets; 2.4 Liver and kidney function tests: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transferase, prealbumin, total protein, albumin, globulin, white / globule ratio , Total bilirubin, direct bilirubin, cholinesterase, urea, creatinine, total carbon dioxide, uric acid glucose, potassium, sodium, chlorine, calcium, corrected calcium, magnesium, phosphorus, calcium and phosphorus product, anion gap, penetration Pressure, total cholesterol, triacylglycerol, high density lipoprotein cholesterol, Low density lipoprotein cholesterol, lipoprotein a, creatine kinase, lactate dehydrogenase, estimated glomerular filtration rate. 2.5 Inflammation indicators: hypersensitive C-reactive protein, serum amyloid (SAA); 2.6 Infectious disease testing: Hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), Hepatitis C (Anti-HCV), AIDS (HIVcombin), syphilis (Anti-TP), cytomegalovirus CMV-IgM, cytomegalovirus CMV-IgG; only during the screening period and follow-up period D90 ± 3. 2.7 Immunological testing: Collect peripheral blood to detect the phenotype of T lymphocyte, B lymphocyte, natural killer cell, Macrophage and neutrophil by using flow cytometry. Collect peripheral blood to detect the gene profile of mononuclear cells by using single-cell analyses. Collect peripheral blood serum to detect various immunoglobulin changes: IgA, IgG, IgM, total IgE; Collect peripheral blood serum to explore the changes of cytokines, Th1 cytokines (IL-1 ß, IL-2, TNF-a, ITN-γ), Th2 cytokines (IL-4, IL-6, IL -10). 2.8 Pregnancy test: blood ß-HCG, female subjects before menopause are examined during the screening period and follow-up period D90 ± 3. 2.9 Urine routine: color, clarity, urine sugar, bilirubin, ketone bodies, specific gravity, pH, urobilinogen, nitrite, protein, occult blood, leukocyte enzymes, red blood cells, white blood cells, epithelial cells, non-squamous epithelial cells , Transparent cast, pathological cast, crystal, fungus; 2.10 Stool Routine: color, traits, white blood cells, red blood cells, fat globules, eggs of parasites, fungi, occult blood (chemical method), occult blood (immune method), transferrin (2h ± 30min after the injection and not detected after discharge). RANDOMIZATION: Block randomization method will be applied by computer to allocate the participants into experimental and control groups. The random ratio is 1:1. BLINDING (MASKING): Participants, outcomes assessors and investigators (including personnel in laboratory and imaging department who issue the sample report or image observations) will be blinded. Injections of cell suspension and saline will be coded in accordance with the patient's randomisation group. The blind strategy is kept by an investigator who does not deliver the medical care or assess primary outcome results. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Twenty participants will be randomized to the experimental and control groups (10 per group). TRIAL STATUS: Protocol version number, hDPSC-CoVID-2019-02-2020 Version 2.0, March 13, 2020. Patients screening commenced on 16th April and an estimated date of the recruitment of the final participants will be around end of July. . TRIAL REGISTRATION: Registration: World Health Organization Trial Registry: ChiCTR2000031319; March 27,2020. ClinicalTrials.gov Identifier: NCT04336254; April 7, 2020 Other Study ID Numbers: hDPSC-CoVID-2019-02-2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Coronavirus Infections/therapy , Dental Pulp/cytology , Pneumonia, Viral/therapy , Randomized Controlled Trials as Topic , Stem Cell Transplantation/methods , Adolescent , Adult , Aged , Betacoronavirus , COVID-19 , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Pandemics , SARS-CoV-2 , Stem Cell Transplantation/adverse effects , Transplantation, Homologous , Young Adult
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